The purpose of this study was to determine if dual-energy CT (DECT) vital iodine tumor burden (ViTB), a direct assessment of tumor vascularity, allows reliable response assessment in patients with GIST compared to established CT criteria such as RECIST1.1 and modified Choi (mChoi). From 03/2014 to 12/2019, 138 patients (64 years [32-94 years]) with biopsy proven GIST were entered in this prospective, multi-center trial. All patients were treated with tyrosine kinase inhibitors (TKI) and underwent pre-treatment and follow-up DECT examinations for a minimum of 24 months. Response assessment was performed according to RECIST1.1, mChoi, vascular tumor burden (VTB) and DECT ViTB. A change in therapy management could be because of imaging (RECIST1.1 or mChoi) and/or clinical progression. The DECT ViTB criteria had the highest discrimination ability for progression-free survival (PFS) of all criteria in both first line and second line and thereafter treatment, and was significantly superior to RECIST1.1 and mChoi (p < .034). Both, the mChoi and DECT ViTB criteria demonstrated a significantly early median time-to-progression (both delta 2.5 months; both p < .036). Multivariable analysis revealed 6 variables associated with shorter overall survival: secondary mutation (HR = 4.62), polymetastatic disease (HR = 3.02), metastatic second line and thereafter treatment (HR = 2.33), shorter PFS determined by the DECT ViTB criteria (HR = 1.72), multiple organ metastases (HR = 1.51) and lower age (HR = 1.04). DECT ViTB is a reliable response criteria and provides additional value for assessing TKI treatment in GIST patients. A significant superior response discrimination ability for median PFS was observed, including non-responders at first follow-up and patients developing resistance while on therapy..

IMPORTANCE: Desmoid tumor (DT) is a rare and locally aggressive monoclonal, fibroblastic proliferation characterized by a variable and often unpredictable clinical course. Previously, surgery was the standard primary treatment modality; however, within the past decade, a paradigm shift toward less-invasive management has been introduced and an effort to harmonize the strategy among clinicians has been made. To update the 2020 global evidence-based consensus guideline on the management of patients with DT, the Desmoid Tumor Working Group convened a 1-day consensus meeting in Milan, Italy, on June 30, 2023, under the auspices of the European Reference Network on Rare Adult Solid Cancers and Sarcoma Patient Advocacy Global Network, the Desmoid Foundation Italy, and the Desmoid Tumor Research Foundation. The meeting brought together over 90 adult and pediatric sarcoma experts from different disciplines as well as patients and patient advocates from around the world. OBSERVATIONS: The 2023 update of the global evidence-based consensus guideline focused on the positioning of local therapies alongside surgery and radiotherapy in the treatment algorithm as well as the positioning of the newest class of medical agents, such as γ-secretase inhibitors. Literature searches of MEDLINE and Embase databases were performed for English-language randomized clinical trials (RCTs) of systemic therapies to obtain data to support the consensus recommendations. Of the 18 full-text articles retrieved, only 4 articles met the inclusion criteria. The 2023 consensus guideline is informed by a number of new aspects, including data for local ablative therapies such as cryotherapy; other indications for surgery; and the γ-secretase inhibitor nirogacestat, the first representative of the newest class of medical agents and first approved drug for DT. Management of DT is complex and should be carried out exclusively in designated DT referral centers equipped with a multidisciplinary tumor board. Selection of the appropriate strategy should consider DT-related symptoms, associated risks, tumor location, disease morbidities, available treatment options, and preferences of individual patients. CONCLUSIONS AND RELEVANCE: The therapeutic armamentarium of DT therapy is continually expanding. It is imperative to carefully select the management strategy for each patient with DT to optimize tumor control and enhance quality of life..

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This Good Practice Paper provides recommendations for the use of advanced imaging for earlier diagnosis and morbidity prevention in multiple myeloma. It describes how advanced imaging contributes to optimal healthcare resource utilisation by in newly diagnosed and relapsed myeloma, and provides a perspective on future directions of myeloma imaging, including machine learning assisted reporting..

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OBJECTIVES: MAchine Learning In MyelomA Response (MALIMAR) is an observational clinical study combining "real-world" and clinical trial data, both retrospective and prospective. Images were acquired on three MRI scanners over a 10-year window at two institutions, leading to a need for extensive curation. METHODS: Curation involved image aggregation, pseudonymisation, allocation between project phases, data cleaning, upload to an XNAT repository visible from multiple sites, annotation, incorporation of machine learning research outputs and quality assurance using programmatic methods. RESULTS: A total of 796 whole-body MR imaging sessions from 462 subjects were curated. A major change in scan protocol part way through the retrospective window meant that approximately 30% of available imaging sessions had properties that differed significantly from the remainder of the data. Issues were found with a vendor-supplied clinical algorithm for "composing" whole-body images from multiple imaging stations. Historic weaknesses in a digital video disk (DVD) research archive (already addressed by the mid-2010s) were highlighted by incomplete datasets, some of which could not be completely recovered. The final dataset contained 736 imaging sessions for 432 subjects. Software was written to clean and harmonise data. Implications for the subsequent machine learning activity are considered. CONCLUSIONS: MALIMAR exemplifies the vital role that curation plays in machine learning studies that use real-world data. A research repository such as XNAT facilitates day-to-day management, ensures robustness and consistency and enhances the value of the final dataset. The types of process described here will be vital for future large-scale multi-institutional and multi-national imaging projects. CRITICAL RELEVANCE STATEMENT: This article showcases innovative data curation methods using a state-of-the-art image repository platform; such tools will be vital for managing the large multi-institutional datasets required to train and validate generalisable ML algorithms and future foundation models in medical imaging. KEY POINTS: • Heterogeneous data in the MALIMAR study required the development of novel curation strategies. • Correction of multiple problems affecting the real-world data was successful, but implications for machine learning are still being evaluated. • Modern image repositories have rich application programming interfaces enabling data enrichment and programmatic QA, making them much more than simple "image marts"..

Objective.Image quality in whole-body MRI (WB-MRI) may be degraded by faulty radiofrequency (RF) coil elements or mispositioning of the coil arrays. Phantom-based quality control (QC) is used to identify broken RF coil elements but the frequency of these acquisitions is limited by scanner and staff availability. This work aimed to develop a scan-specific QC acquisition and processing pipeline to detect broken RF coil elements, which is sufficiently rapid to be added to the clinical WB-MRI protocol. The purpose of this is to improve the quality of WB-MRI by reducing the number of patient examinations conducted with suboptimal equipment.Approach.A rapid acquisition (14 s additional acquisition time per imaging station) was developed that identifies broken RF coil elements by acquiring images from each individual coil element and using the integral body coil. This acquisition was added to one centre's clinical WB-MRI protocol for one year (892 examinations) to evaluate the effect of this scan-specific QC. To demonstrate applicability in multi-centre imaging trials, the technique was also implemented on scanners from three manufacturers.Main results. Over the course of the study RF coil elements were flagged as potentially broken on five occasions, with the faults confirmed in four of those cases. The method had a precision of 80% and a recall of 100% for detecting faulty RF coil elements. The coil array positioning measurements were consistent across scanners and have been used to define the expected variation in signal.Significance. The technique demonstrated here can identify faulty RF coil elements and positioning errors and is a practical addition to the clinical WB-MRI protocol. This approach was fully implemented on systems from two manufacturers and partially implemented on a third. It has potential to reduce the number of clinical examinations conducted with suboptimal hardware and improve image quality across multi-centre studies..

Mucosal (MM) and acral melanomas (AM) are rare melanoma subtypes of unmet clinical need; 15%-20% harbor KIT mutations potentially targeted by small-molecule inhibitors, but none yet approved in melanoma. This multicenter, single-arm Phase II trial (NICAM) investigates nilotinib safety and activity in KIT mutated metastatic MM and AM. KIT mutations are identified in 39/219 screened patients (18%); of 29/39 treated, 26 are evaluable for primary analysis. Six patients were alive and progression free at 6 months (local radiology review, 25%); 5/26 (19%) had objective response at 12 weeks; median OS was 7.7 months; ddPCR assay correctly identifies KIT alterations in circulating tumor DNA (ctDNA) in 16/17 patients. Nilotinib is active in KIT-mutant AM and MM, comparable to other KIT inhibitors, with demonstrable activity in nonhotspot KIT mutations, supporting broadening of KIT evaluation in AM and MM. Our results endorse further investigations of nilotinib for the treatment of KIT-mutated melanoma. This clinical trial was registered with ISRCTN (ISRCTN39058880) and EudraCT (2009-012945-49)..

(1) Background: We assessed the test-re-test repeatability of radiomics in metastatic castration-resistant prostate cancer (mCPRC) bone disease on whole-body diffusion-weighted (DWI) and T1-weighted Dixon MRI. (2) Methods: In 10 mCRPC patients, 1.5 T MRI, including DWI and T1-weighted gradient-echo Dixon sequences, was performed twice on the same day. Apparent diffusion coefficient (ADC) and relative fat-fraction-percentage (rFF%) maps were calculated. Per study, up to 10 target bone metastases were manually delineated on DWI and Dixon images. All 106 radiomic features included in the Pyradiomics toolbox were derived for each target volume from the ADC and rFF% maps. To account for inter- and intra-patient measurement repeatability, the log-transformed individual target measurements were fitted to a hierarchical model, represented as a Bayesian network. Repeatability measurements, including the intraclass correlation coefficient (ICC), were derived. Feature ICCs were compared with mean ADC and rFF ICCs. (3) Results: A total of 65 DWI and 47 rFF% targets were analysed. There was no significant bias for any features. Pairwise correlation revealed fifteen ADC and fourteen rFF% feature sub-groups, without specific patterns between feature classes. The median intra-patient ICC was generally higher than the inter-patient ICC. Features that describe extremes in voxel values (minimum, maximum, range, skewness, and kurtosis) showed generally lower ICCs. Several mostly shape-based texture features were identified, which showed high inter- and intra-patient ICCs when compared with the mean ADC or mean rFF%, respectively. (4) Conclusions: Pyradiomics texture features of mCRPC bone metastases varied greatly in inter- and intra-patient repeatability. Several features demonstrated good repeatability, allowing for further exploration as diagnostic parameters in mCRPC bone disease..

BACKGROUND: Whole-Body Diffusion-Weighted Imaging (WBDWI) is an established technique for staging and evaluating treatment response in patients with multiple myeloma (MM) and advanced prostate cancer (APC). However, WBDWI scans show inter- and intra-patient intensity signal variability. This variability poses challenges in accurately quantifying bone disease, tracking changes over follow-up scans, and developing automated tools for bone lesion delineation. Here, we propose a novel automated pipeline for inter-station, inter-scan image signal standardisation on WBDWI that utilizes robust segmentation of the spinal canal through deep learning. METHODS: We trained and validated a supervised 2D U-Net model to automatically delineate the spinal canal (both the spinal cord and surrounding cerebrospinal fluid, CSF) in an initial cohort of 40 patients who underwent WBDWI for treatment response evaluation (80 scans in total). Expert-validated contours were used as the target standard. The algorithm was further semi-quantitatively validated on four additional datasets (three internal, one external, 207 scans total) by comparing the distributions of average apparent diffusion coefficient (ADC) and volume of the spinal cord derived from a two-component Gaussian mixture model of segmented regions. Our pipeline subsequently standardises WBDWI signal intensity through two stages: (i) normalisation of signal between imaging stations within each patient through histogram equalisation of slices acquired on either side of the station gap, and (ii) inter-scan normalisation through histogram equalisation of the signal derived within segmented spinal canal regions. This approach was semi-quantitatively validated in all scans available to the study (N = 287). RESULTS: The test dice score, precision, and recall of the spinal canal segmentation model were all above 0.87 when compared to manual delineation. The average ADC for the spinal cord (1.7 × 10-3 mm2/s) showed no significant difference from the manual contours. Furthermore, no significant differences were found between the average ADC values of the spinal cord across the additional four datasets. The signal-normalised, high-b-value images were visualised using a fixed contrast window level and demonstrated qualitatively better signal homogeneity across scans than scans that were not signal-normalised. CONCLUSION: Our proposed intensity signal WBDWI normalisation pipeline successfully harmonises intensity values across multi-centre cohorts. The computational time required is less than 10 s, preserving contrast-to-noise and signal-to-noise ratios in axial diffusion-weighted images. Importantly, no changes to the clinical MRI protocol are expected, and there is no need for additional reference MRI data or follow-up scans..

OBJECTIVES: Whole-body magnetic resonance imaging (WB-MRI) has been demonstrated to be efficient and cost-effective for cancer staging. The study aim was to develop a machine learning (ML) algorithm to improve radiologists' sensitivity and specificity for metastasis detection and reduce reading times. MATERIALS AND METHODS: A retrospective analysis of 438 prospectively collected WB-MRI scans from multicenter Streamline studies (February 2013-September 2016) was undertaken. Disease sites were manually labeled using Streamline reference standard. Whole-body MRI scans were randomly allocated to training and testing sets. A model for malignant lesion detection was developed based on convolutional neural networks and a 2-stage training strategy. The final algorithm generated lesion probability heat maps. Using a concurrent reader paradigm, 25 radiologists (18 experienced, 7 inexperienced in WB-/MRI) were randomly allocated WB-MRI scans with or without ML support to detect malignant lesions over 2 or 3 reading rounds. Reads were undertaken in the setting of a diagnostic radiology reading room between November 2019 and March 2020. Reading times were recorded by a scribe. Prespecified analysis included sensitivity, specificity, interobserver agreement, and reading time of radiology readers to detect metastases with or without ML support. Reader performance for detection of the primary tumor was also evaluated. RESULTS: Four hundred thirty-three evaluable WB-MRI scans were allocated to algorithm training (245) or radiology testing (50 patients with metastases, from primary 117 colon [n = 117] or lung [n = 71] cancer). Among a total 562 reads by experienced radiologists over 2 reading rounds, per-patient specificity was 86.2% (ML) and 87.7% (non-ML) (-1.5% difference; 95% confidence interval [CI], -6.4%, 3.5%; P = 0.39). Sensitivity was 66.0% (ML) and 70.0% (non-ML) (-4.0% difference; 95% CI, -13.5%, 5.5%; P = 0.344). Among 161 reads by inexperienced readers, per-patient specificity in both groups was 76.3% (0% difference; 95% CI, -15.0%, 15.0%; P = 0.613), with sensitivity of 73.3% (ML) and 60.0% (non-ML) (13.3% difference; 95% CI, -7.9%, 34.5%; P = 0.313). Per-site specificity was high (>90%) for all metastatic sites and experience levels. There was high sensitivity for the detection of primary tumors (lung cancer detection rate of 98.6% with and without ML [0.0% difference; 95% CI, -2.0%, 2.0%; P = 1.00], colon cancer detection rate of 89.0% with and 90.6% without ML [-1.7% difference; 95% CI, -5.6%, 2.2%; P = 0.65]). When combining all reads from rounds 1 and 2, reading times fell by 6.2% (95% CI, -22.8%, 10.0%) when using ML. Round 2 read-times fell by 32% (95% CI, 20.8%, 42.8%) compared with round 1. Within round 2, there was a significant decrease in read-time when using ML support, estimated as 286 seconds (or 11%) quicker ( P = 0.0281), using regression analysis to account for reader experience, read round, and tumor type. Interobserver variance suggests moderate agreement, Cohen κ = 0.64; 95% CI, 0.47, 0.81 (with ML), and Cohen κ = 0.66; 95% CI, 0.47, 0.81 (without ML). CONCLUSIONS: There was no evidence of a significant difference in per-patient sensitivity and specificity for detecting metastases or the primary tumor using concurrent ML compared with standard WB-MRI. Radiology read-times with or without ML support fell for round 2 reads compared with round 1, suggesting that readers familiarized themselves with the study reading method. During the second reading round, there was a significant reduction in reading time when using ML support..

OBJECTIVE: To establish optimised diffusion weightings ('b-values') for acquisition of whole-body diffusion-weighted MRI (WB-DWI) for estimation of the apparent diffusion coefficient (ADC) in patients with metastatic melanoma (MM). Existing recommendations for WB-DWI have not been optimised for the tumour properties in MM; therefore, evaluation of acquisition parameters is essential before embarking on larger studies. METHODS: Retrospective clinical data and phantom experiments were used. Clinical data comprised 125 lesions from 14 examinations in 11 patients with multifocal MM, imaged before and/or after treatment with immunotherapy at a single institution. ADC estimates from these data were applied to a model to estimate the optimum b-value. A large non-diffusing phantom was used to assess eddy current-induced geometric distortion. RESULTS: Considering all tumour sites from pre- and post-treatment examinations together, metastases exhibited a large range of mean ADC values, [0.67-1.49] × 10-3 mm2/s, and the optimum high b-value (bhigh) for ADC estimation was 1100 (10th-90th percentile: 740-1790) s/mm2. At higher b-values, geometric distortion increased, and longer echo times were required, leading to reduced signal. CONCLUSIONS: Theoretical optimisation gave an optimum bhigh of 1100 (10th-90th percentile: 740-1790) s/mm2 for ADC estimation in MM, with the large range of optimum b-values reflecting the wide range of ADC values in these tumours. Geometric distortion and minimum echo time increase at higher b-values and are not included in the theoretical optimisation; bhigh in the range 750-1100 s/mm2 should be adopted to maintain acceptable image quality but performance should be evaluated for a specific scanner. KEY POINTS: • Theoretical optimisation gave an optimum high b-value of 1100 (10th-90th percentile: 740-1790) s/mm2 for ADC estimation in metastatic melanoma. • Considering geometric distortion and minimum echo time (TE), a b-value in the range 750-1100 s/mm2 is recommended. • Sites should evaluate the performance of specific scanners to assess the effect of geometric distortion and minimum TE..

BACKGROUND: Owing to the rarity and heterogeneity in biology and presentation, there are multiple areas in the diagnosis, treatment and follow-up of soft tissue sarcoma (STS), with no, low-level or conflicting evidence. METHODS: During the first Consensus Conference on the State of Science in Sarcoma (CSSS), we used a modified Delphi process to identify areas of controversy in the field of sarcoma, to name topics with limited evidence-based data in which a scientific and knowledge gap may remain and a consensus statement will help to guide patient management. We determined scientific questions which need to be addressed in the future in order to generate evidence and to inform physicians and caregivers in daily clinical practice in order to improve the outcomes of patients with sarcoma. We conducted a vote on STS key questions and controversies prior to the CSSS meeting, which took place in May 2022. RESULTS: Sixty-two European sarcoma experts participated in the survey. Sixteen strong consensus (≥95%) items were identified by the experts, as well as 30 items with a ≥75% consensus on diagnostic and therapeutic questions. Ultimately, many controversy topics remained without consensus. CONCLUSIONS: In this manuscript, we summarise the voting results and the discussion during the CSSS meeting. Future scientific questions, priorities for clinical trials, registries, quality assurance, and action by stakeholders are proposed. Platforms and partnerships can support innovative approaches to improve management and clinical research in STS..

UNLABELLED: Understanding the evolutionary pathways to metastasis and resistance to immune-checkpoint inhibitors (ICI) in melanoma is critical for improving outcomes. Here, we present the most comprehensive intrapatient metastatic melanoma dataset assembled to date as part of the Posthumous Evaluation of Advanced Cancer Environment (PEACE) research autopsy program, including 222 exome sequencing, 493 panel-sequenced, 161 RNA sequencing, and 22 single-cell whole-genome sequencing samples from 14 ICI-treated patients. We observed frequent whole-genome doubling and widespread loss of heterozygosity, often involving antigen-presentation machinery. We found KIT extrachromosomal DNA may have contributed to the lack of response to KIT inhibitors of a KIT-driven melanoma. At the lesion-level, MYC amplifications were enriched in ICI nonresponders. Single-cell sequencing revealed polyclonal seeding of metastases originating from clones with different ploidy in one patient. Finally, we observed that brain metastases that diverged early in molecular evolution emerge late in disease. Overall, our study illustrates the diverse evolutionary landscape of advanced melanoma. SIGNIFICANCE: Despite treatment advances, melanoma remains a deadly disease at stage IV. Through research autopsy and dense sampling of metastases combined with extensive multiomic profiling, our study elucidates the many mechanisms that melanomas use to evade treatment and the immune system, whether through mutations, widespread copy-number alterations, or extrachromosomal DNA. See related commentary by Shain, p. 1294. This article is highlighted in the In This Issue feature, p. 1275..

T2-weighted magnetic resonance imaging (MRI) and diffusion-weighted imaging (DWI) are essential components of cervical cancer diagnosis. However, combining these channels for the training of deep learning models is challenging due to image misalignment. Here, we propose a novel multi-head framework that uses dilated convolutions and shared residual connections for the separate encoding of multiparametric MRI images. We employ a residual U-Net model as a baseline, and perform a series of architectural experiments to evaluate the tumor segmentation performance based on multiparametric input channels and different feature encoding configurations. All experiments were performed on a cohort of 207 patients with locally advanced cervical cancer. Our proposed multi-head model using separate dilated encoding for T2W MRI and combined b1000 DWI and apparent diffusion coefficient (ADC) maps achieved the best median Dice similarity coefficient (DSC) score, 0.823 (confidence interval (CI), 0.595-0.797), outperforming the conventional multi-channel model, DSC 0.788 (95% CI, 0.568-0.776), although the difference was not statistically significant (p > 0.05). We investigated channel sensitivity using 3D GRAD-CAM and channel dropout, and highlighted the critical importance of T2W and ADC channels for accurate tumor segmentation. However, our results showed that b1000 DWI had a minor impact on the overall segmentation performance. We demonstrated that the use of separate dilated feature extractors and independent contextual learning improved the model's ability to reduce the boundary effects and distortion of DWI, leading to improved segmentation performance. Our findings could have significant implications for the development of robust and generalizable models that can extend to other multi-modal segmentation applications..

BACKGROUND: Pelvic soft tissue sarcomas are rare. Potentially curative resection remains challenging due to anatomical constraints of true pelvis and tumour spread through various anatomical hiatus. We sought to review the oncological outcomes of surgically managed cases at our centre and determine whether outcomes differ for patients with localised (limited to pelvis) versus extensive disease (with extra-pelvic extension). METHODS: Sixty-seven patients who underwent surgical resection with curative intent at the centre for primary, non-metastatic, WHO intermediate to high-grade soft tissue sarcoma of the true pelvis from January 2012 through January 2020 were analysed. Establishment of the extent of disease was made by review of pre-treatment imaging and surgical notes. Oncologic endpoints examined were resection margin, recurrence rate, disease-free and overall survival. RESULTS: Rates of complete oncological resection and disease control were similar for tumours with localised or extensive disease. On logistic regression analysis, tumour grade, and a negative resection margin (R0) correlated with the risk of recurrence (p=<0.05). On further multinomial analysis, R0 resection was associated with improved local control, but not metastatic relapse (p = 0.003). 5-year local recurrence-free and distant metastasis-free survival were 61.3% and 67.1%, respectively. Five and 10-year overall survival were 64% and 36%, respectively. Age >50 years and high tumour grade were associated with a worse outcome (p < 0.05). CONCLUSIONS: When potentially curative surgery is performed for pelvic sarcoma, disease-extent does not influence oncologic outcomes. While a complete oncologic resection determines the risk of local recurrence, tumour grade and metastatic relapse remain primary prognostic determinants for overall survival..

PURPOSE: The multicenter OPTIMUM (MUKnine) phase II trial investigated daratumumab, low-dose cyclophosphamide, lenalidomide, bortezomib, and dexamethasone (Dara-CVRd) before and after autologous stem-cell transplant (ASCT) in newly diagnosed patients with molecularly defined ultra-high-risk (UHiR) multiple myeloma (NDMM) or plasma cell leukemia (PCL). To provide clinical context, progression-free survival (PFS) and overall survival (OS) were referenced to contemporaneous outcomes seen in patients with UHiR NDMM treated in the recent Myeloma XI (MyeXI) trial. METHODS: Transplant-eligible all-comers NDMM patients were profiled for UHiR disease, defined by presence of ≥2 genetic risk markers t(4;14)/t(14;16)/t(14;20), del(1p), gain(1q), and del(17p), and/or SKY92 gene expression risk signature. Patients with UHiR MM/PCL were offered treatment with Dara-CVRd induction, V-augmented ASCT, extended Dara-VR(d) consolidation, and Dara-R maintenance. UHiR patients treated in MyeXI with carfilzomib, lenalidomide, dexamethasone, and cyclophosphamide, or lenalidomide, dexamethasone, and cyclophosphamide, ASCT, and R maintenance or observation were identified by mirrored molecular screening. OPTIMUM PFS at 18 months (PFS18m) was compared against MyeXI using a Bayesian framework, and patients were followed up to the end of consolidation for PFS and OS. RESULTS: Of 412 screened NDMM OPTIMUM patients, 103 were identified as UHiR or PCL and subsequently treated on trial with Dara-CVRd; 117 MyeXI patients identified as UHiR formed the external comparator arm, with comparable clinical and molecular characteristics to OPTIMUM. Comparison of PFS18m per Bayesian framework resulted in a 99.5% chance of OPTIMUM being superior to MyeXI. At 30 months' follow-up, PFS was 77% for OPTIMUM versus 39.8% for MyeXI, and OS 83.5% versus 73.5%, respectively. Extended post-ASCT Dara-VRd consolidation therapy was highly deliverable, with limited toxicity. CONCLUSION: Our results suggest that Dara-CVRd induction and extended post-ASCT Dara-VRd consolidation markedly improve PFS for UHiR NDMM patients over conventional management, supporting further evaluation of this strategy..

AIM: To evaluate the incidence of pseudoprogression in patients with metastatic or inoperable uterine leiomyosarcoma (LMS) treated with first-line single-agent doxorubicin. METHODS: The Royal Marsden NHS Foundation Trust Sarcoma Unit database was searched to identify all patients with metastatic or inoperable LMS treated with first-line doxorubicin from January 2006 to January 2022. Patients with available computed tomography scans performed at baseline and during doxorubicin therapy were included. Response evaluation criteria in solid tumours v1.1 and Choi criteria were applied. Any increase in the sum of the longest diameter that decreased on the subsequent scan was labelled as pseudoprogression. RESULTS: The total number of patients evaluated was 52. In total, 19% (n = 10) of patients treated with doxorubicin showed pseudoprogression. However, pseudoprogression at the time of the second scan was not associated with time to doxorubicin failure. Choi criteria identified 30% (n = 3) of pseudoprogressors as responding. CONCLUSION: Despite the use of doxorubicin as first-line therapy for soft-tissue sarcomas for over 40 years, pseudoprogression has not been described. This retrospective study shows that pseudoprogression occurs in 19% of patients with metastatic/inoperable uterine LMS treated with first-line doxorubicin. Choi criteria were not consistently able to differentiate pseudoprogression from true progression. It is imperative that oncologists and radiologists are aware of this as symptomatically stable/improving patients may benefit from continued treatment despite initial radiological growth in tumour size..

OBJECTIVES: To assess the repeatability of quantitative multiparametric whole-body MRI (mpWB-MRI) parameters in advanced prostate cancer (APC) bone metastases. METHODS: 1.5T MRI was performed twice on the same day in 10 APC patients. MpWB-MRI-included diffusion weighted imaging (DWI) and T1-weighted gradient-echo 2-point Dixon sequences. ADC and relative fat-fraction percentage (rFF%) maps were calculated, respectively. A radiologist delineated up to 10 target bone metastases per study. Means of ADC, b900 signal intensity(SI), normalised b900 SI, rFF% and maximum diameter (MD) for each target lesion and overall parameter averages across all targets per patient were recorded. The total disease volume (tDV in ml) was manually delineated on b900 images and mean global (g)ADC was derived. Bland-Altman analyses were performed with calculation of 95% repeatability coefficients (RC). RESULTS: Seventy-three individual targets (median MD 26 mm) were included. Lesion mean ADC RC was 12.5%, mean b900 SI RC 137%, normalised mean b900 SI RC 110%, rFF% RC 3.2 and target MD RC 5.5 mm (16.3%). Patient target lesion average mean ADC RC was 6.4%, b900 SI RC 104% and normalised mean b900 SI RC 39.6%. Target average rFF% RC was 1.8, average MD RC 1.3 mm (4.8%). tDV segmentation RC was 6.4% and mean gADC RC 5.3%. CONCLUSIONS: APC bone metastases' ADC, rFF% and maximum diameter, tDV and gADC show good repeatability. ADVANCES IN KNOWLEDGE: APC bone metastases' mean ADC and rFF% measurements of single lesions and global disease volumes are repeatable, supporting their potential role as quantitative biomarkers in metastatic bone disease..

BACKGROUND: Retroperitoneal sarcomas are tumours with a poor prognosis. Upfront characterisation of the tumour is difficult, and under-grading is common. Radiomics has the potential to non-invasively characterise the so-called radiological phenotype of tumours. We aimed to develop and independently validate a CT-based radiomics classification model for the prediction of histological type and grade in retroperitoneal leiomyosarcoma and liposarcoma. METHODS: A retrospective discovery cohort was collated at our centre (Royal Marsden Hospital, London, UK) and an independent validation cohort comprising patients recruited in the phase 3 STRASS study of neoadjuvant radiotherapy in retroperitoneal sarcoma. Patients aged older than 18 years with confirmed primary leiomyosarcoma or liposarcoma proceeding to surgical resection with available contrast-enhanced CT scans were included. Using the discovery dataset, a CT-based radiomics workflow was developed, including manual delineation, sub-segmentation, feature extraction, and predictive model building. Separate probabilistic classifiers for the prediction of histological type and low versus intermediate or high grade tumour types were built and tested. Independent validation was then performed. The primary objective of the study was to develop radiomic classification models for the prediction of retroperitoneal leiomyosarcoma and liposarcoma type and histological grade. FINDINGS: 170 patients recruited between Oct 30, 2016, and Dec 23, 2020, were eligible in the discovery cohort and 89 patients recruited between Jan 18, 2012, and April 10, 2017, were eligible in the validation cohort. In the discovery cohort, the median age was 63 years (range 27-89), with 83 (49%) female and 87 (51%) male patients. In the validation cohort, median age was 59 years (range 33-77), with 46 (52%) female and 43 (48%) male patients. The highest performing model for the prediction of histological type had an area under the receiver operator curve (AUROC) of 0·928 on validation, based on a feature set of radiomics and approximate radiomic volume fraction. The highest performing model for the prediction of histological grade had an AUROC of 0·882 on validation, based on a radiomics feature set. INTERPRETATION: Our validated radiomics model can predict the histological type and grade of retroperitoneal sarcomas with excellent performance. This could have important implications for improving diagnosis and risk stratification in retroperitoneal sarcomas. FUNDING: Wellcome Trust, European Organisation for Research and Treatment of Cancer-Soft Tissue and Bone Sarcoma Group, the National Institutes for Health, and the National Institute for Health and Care Research Biomedical Research Centre at The Royal Marsden NHS Foundation Trust and The Institute of Cancer Research..

OBJECTIVES: To compare relative fat fraction (rFF) of active bone lesions from breast, prostate and myeloma malignancies and normal bone marrow; to assess its inter-reader agreement. METHODS: Patients with breast (n = 26), myeloma (n = 32) and prostate cancer (n = 52) were retrospectively evaluated. 110 baseline rFF maps from whole-body MRI were reviewed by two radiologists. Regions of interest for up to four focal active lesions in each patient were drawn on rFF maps, one each at the cervicothoracic spine, lumbosacral spine, pelvis and extremity. The mean and standard deviation of rFF were recorded. The rFF of normal marrow was measured in the pelvis for patients without diffuse bone disease (n = 88). We compared the rFF of malignant bone lesions and normal marrow using Mann-Whitney test. Interobserver agreement was assessed by interclass correlation coefficient. RESULTS: Malignant bone lesions showed significantly lower median rFF (13.87%) compared with normal marrow (89.76%) with little overlap (p < 0.0001). There was no significant difference in the median rFF of malignant lesions from breast (14.46%), myeloma (13.12%) and prostate cancer (13.67%) (p > 0.017, Bonferroni correction) and in the median rFF of bone disease according to their anatomical locations (p > 0.008, Bonferroni correction). There was excellent interobserver agreement (0.95). CONCLUSION: The low rFF of active bone lesions in breast, prostate and myeloma malignancies provides high image contrast relative to normal marrow that may be used to detect bone metastases. ADVANCES IN KNOWLEDGE: This study shows the importance of rFF towards detecting bone metastases..

BACKGROUND: The aim of this work is to evaluate the performance of radiomics predictions for a range of molecular, genomic and clinical targets in patients with clear cell renal cell carcinoma (ccRCC) and demonstrate the impact of novel feature selection strategies and sub-segmentations on model interpretability. METHODS: Contrast-enhanced CT scans from the first 101 patients recruited to the TRACERx Renal Cancer study (NCT03226886) were used to derive radiomics classification models to predict 20 molecular, histopathology and clinical target variables. Manual 3D segmentation was used in conjunction with automatic sub-segmentation to generate radiomics features from the core, rim, high and low enhancing sub-regions, and the whole tumour. Comparisons were made between two classification model pipelines: a Conventional pipeline reflecting common radiomics practice, and a Proposed pipeline including two novel feature selection steps designed to improve model interpretability. For both pipelines nested cross-validation was used to estimate prediction performance and tune model hyper-parameters, and permutation testing was used to evaluate the statistical significance of the estimated performance measures. Further model robustness assessments were conducted by evaluating model variability across the cross-validation folds. RESULTS: Classification performance was significant (p < 0.05, H0:AUROC = 0.5) for 11 of 20 targets using either pipeline and for these targets the AUROCs were within ± 0.05 for the two pipelines, except for one target where the Proposed pipeline performance increased by > 0.1. Five of these targets (necrosis on histology, presence of renal vein invasion, overall histological stage, linear evolutionary subtype and loss of 9p21.3 somatic alteration marker) had AUROC > 0.8. Models derived using the Proposed pipeline contained fewer feature groups than the Conventional pipeline, leading to more straightforward model interpretations without loss of performance. Sub-segmentations lead to improved performance and/or improved interpretability when predicting the presence of sarcomatoid differentiation and tumour stage. CONCLUSIONS: Use of the Proposed pipeline, which includes the novel feature selection methods, leads to more interpretable models without compromising prediction performance. TRIAL REGISTRATION: NCT03226886 (TRACERx Renal)..

BACKGROUND: The Myeloma Response Assessment and Diagnosis System (MY-RADS) guidelines establish a standardised acquisition and analysis pipeline for whole-body MRI (WB-MRI) in patients with myeloma. This is the first study to assess image quality in a multi-centre prospective trial using MY-RADS. METHODS: The cohort consisted of 121 examinations acquired across ten sites with a range of prior WB-MRI experience, three scanner manufacturers and two field strengths. Image quality was evaluated qualitatively by a radiologist and quantitatively using a semi-automated pipeline to quantify common artefacts and image quality issues. The intra- and inter-rater repeatability of qualitative and quantitative scoring was also assessed. RESULTS: Qualitative radiological scoring found that the image quality was generally good, with 94% of examinations rated as good or excellent and only one examination rated as non-diagnostic. There was a significant correlation between radiological and quantitative scoring for most measures, and intra- and inter-rater repeatability were generally good. When the quality of an overall examination was low, this was often due to low quality diffusion-weighted imaging (DWI), where signal to noise ratio (SNR), anterior thoracic signal loss and brain geometric distortion were found as significant predictors of examination quality. CONCLUSIONS: It is possible to successfully deliver a multi-centre WB-MRI study using the MY-RADS protocol involving scanners with a range of manufacturers, models and field strengths. Quantitative measures of image quality were developed and shown to be significantly correlated with radiological assessment. The SNR of DW images was identified as a significant factor affecting overall examination quality. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03188172 , Registered on 15 June 2017. CRITICAL RELEVANCE STATEMENT: Good overall image quality, assessed both qualitatively and quantitatively, can be achieved in a multi-centre whole-body MRI study using the MY-RADS guidelines. KEY POINTS: • A prospective multi-centre WB-MRI study using MY-RADS can be successfully delivered. • Quantitative image quality metrics were developed and correlated with radiological assessment. • SNR in DWI was identified as a significant predictor of quality, allowing for rapid quality adjustment..

We propose that an information technology and computational framework that would unify access to hospital digital information silos, and enable integration of this information using machine learning methods, would bring a new paradigm to patient management and research. This is the core principle of Integrated Diagnostics (ID): the amalgamation of multiple analytical modalities, with evolved information technology, applied to a defined patient cohort, and resulting in a synergistic effect in the clinical value of the individual diagnostic tools. This has the potential to transform the practice of personalized oncology at a time at which it is very much needed. In this article we present different models from the literature that contribute to the vision of ID and we provide published exemplars of ID tools. We briefly describe ongoing efforts within a universal healthcare system to create national clinical datasets. Following this, we argue the case to create "hospital units" to leverage this multi-modal analysis, data integration and holistic clinical decision-making. Finally, we describe the joint model created in our institutions..

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Genetic intra-tumour heterogeneity fuels clonal evolution, but our understanding of clinically relevant clonal dynamics remain limited. We investigated spatial and temporal features of clonal diversification in clear cell renal cell carcinoma through a combination of modelling and real tumour analysis. We observe that the mode of tumour growth, surface or volume, impacts the extent of subclonal diversification, enabling interpretation of clonal diversity in patient tumours. Specific patterns of proliferation and necrosis explain clonal expansion and emergence of parallel evolution and microdiversity in tumours. In silico time-course studies reveal the appearance of budding structures before detectable subclonal diversification. Intriguingly, we observe radiological evidence of budding structures in early-stage clear cell renal cell carcinoma, indicating that future clonal evolution may be predictable from imaging. Our findings offer a window into the temporal and spatial features of clinically relevant clonal evolution..

OBJECTIVE: A commercially available CT-guided robot offers enhanced abilities in planning, targeting, and confirming accurate needle placement. In this short communication, we describe our first UK experience of robotic interventional oncology procedures. METHODS: We describe the device, discuss installation, operation, and report upon needle insertion success, accuracy (path deviation; PD and tip deviation; TD), number of adjustments, complications, and procedural success. RESULTS: Nine patients (seven males), median age 66 years (range 43-79) were consented for biopsy or ablation between March and April 2021. Needle placement in biopsy was more accurate than ablation (median 1 vs 11 mm PD and 1 vs 20 mm TD) and required fewer adjustments (median 0 vs 5). No complications arose, and all procedures were successful (diagnostic material obtained or complete ablation at follow-up). CONCLUSION: Short procedure times and very high levels of accuracy were readily achieved with biopsy procedures, although tumour ablation was less accurate which likely reflects higher procedural complexity. ADVANCES IN KNOWLEDGE: Achieving highly accurate robotic biopsy with is feasible within a very short time span. Further work is required to maximise the potential of robotic guidance in tumour ablation procedures, which is likely due to higher complexity giving a longer learning curve..

Fat-containing tumors are very commonly found in daily practice with benign lipoma accounting for the majority of superficial tumors. Overlap in imaging findings between benign and intermediate or malignant fat-containing tumor is common. Guidelines recommend a core needle biopsy (CNB) for all deep tumors, and superficial tumors over 3 cm. However, specific strategy for diagnosis and referral to a sarcoma center should be applied on adipocytic tumors. The aim of this consensus statement is to provide a specific algorithm for adipocytic tumors, to discriminate patients who do require a CNB for preoperative diagnosis from those who can simply undergo active surveillance or a simple excision..

BACKGROUND. CT-based criteria for assessing the gastrointestinal stromal tumor (GIST) response to tyrosine kinase inhibitor (TKI) therapy are limited in part because tumor attenuation is influenced by treatment-related changes including hemorrhage and calcification. The iodine concentration may be less impacted by such changes. OBJECTIVE. The purpose of this study was to determine whether the dual-energy CT (DECT) vital iodine tumor burden (TB) allows improved differentiation between treatment responders and nonresponders among patients with metastatic GIST who are undergoing TKI therapy compared with established CT and PET/CT criteria. METHODS. An anthropomorphic phantom with spherical inserts mimicking GIST lesions of varying iodine concentrations and having nonenhancing central necrotic cores underwent DECT to determine a threshold iodine concentration. Forty patients (25 women and 15 men; median age, 57 years) who were treated with TKI for metastatic GIST were retrospectively evaluated. Patients underwent baseline and follow-up DECT and FDG PET/CT. Response assessment was performed using RECIST 1.1, modified Choi (mChoi) criteria, vascular tumor burden (VTB) criteria, DECT vital iodine TB criteria, and European Organization for Research and Treatment of Cancer (EORTC) PET criteria. DECT vital iodine TB criteria used the same percentage changes as RECIST 1.1 response categories. Progression-free survival was compared between responders and nonresponders for each response criterion by use of Cox proportional hazard ratios and Harrell C-indexes (i.e., concordance indexes). RESULTS. The phantom experiment identified a threshold of 0.5 mg/mL to differentiate vital from nonvital tissue. With use of the DECT vital iodine TB, median progression-free survival was significantly different between responders and nonresponders (623 vs 104 days; p < .001).. For nonresponders versus responders, the hazard ratio for disease progression for DECT vital iodine TB was 6.9 versus 7.6 for EORTC PET criteria, 3.3 for VTB criteria, 2.3 for RECIST 1.1, and 2.1 for mChoi criteria. The C-index was 0.74 for EORTC PET criteria, 0.73 for DECT vital iodine TB criteria, 0.67 for VTB criteria, 0.61 for RECIST 1.1, and 0.58 for mChoi criteria. The C-index was significantly greater for DECT vital iodine TB criteria than for RECIST 1.1 (p = .02) and mChoi criteria (p = .002), but it was not different from that for VTB and EORTC PET criteria (p > .05). CONCLUSION. DECT vital iodine TB criteria showed performance comparable to that of EORTC PET criteria and outperformed RECIST 1.1 and mChoi criteria for response assessment of metastatic GIST treated with TKI therapy. CLINICAL IMPACT. DECT vital iodine TB could help guide early management decisions in patients receiving TKI therapy..

INTRODUCTION: Whole-body MRI (WB-MRI) is recommended by the National Institute of Clinical Excellence as the first-line imaging tool for diagnosis of multiple myeloma. Reporting WB-MRI scans requires expertise to interpret and can be challenging for radiologists who need to meet rapid turn-around requirements. Automated computational tools based on machine learning (ML) could assist the radiologist in terms of sensitivity and reading speed and would facilitate improved accuracy, productivity and cost-effectiveness. The MALIMAR study aims to develop and validate a ML algorithm to increase the diagnostic accuracy and reading speed of radiological interpretation of WB-MRI compared with standard methods. METHODS AND ANALYSIS: This phase II/III imaging trial will perform retrospective analysis of previously obtained clinical radiology MRI scans and scans from healthy volunteers obtained prospectively to implement training and validation of an ML algorithm. The study will comprise three project phases using approximately 633 scans to (1) train the ML algorithm to identify active disease, (2) clinically validate the ML algorithm and (3) determine change in disease status following treatment via a quantification of burden of disease in patients with myeloma. Phase 1 will primarily train the ML algorithm to detect active myeloma against an expert assessment ('reference standard'). Phase 2 will use the ML output in the setting of radiology reader study to assess the difference in sensitivity when using ML-assisted reading or human-alone reading. Phase 3 will assess the agreement between experienced readers (with and without ML) and the reference standard in scoring both overall burden of disease before and after treatment, and response. ETHICS AND DISSEMINATION: MALIMAR has ethical approval from South Central-Oxford C Research Ethics Committee (REC Reference: 17/SC/0630). IRAS Project ID: 233501. CPMS Portfolio adoption (CPMS ID: 36766). Participants gave informed consent to participate in the study before taking part. MALIMAR is funded by National Institute for Healthcare Research Efficacy and Mechanism Evaluation funding (NIHR EME Project ID: 16/68/34). Findings will be made available through peer-reviewed publications and conference dissemination. TRIAL REGISTRATION NUMBER: NCT03574454..

Multiple myeloma and its precursor and variant types represent some of the most common hematologic malignancies in adults. These plasma cell dyscrasias are well-known in modern medicine. There are well-established clinical, laboratory, and pathologic criteria for diagnosis and staging. There is debate about the diagnosis of some of the earliest cases of myeloma described in the literature. We present a critical review of one such case..

BACKGROUND: The assessment of metastatic breast cancer (MBC) can be limited with routine imaging such as computed tomography (CT) especially in bone-only or bone-predominant disease. This analysis investigates the effects of the use of WBMRI in addition to the use of routine CT, bone scintigraphy (BS) and fluorine-18-fluorodeoxyglucose positron emission tomography with computed tomography (FDG-PET/CT) on influencing systemic anti-cancer treatment (SACT) decisions in patients with known MBC. METHODS: MBC patients undergoing SACT who had WBMRI undertaken within 8 weeks of either a routine CT, BS or FDG-PET/CT were reviewed retrospectively. The clinical indications for undertaking the WBMRI examinations were recorded. Data on the extent and distribution of the disease were collected and discordance/concordance of disease status across the imaging modalities were compared. SACT decisions at each time point were also evaluated. RESULTS: There were 105 MBC patients with 148 WBMRI studies paired with CT, BS or FDG-PET/CT. 50 pairs (33.8%) showed differences in the extent of disease, with 44 pairs due to additional sites (AS) reported on WBMRI alone. 81 patients (Group 1) had one WBMRI paired with routine imaging due to a variety of indications, with clinical symptoms (such as bone pain) being the most common (24.7%). 24 patients (Group 2) had more than one WBMRI study paired with routine imaging comprising 67 pairs. 13/67 pairs (19.4%) showed discordance in assessments. 10/13 pairs had progressive disease (PD) reported on WBMRI alone. SACT change due to AS reported on WBMRI alone occurred in 21/23 pairs (91.3%) in Group 1. SACT change due to PD reported on WBMRI alone in Group 2 occurred in 6/14 pairs (42.9%). SACT change due to AS/PD in both groups occurred in 11/102 pairs (10.8%) with known invasive ductal carcinoma (IDC) and 13/28 pairs (46.4%) with invasive lobular carcinoma (ILC). CONCLUSIONS: The use of WBMRI in MBC led to earlier recognition of PD and SACT change compared with the other imaging modalities. A higher proportion of discordant response assessments and SACT changes were observed in ILC compared with IDC in our patient group, although larger-scale studies are required to investigate this further..

Invasive lobular breast carcinomas (ILC) account for approximately 15% of breast cancer diagnoses. They can be difficult to diagnose both clinically and radiologically, due to their infiltrative growth pattern. The pattern of metastasis of ILC is unusual, with spread to the serosal surfaces (pleura and peritoneum), retroperitoneum and gastrointestinal (GI)/genitourinary (GU) tracts and a higher rate of leptomeningeal spread than IDC. Routine staging and response assessment with computed tomography (CT) can be undertaken quickly and measurements can be reproduced easily, but this is challenging with metastatic ILC as bone-only/bone-predominant patterns are frequently seen and assessment of the disease status is limited in these scenarios. Functional imaging such as whole-body MRI (WBMRI) allows the assessment of bone and soft tissue disease by providing functional information related to differences in cellular density between malignant and benign tissues. A number of recent studies have shown that WBMRI can detect additional sites of disease in metastatic breast cancer (MBC), resulting in a change in systemic anti-cancer therapy. Although WBMRI and fluorodeoxyglucose-positron-emission tomography-computed tomography (FDG-PET/CT) have a comparable performance in the assessment of MBC, WBMRI can be particularly valuable as a proportion of ILC are non-FDG-avid, resulting in the underestimation of the disease extent. In this review, we explore the added value of WBMRI in the evaluation of metastatic ILC and compare it with other imaging modalities such as CT and FDG-PET/CT. We also discuss the spectrum of WBMRI findings of the different metastatic sites of ILC with CT and FDG-PET/CT correlation. KEY POINTS: • ILC has an unusual pattern of spread compared to IDC, with metastases to the peritoneum, retroperitoneum and GI and GU tracts, but the bones and liver are the commonest sites. • WBMRI allows functional assessment of metastatic disease, particularly in bone-only and bone-predominant metastatic cancers such as ILC where evaluation with CT can be challenging and limited. • WBMRI can detect more sites of disease compared with CT, can reveal disease progression earlier and provides the opportunity to change ineffective systemic treatment sooner..

AIM: To report the first UK experience of cryoablation in desmoid fibromatosis (DF) with particular focus on technique, safety, and efficacy. MATERIALS AND METHODS: Patients were selected at multidisciplinary tumour board meetings at a specialist cancer hospital. Radiation dose, procedure duration, and number of cryoprobes were compared for small versus large tumours (>10 cm long axis). Response at magnetic resonance imaging (MRI) was evaluated using different criteria, and percentage agreement with clinical response as assessed in oncology clinic calculated. RESULTS: Thirteen procedures were performed in 10 patients (eight women, median age 51 years, IQR 42-69 years) between February 2019 and August 2021. Procedures for large tumours had higher radiation dose (2,012 ± 1,012 versus 1,076 ± 519 mGy·cm, p=0.048) used more cryoprobes (13 ± 7 versus 4 ± 2, p=0.009), and were more likely to have residual unablated tumour (38 ± 37% versus 7.5 ± 10%, p=0.045). Adverse events were minor apart from one transient radial nerve palsy. Eight of 10 patients had symptomatic benefit at clinical follow-up (median 353 days, IQR 86-796 days), and three started systemic therapy mean 393 days later. All patients who had complete ablation demonstrated symptomatic response, with no instances of repeat treatment, recurrence, or need for systemic therapy during the study period. All progression occurred outside ablation zones. CONCLUSION: Cryoablation for symptomatic DF is a reproducible technique with low, transient toxicity, where one or two treatments can achieve a meaningful response. Where possible, the ablation ice ball should fully cover DF tumours..

PURPOSE: To use deep learning to calculate the uncertainty in apparent diffusion coefficient (σADC) voxel-wise measurements to clinically impact the monitoring of treatment response and improve the quality of ADC maps. MATERIALS AND METHODS: We use a uniquely designed diffusion-weighted imaging (DWI) acquisition protocol that provides gold-standard measurements of σADC to train a deep learning model on two separate cohorts: 16 patients with prostate cancer and 28 patients with mesothelioma. Our network was trained with a novel cost function, which incorporates a perception metric and a b-value regularisation term, on ADC maps calculated by combinations of 2 or 3 b-values (e.g. 50/600/900, 50/900, 50/600, 600/900 s/mm2). We compare the accuracy of the deep-learning based approach for estimation of σADC with gold-standard measurements. RESULTS: The model accurately predicted the σADC for every b-value combination in both cohorts. Mean values of σADC within areas of active disease deviated from those measured by the gold-standard by 4.3% (range, 2.87-6.13%) for the prostate and 3.7% (range, 3.06-4.54%) for the mesothelioma cohort. We also showed that the model can easily be adapted for a different DWI protocol and field-of-view with only a few images (as little as a single patient) using transfer learning. CONCLUSION: Deep learning produces maps of σADC from standard clinical diffusion-weighted images (DWI) when 2 or more b-values are available..

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BACKGROUND: Magnetic resonance imaging (MRI) can be used to target tumour components in biopsy procedures, while the ability to precisely correlate histology and MRI signal is crucial for imaging biomarker validation. Robotic MRI/computed tomography (CT) fusion biopsy offers the potential for this without in-gantry biopsy, although requires development. METHODS: Test-retest T1 and T2 relaxation times, attenuation (Hounsfield units, HU), and biopsy core quality were prospectively assessed (January-December 2021) in a range of gelatin, agar, and mixed gelatin/agar solutions of differing concentrations on days 1 and 8 after manufacture. Suitable materials were chosen, and four biopsy phantoms were constructed with twelve spherical 1-3-cm diameter targets visible on MRI, but not on CT. A technical pipeline was developed, and intraoperator and interoperator reliability was tested in four operators performing a total of 96 biopsies. Statistical analysis included T1, T2, and HU repeatability using Bland-Altman analysis, Dice similarity coefficient (DSC), and intraoperator and interoperator reliability. RESULTS: T1, T2, and HU repeatability had 95% limits-of-agreement of 8.3%, 3.4%, and 17.9%, respectively. The phantom was highly reproducible, with DSC of 0.93 versus 0.92 for scanning the same or two different phantoms, respectively. Hit rate was 100% (96/96 targets), and all operators performed robotic biopsies using a single volumetric acquisition. The fastest procedure time was 32 min for all 12 targets. CONCLUSIONS: A reproducible biopsy phantom was developed, validated, and used to test robotic MRI/CT-fusion biopsy. The technique was highly accurate, reliable, and achievable in clinically acceptable timescales meaning it is suitable for clinical application..

BACKGROUND: Whole-body (WB) MRI, which includes diffusion-weighted imaging (DWI) and T1-w Dixon, permits sensitive detection of marrow disease in addition to qualitative and quantitative measurements of disease and response to treatment of bone marrow. We report on the first study to embed standardised WB-MRI within a prospective, multi-centre myeloma clinical trial (IMAGIMM trial, sub-study of OPTIMUM/MUKnine) to explore the use of WB-MRI to detect minimal residual disease after treatment. METHODS: The standardised MY-RADS WB-MRI protocol was set up on a local 1.5 T scanner. An imaging manual describing the MR protocol, quality assurance/control procedures and data transfer was produced and provided to sites. For non-identical scanners (different vendor or magnet strength), site visits from our physics team were organised to support protocol optimisation. The site qualification process included review of phantom and volunteer data acquired at each site and a teleconference to brief the multidisciplinary team. Image quality of initial patients at each site was assessed. RESULTS: WB-MRI was successfully set up at 12 UK sites involving 3 vendor systems and two field strengths. Four main protocols (1.5 T Siemens, 3 T Siemens, 1.5 T Philips and 3 T GE scanners) were generated. Scanner limitations (hardware and software) and scanning time constraint required protocol modifications for 4 sites. Nevertheless, shared methodology and imaging protocols enabled other centres to obtain images suitable for qualitative and quantitative analysis. CONCLUSIONS: Standardised WB-MRI protocols can be implemented and supported in prospective multi-centre clinical trials. Trial registration NCT03188172 clinicaltrials.gov; registration date 15th June 2017 https://clinicaltrials.gov/ct2/show/study/NCT03188172..

BACKGROUND: Soft-tissue sarcomas (STS) constitute a rare group of heterogeneous mesenchymal tumours containing more than 100 histologic subtypes. Here, we investigate whether, and if so, to what extent, skeletal metastases affect the outcome of patients with advanced or metastatic disease. MATERIALS AND METHODS: Selected patients participated in five clinical trials of EORTC-STBSG. Individuals were included if they started treatment with an active drug and had advanced/metastatic STS. The endpoints of interest were overall survival (OS) and progression-free survival (PFS). Univariate and multivariate pooled analyses (after correcting for 12 covariates) were employed with Kaplan-Meier and Cox regression to model the impact of bone metastasis at presentation per treatment line stratified by study. For the subset of patients with bone metastasis, the impact of another metastatic organ site was explored with multivariate Cox regression models. RESULTS: 565 out of 1034 (54.6%) patients received first-line systemic treatment for locally advanced or metastatic disease. Bone metastases were present in 140 patients (77 first-line, 63 second-line or higher). The unadjusted difference in OS/PFS with or without bone metastasis was statistically significant only for first-line patients. For OS, the adjusted hazard ratios for bone metastasis presence were 1.33 (95%-CI: 0.99-1.78) and 1.11 (95%-CI: 0.81-1.52) for first-line/second-line or higher treated patients, respectively. Likewise, the adjusted hazard ratios for PFS were 1.31 (95%-CI: 1.00-1.73) and 1.07 (95%-CI: 0.80-1.43). Effects were not statistically significant, despite a trend in first-line patients for both endpoints. Subgroup analyses indicated bone and lymph node metastasis as the most detrimental combination for OS and bone and lung metastasis for PFS. CONCLUSIONS: Adult STS patients receiving palliative systemic therapy with bone metastasis carried an overall worse prognosis than STS patients without bone metastases. Skeletal metastasis was detrimental for both OS and PFS, independent of the treatment line. Findings may have implications for the management of these patients..

INTRODUCTION: The spleen is a lymphoid organ and we hypothesize that clinical benefit to immunotherapy may present with an increase in splenic volume during treatment. The purpose of this study was to investigate whether changes in splenic volume could be observed in those showing clinical benefit versus those not showing clinical benefit to pembrolizumab treatment in non-small cell lung cancer (NSCLC) patients. MATERIALS AND METHODS: In this study, 70 patients with locally advanced or metastatic NSCLC treated with pembrolizumab; and who underwent baseline CT scan within 2 weeks before treatment and follow-up CT within 3 months after commencing immunotherapy were retrospectively evaluated. The splenic volume on each CT was segmented manually by outlining the splenic contour on every image and the total volume summated. We compared the splenic volume in those achieving a clinical benefit and those not achieving clinical benefit, using non-parametric Wilcoxon signed-rank test. Clinical benefit was defined as stable disease or partial response lasting for greater than 24 weeks. A p-value of <0.05 was considered statistically significant. RESULTS: There were 23 responders and 47 non-responders based on iRECIST criteria and 35 patients with clinical benefit and 35 without clinical benefit. There was no significant difference in the median pre-treatment volume (175 vs 187 cm3, p = 0.34), post-treatment volume (168 vs 167 cm3, p = 0.39) or change in splenic volume (-0.002 vs 0.0002 cm3, p = 0.97) between the two groups. No significant differences were also found between the splenic volume of patients with partial response, stable disease or progressive disease (p>0.017). Moreover, there was no statistically significant difference between progression-free survival and time to disease progression when the splenic volume was categorized as smaller or larger than the median pre-treatment or post-treatment volume (p>0.05). CONCLUSION: No significant differences were observed in the splenic volume of those showing clinical benefit versus those without clinical benefit to pembrolizumab treatment in NSCLC patients. CT splenic volume cannot be used as a potentially simple biomarker of response to immunotherapy..

A shift in radiology to a data-driven specialty has been unlocked by synergistic developments in imaging biomarkers (IB) and computational science. This is advancing the capability to deliver "virtual biopsies" within oncology. The ability to non-invasively probe tumour biology both spatially and temporally would fulfil the potential of imaging to inform management of complex tumours; improving diagnostic accuracy, providing new insights into inter- and intra-tumoral heterogeneity and individualised treatment planning and monitoring. Soft tissue sarcomas (STS) are rare tumours of mesenchymal origin with over 150 histological subtypes and notorious heterogeneity. The combination of inter- and intra-tumoural heterogeneity and the rarity of the disease remain major barriers to effective treatments. We provide an overview of the process of successful IB development, the key imaging and computational advancements in STS including quantitative magnetic resonance imaging, radiomics and artificial intelligence, and the studies to date that have explored the potential biological surrogates to imaging metrics. We discuss the promising future directions of IBs in STS and illustrate how the routine clinical implementation of a virtual biopsy has the potential to revolutionise the management of this group of complex cancers and improve clinical outcomes..

BACKGROUND: Size-based assessments are inaccurate indicators of tumor response in soft-tissue sarcoma (STS), motivating the requirement for new response imaging biomarkers for this rare and heterogeneous disease. In this study, we assess the test-retest repeatability of radiomic features from MR diffusion-weighted imaging (DWI) and derived maps of apparent diffusion coefficient (ADC) in retroperitoneal STS and compare baseline repeatability with changes in radiomic features following radiotherapy (RT). MATERIALS AND METHODS: Thirty patients with retroperitoneal STS received an MR examination prior to treatment, of whom 23/30 were investigated in our repeatability analysis having received repeat baseline examinations and 14/30 patients were investigated in our post-treatment analysis having received an MR examination after completing pre-operative RT. One hundred and seven radiomic features were extracted from the full manually delineated tumor region using PyRadiomics. Test-retest repeatability was assessed using an intraclass correlation coefficient (baseline ICC), and post-radiotherapy variance analysis (post-RT-IMS) was used to compare the change in radiomic feature value to baseline repeatability. RESULTS: For the ADC maps and DWI images, 101 and 102 features demonstrated good baseline repeatability (baseline ICC > 0.85), respectively. Forty-three and 2 features demonstrated both good baseline repeatability and a high post-RT-IMS (>0.85), respectively. Pearson correlation between the baseline ICC and post-RT-IMS was weak (0.432 and 0.133, respectively). CONCLUSIONS: The ADC-based radiomic analysis shows better test-retest repeatability compared with features derived from DWI images in STS, and some of these features are sensitive to post-treatment change. However, good repeatability at baseline does not imply sensitivity to post-treatment change..

Diagnosis of patients suspected of multiple myeloma requires a combination of serological and biochemical tests, bone marrow aspirate (BMA) and/or bone marrow trephine (BMT) biopsies as well as complementary information provided by whole-body cross-sectional imaging studies. However, given the heterogeneous nature of multiple myeloma, discrepancies can arise between disease burden on trephine and extent of disease within the marrow on whole-body magnetic resonance imaging (WB-MRI). Here, for the first time, we report on a series of symptomatic multiple myeloma patients for whom there was substantial discordance between disease burden on trephine and WB-MRI..

OBJECTIVE: To assess intra- and inter-reader variability of apparent diffusion coefficient (ADC) and fat fraction (FF) measurement in focal myeloma bone lesions and the influence of lesion size. METHODS: 22 myeloma patients with focal active disease on whole body MRI were included. Two readers outlined a small (5-10 mm) and large lesion (>10 mm) in each subject on derived ADC and FF maps; one reader performed this twice. Intra- and inter-reader agreement for small and large lesion groups were calculated for derived statistics from each map using within-subject standard deviation, coefficient of variation, interclass correlation coefficient measures, and visualized with Bland-Altman plots. RESULTS: For mean ADC, intra- and inter-reader repeatability demonstrated equivalently low coefficient of variation (3.0-3.6%) and excellent interclass correlation coefficient (0.975-0.982) for both small and large lesions. For mean FF, intra- and inter-reader repeatability was significantly poorer for small lesions compared to large lesions (intra-reader within-subject standard variation estimate is 2.7 times higher for small lesions than large lesions (p = 0.0071), and for inter-reader variations is 3.8 times higher (p = 0.0070)). CONCLUSION: There is excellent intra- and inter-reader agreement for mean ADC estimates, even for lesions as small as 5 mm. For FF measurements, there is a significant increase in coefficient of variation for smaller lesions, suggesting lesions >10 mm should be selected for lesion FF measurement. ADVANCES IN KNOWLEDGE: ADC measurements of focal myeloma have excellent intra- and inter-reader agreement. FF measurements are more susceptible to lesion size as intra- and inter-reader agreement is significantly impaired in lesions less than 10 mm..

OBJECTIVES: Myxoid liposarcomas (MLS) show enhanced response to radiotherapy due to their distinctive vascular pattern and therefore could be effectively treated with lower radiation doses. This is a descriptive study to explore the use of functional MRI to identify response in a uniform cohort of MLS patients treated with reduced dose radiotherapy. METHODS: 10 patients with MLS were imaged pre-, during, and post-radiotherapy receiving reduced dose radiotherapy and the response to treatment was histopathologically assessed post-radiotherapy. Apparent diffusion coefficient (ADC), T2* relaxation time, volume transfer constant (Ktrans), initial area under the gadolinium curve over 60 s (IAUGC60) and (Gd) were estimated for a central tumour volume. RESULTS: All parameters showed large inter- and intrasubject variabilities. Pre-treatment (Gd), IAUGC60 and Ktrans were significantly different between responders and non-responders. Post-radiotherapy reductions from baseline were demonstrated for T2*, (Gd), IAUGC60 and Ktrans for responders. No statistically significant ADC differences were demonstrated between the two response groups. Significantly greater early tumour volume reductions were observed for responders. CONCLUSIONS: MLS are heterogenous lesions, characterised by a slow gradual contrast-agent uptake. Pre-treatment vascular parameters, early changes to tumour volume, vascular parameters and T2* have potential in identifying response to treatment. The delayed (Gd) is a suitable descriptive parameter, relying simply on T1 measurements. Volume changes precede changes in MLS functionality and could be used to identify early response. ADVANCES IN KNOWLEDGE: MLS are are characterised by slow gradual contrast-agent uptake. Measurement of the delayed contrast-agent uptake (Gd) is simple to implement and able to discriminate response..

This is a case of recurrent intravascular leiomyomatosis in a pre-menopausal woman of African-Caribbean heritage. She presented in 2006 with multiple uterine leiomyomata, tumour invading the inferior vena cava (IVC) extending into the right atrium, and pulmonary metastases. Her initial presentation was treated surgically. On recurrence she was treated by oestrogen suppression using a combination of goserelin and letrozole, with a substantial response. She subsequently reported further regression of disease following exposure to strong sunlight enabling her to discontinue oestrogen suppression without relapse. The hypothesis is that the benefit was due to vitamin D. The role of hypovitaminosis D in the pathogenesis of uterine leiomyomata is discussed, including epidemiology data demonstrating a link between ethnicity and risk and the proven mechanisms by which vitamin D controls oestrogen and progesterone receptor expression and influences other signalling pathways involved in the pathogenesis of leiomyomas. Data indicating the intermediate malignancy nature of intravascular leiomyomatosis, are discussed. We are not aware of other reports indicating a link between intravascular leiomyomatosis and a lack of vitamin D..

Soft tissue sarcomas (STS) represent a broad family of rare tumours for which surgery with radiotherapy represents first-line treatment. Recently, neoadjuvant chemo-radiotherapy has been increasingly used in high-risk patients in an effort to reduce surgical morbidity and improve clinical outcomes. An adequate understanding of the efficacy of neoadjuvant therapies would optimise patient care, allowing a tailored approach. Although response evaluation criteria in solid tumours (RECIST) is the most common imaging method to assess tumour response, Choi criteria and functional and molecular imaging (DWI, DCE-MRI and 18F-FDG-PET) seem to outperform it in the discrimination between responders and non-responders. Moreover, the radiologic-pathology correlation of treatment-related changes remains poorly understood. In this review, we provide an overview of the imaging assessment of tumour response in STS undergoing neoadjuvant treatment, including conventional imaging (CT, MRI, PET) and advanced imaging analysis. Future directions will be presented to shed light on potential advances in pre-surgical imaging assessments that have clinical implications for sarcoma patients..

PURPOSE/OBJECTIVE: Total body irradiation (TBI) remains a key component of conditioning for allogeneic haemopoietic stem cell transplant (HSCT), with interstitial pneumonitis (IP) and chronic kidney disease (CKD) important late sequelae. We undertook a retrospective service evaluation of TBI patients treated with a forward-planned intensity modulated radiotherapy technique (FP IMRT). MATERIAL/METHODS: 74 adult patients were identified; all received step and shoot FP IMRT TBI, 14.4 Gy in 8 fractions over 4 days. Mean doses to the lungs and kidneys were 12-12.5 Gy. Toxicities were defined as per CTCAE v4.0: IP as multilobar infiltrates on CT with symptoms of dyspnoea, and renal dysfunction as an Estimated Glomerular Filtration rate (eGFR) < 60 ml/min/1.73 m2 for > 3 months. Secondary endpoints were overall survival (OS), progression free survival (PFS), cumulative incidence of non-relapse mortality (NRM), relapse risk and of acute and chronic GvHD. RESULTS: Patients received treatment for the following diagnosis: ALL/LBL (n = 37); AML (n = 33), CML-BC (n = 2) and High grade NHL (n = 2). The rate of IP due to any cause was 30%; positive microbiological evidence in 73% (16 /22). Idiopathic IP was seen in 8%, with only 4% (n = 3) having IP Grade ≥ 3. Two (4%) of 52 long term survivors developed CKD, one with thrombotic microangiopathy. 4 year NRM was 16% (CI 11-32%); no treatment related deaths in matched sibling or umbilical cord blood HSCT. CONCLUSION: FP IMRT TBI, reducing dose to the lungs and kidneys, has lower rates of idiopathic IP and CKD compared to the literature. This technique is safe and effective conditioning for full intensity HSCT..

Ovarian sarcomas account for 1% of all ovarian malignancies and amongst these, primary ovarian leiomyosarcoma is the rarest subtype. Primary ovarian leiomyosarcoma has a very poor prognosis, with less than 20% of patients being alive at 5 years. Only a few cases have been published in the literature and there is very limited knowledge on the clinical behaviour and optimal management of these tumours. We have performed a retrospective analysis of a prospectively maintained database to identify all primary ovarian leiomyosarcoma diagnosed and treated at the Royal Marsden NHS Foundation Trust between 1998 and 2020. Sixteen patients were identified from our database and fifteen were eligible for the analysis. Twelve patients presented with localized disease and underwent initial surgery and three patients had metastatic disease at presentation. Recurrence-free survival post-surgery was 16 months. Eight patients received first-line chemotherapy and four patients received second-line chemotherapy. Two patients had indolent metastatic disease and benefited from local therapies only. The median overall survival in the metastatic setting in our cohort was 51 months, which is consistent with previously published cases. Primary ovarian leiomyosarcoma is an extremely rare malignancy with a poor prognosis. This study is the largest case series of primary ovarian leiomyosarcoma published to date, providing clinically important information regarding survival and metastatic rate as well as treatment outcomes in the metastatic setting..

Frequency of scanning has accelerated in the era of personalized medicine and is related, but not restricted, to the exploding number of clinical trials for new cancer treatments. Particularly in drug trials, but also in clinical practice, patients are followed up by scans frequently, which may vary from every 6 to 12 weeks until progression. The authors aimed to raise awareness for this underreported but widely present "Sword of Damocles" scan-related issue also referred to as 'scanxiety.'.

Acknowledging the increasing number of studies describing the use of whole-body MRI for cancer screening, and the increasing number of examinations being performed in patients with known cancers, an international multidisciplinary expert panel of radiologists and a geneticist with subject-specific expertise formulated technical acquisition standards, interpretation criteria, and limitations of whole-body MRI for cancer screening in individuals at higher risk, including those with cancer predisposition syndromes. The Oncologically Relevant Findings Reporting and Data System (ONCO-RADS) proposes a standard protocol for individuals at higher risk, including those with cancer predisposition syndromes. ONCO-RADS emphasizes structured reporting and five assessment categories for the classification of whole-body MRI findings. The ONCO-RADS guidelines are designed to promote standardization and limit variations in the acquisition, interpretation, and reporting of whole-body MRI scans for cancer screening. Published under a CC BY 4.0 license Online supplemental material is available for this article..

Epithelioid hemangioendothelioma (EHE) is an ultra-rare, translocated, vascular sarcoma. EHE clinical behavior is variable, ranging from that of a low-grade malignancy to that of a high-grade sarcoma and it is marked by a high propensity for systemic involvement. No active systemic agents are currently approved specifically for EHE, which is typically refractory to the antitumor drugs used in sarcomas. The degree of uncertainty in selecting the most appropriate therapy for EHE patients and the lack of guidelines on the clinical management of the disease make the adoption of new treatments inconsistent across the world, resulting in suboptimal outcomes for many EHE patients. To address the shortcoming, a global consensus meeting was organized in December 2020 under the umbrella of the European Society for Medical Oncology (ESMO) involving >80 experts from several disciplines from Europe, North America and Asia, together with a patient representative from the EHE Group, a global, disease-specific patient advocacy group, and Sarcoma Patient EuroNet (SPAEN). The meeting was aimed at defining, by consensus, evidence-based best practices for the optimal approach to primary and metastatic EHE. The consensus achieved during that meeting is the subject of the present publication..

BACKGROUND: Diagnosis of lymph node (LN) metastasis in melanoma with non-invasive methods is challenging. The aim of this study was to evaluate the diagnostic accuracy of six LN characteristics on CT in detecting melanoma-positive ilioinguinal LN metastases, and to determine whether inguinal LN characteristics can predict pelvic LN involvement. METHODS: This was a single-centre retrospective study of patients with melanoma LN metastases at a tertiary cancer centre between 2008 and 2016. Patients who had preoperative contrast-enhanced CT assessment and ilioinguinal LN dissection were included. CT scans containing significant artefacts obscuring the pelvis were excluded. CT scans were reanalysed for six LN characteristics (extracapsular spread (ECS), minimum axis (MA), absence of fatty hilum (FH), asymmetrical cortical nodule (CAN), abnormal contrast enhancement (ACE) and rounded morphology (RM)) and compared with postoperative histopathological findings. RESULTS: A total of 90 patients were included. Median age was 58 (range 23-85) years. Eighty-eight patients (98 per cent) had pathology-positive inguinal disease and, of these, 45 (51 per cent) had concurrent pelvic disease. The most common CT characteristics found in pathology-positive inguinal LNs were MA greater than 10 mm (97 per cent), ACE (80 per cent), ECS (38 per cent) and absence of RM (38 per cent). In multivariable analysis, inguinal LN characteristics on CT indicative of pelvic disease were RM (odds ratio (OR) 3.3, 95 per cent c.i. 1.2 to 8.7) and ECS (OR 4.2, 1.6 to 11.3). Cloquet's node is known to be a poor predictor of pelvic spread. Pelvic LN disease was present in 50 per cent patients, but only 7 per cent had a pathology-positive Cloquet's node. CONCLUSION: Additional CT radiological characteristics, especially ECS and RM, may improve diagnostic accuracy and aid clinical decisions regarding the need for inguinal or ilioinguinal dissection..

PURPOSE: To use deep learning to improve the image quality of subsampled images (number of acquisitions = 1 [NOA1]) to reduce whole-body diffusion-weighted MRI (WBDWI) acquisition times. MATERIALS AND METHODS: Both retrospective and prospective patient groups were used to develop a deep learning-based denoising image filter (DNIF) model. For initial model training and validation, 17 patients with metastatic prostate cancer with acquired WBDWI NOA1 and NOA9 images (acquisition period, 2015-2017) were retrospectively included. An additional 22 prospective patients with advanced prostate cancer, myeloma, and advanced breast cancer were used for model testing (2019), and the radiologic quality of DNIF-processed NOA1 (NOA1-DNIF) images were compared with NOA1 images and clinical NOA16 images by using a three-point Likert scale (good, average, or poor; statistical significance was calculated by using a Wilcoxon signed ranked test). The model was also retrained and tested in 28 patients with malignant pleural mesothelioma (MPM) who underwent lung MRI (2015-2017) to demonstrate feasibility in other body regions. RESULTS: The model visually improved the quality of NOA1 images in all test patients, with the majority of NOA1-DNIF and NOA16 images being graded as either "average" or "good" across all image-quality criteria. From validation data, the mean apparent diffusion coefficient (ADC) values within NOA1-DNIF images of bone disease deviated from those within NOA9 images by an average of 1.9% (range, 1.1%-2.6%). The model was also successfully applied in the context of MPM; the mean ADCs from NOA1-DNIF images of MPM deviated from those measured by using clinical-standard images (NOA12) by 3.7% (range, 0.2%-10.6%). CONCLUSION: Clinical-standard images were generated from subsampled images by using a DNIF.Keywords: Image Postprocessing, MR-Diffusion-weighted Imaging, Neural Networks, Oncology, Whole-Body Imaging, Supervised Learning, MR-Functional Imaging, Metastases, Prostate, Lung Supplemental material is available for this article. Published under a CC BY 4.0 license..

Purpose To compare disease detection of myeloma using contemporary whole-body (WB) MRI and fluorine 18 (18F) fluorodeoxyglucose (FDG) PET/CT protocols and to correlate imaging with laboratory estimates of disease burden, including molecular characteristics. Materials and Methods In this observational, prospective study, participants were recruited from November 2015 to March 2018 who had a diagnosis of myeloma, who were planned to undergo chemotherapy and autologous stem cell transplantation, and who underwent baseline WB-MRI and FDG PET/CT (ClinicalTrials.gov identifier NCT02403102). Baseline clinical data, including genetics, were collected. Paired methods were used to compare burden and patterns of disease. Results Sixty participants (mean age, 60 years ± 9 [standard deviation]; 35 men) underwent baseline WB-MRI and FDG PET/CT. WB-MRI showed significantly higher detection for focal lesions at all anatomic sites (except ribs, scapulae, and clavicles) and for diffuse disease at all sites. Two participants presented with two or more focal lesions smaller than 5 mm only at WB-MRI but not FDG PET/CT. Participants with diffuse disease at MRI had higher plasma cell infiltration (percentage of nucleated cells: median, 60% [interquartile range {IQR}, 50%-61%] vs 15% [IQR, 4%-50%]; P = .03) and paraprotein levels (median, 32.0 g/L [IQR, 24.0-48.0 g/L] vs 20.0 g/L [IQR, 12.0-22.6 g/L]; P = .02) compared with those without diffuse disease. All genetically high-risk tumors showed diffuse infiltration at WB-MRI. Conclusion WB-MRI helped detect a higher number of myeloma lesions than FDG PET/CT, and diffuse disease detected at WB-MRI correlated with laboratory measures of disease burden and molecular markers of risk. Keywords: MR-Imaging, Skeletal-Appendicular, Skeletal-Axial, Bone Marrow, Hematologic Diseases, Oncology Clinical trial registration no. NCT02403102. Supplemental material is available for this article. © RSNA, 2021..

Whole-body magnetic resonance imaging (MRI) is now a crucial tool for the assessment of the extent of systemic malignant bone disease and response to treatment, and forms part of national and international recommendations for imaging patients with myeloma or metastatic prostate cancer. Recent developments in scanners have enabled acquisition of good-quality whole-body MRI data within 45 minutes on modern MRI systems from all main manufacturers. This provides complimentary morphological and functional whole-body imaging; however, lack of prior experience and acquisition times required can act as a barrier to adoption in busy radiology departments. This article aims to tackle the former by reviewing the indications and providing guidance for technical delivery and clinical interpretation of whole-body MRI for patients with malignant bone disease..

BACKGROUND: Primary leiomyosarcoma (LMS) of the gastrointestinal (GI) tract is rare. Limited literature exists regarding the clinical characteristics and outcome for patients with localised and metastatic disease. METHODS: A retrospective chart review was performed for patients greater than 18 years of age diagnosed with GI LMS at The Royal Marsden Hospital between 1 January 2000-1 May 2020. Descriptive statistics were performed. Patients were censored at data cut-off date of 27 June 2020. RESULTS: Forty-six patients with a median age at diagnosis of 54 years (range 25-85) were identified. Fifteen percent (n = 7) of patients previously received abdominal radiation for an unrelated cancer. All patients with localised disease (n = 36) had resection with oncological margins. For patients who underwent potentially curative surgery, median recurrence-free survival (mRFS) was 13 months (0.4-183 months), and half of these patients (n = 18) developed recurrent disease post resection (distant n = 16, local n = 2). Median overall survival (mOS) was 27 months for patients with distant recurrence. Twenty-one percent (n = 10) of patients presented with synchronous metastatic disease and their mOS was 19 months. Median progression-free survival (mPFS) for patients treated with conventional chemotherapy ranged from 2.0 to 8.0 months. CONCLUSION: The risk of recurrence is significant, and recurrence-free survival was short even with complete oncologic resection. The relationship of prior abdominal radiotherapy to the development of GI LMS warrants further investigation. Outcomes with systemic therapy for metastatic disease were poor and there is a need for the development of more effective systemic therapies..

Advances in the understanding and treatment of multiple myeloma have led to the need for more sensitive and accurate imaging of intramedullary and extramedullary disease. This role of imaging is underscored by recently revised imaging recommendations of the International Myeloma Working Group (IMWG). This narrative review discusses these recommendations from the IMWG for different disease stages, focusing on advanced whole-body modalities, and addresses related challenges and controversies. In the recommendations, whole-body low-dose CT is central in initial patient assessment, replacing the conventional skeletal survey. Although the recommendations favor MRI for diagnosis because of its superior sensitivity and utility in identifying myeloma-defining events, FDG PET/CT is recommended as the modality of choice for assessing treatment response. Consensus opinions are offered regarding the role of imaging in multiple myeloma for characterization of disease distribution, determination of prognosis, and response evaluation..

Radiomics refers to the extraction of mineable data from medical imaging and has been applied within oncology to improve diagnosis, prognostication, and clinical decision support, with the goal of delivering precision medicine. The authors provide a practical approach for successfully implementing a radiomic workflow from planning and conceptualization through manuscript writing. Applications in oncology typically are either classification tasks that involve computing the probability of a sample belonging to a category, such as benign versus malignant, or prediction of clinical events with a time-to-event analysis, such as overall survival. The radiomic workflow is multidisciplinary, involving radiologists and data and imaging scientists, and follows a stepwise process involving tumor segmentation, image preprocessing, feature extraction, model development, and validation. Images are curated and processed before segmentation, which can be performed on tumors, tumor subregions, or peritumoral zones. Extracted features typically describe the distribution of signal intensities and spatial relationship of pixels within a region of interest. To improve model performance and reduce overfitting, redundant and nonreproducible features are removed. Validation is essential to estimate model performance in new data and can be performed iteratively on samples of the dataset (cross-validation) or on a separate hold-out dataset by using internal or external data. A variety of noncommercial and commercial radiomic software applications can be used. Guidelines and artificial intelligence checklists are useful when planning and writing up radiomic studies. Although interest in the field continues to grow, radiologists should be familiar with potential pitfalls to ensure that meaningful conclusions can be drawn. Online supplemental material is available for this article. Published under a CC BY 4.0 license..

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Although soft-tissue masses are common, sarcomas are rare malignant neoplasms showing variable mesenchymal differentiation and can occur at any anatomical site. Limb soft-tissue sarcomas (STS) are rare, but often lethal tumours. Although there are scores of historical pathological subtypes, this article will deal with the commonest: liposarcoma, leiomyosarcoma (LMS), undifferentiated pleomorphic sarcoma (UPS), synovial sarcoma, myxofibrosarcoma, malignant peripheral nerve sheath tumour (MPNST), epithelioid sarcoma, alveolar rhabdosarcoma, angiosarcoma and radiation-induced sarcoma (RIS). Following a review of >4,000 adult patients with limb sarcoma from our specialist soft-tissue tumour database, we summarise the literature and their imaging findings, with emphasis on radiological hallmarks that can aide in diagnosis and management. Increased awareness of sarcoma when challenged with a new mass in the extremity can ensure timely and appropriate treatment..

Coronavirus disease 2019 (COVID-19) antiviral response in a pan-tumor immune monitoring (CAPTURE) ( NCT03226886 ) is a prospective cohort study of COVID-19 immunity in patients with cancer. Here we evaluated 585 patients following administration of two doses of BNT162b2 or AZD1222 vaccines, administered 12 weeks apart. Seroconversion rates after two doses were 85% and 59% in patients with solid and hematological malignancies, respectively. A lower proportion of patients had detectable titers of neutralizing antibodies (NAbT) against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOC) versus wild-type (WT) SARS-CoV-2. Patients with hematological malignancies were more likely to have undetectable NAbT and had lower median NAbT than those with solid cancers against both SARS-CoV-2 WT and VOC. By comparison with individuals without cancer, patients with hematological, but not solid, malignancies had reduced neutralizing antibody (NAb) responses. Seroconversion showed poor concordance with NAbT against VOC. Previous SARS-CoV-2 infection boosted the NAb response including against VOC, and anti-CD20 treatment was associated with undetectable NAbT. Vaccine-induced T cell responses were detected in 80% of patients and were comparable between vaccines or cancer types. Our results have implications for the management of patients with cancer during the ongoing COVID-19 pandemic..

Patients with cancer have higher COVID-19 morbidity and mortality. Here we present the prospective CAPTURE study, integrating longitudinal immune profiling with clinical annotation. Of 357 patients with cancer, 118 were SARS-CoV-2 positive, 94 were symptomatic and 2 died of COVID-19. In this cohort, 83% patients had S1-reactive antibodies and 82% had neutralizing antibodies against wild type SARS-CoV-2, whereas neutralizing antibody titers against the Alpha, Beta and Delta variants were substantially reduced. S1-reactive antibody levels decreased in 13% of patients, whereas neutralizing antibody titers remained stable for up to 329 days. Patients also had detectable SARS-CoV-2-specific T cells and CD4+ responses correlating with S1-reactive antibody levels, although patients with hematological malignancies had impaired immune responses that were disease and treatment specific, but presented compensatory cellular responses, further supported by clinical recovery in all but one patient. Overall, these findings advance the understanding of the nature and duration of the immune response to SARS-CoV-2 in patients with cancer..

Angiosarcomas are rare, aggressive soft tissue sarcomas originating from endothelial cells of lymphatic or vascular origin and associated with a poor prognosis. The clinical and imaging features of angiosarcomas are heterogeneous with a wide spectrum of findings involving any site of the body, but these most commonly present as cutaneous disease in the head and neck of elderly men. MRI and CT are complementary imaging techniques in assessing the extent of disease, focality and involvement of adjacent anatomical structures at the primary site of disease. CT plays an important role in the evaluation of metastatic disease. Given the wide range of imaging findings, correlation with clinical findings, specific risk factors and patterns of metastatic disease can help narrow the differential diagnosis. The final diagnosis should be confirmed with histopathology and immunohistochemistry in combination with clinical and imaging findings in a multidisciplinary setting with specialist sarcoma expertise. The purpose of this review is to describe the clinical and imaging features of primary sites and metastatic patterns of angiosarcomas utilising CT and MRI..

BACKGROUND: Most MRI radiomics studies to date, even multi-centre ones, have used "pure" datasets deliberately accrued from single-vendor, single-field-strength scanners. This does not reflect aspirations for the ultimate generalisability of AI models. We therefore investigated the development of a radiomics signature from heterogeneous data originating on six different imaging platforms, for a breast cancer exemplar, in order to provide input into future discussions of the viability of radiomics in "real-world" scenarios where image data are not controlled by specific trial protocols but reflective of routine clinical practice. METHODS: One hundred fifty-six patients with pathologically proven breast cancer underwent multi-contrast MRI prior to neoadjuvant chemotherapy and/or surgery. From these, 92 patients were identified for whom T2-weighted, diffusion-weighted and contrast-enhanced T1-weighted sequences were available, as well as key clinicopathological variables. Regions-of-interest were drawn on the above image types and, from these, semantic and calculated radiomics features were derived. Classification models using a variety of methods, both with and without recursive feature elimination, were developed to predict pathological nodal status. Separately, we applied the same methods to analyse the information carried by the radiomic features regarding the originating scanner type and field strength. Repeated, ten-fold cross-validation was employed to verify the results. In parallel work, survival modelling was performed using random survival forests. RESULTS: Prediction of nodal status yielded mean cross-validated AUC values of 0.735 ± 0.15 (SD) for clinical variables alone, 0.673 ± 0.16 (SD) for radiomic features only, and 0.764 ± 0.16 (SD) for radiomics and clinical features together. Prediction of scanner platform from the radiomics features yielded extremely high values of AUC between 0.91 and 1 for the different classes examined indicating the presence of confounding features for the nodal status classification task. Survival analysis, gave out-of-bag prediction errors of 19.3% (clinical features only), 36.9-51.8% (radiomic features from different combinations of image contrasts), and 26.7-35.6% (clinical plus radiomics features). CONCLUSIONS: Radiomic classification models whose predictive ability was consistent with previous single-vendor, single-field strength studies have been obtained from multi-vendor, multi-field-strength data, despite clear confounding information being present. However, our sample size was too small to obtain useful survival modelling results..

The recent rise of deep learning (DL) and its promising capabilities in capturing non-explicit detail from large datasets have attracted substantial research attention in the field of medical image processing. DL provides grounds for technological development of computer-aided diagnosis and segmentation in radiology and radiation oncology. Amongst the anatomical locations where recent auto-segmentation algorithms have been employed, the pelvis remains one of the most challenging due to large intra- and inter-patient soft-tissue variabilities. This review provides a comprehensive, non-systematic and clinically-oriented overview of 74 DL-based segmentation studies, published between January 2016 and December 2020, for bladder, prostate, cervical and rectal cancers on computed tomography (CT) and magnetic resonance imaging (MRI), highlighting the key findings, challenges and limitations..

INTRODUCTION: Multiple myeloma (MM) is a plasma cell tumour with over 5800 new cases each year in the UK. The introduction of biological therapies has improved outcomes for the majority of patients with MM, but in approximately 20% of patients the tumour is characterised by genetic changes which confer a significantly poorer prognosis, generally termed high-risk (HR) MM. It is important to diagnose these genetic changes early and identify more effective first-line treatment options for these patients. METHODS AND ANALYSIS: The Myeloma UK nine OPTIMUM trial (MUKnine) evaluates novel treatment strategies for patients with HRMM. Patients with suspected or newly diagnosed MM, fit for intensive therapy, are offered participation in a tumour genetic screening protocol (MUKnine a), with primary endpoint proportion of patients with molecular screening performed within 8 weeks. Patients identified as molecularly HR are invited into the phase II, single-arm, multicentre trial (MUKnine b) investigating an intensive treatment schedule comprising bortezomib, lenalidomide, daratumumab, low-dose cyclophosphamide and dexamethasone, with single high-dose melphalan and autologous stem cell transplantation (ASCT) followed by combination consolidation and maintenance therapy. MUKnine b primary endpoints are minimal residual disease (MRD) at day 100 post-ASCT and progression-free survival. Secondary endpoints include response, safety and quality of life. The trial uses a Bayesian decision rule to determine if this treatment strategy is sufficiently active for further study. Patients identified as not having HR disease receive standard treatment and are followed up in a cohort study. Exploratory studies include longitudinal whole-body diffusion-weighted MRI for imaging MRD testing. ETHICS AND DISSEMINATION: Ethics approval London South East Research Ethics Committee (Ref: 17/LO/0022, 17/LO/0023). Results of studies will be submitted for publication in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: ISRCTN16847817, May 2017; Pre-results..

BACKGROUND: Computed tomography (CT) and magnetic resonance imaging (MRI) are the mainstay imaging modalities in radiotherapy planning. In MR-Linac treatment, manual annotation of organs-at-risk (OARs) and clinical volumes requires a significant clinician interaction and is a major challenge. Currently, there is a lack of available pre-annotated MRI data for training supervised segmentation algorithms. This study aimed to develop a deep learning (DL)-based framework to synthesize pelvic T1-weighted MRI from a pre-existing repository of clinical planning CTs. METHODS: MRI synthesis was performed using UNet++ and cycle-consistent generative adversarial network (Cycle-GAN), and the predictions were compared qualitatively and quantitatively against a baseline UNet model using pixel-wise and perceptual loss functions. Additionally, the Cycle-GAN predictions were evaluated through qualitative expert testing (4 radiologists), and a pelvic bone segmentation routine based on a UNet architecture was trained on synthetic MRI using CT-propagated contours and subsequently tested on real pelvic T1 weighted MRI scans. RESULTS: In our experiments, Cycle-GAN generated sharp images for all pelvic slices whilst UNet and UNet++ predictions suffered from poorer spatial resolution within deformable soft-tissues (e.g. bladder, bowel). Qualitative radiologist assessment showed inter-expert variabilities in the test scores; each of the four radiologists correctly identified images as acquired/synthetic with 67%, 100%, 86% and 94% accuracy. Unsupervised segmentation of pelvic bone on T1-weighted images was successful in a number of test cases. CONCLUSION: Pelvic MRI synthesis is a challenging task due to the absence of soft-tissue contrast on CT. Our study showed the potential of deep learning models for synthesizing realistic MR images from CT, and transferring cross-domain knowledge which may help to expand training datasets for 21 development of MR-only segmentation models..

OBJECTIVES: Whole-body MRI (WB-MRI) is recommended by the International Myeloma Working Group for all patients with asymptomatic myeloma and solitary plasmacytoma and by the UK NICE guidance for all patients with suspected myeloma. Some centres unable to offer WB-MRI offer low-dose whole-body CT (WB-CT). There are no studies comparing interobserver agreement and disease detection of contemporary WB-MRI (anatomical imaging and DWI) versus WB-CT. Our primary aim is to compare the interobserver agreement between WB-CT and WB-MRI in the diagnosis of myeloma. METHODS: Consecutive patients with newly diagnosed myeloma imaged with WB-MRI and WB-CT were prospectively reviewed. For each body region and modality, two experienced and two junior radiologists scored disease burden with final scores by consensus. Intraclass correlation coefficients (ICC), median scores, Wilcoxon signed-rank test and Spearman's correlation coefficients were calculated. RESULTS: There was no significant difference in overall observer scores between WB-MRI and WB-CT (p = 0.87). For experienced observers, interobserver agreement for WB-MRI was superior to WB-CT overall and for each region, without overlap in whole-skeleton confidence intervals (ICC 0.98 versus 0.77, 95%CI 0.96-0.99 versus 0.45-0.91). For inexperienced observers, although there is a trend for a better interobserver score for the whole skeleton on WB-MRI (ICC 0.95, 95%CI 0.72-0.98) than on WB-CT (ICC 0.72, 95%CI 0.34-0.88), the confidence intervals overlap. CONCLUSIONS: WB-MRI offers excellent interobserver agreement which is superior to WB-CT for experienced observers. Although the overall burden was similar across both modalities, patients with lower disease burdens where MRI could be advantageous are not included in this series. KEY POINTS: • Whole-body MRI is recommended by the International Myeloma Working Group for patients with multiple myeloma and solitary plasmacytoma and by the NICE guidance for those with suspected multiple myeloma. • Some centres unable to offer whole-body MRI (WB-MRI) offer low-dose whole-body CT (WB-CT). • This prospective study demonstrates that contemporary WB-MRI (with anatomical sequences and DWI) provides better interobserver agreement in assessing myeloma disease burden for the whole skeleton and across any individual body region in myeloma patients when compared with low-dose whole-body CT..

AIMS: Embryonal and alveolar rhabdomyosarcoma (ERMS, ARMS) are subtypes of RMS that mainly occur in children, with relatively good outcomes. The incidence in adults is extremely low and survival is significantly worse compared with children. Data are scarce and literature generally combines all RMS subtypes, including pleomorphic RMS, which primarily occurs in adults and behaves more like undifferentiated pleomorphic sarcoma. The aim of this study was to evaluate patient and tumour characteristics, outcome and prognostic factors in adult patients with ERMS and ARMS. MATERIALS AND METHODS: All adult (18 years or older) ERMS and ARMS patients (presenting 1990-2016) were identified from a prospectively maintained database and were included in this analysis. RESULTS: Overall, 66 patients were included (42 men, 24 women). The median age at presentation was 28 years (range 18-71). The median overall survival for all ARMS (n = 42) and ERMS (n = 24) patients was 18 months, with a 5-year overall survival rate of 27%. Patients presenting with localised disease (n = 38, 58%) and metastatic disease (n = 25, 42%), had a 5-year overall survival rate of 36% and 11%, respectively. In univariate analysis we found alveolar subtype, fusion gene positivity, infiltrative tumour and metastatic presentation to be negative prognostic factors. CONCLUSION: Survival in adult ERMS and ARMS patients is poor and the current data may be useful in the design of trials with novel agents. Ideally, paediatric and adult oncologists should set up trials together to get a better understanding of biological, genetic and clinically relevant factors in this disease..

There have been major advances in myeloma imaging over the past few years with focal lesions on imaging now forming part of the disease defining criteria. Whole body diffusion-weighted MRI (WB-MRI) is considered the most sensitive technique for the detection of focal active lesions. This pictorial review will focus on imaging the spectrum of myelomatous disorders on WB-MRI including diffusion and Dixon sequences. The typical imaging patterns of disease are demonstrated including in the contexts of staging, presumed solitary plasmacytoma, smouldering myeloma and examples of paramedullary and extramedullary disease. The utility of diffusion-weighted imaging in response assessment is a major advantage and this will be exemplified here..

Whole-body MRI (WB-MRI) has evolved since its first introduction in the 1970s as an imaging technique to detect and survey disease across multiple sites and organ systems in the body. The development of diffusion-weighted MRI (DWI) has added a new dimension to the implementation of WB-MRI on modern scanners, offering excellent lesion-to-background contrast, while achieving acceptable spatial resolution to detect focal lesions 5 to 10 mm in size. MRI hardware and software advances have reduced acquisition times, with studies taking 40-50 min to complete.The rising awareness of medical radiation exposure coupled with the advantages of MRI has resulted in increased utilization of WB-MRI in oncology, paediatrics, rheumatological and musculoskeletal conditions and more recently in population screening. There is recognition that WB-MRI can be used to track disease evolution and monitor response heterogeneity in patients with cancer. There are also opportunities to combine WB-MRI with molecular imaging on PET-MRI systems to harness the strengths of hybrid imaging. The advent of artificial intelligence and machine learning will shorten image acquisition times and image analyses, making the technique more competitive against other imaging technologies..

BACKGROUND: Initial grading of retroperitoneal leiomyosarcoma (LMS) is performed by core biopsy (CB) however, discrepancy between grade of tumour at initial CB and surgical excision is recognised, raising concerns about the accuracy of CB for directing neoadjuvant therapy. The histological grading system used for staging LMS consists of 3 components: tumour differentiation, mitotic index and proportion of necrosis. We postulate that assessment of necrosis by histopathology alone is inadequate, resulting in under-grading of LMS. We propose and assess a combined grading system that incorporates CT scan findings into pre-surgical grading. METHODS: Retrospective, blinded review of CT, CB histology and final surgical histology of patients with retroperitoneal LMS was undertaken. A modified grading system, CTH-Grade, was derived by replacing the CB necrosis score with a CT-derived necrosis score. The sensitivity and specificity of CTH-Grade, the standard histopathology scoring, H-grade were compared. Inter-observer variability in assessment of CT necrosis was also assessed. RESULTS: 53 patients fulfilled criteria for inclusion. CT was more sensitive at detection of necrosis than CB histology alone with sensitivity of 100% vs 53%. The use of CTHGrade resulted in increased detection of high-grade tumours with CTH-grade having sensitivities of 80% and 35% for Grade 2 and 3 tumours respectively vs 53% and 15% with H-Grade. Assessment of reader agreement demonstrated Kappa scores of 0.8. CONCLUSION: Histology from CB under-grades LMS due to undersampling of tumour necrosis. CT is more sensitive in assessing necrosis and its incorporation into a modified CT-histopathology grading system (CTH-Grade) improves accuracy of grading with significant implications for patient management..

Desmoid tumor (DT; other synonymously used terms: Desmoid-type fibromatosis, aggressive fibromatosis) is a rare and locally aggressive monoclonal, fibroblastic proliferation characterised by a variable and often unpredictable clinical course. Previously surgery was the standard primary treatment modality; however, in recent years a paradigm shift towards a more conservative management has been introduced and an effort to harmonise the strategy amongst clinicians has been made. We present herein an evidence-based, joint global consensus guideline approach to the management of this disease focussing on: molecular genetics, indications for an active treatment, and available systemic therapeutic options. This paper follows a one-day consensus meeting held in Milan, Italy, in June 2018 under the auspices of the European Reference Network for rare solid adult cancers, EURACAN, the European Organisation for Research and Treatment of Cancer (EORTC) Soft Tissue and Bone Sarcoma Group (STBSG) as well as Sarcoma Patients EuroNet (SPAEN) and The Desmoid tumour Research Foundation (DTRF). The meeting brought together over 50 adult and pediatric sarcoma experts from different disciplines, patients and patient advocates from Europe, North America and Japan..

The role of MRI differs considerably between the three main groups of hematological malignancies: lymphoma, leukemia, and myeloma. In myeloma, whole-body MRI (WB-MRI) is recognized as a highly sensitive test for the assessment of myeloma, and is also endorsed by clinical guidelines, especially for detection and staging. In lymphoma, WB-MRI is presently not recommended, and merely serves as an alternative technique to the current standard imaging test, [18 F]FDG-PET/CT, especially in pediatric patients. Even for lymphomas with variable FDG avidity, such as extranodal mucosa-associated lymphoid tissue lymphoma (MALT), contrast-enhanced computed tomography (CT), but not WB-MRI, is presently recommended, despite the high sensitivity of diffusion-weighted MRI and its ability to capture treatment response that has been reported in the literature. In leukemia, neither MRI nor any other cross-sectional imaging test (including positron emission tomography [PET]) is currently recommended outside of clinical trials. This review article discusses current clinical applications as well as the main research topics for MRI, as well as PET/MRI, in the field of hematological malignancies, with a focus on functional MRI techniques such as diffusion-weighted imaging and dynamic contrast-enhanced MRI, on the one hand, and novel, non-FDG PET imaging probes such as the CXCR4 radiotracer [68 Ga]Ga-Pentixafor and the amino acid radiotracer [11 C]methionine, on the other hand. Level of Evidence: 5 Technical Efficacy Stage: 3 J. Magn. Reson. Imaging 2020;51:1325-1335..

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BACKGROUND AND OBJECTIVES: The aim of surgical treatment of gastrointestinal stromal tumors (GIST) is a microscopically complete resection. Initial indications for laparoscopic surgery were limited to smaller tumors, in favorable locations. Over time, indications for minimal invasive surgery (MIS) have expanded, however concerns remain when considering resection of larger GISTs. Our aims were to assess the utility of robotic resection of gastric GISTs for challenging tumors. METHODS: GIST resections, in this study were performed using the Intuitive Da Vinci Surgical Xi System. GIST's were considered challenging if tumor size was >50 mm at the time of surgery and/or the location of the tumor was type II, III, or IV using Privette/Al-Thanai classification. RESULTS: Robotic resections were performed on 12 consecutive patients, 83% were considered challenging cases, 6 out of 12 for location and 5 out of 12 for size. Initial median tumor size on imaging was 53.7 mm, and post-imatinib was 45.8 mm. All tumors were removed with clear margins (R0) via wedge resections, with no complications. Median operative time was 192 minutes (95-250). Length of hospital stay was 2 days (2-6). CONCLUSIONS: Robotic resection of gastric GIST's appears oncologically safe, and may expand the benefits of MIS to a greater cohort of complex cases..

BACKGROUND: Prostate-specific membrane antigen (PSMA) is a prostatic epithelial protein that is used as a radiotracer (68Ga-PSMA-11) for prostate cancer staging. PSMA-PET/CT (positron emission tomography/computed tomography) performed for prostate cancer has been observed to detect melanoma metastases. The aim of this study was to investigate the performance of PSMA immunohistochemistry on resected melanoma metastases to explore its use as a diagnostic imaging biomarker for melanoma. METHODS: A total of 41 specimens with stage III/IV melanoma were stained with PSMA immunohistochemistry. All specimens required both disease and control regions. Two pathologists scored the specimens and a receiver operating characteristic (ROC) curve was plotted. Western blot and multiplex immunofluorescence were also performed. RESULTS: The area under the ROC curve was 0.82, suggesting that PSMA has excellent discriminatory power in melanoma metastases. Sensitivity is 82.9% and specificity 73.2%. Immunohistochemistry and Western blot reveal that PSMA staining in melanoma consistently and most intensely occurs in tumor neovasculature. Multiplex immunofluorescence shows that melanocytes may also weakly express PSMA. CONCLUSION: The performance of PSMA immunohistochemistry in melanoma metastases contrasts with that reported in prostate cancer studies. This study indicates that PSMA shows promise for use as a novel biomarker in melanoma and justifies further research in the clinical setting with potential as a PET/CT radiotracer and intraoperative fluorescence marker for melanoma..

INTRODUCTION: Desmoid tumors (DT) are rare collagen-forming tumors that can exhibit locally aggressive patterns of behavior. The aim of this study was to evaluate the efficacy and safety of treatment of DT with single-agent oral vinorelbine. MATERIALS AND METHODS: A retrospective review of patients treated with vinorelbine 90 mg orally on days 1, 8, and 15 of a 28-day cycle from January 2004 to July 2019 was performed. Response was assessed using RECIST version 1.1. Descriptive statistics were employed. RESULTS: A total of 29 patients were included. Response rate was 20.7% (6/29), and clinical benefit rate (response by RECIST 1.1 and/or clinical symptom improvement) was 65.5% (19/29). No patient experienced grade 3 or above toxicity. Common toxicities were grade 1-2 nausea (14/26, 48.3%), fatigue (9/26, 31.0%), and diarrhea (4/26, 13.8%). CONCLUSION: Single-agent oral vinorelbine is an effective, safe, and well-tolerated treatment for DT. It represents a new oral alternative for management of DT..

BACKGROUND/AIM: Clear cell sarcoma (CCS) is an aggressive sarcoma subtype, resistant to conventional anthracycline-based chemotherapy and radiation. The diagnosis is often challenging due to similarities with malignant melanoma. PATIENTS AND METHODS: We aimed to analyse the activity of gemcitabine-based chemotherapy in a cohort of patients with CCS treated at the Royal Marsden Hospital. RESULTS: Five patients with metastatic CCS received gemcitabine as first- or second-line systemic therapy. The median time-to-progression was 10 weeks. The median number of cycles of gemcitabine-based therapy was 3 (range=2-7 cycles). Median overall survival in our cohort was 66 months from the initial diagnosis but in the metastatic setting, the overall survival was reduced to 28 months. CONCLUSION: Gemcitabine-based therapy has modest activity in CCS. There remains a significant unmet medical need for novel, effective therapies for this disease..

Whole-body magnetic resonance imaging (WB-MRI) is gradually being integrated into clinical pathways for the detection, characterization, and staging of malignant tumors including those arising in the musculoskeletal (MSK) system. Although further developments and research are needed, it is now recognized that WB-MRI enables reliable, sensitive, and specific detection and quantification of disease burden, with clinical applications for a variety of disease types and a particular application for skeletal involvement. Advances in imaging techniques now allow the reliable incorporation of WB-MRI into clinical pathways, and guidelines recommending its use are emerging. This review assesses the benefits, clinical applications, limitations, and future capabilities of WB-MRI in the context of other next-generation imaging modalities, as a qualitative and quantitative tool for the detection and characterization of skeletal and soft tissue MSK malignancies..

BACKGROUND: Whole body magnetic resonance imaging (MRI) is now incorporated into international guidance for imaging patients with multiple myeloma. The aim of this study was to investigate inter-observer agreement of triple reported baseline whole-body MRI in myeloma and highlight potential pitfalls. METHODS: Fifty-seven patients with symptomatic myeloma at first presentation or relapse and planned for autologous stem cell transplant were included. All patients completed baseline whole body MRI within 2 weeks prior to starting treatment. Each scan was reported independently by 3 radiologists using a defined scoring system. Differences in observer scores were compared using analysis of variance (ANOVA) and inter-observer agreement assessed using intra class correlation coefficient (ICC). RESULTS: There was no significant difference in mean observer scores for whole skeleton and ICC demonstrated excellent inter-observer agreement at 0.91. ICC varied between skeletal regions with spine, pelvis and ribs showing good inter-observer agreement, whereas skull and long bones were moderate. Scans with variation in observer scores were re-examined and cause of discrepancies identified. This information was used to describe potential anatomical pitfalls in reporting . CONCLUSION: Whole-body MRI has excellent inter-observer agreement in reporting symptomatic myeloma at baseline. Inter-observer agreement varied between skeletal regions highlighting specific areas of difficulty..

BACKGROUND: Alveolar Soft Part Sarcoma (ASPS) is a rare, slow-growing, but highly vascular soft tissue sarcoma, characterised by a high rate of metastases at presentation. Although imaging features of the primary are well described, less detail is available on the imaging pattern of metastatic ASPS. The EORTC 90101 (CREATE) study assessed the efficacy of Crizotinib in patients with metastatic ASPS and presents a unique opportunity to describe the imaging phenotype of primary and metastatic ASPS, based on prospectively collected imaging. METHODS: A retrospective review of the staging CT scans of 32 patients with ASPS from the CREATE study was undertaken and the imaging features of primary and metastatic disease were assessed. RESULTS: Imaging of the primary tumour was available in 7/32 cases (28%). All primary tumours demonstrated marked vascularity with prominent feeding vessels (7/7, 100%). The most frequent sites of metastases included lung (30/32, 94%), nodal (7/32, 22%), bone (5/32, 16%) and muscle/subcutaneous (5/32, 16%). Features of hypervascularity were identified at all sites, more appreciable in the lungs, with feeding vessels frequently demonstrated in pulmonary metastases (21/32, 66%). CONCLUSION: Analysis of imaging from the CREATE cohort of patients with metastatic ASPS demonstrates that metastases from ASPS are predominantly hypervascular and demonstrate feeding vessels comparable to primary ASPS, suggesting potential sensitivity of this rare sarcoma for antivascular/antiangiogenic treatment approaches..

BACKGROUND: Low-grade fibromyxoid sarcoma (LGFMS) is a rare sarcoma subtype with a generally indolent pattern of clinical behaviour, but treatments for advanced disease are limited. PATIENTS AND METHODS: A retrospective search of a prospectively maintained institutional database identified 102 patients treated from December 1994 to August 2018. We evaluated the outcome of patients and the efficacy and safety of non-surgical therapies in LGFMS. RESULTS: Ninety-four out of 102 (92.2%) underwent primary resection, seven (6.9%) were treated with systemic therapy and one (1.0%) is currently being treated with pre-operative radiotherapy. The RECIST 1.1 response rate to first-line chemotherapy was 0%, and median progression-free survival was 1.84 months (95% confidence intervaI=0.10-3.6 months). CONCLUSION: Conventional systemic therapy has limited efficacy in advanced LGFMS..

BACKGROUND/AIM: Treatment options for patients with metastatic soft tissue sarcomas are limited. Re-challenge with a previously successful gemcitabine-based regimen is common. There are no published data to support this practice. PATIENTS AND METHODS: We conducted a retrospective search to identify patients re-challenged with gemcitabine-based chemotherapy (GBC) from 2003 to 2015. RESULTS: Twenty-nine patients re-challenged with gemcitabine were identified. The response rate for initial GBC was 55% (n=15) and for re-challenge GBC 26% (n=6). The median progression-free survival was 11.1 months (95%CI=7.2-11.9) for initial GBC and 5.3 months (95%CI=2.0-7.5) for re-challenge GBC. Overall survival following gemcitabine re-challenge was 12.2 months (95%CI=7.0-18.2). Twelve out of 26 evaluable patients (46%) treated with re-challenge GBC experienced grade 3-4 adverse events (CTCAE 4.03) with 31% (n=8) of patients requiring dose reduction. CONCLUSION: In selected patients, gemcitabine re-challenge can be considered in advanced sarcomas, however, this approach is associated with toxicity..

In recent years, there have been major advances in the imaging of myeloma with whole body MRI incorporating diffusion-weighted imaging, emerging as the most sensitive modality. Imaging is now a key component in the work-up of patients with a suspected diagnosis of myeloma. The International Myeloma Working Group now specifies that more than one focal lesion on MRI or lytic lesion on whole body low-dose CT or fludeoxyglucose (FDG) PET/CT fulfil the criteria for bone damage requiring therapy. The recent National Institute for Health and Care Excellence myeloma guidelines recommend imaging in all patients with suspected myeloma. In addition, there is emerging data supporting the use of functional imaging techniques (WB-DW MRI and FDG PET/CT) to predict outcome and evaluate response to therapy. This review summarises the imaging modalities used in myeloma, the latest guidelines relevant to imaging and future directions..

Acknowledging the increasingly important role of whole-body MRI for directing patient care in myeloma, a multidisciplinary, international, and expert panel of radiologists, medical physicists, and hematologists with specific expertise in whole-body MRI in myeloma convened to discuss the technical performance standards, merits, and limitations of currently available imaging methods. Following guidance from the International Myeloma Working Group and the National Institute for Clinical Excellence in the United Kingdom, the Myeloma Response Assessment and Diagnosis System (or MY-RADS) imaging recommendations are designed to promote standardization and diminish variations in the acquisition, interpretation, and reporting of whole-body MRI in myeloma and allow response assessment. This consensus proposes a core clinical protocol for whole-body MRI and an extended protocol for advanced assessments. Published under a CC BY 4.0 license. Online supplemental material is available for this article..

OBJECTIVE: Current therapies for multiple myeloma, which include corticosteroids, increase risk of avascular necrosis. The aim of this study was to assess incidental detection of femoral head avascular necrosis on routine whole body MRI including diffusion weighted MRI. METHODS: All whole body MRI studies, performed on patients with known multiple myeloma between 1 January 2010 to 1 May 2017 were assessed for features of avascular necrosis. RESULTS: 650 whole body MR scans were analysed. 15 patients (6.6%) had typical MR features of avascular necrosis: 2/15 (13.3%) had femoral head collapse, 4/15 (26.7%) had bilateral avascular necrosis and 9/15 (60%) were asymptomatic. CONCLUSION: This is the first report of avascular necrosis detected on routine whole body MRI in patients with multiple myeloma. Targeted review of femoral heads in multiple myeloma patients undergoing whole body MR is recommended, including in patients without symptoms. ADVANCES IN KNOWLEDGE: Whole body MR which includes diffusion-weighted MRI is extremely sensitive for evaluation of bone marrow. Although whole body MRI is primarily used for evaluation of multiple myeloma disease burden, it also presents an unique opportunity to evaluate the femoral heads for signs of avascular necrosis which can predate symptoms..

BACKGROUND/AIM: Epithelioid haemangioendothelioma (EHE) is a rare tumor with a wide spectrum of clinical behavior. There is no consensus on the role of local therapy in symptomatic, multi-focal disease. PATIENTS AND METHODS: A retrospective review of patients presenting to the Royal Marsden Hospital between January 2000 and December 2017 was conducted. RESULTS: Fifty-three patients with EHE were identified, of which 18 patients (34.0%) received local therapy, and 11 patients (20.8%) underwent active surveillance. A variety of local treatment modalities were used with few toxicities, and local recurrence was managed with other local treatments or systemic therapy. Distal disease progression was infrequent (n=4, 7.5%). Patients who developed pleural effusion (n=5, 9.4%) had poor outcome irrespective of treatment. CONCLUSION: Local therapy has a role in a selected patient group managed in a multidisciplinary setting, including patients with indolent disease, and patients with a solitary area of progression/symptomatic disease..

BACKGROUND/AIM: To describe imaging features of head and neck soft-tissue sarcomas. PATIENTS AND METHODS: Patients with a diagnosis of head and neck sarcoma between 2011 and 2015 were reviewed. RESULTS: There were a total of 62 patients (24 female; median age=60 years). Most common sarcomas were angiosarcoma, undifferentiated pleomorphic sarcoma and sarcoma not otherwise specified. They were most commonly located in cranial and neck superficial soft tissues. Average tumour size at presentation was 45 mm. One patient had metastasis at presentation (rhabdomyosarcoma); two had nodal disease (rhabdomyosarcoma and angiosarcoma) and two tumours contained calcification (chondrosarcoma and synovial sarcoma). Four arose after prior radiotherapy. CONCLUSION: Unlike the more common diagnosis of squamous cell carcinoma, the majority of head and neck sarcomas present as large, solitary, superficial masses without lymph node enlargement. Identification of these features on imaging should raise suspicion of a sarcoma diagnosis, particularly in the setting of previous irradiation or genetic susceptibility..

BACKGROUND: Deep lipomatous tumours can be benign lipomas or intermediate/locally recurring atypical lipomatous tumours (ALTs). Differentiating between these two entities clinically and radiologically is difficult. The aims of this study were to report a series of deep lipomatous tumours, comparing the clinical, radiological and pathological features of ALTs and lipomas; and to predict the likelihood of a lipomatous tumour being ALT based on anatomical site and MRI characteristics. METHODS: This was a retrospective review of patients with deep lipomatous tumours presenting over 6 years to a tertiary sarcoma centre, with preoperative MRI, and preoperative or postoperative histology including MDM2 gene analysis. Sensitivity, specificity, predictive values and accuracy in diagnosing ALT were calculated for MRI and histopathological features. RESULTS: Some 248 patients were included; 81 (32·7 per cent) had a final diagnosis of ALT. ALTs were larger than lipomas (median 19 versus 10 cm; P < 0·001); there was no ALT smaller than 5 cm. A tumour presenting in the lower limb was more likely to be an ALT than a lesion at any other site (48·4 versus 13·5 per cent; P < 0·001). In patients with lipomatous tumours at sites other than the lower limbs, MRI had a negative predictive value of 95 per cent for excluding ALT. CONCLUSION: Despite concern, most deep lipomatous tumours (nearly 70 per cent) are benign lipomas. Certain features imply that tumours are almost never ALT: smaller than 5 cm or located outside the lower limb with no suspicious characteristics on MRI. Tumours with these features might safely and confidently be managed outside tertiary sarcoma centres..

BACKGROUND: The behavior of desmoid tumors is unpredictable and varies from spontaneous remission to symptomatic and radiologic progression. This study aimed to evaluate the radiologic and symptomatic course of the disease in patients initially managed with active surveillance. METHODS: Patients with a primary desmoid tumor at any anatomic location diagnosed between 1998 and 2016 were identified in a prospectively maintained database from a single sarcoma reference center in the United Kingdom. Inverse univariate Cox proportional hazard regression analyses were conducted to evaluate the course of the disease and indications for initiating treatment. RESULTS: The study identified 168 patients with a primary desmoid tumor initially managed with active surveillance. The tumors were located in the abdominal wall (n = 61, 36%), an extremity (n = 51, 30%), chest wall (n = 30, 18%), intra-abdominal site (n = 15, 9%), or elsewhere (n = 11, 6%). Of all the patients, 36% experienced radiologic progressive disease, 36% had stable disease, and 27% regressed. The patients younger than 50 years were more likely to progress (p = 0.046), whereas the patients with chest wall or upper-extremity tumors reported significantly more pain (p = 0.01). Eventually, 46% of the patients proceeded to treatment. The median time to start of treatment after initial surveillance was 31 months, whereas the median follow-up time for the patients not receiving any treatment was 40.5 months. The indications for initiation of treatment were pain (32%), progression (31%), or both (13%). CONCLUSIONS: Patients with desmoid tumors can be managed with initial active surveillance, although almost half of patients may eventually need treatment. Pain, tumor progression, or both are the most common indications for the initiation of treatment..

Soft tissue myoepithelial carcinomas are a rare, malignant subgroup of myoepithelial tumours mostly arising in the extremities with equal predilection for women and men. The mainstay of management of localised disease is complete surgical resection. Despite optimal treatment, 40-45% of tumours recur. Data regarding the efficacy of systemic therapy for advanced and metastatic disease are lacking. The primary aim of this study was to evaluate the outcome of all patients with soft tissue myoepithelial carcinoma treated at a single referral centre. The secondary aim was to establish the efficacy of systemic therapies in patients with advanced disease. A retrospective review of the prospectively maintained Royal Marsden Sarcoma Unit database was performed to identify soft tissue myoepithelial carcinoma patients treated between 1996 and 2019. Patient baseline characteristics and treatment history were recorded. Response to systemic therapy was evaluated using RECIST 1.1. We identified 24 patients treated at our institution between 1996 and 2019,12 males and 12 females. Median age at presentation was 49.6 years [interquartile range (IQR) 40.5-63.3 years]. Twenty-two out of 24 patients (91.7%) underwent primary surgical resection. Nine patients (37.5%) received systemic treatment. A partial response was documented in one patient treated with doxorubicin. The median progression-free survival for first-line chemotherapy was 9.3 months. Myoepithelial carcinoma frequently recurs after complete surgical resection. Conventional chemotherapy demonstrated some activity in myoepithelial carcinoma, however, more effective systemic therapies are required and enrolment in clinical trial should be encouraged..

Purpose: To evaluate repeatability of quantitative multi-parametric MRI in retroperitoneal sarcomas, assess parameter changes with radiotherapy, and correlate pre-operative values with histopathological findings in the surgical specimens. Materials and Methods: Thirty patients with retroperitoneal sarcoma were imaged at baseline, of whom 27 also underwent a second baseline examination for repeatability assessment. 14/30 patients were treated with pre-operative radiotherapy and were imaged again after completing radiotherapy (50.4 Gy in 28 daily fractions, over 5.5 weeks). The following parameter estimates were assessed in the whole tumor volume at baseline and following radiotherapy: apparent diffusion coefficient (ADC), parameters of the intra-voxel incoherent motion model of diffusion-weighted MRI (D, f, D*), transverse relaxation rate, fat fraction, and enhancing fraction after gadolinium-based contrast injection. Correlation was evaluated between pre-operative quantitative parameters and histopathological assessments of cellularity and fat fraction in post-surgical specimens (ClinicalTrials.gov, registration number NCT01902667). Results: Upper and lower 95% limits of agreement were 7.1 and -6.6%, respectively for median ADC at baseline. Median ADC increased significantly post-radiotherapy. Pre-operative ADC and D were negatively correlated with cellularity (r = -0.42, p = 0.01, 95% confidence interval (CI) -0.22 to -0.59 for ADC; r = -0.45, p = 0.005, 95% CI -0.25 to -0.62 for D), and fat fraction from Dixon MRI showed strong correlation with histopathological assessment of fat fraction (r = 0.79, p = 10-7, 95% CI 0.69-0.86). Conclusion: Fat fraction on MRI corresponded to fat content on histology and therefore contributes to lesion characterization. Measurement repeatability was excellent for ADC; this parameter increased significantly post-radiotherapy even in disease categorized as stable by size criteria, and corresponded to cellularity on histology. ADC can be utilized for characterizing and assessing response in heterogeneous retroperitoneal sarcomas..

Background: Multi-parametric MRI provides non-invasive methods for response assessment of soft-tissue sarcoma (STS) from non-surgical treatments. However, evaluation of MRI parameters over the whole tumor volume may not reveal the full extent of post-treatment changes as STS tumors are often highly heterogeneous, including cellular tumor, fat, necrosis, and cystic tissue compartments. In this pilot study, we investigate the use of machine-learning approaches to automatically delineate tissue compartments in STS, and use this approach to monitor post-radiotherapy changes. Methods: Eighteen patients with retroperitoneal sarcoma were imaged using multi-parametric MRI; 8/18 received a follow-up imaging study 2-4 weeks after pre-operative radiotherapy. Eight commonly-used supervised machine-learning techniques were optimized for classifying pixels into one of five tissue sub-types using an exhaustive cross-validation approach and expert-defined regions of interest as a gold standard. Final pixel classification was smoothed using a Markov Random Field (MRF) prior distribution on the final machine-learning models. Findings: 5/8 machine-learning techniques demonstrated high median cross-validation accuracies (82.2%, range 80.5-82.5%) with no significant difference between these five methods. One technique was selected (Naïve-Bayes) due to its relatively short training and class-prediction times (median 0.73 and 0.69 ms, respectively on a 3.5 GHz personal machine). When combined with the MRF-prior, this approach was successfully applied in all eight post-radiotherapy imaging studies and provided visualization and quantification of changes to independent STS sub-regions following radiotherapy for heterogeneous response assessment. Interpretation: Supervised machine-learning approaches to tissue classification in multi-parametric MRI of soft-tissue sarcomas provide quantitative evaluation of heterogeneous tissue changes following radiotherapy..

Patients with retroperitoneal sarcoma can present to a variety of clinicians with non-specific symptoms and retroperitoneal sarcomas can be incidental findings. Failure to recognize retroperitoneal sarcomas on imaging can lead to inappropriate management in non-specialist centers. Therefore it is critical that the possibility of retroperitoneal sarcoma should be considered with prompt referral to a soft tissue sarcoma unit. This review guides clinicians through a diagnostic pathway, introduces concepts in response assessment and new imaging developments..

OBJECTIVES: Treatment options for metastatic soft-tissue sarcomas are limited. The aim of this study was to investigate the clinical activity of ifosfamide rechallenge in synovial sarcoma (SS), liposarcoma (LPS), leiomyosarcoma (LMS), and high-grade sarcomas not otherwise specified. METHODS: A retrospective search of the Royal Marsden Sarcoma Unit Database was performed to identify patients initially treated with ifosfamide (as single agent or in combination) and who were subsequently rechallenged with single-agent ifosfamide. Baseline demographics and response assessment were retrospectively obtained. RESULTS: Sixty-seven patients were identified and the median age at diagnosis was 41 years (range, 18 to 71 y). There were 29 cases of SS, 17 of LPS, 12 of LMS, and 9 of sarcomas not otherwise specified. First-line ifosfamide-containing therapy was given to 14 patients as adjuvant therapy (adjuvant group) and 53 patients as palliative therapy (palliative group). Clinical activity (partial response or stable disease) with single-agent ifosfamide rechallenge was documented in 50.0% of patients in the adjuvant group (7 in the second line) and 34.0% of patients in the palliative group (15 in the second line, 1 in third line, and 2 in the fourth line). The median progression-free survival in patients with documented clinical activity was 11.5 months (95% CI, 8.8-12.3) and 6.9 months (95% CI, 5.1-9.0), respectively, in the adjuvant and palliative group. Ifosfamide rechallenge was mostly active in SS patients (49.3%, 14 out of 29 patients with partial remission or stable disease). CONCLUSIONS: Ifosfamide rechallenge has clinical activity in soft-tissue sarcoma and can be considered a viable option in treating metastatic disease..

BACKGROUND/AIM: Clear cell sarcoma-like tumor of the gastrointestinal tract (CCSLTGT) is a very rare and relatively recently characterized mesenchymal neoplasm arising within the wall of the small bowel, stomach, or large bowel, predominantly in adolescents and young adults. Only few anecdotal reports or small series have been published and a consensus on treatment has not been formulated. Complete resection remains the only curative option for localized disease, but despite optimal surgery, CCSLTGT typically shows highly aggressive behavior with a high rate of local recurrence, metastases, and death from disease. The hallmark of CCSLTGT is the presence of EWSR1-CREB1 or EWSR1-ATF1 gene fusions, detectable with reverse transcription-polymerase chain reaction (PCR). The aim of this study was to assess all referred cases of CCSLTGT, and document the pathological features, treatment and outcome of these patients. PATIENTS AND METHODS: We retrospectively reviewed all cases of histologically- and molecularly-confirmed CCSLTGT with EWSR1-CREB1 or EWSR1-ATF1 fusions at our tertiary sarcoma center, between 2009 and 2016. RESULTS: We assessed six patients diagnosed with CCSLTGT. In a median follow-up of 8 months, all patients received surgery, and additionally one patient was treated with chemotherapy and had progressive disease. Five of six patients experienced recurrence or progression of disease and 4 of 6 patients died of disease. CONCLUSION: Our study confirms that CCSLTGT is a very rare aggressive sarcoma subtype with a very poor outcome. Greater international collaboration is required to obtain a better understanding of this disease..

OBJECTIVES: The aim of this study was to identify apparent diffusion coefficient (ADC) values for typical haemangiomas in the spine and to compare them with active malignant focal deposits. METHODS: This was a retrospective single-institution study. Whole-body magnetic resonance imaging (MRI) scans of 106 successive patients with active multiple myeloma, metastatic prostate or breast cancer were analysed. ADC values of typical vertebral haemangiomas and malignant focal deposits were recorded. RESULTS: The ADC of haemangiomas (72 ROIs, median ADC 1,085×10-6mm2s-1, interquartile range 927-1,295×10-6mm2s-1) was significantly higher than the ADC of malignant focal deposits (97 ROIs, median ADC 682×10-6mm2s-1, interquartile range 583-781×10-6mm2s-1) with a p-value < 10-6. Receiver operating characteristic (ROC) analysis produced an area under the curve of 0.93. An ADC threshold of 872×10-6mm2s-1 separated haemangiomas from malignant focal deposits with a sensitivity of 84.7 % and specificity of 91.8 %. CONCLUSIONS: ADC values of classical vertebral haemangiomas are significantly higher than malignant focal deposits. The high ADC of vertebral haemangiomas allows them to be distinguished visually and quantitatively from active sites of disease, which show restricted diffusion. KEY POINTS: • Whole-body diffusion-weighted MRI is becoming widely used in myeloma and bone metastases. • ADC values of vertebral haemangiomas are significantly higher than malignant focal deposits. • High ADCs of haemangiomas allows them to be distinguished from active disease..

BACKGROUND: Sclerosing epithelioid fibrosarcoma (SEF) is a very rare soft tissue sarcoma subtype. Clinically it is an aggressive tumour; however, to our knowledge there are no published reports regarding the efficacy of chemotherapy in SEF. Therefore, the aim of this study was to document the outcome of a series of patients with SEF treated at a single referral centre with reference to systemic therapy. METHODS: A retrospective search of a prospectively maintained database was performed to identify all patients diagnosed with SEF between 1990 and 2017. The diagnosis was confirmed in each case by a dedicated soft tissue sarcoma pathologist. We analysed those with recurrent disease and the effect of systemic chemotherapy in the metastatic setting. RESULTS: Thirteen patients were identified, median overall survival from diagnosis and metastasis were 47.3 (95% CI 25.0-131.9) and 16.3 (95% CI 5.3-20.6) months, respectively. In total, 12 (92.3%) patients developed metastatic disease of which 10 died of disease, 1 was lost to follow-up and 1 had recently commenced palliative treatment. Among the 10 patients with metastatic disease, 7 received palliative chemotherapy. Palliative chemotherapy resulted in partial response in 1 patient, stable disease in 3 patients and progressive disease in 3 patients. Median time to disease progression was 2.7 (95% CI 1.2-4.4) months. Two of 13 patients were treated with adjuvant chemotherapy, receiving 6 cycles of liposomal doxorubicin and 1 cycle of doxorubicin, respectively, with a metastasis-free survival of 28.2 and 7.1 months, respectively. CONCLUSION: SEF is an aggressive sarcoma subtype with a poor outcome and with limited responsiveness to conventional chemotherapy. Patients with this subtype should be considered for participation in clinical trials with novel agents. Further investigation into the biology of this rare disease is required to improve outcomes..

BACKGROUND: Gastrointestinal stomal tumours (GISTs) are the most frequently diagnosed mesenchymal tumour of the gastrointestinal tract. The response of most GISTs to tyrosine kinase inhibitor (TKIs) treatment is spectacular; however progression and/or secondary resistance inevitably occurs with long-term treatment of recurrent or metastatic disease. Randomised studies investigating the potential additive benefit of metastasectomy in addition to TKI treatment unfortunately failed to accrue sufficient patients. Therefore, the apparent benefit of surgery in the setting of metastatic disease is based on retrospective institutional series or extrapolation of data from studies which were not intended directly to investigate the impact of surgery. The aim of this review is to summarise the current literature to inform an approach to the surgical management of metastatic GIST. METHODS: Relevant articles were retrieved from a comprehensive literature search using the PubMed database. Keywords included: GIST, metastasis, surgery, tyrosine kinase inhibitor. No restrictions on publication date were used. RESULTS: An overview of relevant literature and suggestions for multidisciplinary decision making are formulated. CONCLUSIONS: Our narrative review has identified studies which suggest that surgery may be beneficial in selected patients with metastatic GIST with responsive or stable disease during TKI treatment. Similarly, surgery for isolated clonal proliferative progressive disease may improve progression free survival and delay switch to second-line TKI in some cases..

BACKGROUND/AIM: Synovial sarcoma is a soft tissue sarcoma that tends to affect young adults. There are few reports on primary synovial sarcoma of the thyroid and the aim of this study was to document the clinical and pathological features of synovial sarcoma occurring at this site. CASE PRESENTATION: A retrospective review of a prospectively maintained database was performed to identify patients with synovial sarcoma of the thyroid treated at the Royal Marsden Hospital between 2000 and 2017. Five patients were identified that underwent initial surgical management of localized disease. The mean age at presentation was 38 years, and male to female ratio was 4:1. In 3 out of 5 cases, the diagnosis of synovial sarcoma was made on the post-operative excision specimen. Two of these patients were treated at our institution on the development of metastatic disease. We conducted a literature review and identified 12 previously reported cases of synovial sarcoma of the thyroid. CONCLUSION: Synovial sarcoma of the thyroid is rare and can be challenging to diagnose. The clinical presentation is typically indistinguishable from that of thyroid cancer and most cases are diagnosed post-operatively on an excision specimen. The clinical and pathological features are similar to synovial sarcoma arising at other sites. In our experience, the rarity of the diagnosis can lead to difficulty in establishing the correct diagnosis and determining the appropriate treatment pathway. It is important that physicians are aware of this diagnosis to facilitate prompt referral to a specialist centre, for specialist follow-up and treatment which is different to the thyroid cancer pathway..

Surgery is potentially curative for primary nonmetastatic extremity soft tissue sarcomas. After surgery alone, patients may remain at risk for local recurrences and/or metastatic disease. To reduce the likelihood of a local relapse, the addition of radiotherapy (RT) to limb-sparing surgery may result in higher local control rates of at least 85%. Generally, it can be stated that local control after both preoperative and postoperative RT is comparable, but that preoperative RT comes with a more favorable toxicity profile after prolonged follow-up, albeit at the cost of a higher wound complication rate. Furthermore, recent data suggest that preoperative RT is more cost effective. To reduce the risk of subsequent metastatic disease, systemic chemotherapy can be introduced early during the primary management of these patients. These systemic chemotherapy regimens can also be applied both preoperatively and postoperatively. Finally, with the aim of increasing the antitumor response of perioperative RT, these agents may even be combined with RT, concurrently and sequentially. While designing new preoperative combination regimens, responses should be carefully monitored by both sophisticated radiologic and pathologic evaluations. This article reviews all these aspects, in addition to limb-sparing surgery..

Whole-body diffusion-weighted MRI has emerged as a powerful diagnostic tool for disease detection and staging mainly used in systemic bone disease. The large field-of-view functional imaging technique highlights cellular tumor and suppresses normal tissue signal, allowing quantification of an estimate of total disease burden, summarized as the total diffusion volume (tDV), as well as global apparent diffusion coefficient (gADC) measurements. Both tDV and gADC have been shown to be repeatable quantitative parameters that indicate tumor heterogeneity and treatment effects, thus potential, noninvasive, imaging biomarkers informing on disease prognosis and therapy response..

This article outlines current international guidance for the role of imaging in myeloma and summarizes evidence regarding the role of whole-body MR imaging in diagnosis and response assessment. Whole-body MR imaging protocols, including diffusion-weighted MR imaging, are suggested as well as notes on pearls, pitfalls, and variants..

The prognosis of adult soft tissue sarcoma (STS) patients with metastases is generally poor. As little is known about the impact of the involvement of different metastatic sites and the extent of pulmonary lesions on the outcome for patients receiving first-line chemotherapy, we aimed to establish prognostic factors for STS patients with lung metastases only. A retrospective, exploratory analysis was performed on 2,913 metastatic STS patients who received first-line chemotherapy. Detailed information from 580 patients who had lung metastases only, was used for prognostic factor analysis. Patients with lung metastases only were more often asymptomatic and had undergone complete primary tumor resection more frequently compared to patients with additional metastases outside the lung or without lung metastases. For extremity STS, the incidence of lung metastases only was much higher compared to non-extremity STS. Lung involvement only was an independent favorable prognostic factor for overall survival (OS) with regard to metastatic site. Within this subgroup, in a multivariate model, other factors associated with improved OS included: good performance status (PS), no progression at primary site, low histological grade, younger age, long interval between initial diagnosis and trial registration, and smaller diameter of the largest lung lesion. This unique analysis on prognostic factors in STS patients with lung metastases confirms well-known patient factors (such as age and PS), and tumor characteristics (including tumor grade, interval between primary diagnosis, and metastases), but also identifies diameter of the largest lung lesion as a new prognostic factor. Knowledge about these factors may support decision-making within multidisciplinary tumor boards..

The outcome for patients with unresectable or metastatic soft tissue sarcoma remains poor with few treatment options. Synovial sarcoma is a rare type of sarcoma, predominantly affecting adolescents and young adults. Following failure of first-line anthracycline-based chemotherapy, several salvage options are available. We reviewed the safety and efficacy of gemcitabine/docetaxel chemotherapy in two tertiary oncology centres. We identified patients treated with gemcitabine/docetaxel between 2004 and 2016 in a UK and a US oncology centre using retrospective pharmacy and medical records. Treatment response, toxicity and outcome data were collected. Twenty one patients were treated with gemcitabine/docetaxel, the majority as a second- or third-line treatment for metastatic disease. The response rate was 5% with a median progression-free survival of 2 months (95% CI 1.3-3.7). Toxicities reported were as expected for this chemotherapy combination. Treatment was not discontinued due to toxicity. Gemcitabine/docetaxel chemotherapy shows little efficacy in synovial sarcoma and should not be offered to this patient group outside a clinical trial context..

BACKGROUND: One of the commonly used systemic agents for the treatment of aggressive fibromatosis is the anti-oestrogen drug tamoxifen. However, data on efficacy and optimum methods of response assessment are limited, consisting mainly of small case series and reports. METHODS: A retrospective database was used to identify consecutive patients diagnosed with aggressive fibromatosis (AF) and treated with tamoxifen plus/minus non-steroidal anti-inflammatory drugs at our tertiary referral centre between 2007 and 2014. MRI and symptom changes were recorded. RESULTS: Thirty-two patients (13 male 19 female, median age 41 years) were included. Median duration of treatment with tamoxifen was 316 days. Of 9 patients with progressive disease by RECIST 1.1 (28%): 4 patients experienced worsening symptoms; 3 patients had improved symptoms and 2 had no change in symptoms. Of 22 patients with stable disease (69%): 11 had no change in symptoms; 6 had improved symptoms and 5 patients had worsening symptoms. One patient achieved a partial response with improved symptoms. CONCLUSIONS: No relationship was identified between symptomatic benefit and response by RECIST 1.1 on MRI. Prospective studies in AF should incorporate endpoints focusing on patient symptoms..

BACKGROUND: The efficacy and potential toxicity of rechallenge with combination ipilimumab and nivolumab has not been described. Retreatment of patients with immune checkpoint inhibitors in the setting of prior significant toxicity lacks evidence-based guidance. METHODS: We present the first three, consecutive patients who received re-treatment with combination ipilimumab and nivolumab for metastatic melanoma managed at our institution. RESULTS: Rechallenge with combination ipilimumab and nivolumab in the setting of prior grade 3 toxicity with initial combination therapy is feasible, and responses are seen. We highlight the fact that grade 3 toxicity is likely to recur, but if so, can be manageable. CONCLUSIONS: Retreatment with ipi + nivo may be considered an option in carefully selected, well-informed patients. More research is required to delineate the benefits and risks with this approach..

Desmoid-type fibromatosis is a rare and locally aggressive monoclonal, fibroblastic proliferation characterized by a variable and often unpredictable clinical course. Currently, there is no established or evidence-based treatment approach available for this disease. Therefore, in 2015 the European Desmoid Working Group published a position paper giving recommendations on the treatment of this intriguing disease. Here, we present an update of this consensus approach based on professionals' AND patients' expertise following a round table meeting bringing together sarcoma experts from the European Organization for Research and Treatment of Cancer/Soft Tissue and Bone Sarcoma Group with patients and patient advocates from Sarcoma PAtients EuroNet. In this paper, we focus on new findings regarding the prognostic value of mutational analysis in desmoid-type fibromatosis patients and new systemic treatment options..

OBJECTIVE: To describe the major imaging features, together with clinical data, of paratesticular sarcomas. MATERIALS AND METHODS: A retrospective analysis was performed of available imaging and clinical data of 77 consecutive cases of paratesticular sarcoma referred to the soft tissue sarcoma center at the Royal Marsden hospital between January 2006 and January 2015. RESULTS: Of the total cases, 87% had been referred postoperatively, 43% of which had been imaged preoperatively and 24% of which required re-resection due to incomplete initial excision. On imaging, abnormal fat was present in 73% of paratesticular liposarcomas, with solid or enhancing components indicating high-grade tumors. Leiomyosarcomas and rhabdomyosarcomas were all purely solid masses. CONCLUSION: Paratesticular sarcomas are rare, and lack of awareness may compromise treatment and outcome. They may be mistaken for common clinical problems such as inguinal hernias and epididymal cysts. Surgery for these presumed diagnoses may result in inadequate clearance and an increased risk of recurrence. A low threshold for imaging atypical paratesticular masses is needed, as this may better inform management..

Desmoid tumour/aggressive fibromatosis (DT/AF) is a rare soft-tissue neoplasm that is locally aggressive but does not metastasize. There is no standard systemic treatment for symptomatic patients, although a number of agents are used. Tyrosine kinase inhibitors have recently been reported to show useful activity. We reviewed our bi-institutional (Royal Marsden Hospital, Cambridge University Hospitals) experience with the tyrosine kinase inhibitor pazopanib in the treatment of progressing DT/AF. Eight patients with DT/AF were treated with pazopanib at Royal Marsden Hospital and Cambridge University Hospitals between June 2012 and June 2016. The median age of the patients was 37.5 (range: 27-60) years. The median duration of pazopanib treatment was 12 (range: 5-22) months and for three patients the treatment is ongoing. Three patients discontinued treatment early (patient preference, intolerable toxicity and logistical reasons, respectively). None of the patients showed radiological progression while on treatment, best responses according to Response Evaluation Criteria In Solid Tumors 1.1 were partial response in 3/8 and stable disease in 5/8 cases. Six patients derived clinical benefit from treatment in terms of improved function and/or pain reduction. Median progression-free survival was 13.5 (5-36) months. Only one patient experienced intolerable toxicity (grade 3 hypertension) leading to early treatment discontinuation. In our series of patients with DT/AF, pazopanib demonstrated important activity both in terms of symptom control (75%) and absence of radiological progression (100%). Results of ongoing confirmatory trials are eagerly awaited..

Purpose To assess the repeatability of apparent diffusion coefficient (ADC) estimates in extracranial soft-tissue diffusion-weighted magnetic resonance imaging across a wide range of imaging protocols and patient populations. Materials and Methods Nine prospective patient studies and one prospective volunteer study, performed between 2006 and 2016 with research ethics committee approval and written informed consent from each subject, were included in this single-institution study. A total of 141 tumors and healthy organs were imaged twice (interval between repeated examinations, 45 minutes to 10 days, depending the on study) to assess the repeatability of median and mean ADC estimates. The Levene test was used to determine whether ADC repeatability differed between studies. The Pearson linear correlation coefficient was used to assess correlation between coefficient of variation (CoV) and the year the study started, study size, and volumes of tumors and healthy organs. The repeatability of ADC estimates from small, medium, and large tumors and healthy organs was assessed irrespective of study, and the Levene test was used to determine whether ADC repeatability differed between these groups. Results CoV aggregated across all studies was 4.1% (range for each study, 1.7%-6.5%). No correlation was observed between CoV and the year the study started or study size. CoV was weakly correlated with volume (r = -0.5, P = .1). Repeatability was significantly different between small, medium, and large tumors (P < .05), with the lowest CoV (2.6%) for large tumors. There was a significant difference in repeatability between studies-a difference that did not persist after the study with the largest tumors was excluded. Conclusion ADC is a robust imaging metric with excellent repeatability in extracranial soft tissues across a wide range of tumor sites, sizes, patient populations, and imaging protocol variations. Online supplemental material is available for this article..

Although retroperitoneal sarcomas are rare tumours, they can be encountered by a wide variety of clinicians as they can be incidental findings on imaging or present with non specific symptoms and signs. Surgical resection can offer hope of cure and patient outcomes are improved when patients are managed in high-volume specialist centers. Failure to recognize retroperitoneal sarcomas on imaging can lead to inappropriate management in inexperienced centers. Therefore it is critical that a diagnosis of retroperitoneal sarcoma should be considered in the differential diagnosis of a retroperitoneal mass with prompt referral to a soft tissue sarcoma unit. In particular, the most common retroperitoneal sarcoma subtypes, liposarcoma and leiomyosarcoma, have characteristic imaging appearances which are discussed. This review therefore aims to set the context and guide clinicians through a diagnostic pathway for retroperitoneal masses in adults which arise extrinsic to the solid abdominal viscera..

BACKGROUND: The European Organization for Research and Treatment of Cancer (EORTC) 62012 study was a Phase III trial of doxorubicin versus doxorubicin-ifosfamide chemotherapy in 455 patients with advanced soft tissue sarcoma (STS). Analysis of the main study showed that combination chemotherapy improved tumor response and progression-free survival, but differences in overall survival (OS) were not statistically significant. We analyzed factors prognostic for tumor response and OS, and assessed histological subgroup and tumor grade as predictive factors to identify patients more likely to benefit from combination chemotherapy. METHODS: Central pathology review was performed by six reference pathologists. Gender, age, performance status, time from first presentation with sarcoma to starting palliative chemotherapy, tumor grade, histological subgroup, primary tumor site involvement, and sites of metastases were assessed as prognostic factors. RESULTS: Three hundred and ten patients were included in this study. Discordance between local and central pathology opinion of tumor histology and tumor grade was observed in 98 (32%) and 122 (39%) cases, respectively. In multivariate analysis, liposarcoma patients had improved tumor response compared to other histological subgroups, whilst patients with metastases other than lung, liver or bone had a poorer response [odds ratio (OR) 0.42, 95% confidence interval (CI) 0.23-0.78; p = 0.006]. Patients with bone metastases had reduced OS [hazard ratio (HR) 1.56, 95% CI 1.16-2.09; p = 0.003]. By central pathology review, patients with undifferentiated pleomorphic sarcoma (UPS) had improved tumor response and OS with doxorubicin-ifosfamide compared to single-agent doxorubicin (OR 9.90, 95% CI 1.93-50.7 and HR 0.44, 95% CI 0.26-0.79, respectively). Grade III tumors had improved response with combination chemotherapy but there was no interaction between chemotherapy and grade on OS. CONCLUSIONS: Prospective central pathology review of tumor histology should be integrated into future STS clinical trials. Doxorubicin-ifosfamide may be most appropriate for young, fit patients with poorly differentiated Grade III tumors including UPS..

PURPOSE OF REVIEW: Retroperitoneal sarcomas are rare tumors and with complex treatment. In this manuscript we give an overview of current standards in treatment of this disease and discuss new developments. RECENT FINDINGS: Surgery with complete resection of the primary tumor is still the only curative modality. The role of preoperative radiotherapy is not clear and is currently being investigated in a clinical trial. Neo-adjuvant chemotherapy is not the standard of care but can be considered occasionally when complete resection is uncertain. Local and distant recurrent disease carries a dismal prognosis, although long-term survival can be achieved. Liposarcomas tend to recur locally, whereas distant recurrences are more often seen in leiomyosarcoma and other subtypes. Outcome improves when patients are treated in high volume sarcoma centers. In the metastatic setting, newer systemic agents have recently been approved. SUMMARY: Treatment of retroperitoneal sarcomas is complex and all patients should be treated in multidisciplinary sarcoma centers. Increasing international collaboration of expert centers in sharing expertise and performing clinical trials might lead to better treatment and improved survival..

BACKGROUND: Soft tissue tumours of the abdominal wall account for approximately 10% of all soft tissue tumours. Tumours at this site comprise a heterogeneous group of pathologies with distinct clinical behaviours and responses to treatment. The management of these tumours has largely been extrapolated from studies of soft tissue tumours at other sites. This review aims to summarise the existing data relating to abdominal wall tumours and suggest principles for managing soft tissue tumours at this site. METHODS: Relevant articles were retrieved from a comprehensive literature search using the PubMed database. Key words included abdominal wall, soft tissue tumours, surgery, radiotherapy and chemotherapy. No restrictions on publication date were used. RESULTS: The most common pathologies presenting in the abdominal wall are desmoid tumours, soft-tissue sarcoma and dermatofibrosarcoma protuberans (DFSP). Desmoid tumours should be managed with an initial period of observation, with surgery reserved for progressive lesions. Surgery should be the primary treatment for soft-tissue sarcomas and DFSP, with radiotherapy reserved for large-high grade tumours and preferentially given pre-operatively. CONCLUSIONS: Abdominal wall tumours are rare and should be managed in centres with experience in the management of soft tissue tumours. Management should be tailored to the biological behaviour of specific pathologies..

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Two hundred and ten nuclear medicine physicians, radiologists, and hematologists from 26 countries attended the 6th International Workshop on Positron Emission Tomography (PET) in Lymphoma and Myeloma held in Menton, France, in September 2016. The meeting was under the auspices of the European Lymphoma Institute (ELI), the European Association of Nuclear Medicine (EANM) the Lymphoma Study Association (LYSA), the Italian Foundation on Lymphoma (FIL) and the Carnot Institute for Lymphoma (CALYM). Forty scientific posters were presented. For the first time, specialists in the field of multiple myeloma (MM) were involved in the expert session. The aim was to establish from the experience of Italian and French studies new guidelines of FDG-PET/CT reporting for myeloma staging and restaging. The meeting dedicated an entire session to MM imaging followed by a session on the role of PET in Peripheral T cell Lymphoma. An entire session addressed the issues of Deauville scale particularly for end treatment assessment and the challenging consequences of immunomodulatory treatments on PET reporting. A specific session presented the potential role of baseline metabolic tumor measurement to predict outcome and identify different risk categories and the main results obtained in different lymphoma entities were described. Whether it could replace clinical staging has been extensively discussed. The more recent results obtained in the H10 trial have been presented and compared to the published data in early stage Hodgkin lymphoma. Finally, the ongoing studies using PET for guiding therapeutic strategies have been reported by the various lymphoma cooperative groups that participated to the meeting..

OBJECTIVE: The purpose of this article is to review current image acquisition and interpretation for whole-body MRI, clinical applications, and the emerging roles in oncologic imaging, especially in the assessment of bone marrow diseases. CONCLUSION: Whole-body MRI is an emerging technique used for early diagnosis, staging, and assessment of therapeutic response in oncology. The improved accessibility and advances in technology, including widely available sequences (Dixon and DWI), have accelerated its deployment and acceptance in clinical practice..

Here, we retrospectively review imaging of 68 consecutive unselected patients with BRAF V600-mutant metastatic melanoma for organ-specific response and progression on vemurafenib. Complete or partial responses were less often seen in the central nervous system (CNS) (36%) and bone (16%) compared to lung (89%), subcutaneous (83%), spleen (71%), liver (85%) and lymph nodes/soft tissue (83%), P < 0.001. CNS was also the most common site of progression. Based on this, we tested in vitro the efficacy of the BRAF inhibitors PLX4720 and dabrafenib in the presence of cerebrospinal fluid (CSF). Exogenous CSF dramatically reduced cell death in response to both BRAF inhibitors. Effective cell killing was restored by co-administration of a PI-3 kinase inhibitor. We conclude that the efficacy of vemurafenib is variable in different organs with CNS being particularly prone to resistance. Extrinsic factors, such as ERK- and PI3K-activating factors in CSF, may mediate BRAF inhibitor resistance in the CNS..

At present, there is not a commonly used and generally accepted standardized approach for the pathologic evaluation of pretreated soft tissue sarcomas. Also, it is still unclear whether the cut-off for prognostic relevance is similar in the many different histological subtypes of STS. This manuscript, produced by a European Organization for Research and Treatment of Cancer - Soft Tissue and Bone Sarcoma Group (EORTC-STBSG) endorsed task force, aims to propose standardization of the pathological examination process and the reporting of STS resection specimens after neoadjuvant radio- and/or chemotherapy..

INTRODUCTION: Elastofibromas are rare, pseudo-tumours arising at the inferior pole of the scapula that have a characteristic presentation. Due to their tissue of origin and size, they may often be mistaken for soft tissue sarcomas. We present the management of patients diagnosed with elastofibroma at a single institution. METHODS: Patients diagnosed with elastofibroma between January 1995 and January 2015 were identified from a prospectively maintained histopathology database. Electronic patient records, imaging and pathology reports were retrieved and reviewed. RESULTS: Thirty seven patients were identified, with a median age of 66 years and a male-to-female ratio of 1:1.6. All tumours occurred in the characteristic subscapular location. The median maximum tumour diameter was 8.2 cm. A synchronous contralateral lesion (15.8%) was found in six patients. Cross-sectional imaging was performed in 29 patients, with magnetic resonance imaging the most common modality (59.5%). Diagnosis was confirmed with percutaneous biopsy in all but one patient, who proceeded directly to surgery. Eighteen patients were managed non-operatively; 19 opted for surgical excision due to significant symptoms. Excision was performed in a marginal fashion and, at a median follow-up of 5 months, no functional impairment or local recurrences were observed. CONCLUSIONS: Soft tissue masses greater than 5 cm in diameter should prompt the clinician to exclude soft tissue sarcoma. The diagnosis of elastofibroma may be alluded to by its typical presentation and can be confirmed by percutaneous biopsy. After excluding malignancy, these lesions can be safely managed non-operatively, with surgery reserved for symptomatic patients..

At present, there is no standardised approach for the radiological evaluation of soft tissue sarcomas following radiotherapy (RT). This manuscript, produced by a European Organisation for Research and Treatment of Cancer-Soft Tissue and Bone Sarcoma Group (EORTC-STBSG) and Imaging Group endorsed task force, aims to propose standardisation of magnetic resonance imaging techniques and interpretation after neoadjuvant RT for routine use and within clinical trials..

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OBJECTIVES: To assess the utility of diffusion weighted imaging for monitoring early treatment effects associated with a VEGF inhibitor. MATERIALS AND METHODS: Twenty-nine patients with metastatic abdominal and pelvic tumours were recruited and imaged with DW-MRI: twice at baseline, and after 7 and 28 days of treatment with cediranib. Tumour measures were derived using mono-exponential, bi-exponential and stretched-exponential models, and parameter repeatability and treatment effects seen after 7 and 28 days were assessed. Correlations with volume changes and DCE-MRI metrics were also assessed. RESULTS: Diffusion coefficient repeatabilities from all models were < 6%; f and D* (bi-exponential) were 22% and 44%; α (stretched-exponential) was 4.2%. Significant increases in the diffusion coefficients from all models were observed at day 28 but not day 7. Significant decreases in D* and f.D* were observed at day 7 and in f at day 28; significant increases in α were observed at both time-points. Weak correlations between DW-MRI changes and volume changes and DCE-MRI changes were observed. CONCLUSION: DW-MRI is sensitive to early and late treatment changes caused by a VEGF inhibitor using non-mono-exponential models. Evidence of over-fitting using the bi-exponential model suggests that the stretched-exponential model is best suited to monitor such changes. KEY POINTS: • Non-mono-exponential diffusion models widen sensitivity to a broader class of tissue properties. • A stretched-exponential model robustly detects changes after 7 days of VEGF-inhibitor treatment. • There are very weak correlations between DWI-IVIM perfusion and similar DCE-MRI measures. • Diffusion-weighted MRI is a highly informative technique for assessing novel tumour therapies..

INTRODUCTION: Previous studies in metastatic soft tissue sarcomas (STS) showed that synovial sarcomas tend to have better survival rates and a higher chemosensitivity than other STS subtypes. However, data are derived from relatively small subgroups and statistical significance of these observations is lacking. Larger cohorts are necessary to define and confirm the specific characteristics of this subtype. PATIENTS AND METHODS: Patient data were retrieved from 15 European Organisation for Research and Treatment of Cancer advanced first-line STS trials. Patient characteristics, survival and treatment response of synovial sarcoma patients were compared to other STS patients. Univariable and multivariable analyses were performed to evaluate prognostic factors. RESULTS: In total, 3330 advanced STS patients were retrieved, of whom 313 had a synovial sarcoma. Synovial sarcoma patients were significantly younger (median 40 versus 52 years), more often had extremity primary tumours and had a better performance status (PS 0: 50.2 versus 43.4%) compared to other STS patients. Additionally, synovial sarcoma patients had a significantly better response to chemotherapy (responders: 27.8 versus 18.8%) and better survival rates (progression free survival [PFS]: 6.3 versus 3.7 months; Overall survival [OS]: 15.0 versus 11.7 months). Age, PS, and presence of metastatic disease were defined as prognostic factors for PFS and OS in the univariable analysis. The last two factors were confirmed in the multivariable analysis for OS. DISCUSSION: Advanced synovial sarcomas are a distinct subgroup of STS, with a better response to systemic chemotherapy and longer PFS and OS. These results should be taken into account in the design of future synovial sarcoma specific studies..

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OBJECTIVES: Pharmacokinetic (PK) modelling of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) data requires a reliable measure of the arterial input function (AIF) to robustly characterise tumour vascular properties. This study compared repeatability and treatment-response effects of DCE-MRI-derived PK parameters using a population-averaged AIF and three patient-specific AIFs derived from pre-bolus MRI, DCE-MRI and dynamic contrast computed tomography (DC-CT) data. METHODS: The four approaches were compared in 13 patients with abdominal metastases. Baseline repeatability [Bland-Altman statistics; coefficient of variation (CoV)], cohort percentage change and p value (paired t test) and number of patients with significant DCE-MRI parameter change post-treatment (limits of agreement) were assessed. RESULTS: Individual AIFs were obtained for all 13 patients with pre-bolus MRI and DC-CT-derived AIFs, but only 10/13 patients had AIFs measurable from DCE-MRI data. The best CoV (7.5 %) of the transfer coefficient between blood plasma and extravascular extracellular space (K (trans)) was obtained using a population-averaged AIF. All four AIF methods detected significant treatment changes: the most significant was the DC-CT-derived AIF. The population-based AIF was similar to or better than the pre-bolus and DCE-MRI-derived AIFs. CONCLUSIONS: A population-based AIF is the recommended approach for measuring cohort and individual effects since it has the best repeatability and none of the PK parameters derived using measured AIFs demonstrated an improvement in treatment sensitivity. KEY POINTS: • Pharmacokinetic modelling of DCE-MRI data requires a reliable measure of AIF. • Individual MRI-DCE-derived AIFs cannot reliably be extracted from patients. • All four AIF methods detected significant K (trans) changes after treatment. • A population-based AIF can be recommended for measuring cohort treatment responses in trials..

BACKGROUND: Anthracycline-based chemotherapy remains the mainstay of first-line treatment in metastatic or advanced soft-tissue sarcoma (STS). Age, performance status, tumour histology and tumour grade are recognised prognostic factors; however, the prognostic value of tumour response and tumour shrinkage is ill-defined. METHODS: Patients recruited to the European Organisation for Research and Treatment of Cancer 62012 trial with advanced intermediate or high-grade STS, who received at least one cycle of chemotherapy and one tumour assessment of response, were eligible for this study. Kaplan-Meier estimates of overall survival (OS) by tumour response were computed using a landmark approach after two, four, and six cycles of chemotherapy. The prognostic role of the kinetics of tumour response was analysed by Cox proportional hazards. RESULTS: Three hundred eighty-nine patients were included in this study. Compared to stable or responding patients, patients with progressive disease (PD) after two, four and six cycles of chemotherapy achieved a worse OS: hazard ratio [HR] 2.62 (95% confidence interval [CI] 1.72-4.00), p < 0.001; HR 2.23 (95% CI 1.4-3.56), p = 0.0001; and HR 3.16 (95% CI 1.96-5.08), p = 0.0001, respectively. However, patients with stable or responding disease achieved similar OS outcomes. Correspondingly, patients with an increase in tumour size by 10% or more correlated with a worse OS in Cox proportional hazard analysis. CONCLUSIONS: No association between prognosis and amount of tumour shrinkage was detected. Interestingly, an increase in tumour size by at least 10% correlated with a worse OS, but re-defining PD as a ≥10% increase in tumour size did not translate into a better discrimination of survival outcomes for responders versus stable disease. Disease control rather than tumour response is a valuable end-point in advanced or metastatic STS receiving palliative anthracycline-based chemotherapy, supporting the use of time-to-event end-points in future STS trials..

While endometriosis, defined as the presence of endometrial tissue in extrauterine sites, is most frequently encountered within the peritoneal cavity, a small but significant proportion of cases occur at extra-abdominal soft tissue sites, particularly in relation to previous abdominal surgery. We reviewed the cases of endometriosis of soft tissue sites seen at a tertiary soft tissue center. All cases of extra-abdominal soft tissue endometriosis diagnosed at this institution over a 13-year period were reviewed, and clinical and pathologic findings were recorded. Forty-five patients had diagnoses of soft tissue endometriosis and there were 34 diagnostic biopsies and 26 surgical excision specimens. All but 1 case were abdominal wall lesions, with 1 located in the upper arm. A total of 33 patients presented with lesions in scars of previous operations (31 in Pfannenstiel incisions for Caesarean sections, presenting with a median interval of 6 years (range 1-16 years) following surgery). The lesions ranged in size from 1 to 8 cm (median 3.5 cm). One case showed decidualized stroma with trophoblast cells, while 2 had secondary adenocarcinoma arising from endometriosis. Eighteen cases were tested for β-catenin expression immunohistochemically, of which 5 showed at least focal nuclear positivity in the surrounding fibrous tissue (although not within glands or stroma). Soft tissue endometriosis is seen most commonly in surgical scars, particularly following Caesarean sections. Spontaneous endometriosis also most commonly occurs in the abdominal wall, although can occur exceptionally at unusual sites, such as extremities. Secondary changes, including carcinomas, can arise from endometriosis. The differential diagnosis of these lesions includes fibromatosis, which may be erroneously diagnosed on small, nonrepresentative core biopsy specimens..

(1) H MRS measurements of lactate are often confounded by overlapping lipid signals. Double-quantum (DQ) filtering eliminates lipid signals and permits single-shot measurements, which avoid subtraction artefacts in moving tissues. This study evaluated a single-voxel-localized DQ filtering method qualitatively and quantitatively for measuring lactate concentrations in the presence of lipid, using high-grade brain tumours in which the results could be compared with standard acquisition as a reference. Paired standard acquisition and DQ-filtered (1) H MR spectra were acquired at 3T from patients receiving treatment for glioblastoma, using fLASER (localization by adiabatic selective refocusing using frequency offset corrected inversion pulses) single-voxel localization. Data were acquired from 2 × 2 × 2 cm(3) voxels, with a repetition time of 1 s and 128 averages (standard acquisition) or 256 averages (DQ-filtered acquisition), requiring 2.15 and 4.3 min respectively. Of 37 evaluated data pairs, 20 cases (54%) had measureable lactate (fitted Cramér-Rao lower bounds ≤ 20%) in either the DQ-filtered or the standard acquisition spectra. The measured DQ-filtered lactate signal was consistently downfield of lipid (1.33 ± 0.03 ppm vs 1.22 ± 0.08 ppm; p = 0.002), showing that it was not caused by lipid breakthrough, and that it matched the lactate signal seen in standard measurements (1.36 ± 0.02 ppm). In the absence of lipid, similar lactate concentrations were measured by the two methods (mean ratio DQ filtered/standard acquisition = 1.10 ± 0.21). In 7/20 cases with measurable lactate, signal was not measureable in the standard acquisition owing to lipid overlap but was quantified in the DQ-filtered acquisition. Conversely, lactate was undetected in seven DQ-filtered acquisitions but visible using the standard acquisition. In conclusion, the DQ filtering method has proven robust in eliminating lipid and permits uncontaminated measurement of lactate. This is important validation prior to use in tissues outside the brain, which contain large amounts of lipid and which are often susceptible to motion..

A fit and active amateur cyclist was referred by his general practitioner to a surgical oncology outpatient clinic with a slowly-growing perineal mass. Following clinical examination, the patient underwent imaging and biopsy at a tertiary soft tissue tumour centre, which diagnosed perineal nodular induration: a rare, benign tumour caused by repetitive trauma associated with 'saddle sports' such as cycling or horse riding. It is important to consider soft tissue tumours in patients who present with 'lumps and bumps'; they can occur anywhere in the body including the groin or perineum, where it is sometimes referred to as a 'third' or 'accessory' testicle in men. Although unusual, the case emphasises the importance of rapid specialist referral from primary care, and consideration of a patient's occupation and hobbies when formulating diagnoses..

INTRODUCTION: Retroperitoneal soft tissue sarcomas (RPS) are rare tumors. Surgery is the mainstay of curative therapy, but local recurrence is common. No recommendations concerning the best management of recurring disease have been developed so far. Although every effort should be made to optimize the initial approach, recommendations to treat recurring RPS will be helpful to maximize disease control at recurrence. METHODS: An RPS transatlantic working group was established in 2013. The goals of the group were to share institutional experiences, build large multi-institutional case series, and develop consensus documents on the approach to this difficult disease. The outcome of this document applies to recurrent RPS that is nonvisceral in origin. Included are sarcomas of major veins, undifferentiated pleomorphic sarcoma of psoas, ureteric leiomyosarcoma (LMS). Excluded are desmoids-type fibromatosis, angiomyolipoma, gastrointestinal stromal tumors, sarcomas arising from the gut or its mesentery, uterine LMS, prostatic sarcoma, paratesticular/spermatic cord sarcoma, Ewing sarcoma, alveolar/embryonal rhabdomyosarcoma, sarcoma arising from teratoma, carcinosarcoma, sarcomatoid carcinoma, clear cell sarcoma, radiation-induced sarcoma, paraganglioma, and malignant pheochromocytoma. RESULTS: Recurrent RPS management was evaluated from diagnosis to follow-up. It is a rare and complex malignancy that is best managed by an experienced multidisciplinary team in a specialized referral center. The best chance of cure is at the time of primary presentation, but some patients may experience prolonged disease control also at recurrence, when the approach is optimized and follows the recommendations contained herein. CONCLUSIONS: International collaboration is critical for adding to the present knowledge. A transatlantic prospective registry has been established..

Desmoplastic small round cell tumor (DSRCT) is an aggressive small round cell neoplasm which predominantly occurs intra-abdominally in adolescents and young adults with a male predominance, and which is characterized by a recurrent t(11;22)(p13;q12) translocation leading to formation of the EWSR1-WT1 fusion gene, which generates a chimeric protein with transcriptional regulatory activity. Histologically, DSRCT has a characteristic morphology, of islands of monotonous small cells within prominent sparsely cellular fibroblastic stroma, and immunohistochemically it shows polyphenotypic multidirectional differentiation, with expression of epithelial, muscle, and neural markers. However, DSRCT can arise more rarely in other sites and exhibit a spectrum of both histologic features and immunoprofile, which may confuse diagnosis with other small round cell neoplasms. Correct diagnosis is important to ensure correct treatment and prognostication; DSRCT are almost universally fatal neoplasms with patients usually succumbing to disease within the first 2 years of diagnosis. While combination treatment strategies can confer a survival benefit, the overall prognosis remains poor. Further insight into the tumorigenic molecular changes generated by the fusion oncogene may lead to the generation of specific targeted therapies. We review DSRCT, discussing morphology and immunohistochemistry, molecular genetic findings, potential targeted treatments, and the differential diagnosis..

AIM: Aggressive angiomyxomas (AA) are rare tumors, most commonly presenting in the pelvis of women of childbearing age. This study presents the results of selective marginal resection of this disease in patients managed at a single institution. METHODS: Patients diagnosed with AA from July 2001 to July 2015 were identified from a prospectively maintained histopathology database. RESULTS: Seventeen patients were diagnosed with AA in the study period. The median age at diagnosis was 48 years. Females were more commonly affected with a M:F of 1:8.5. The most common differential diagnoses were an ischiorectal abscess or Bartholin's cyst. Fifteen cases occurred in the pelvis, with two cases at other sites. Median maximum tumor diameter was 10 cm. Of the pelvic cases, 12 were managed operatively via perineal, abdominal, or abdominoperineal approaches. Excision was performed in a marginal fashion with minimal morbidity. Local recurrence developed in 58.3% with a median local recurrence free survival of 25 months. No patients developed metastatic disease or died from disease. CONCLUSION: AA are rare tumors with a propensity for local recurrence. Atypical presentations of other perineal pathologies should prompt further investigation. Surgery should be reserved for symptomatic patients and is associated with low rates of morbidity. J. Surg. Oncol. 2016;114:828-832. © 2016 2016 Wiley Periodicals, Inc..

Lactate is a product of glucose metabolism. In tumour tissues, which exhibit enhanced glycolytic metabolism, lactate signals may be elevated, making lactate a potential useful tumour biomarker. Methods of lactate quantitation are complicated because of overlap between the lactate methyl doublet CH3 resonance and a lipid resonance at 1.3 ppm. This study presents the use of a selective homonuclear multiple quantum coherence transfer sequence (SelMQC-CSI), at 1.5 T, to better quantify lactate in the presence of lipids. Work performed on phantoms showed good lactate detection (49%) and lipid suppression (98%) efficiencies. To evaluate the method in the brain, the sequence was tested on a group of 23 patients with treated brain tumours, either glioma (N=20) or secondary metastases in the brain (N=3). Here it was proved to be of use in determining lactate concentrations in vivo. Lactate was clearly seen in SelMQC spectra of glioma, even in the presence of lipids, with high grade glioma (7.3 ± 1.9 mM, mean ± standard deviation) having higher concentrations than low grade glioma (1.9 ± 1.5 mM, p=0.048). Lactate was not seen in secondary metastases in the brain. SelMQC-CSI is shown to be a useful technique for measuring lactate in tumours whose signals are otherwise contaminated by lipid..

Measurement of tissue lactate using (1) H MRS is often confounded by overlap with intense lipid signals at 1.3 ppm. Single-voxel localization using PRESS is also compromised by the large chemical shift displacement between voxels for the 4.1 ppm (-CH) resonance and the 1.3 ppm -CH3 resonance, leading to subvoxels with signals of opposite phase and hence partial signal cancellation. To reduce the chemical shift displacement to negligible proportions, a modified semi-LASER sequence was written ("FOCI-LASER", abbreviated as fLASER) using FOCI pulses to permit high RF bandwidth even with the limited RF amplitude characteristic of clinical MRI scanners. A further modification, MQF-fLASER, includes a selective multiple-quantum filter to detect lactate and reject lipid signals. The sequences were implemented on a Philips 3 T Achieva TX system. In a solution of brain metabolites fLASER lactate signals were 2.7 times those of PRESS. MQF-fLASER lactate was 47% of fLASER (the theoretical maximum is 50%) but still larger than PRESS lactate. In oil, the main 1.3 ppm lipid peak was suppressed to less than 1%. Enhanced suppression was possible using increased gradient durations. The minimum detectable lactate concentration was approximately 0.5 mM. Coherence selection gradients needed to be at the magic angle to avoid large water signals derived from intermolecular multiple-quantum coherences. In pilot patient measurements, lactate peaks were often observed in brain tumours, but not in cervix tumours; lipids were effectively suppressed. In summary, compared with PRESS, the fLASER sequence yields greatly superior sensitivity for direct detection of lactate (and equivalent sensitivity for other metabolites), while the single-voxel single-shot MQF-fLASER sequence surpasses PRESS for lactate detection while eliminating substantial signals from lipids. This sequence will increase the potential for in vivo lactate measurement as a biomarker in targeted anti-cancer treatments as well as in measurements of tissue hypoxia..

AIM: To estimate and compare the extent of myeloma bone disease by skeletal region using whole-body diffusion-weighted imaging (WB-DWI) and skeletal survey (SS) and record interobserver agreement, and to investigate differences in imaging assessments of disease extent and apparent diffusion coefficient (ADC) between patients with pathological high versus low disease burden. MATERIALS AND METHODS: Twenty patients with relapsed myeloma underwent WB-DWI and SS. Lesions were scored by number and size for each skeletal region by two independent observers using WB-DWI and SS. Observer scores, ADC, and ADC-defined volume of tumour-infiltrated marrow were compared between patients with high and low disease burden (assessed by serum paraproteins and marrow biopsy). RESULTS: Observer scores were higher on WB-DWI than SS in every region (p<0.05) except the skull, with greater interobserver reliability in rating the whole skeleton (WB-DWI: ICC = 0.74, 95% CI: 0.443-0.886; SS: ICC = 0.44, 95% CI: 0.002-0.730) and individual body regions. WB-DWI scores were not significantly higher in patients with high versus low disease burden (observer 1: mean ± SD: 48.8 ± 7, 38.6 ± 14.5, observer 2: mean ± SD: 37.3 ± 13.5, 30.4 ± 15.5; p = 0.06, p = 0.35). CONCLUSION: WB-DWI demonstrated more lesions than SS in all regions except the skull with greater interobserver agreement. Sensitivity is not a limiting factor when considering WB-DWI in the management pathway of patients with myeloma..

BACKGROUND: Gastrointestinal stromal tumours (GISTs) of the rectum often require radical surgery to achieve complete resection. This study investigated the management and outcome of surgery for rectal GISTs and the role of imatinib. METHODS: A cohort study was undertaken of patients identified from a database at one tertiary sarcoma referral centre over a continuous period, from January 2001 to January 2013. RESULTS: Over 12 years, 19 patients presented with a primary rectal GIST. Median age was 57 (range 30-77) years. Neoadjuvant imatinib was used in 15 patients, significantly reducing mean tumour size from 7·6 (95 per cent c.i. 6·1 to 9·0) to 4·1 (2·8 to 5·3) cm (P < 0·001). Nine of these patients underwent surgical resection. Imatinib therapy enabled sphincter-preserving surgery to be undertaken in seven patients who would otherwise have required abdominoperineal resection or pelvic exenteration for tumour clearance. Neoadjuvant imatinib treatment also led to a significant reduction in mean(s.d.) tumour mitotic count from 16(16) to 4(9) per 50 high-power fields (P = 0·015). Imatinib was used only as adjuvant treatment in two patients. There were three deaths, all from unrelated causes. Eleven of the 13 patients who underwent resection were alive without evidence of recurrence at latest follow-up, with a median disease-free survival of 38 (range 20-129) months and overall survival of 62 (39-162) months. CONCLUSION: The use of neoadjuvant imatinib for rectal GISTs significantly decreased both tumour size and mitotic activity, which permitted less radical sphincter-preserving surgery..

Desmoid-type fibromatosis is a rare, locally infiltrative, mesenchymal neoplasm that is associated with high rates of local recurrence but lacks the potential to metastasise. The disease affects younger individuals, with a peak age of 30 years, and is the most common cause of an anterior abdominal wall mass in young women of childbearing age. It may, however, involve nearly every body part, including the extremities, head and neck, trunk, and abdominal cavity; as such, desmoid-type fibromatosis may present to a range of general and subspecialty radiologists. These rare tumours have a widely variable clinical presentation and unpredictable natural history, hence input from a soft-tissue tumour centre is recommended, although much of the imaging may be performed at the patient's local hospital. The consensus for treatment has changed over the past decade, with most centres moving away from primary radical surgery towards a front-line 'watch-and-wait' policy. Therefore, imaging has an increasingly important role to play in both the diagnosis and follow-up of these patients. This review will discuss the typical imaging characteristics of these lesions and suggest diagnostic and follow-up magnetic resonance imaging protocols, with details of suitable sequences and scanning intervals..

Distinguishing well-differentiated liposarcoma (WDL) from lipoma is of clinical and prognostic importance, but can be difficult on imaging and histology alone. WDL characteristically harbor amplifications of the MDM2 and CDK4 cell cycle oncogenes and overexpress the cell cycle regulator p16. Fluorescence in situ hybridization (FISH) to assess for MDM2 and CDK4 gene amplification is the diagnostic gold standard, and immunohistochemistry for the overexpressed MDM2 and CDK4 proteins is also useful but may not be routinely offered by pathology laboratories. p16 immunohistochemistry is a sensitive marker for WDL and is in the repertoire of most laboratories, and it has been suggested as a useful method of distinguishing WDL from lipomas when other ancillary modalities are not readily available. We describe a case of a large retroperitoneal adipocytic mass occurring in a 27-year-old male, which was clinically and radiologically in keeping with WDL. Histologically this was a differentiated adipocytic neoplasm with prominent fibrous septa and fat necrosis, more suggestive of retroperitoneal lipoma. Immunohistochemistry showed diffuse, strong nuclear expression of p16 in the areas of fat necrosis. However, CDK4 was negative and the lesion lacked evidence of MDM2 amplification with FISH. Diffuse expression of p16 in areas of fat necrosis in large or deep lipomas highlights the potential for diagnostic misinterpretation as well differentiated liposarcoma, and we therefore emphasize that p16 immunohistochemistry should always be interpreted as part of a panel with CDK4 +/- MDM2 in the differential diagnosis of WDL and lipoma..

The recent consensus statement from the International Myeloma Working Group has introduced the role of whole body (WB) magnetic resonance imaging (MRI) into the management pathway for patients with multiple myeloma. The speed, coverage and high sensitivity of WB diffusion weighted (DW)-MRI and the unique capability to quantify both burden of disease and response to treatment has led to increasing implementation at leading centres worldwide for imaging malignant marrow disease, both primary and metastatic. WB DW-MRI is likely to have a significant impact on management decisions and pathways for patients with multiple myeloma. This review will introduce the basic principles of DW-MRI, present current evidence for patients with myeloma and will discuss practicalities and exciting future applications..

BACKGROUND: Solitary Fibrous Tumour (SFT) is a rare soft tissue neoplasm, described in several locations in the body. It is classified as intermediate malignant potential with low risk of metastasis and has a low tendency to recur after primary surgery. METHODS: We performed a prospective data collection of the patients with SFT presented to the Royal Marsden Hospital from January to December 2013, and treated with pazopanib in first line. Demographics, anatomic primary sites, treatment and survival outcomes were collected from patients' electronic records. RESULTS: 13 patients (54% females) were identified with a median age of 51 years (range 37-77). Most of the patients (77%) were diagnosed with extra-thoracic SFT. All the patients received first line treatment with pazopanib for metastatic disease. Median overall survival (OS) was 13.3 months. Median progression free survival (PFS) was 4.7 months. No statistically significant difference was found in OS and PFS between primary thoracic SFT and primary extra-thoracic SFT. According to RECIST, one partial response (9%) and eight disease stabilizations (73%) were found as best responses. Using Choi criteria, there were 5 partial responses (46%) and 4 stabilizations (36%). CONCLUSION: Our prospective data confirm that anti-angiogenic drugs are active in SFT. PFS and overall response do not appear significantly lower than other reported series on the same disease. Furthermore, pazopanib is a drug already licensed in soft tissue sarcomas and these data suggest its activity also in this particular subtype of sarcomas..

OBJECTIVE: To investigate the effect of sclerosis on apparent diffusion coefficient measurements in bone metastases from prostate cancer undergoing treatment. MATERIALS AND METHODS: Sixteen patients underwent CT scans and MRI at baseline and 12 weeks following commencement of chemotherapy. For each patient, up to five bone metastases were selected. Hounsfield units were measured on CT and apparent diffusion coefficient (ADC) was measured on diffusion weighted MRI at both time points. Correlations between changes in apparent diffusion coefficient and Hounsfield units were investigated. RESULTS: Corresponding pre- and post-treatment apparent diffusion coefficient and Hounsfield units were available on 60 lesions from 16 patients. Overall, there was no significant correlation between changes in apparent diffusion coefficient with Hounsfield units. However, where changes in Hounsfield units increased by more than 50 %, there was a trend for an associated ADC rise. CONCLUSIONS: Increasing sclerosis of bone metastases on treatment does not significantly impede diffusion..

Soft tissue sarcomas are a group of heterogeneous neoplasms with more than 50 histological subtypes exhibiting major differences in terms of pathogenesis, genetic alterations and clinical behavior. Sarcomas represent approximately 1% of malignancies with retroperitoneal sarcomas representing 10-15% of all soft tissue sarcomas. Surgery is currently the only modality which offers the chance of cure. Surgery for retroperitoneal sarcomas presents specific challenges due their location in a complex space surrounded by vital structures and visceral organs often prohibiting resection with wide margins. Furthermore, even after complete resection local recurrence is common and the leading cause of death. In this article the authors describe the initial investigations, prognostic factors and optimal surgical management. The evidence and current research as regards the role of multimodality treatment is reviewed and discussed..

PURPOSE: To determine the feasibility of whole-body diffusion-weighted (DW) magnetic resonance (MR) imaging for assessment of treatment response in myeloma. MATERIALS AND METHODS: This prospective single-institution study was HIPAA-compliant with local research ethics committee approval. Written informed consent was obtained from each subject. Eight healthy volunteers (cohort 1a) and seven myeloma patients (cohort 1b) were imaged twice to assess repeatability of quantitative apparent diffusion coefficient (ADC) estimates. Thirty-four additional myeloma patients (cohort 2) underwent whole-body DW imaging before treatment; 26 completed a posttreatment imaging. Whole-body DW data were compared before and after treatment by using qualitative (ie, observer scores) and quantitative (ie, whole-body segmentation of marrow ADC) methods. Serum paraproteins and/or light chains or bone marrow biopsy defined response. RESULTS: Whole-body DW imaging scores were significantly different between observers (P < .001), but change in scores between observers after treatment was not (P = .49). Sensitivity and specificity for detecting response according to observer scores were 86% (18 of 21 patients) and 80% (4 of 5 patients) for both observers. ADC measurement was repeatable: mean coefficient of variation was 3.8% in healthy volunteers and 2.8% in myeloma patients. Pretreatment ADC in cohort 2 was significantly different from that in cohort 1a (P = .03), but not from that in cohort 1b (P = .2). Mean ADC increased in 95% (19 of 20) of responding patients and decreased in all (five of five) nonresponders (P = .002). A 3.3% increase in ADC helped identify response with 90% sensitivity and 100% specificity; an 8% increase (greater than repeatability of cohort 1b) resulted in 70% sensitivity and 100% specificity. There was a significant negative correlation between change in ADC and change in laboratory markers of response (r = -0.614; P = .001). CONCLUSION: Preliminary work demonstrates whole-body DW imaging is a repeatable, quantifiable technique for assessment of treatment response in myeloma..

Masses involving the abdominal wall arise from a large number of aetiologies. This article will describe a diagnostic approach, imaging features of the most common causes of abdominal wall masses, and highly specific characteristics of less common diseases. A diagnostic algorithm for abdominal wall masses combines clinical history and imaging appearances to classify lesions..

Assessment of the response to treatment of metastases is crucial in daily oncological practice and clinical trials. For soft tissue metastases, this is done using computed tomography (CT), Magnetic Resonance Imaging (MRI) or Positron Emission Tomography (PET) using validated response evaluation criteria. Bone metastases, which frequently represent the only site of metastases, are an exception in response assessment systems, because of the nature of the fixed bony defects, their complexity, which ranges from sclerotic to osteolytic and because of the lack of sensitivity, specificity and spatial resolution of the previously available bone imaging methods, mainly bone scintigraphy. Techniques such as MRI and PET are able to detect the early infiltration of the bone marrow by cancer, and to quantify this infiltration using morphologic images, quantitative parameters and functional approaches. This paper highlights the most recent developments of MRI and PET, showing how they enable early detection of bone lesions and monitoring of their response. It reviews current knowledge, puts the different techniques into perspective, in terms of indications, strengths, weaknesses and complementarity, and finally proposes recommendations for the choice of the most adequate imaging technique..

Background. Endometrial stromal sarcomas (ESS) are a subtype of gynaecological sarcomas characterized by the overexpression of hormone receptors. Hormone treatment is widely used in ESS but primary or acquired resistance is common. The mammalian target of rapamycin (mTOR) pathway has been suggested to play a key role in the mechanisms of hormone resistance. Recent studies in breast and prostate cancer demonstrate that this resistance can be reversed with the addition of an mTOR inhibitor. This phenomenon has never been reported in ESS. Methods. We report the outcome of one patient with pretreated, progressing low grade metastatic ESS treated with medroxyprogesterone acetate in combination with the mTOR inhibitor sirolimus. Results. Partial response was achieved following the addition of sirolimus to the hormone treatment. Response has been maintained for more than 2 years with minimal toxicity and treatment is ongoing. Conclusion. This case suggests that the resistance to the hormone manipulation in ESS can be reversed by the addition of an mTOR pathway inhibitor. This observation is highly encouraging and deserves further investigation..

BACKGROUND: Tyrosine kinase inhibitors (TKI) have revolutionized the treatment of gastrointestinal stromal tumors (GIST) although most patients develop resistance to first and second-line therapies. Regorafenib, an oral multi-targeted TKI, has demonstrated benefit in previously treated GIST patients. METHODS: We assessed safety and activity of regorafenib in patients treated within the Managed Access Program (MAP). All consecutive patients with advanced GIST who had progressed on or were intolerant to imatinib and sunitinib were recruited from the Royal Marsden and University College Hospitals. We retrospectively reviewed the data for response, toxicity, treatment duration and survival. Response was assessed by RECIST and Choi criteria. Toxicity was graded according to CTCAE v4.0 criteria. RESULTS: 20 patients were included in the MAP in the UK between 3/2013 and 9/2013. Median age was 68 (range 45-87), 65% of patients were male. Performance Status was 0-1 for 18 patients (90%), 2 for 2 patients (10%). The median treatment duration was 9.25 months (range 0.1-15.33). 18 patients were assessable for response and all patients attained a best response of at least stable disease. At a median follow-up of 12.6 months, there were 2 partial responses (11%) by RECIST and 7 partial responses (39%) according to Choi criteria. 7 patients remain on regorafenib. 3 patients discontinued treatment due to unacceptable adverse events; fistulation, myalgia and fatigue. 10 (50%) patients had grade 3 toxicities and 11 (55%) patients required a dose reduction. Median PFS was 9.4 months (95% Cl: 6.2-not calculable) and median OS was 12.2 months (95% Cl: 10.5-not calculable). Notably, prolonged stable disease was seen in 1 patient with exon 9 mutation and 1 patient with PDGFR D842V mutation. CONCLUSIONS: These data demonstrate encouraging activity and tolerability of regorafenib in routine clinical practice. The documented adverse events are in line with previous trial data..

PURPOSE: The CC-chemokine ligand 2 (CCL2) is highly expressed in various malignancies and promotes carcinogenesis. Blocking CCL2 has preclinical antitumor activity. A phase 1 trial of carlumab (CNTO 888), a human anti-CCL2 IgG1κ mAb, was conducted to evaluate the safety, tolerability, pharmacokinetic-pharmacodynamic profile, and antitumor activity. METHODS: Patients with advanced solid malignancy received escalating doses of carlumab 0.3, 1, 3, 10, or 15 mg/kg by 90-min intravenous infusion on days 1, 28, and every 2 weeks thereafter (dose escalation) or 10 or 15 mg/kg every 2 weeks (dose-expansion). Pharmacodynamic assessments were also performed. RESULTS: Forty-four patients received 206 doses of carlumab. MTD was not established. Carlumab-related adverse events included grade 1-2 fatigue (9 %), nausea (7 %), headache (7 %), vomiting (5 %), and pruritus (5 %). The recommended phase II dose was 15 mg/kg every 2 weeks. Carlumab concentrations declined bi-exponentially with a terminal half-life of 6.6-9.6 days. Free CCL2 was transiently suppressed, while total CCL2 increased dose-dependently >1,000-fold post-treatment. A patient with ovarian cancer and a patient with prostate cancer achieved CA125 and PSA reductions of >50 % and RECIST SD for 10.5 and 5 months, respectively. Two other patients had RECIST SD for 7.2 and 15.7 months. CONCLUSIONS: Carlumab was well tolerated with evidence of transient free CCL2 suppression and preliminary antitumor activity..

BACKGROUND: Desmoid tumours/aggressive fibromatosis (DT/AF) are infrequent soft-tissue neoplasms. They usually behave as indolent diseases. However, they may grow locally infiltrating or compressing adjacent structures. The role of local treatment is limited and only a few drugs have shown activity. CASES PRESENTATION: We report the outcome of two patients affected by progressive DT/AF treated with the angiogenesis inhibitor pazopanib in two different institutions. Both patients achieved dramatic improvement in their symptoms and radiological signs of response. The clinical benefit lasted for more than 1 year and it is still ongoing. CONCLUSIONS: Pazopanib is an active treatment in DT/AF. It is the first time this has been reported..

Background. Soft-tissue sarcomas (STS) are a heterogeneous group of diseases with lack of effective treatments in most cases. Previous data suggest that continuous infusional ifosfamide regimens might improve cytotoxicity and tolerability compared to standard schedules. Methods. We retrospectively report the outcome of 35 patients affected by STS treated with a 14-day infusional ifosfamide regimen (1000 mg/m(2)/day) in our institution. Predictive factors for toxicity were also explored. Results. Median age was 53 years. There were 16 males and 19 females. Classification by histology was dedifferentiated liposarcoma (DDLPS): 22 (62.8%), synovial sarcoma: 7 (20%), myxoid/round-cell liposarcoma: 3 (8.5%), and others: 3 (8.5%). Overall, 7 patients (20%) achieved partial response (PR) and 10 patients (29%) achieved stable disease (SD). DDLPS showed special sensitivity: 5 patients (22.7%) had PR, 7 patients (31.8%) had SD, and disease control rate was 54.5%. Median progression-free survival and overall survival were 4.2 and 11.2 months, respectively. The most common toxicities were fatigue, nausea, and vomiting (all grades: 85.7%, 83%, and 54.3%, resp.). Neither hypoalbuminaemia nor gender was found to predict toxicity, although encephalopathy predominantly affected females. Conclusion. Ifosfamide administered as a 14-day continuous infusion is a safe regimen in STS with notable activity in DDLPS..

PURPOSE: To assess baseline reproducibility and compare performance of dynamic contrast material-enhanced (DCE) magnetic resonance (MR) imaging versus DCE computed tomographic (CT) measures of early vascular response in the same patients treated with cediranib (30 or 45 mg daily). MATERIALS AND METHODS: After institutional review board approval, written informed consent was obtained from 29 patients with advanced solid tumors who had lesions 3 cm or larger and in whom simultaneous imaging of an adjacent artery was possible. Two baseline DCE MR acquisitions and two baseline DCE CT acquisitions 7 days or fewer apart (within 14 days of starting treatment) and two posttreatment acquisitions with each modality at day 7 and 28 (±3 days) were obtained. Nonmodeled and modeled parameters were derived (measured arterial input function [AIF] for CT, population-based AIF for MR imaging; temporal sampling rate of 0.5 second for CT, 3-6 seconds for MR imaging). Baseline variability was assessed by using intra- and intersubject analysis of variance and Bland-Altman analysis; a paired t test assessed change from baseline to after treatment. RESULTS: The most reproducible parameters were DCE MR imaging enhancement fraction (baseline intrapatient coefficient of variation [CV]=8.6%), volume transfer constant (CV=13.9%), and integrated area under the contrast agent uptake curve at 60 seconds (CV=15.5%) and DCE CT positive enhancement integral (CV=16.0%). Blood plasma volume was highly variable and the only parameter with CV greater than 30%. Average reductions (percentage change) from baseline were consistently observed for all DCE MR imaging and DCE CT parameters at day 7 and 28 for both starting-dose groups (45 and 30 mg), except for DCE CT mean transit time. Percentage change from baseline for parameters reflecting blood flow and permeability were comparable, and reductions from baseline at day 7 were maintained at day 28. CONCLUSION: DCE MR imaging and DCE CT can depict vascular response to antiangiogenic agents with response evident at day 7. Improved reproducibility with MR imaging favors its use in trials with small patient numbers..

OBJECTIVES: To measure apparent diffusion coefficient (ADC) values in patients with active myeloma and remission and to determine whether changes differ in those responding/progressing on treatment. The relationship between changes in marrow fat and ADC was also explored. METHODS: 20 patients were recruited. T(1 )weighted, T(2) weighted, short tau inversion-recovery, diffusion-weighted and two-point Dixon MRI of the lumbar spine and pelvis were performed at baseline, 4-6 weeks and 20 weeks. RESULTS: ADC values of active disease (mean 761.2 ± 255×10(-6) mm(2) s(-1)) were significantly higher (p=0.047) than marrow in remission (mean 601.8 ± 459×10(-6) mm(2) s(-1)). Changes in ADC in responders showed a significant increase at 4-6 weeks (p=0.005) but no significant change between baseline and 20 weeks (p=0.733). ADCs in progressing and stable patients did not change significantly between either time point. Pearson's correlation coefficient between change in fat fraction and change in the number of pixels with an ADC of ≤655×10(-6) mm(2) s(-1) was 0.924, indicating a significant correlation (p<0.001). CONCLUSION: ADC values in active myeloma are significantly higher than marrow in remission, indicating the potential for diffusion-weighted MRI to quantify the transition from active disease to remission and vice versa. This study confirms significant changes in ADC in patients responding to treatment and indirect evidence from two-point Dixon MRI suggests that these changes are influenced by changes in marrow fat. ADVANCES IN KNOWLEDGE: ADC of active myeloma is significantly higher than marrow in remission; the direction of ADC changes on treatment is dependent on the timing of measurements and is influenced by changes in marrow fat..

BACKGROUND: New or worsening bone lesions in patients responding to treatment, known as the flare phenomenon is well described on (99m)Tc-MDP bone scintigraphy, but to our knowledge has not previously been described on CT. The appearance of new or worsening bone sclerosis on CT in patients with prostate cancer may therefore be erroneously classified as disease progression. PURPOSE: To assess the incidence of osteoblastic healing flare response at 3-month CT assessment in patients with castrate-resistant prostate cancer and to identify associated features that enable differentiation from progressive metastatic bone disease at 3 months. MATERIAL AND METHODS: CT scans of 67 patients with castrate-resistant prostate cancer undergoing treatment were reviewed by a radiologist blinded to clinical outcome. Changes in number, size, and density of metastatic bone lesions were documented and Response Evaluation Criteria in Solid Tumours (RECIST) in soft tissue lesions, alkaline phosphatase, prostate specific antigen, and (99m)Tc-MDP bone scans were used for correlation. RESULTS: Of the 39 patients who had 3- and 6-month follow-up, eight patients (21%) demonstrated an increase in number, size, or density of sclerotic lesions on the 3-month CT scan despite improvement in PSA and soft tissue lesions. Three out of eight patients (8%) maintained partial response/remained stable at follow-up and were defined as showing a flare response: in this group bone metastases evident on CT showed a qualitative and quantitative increase in density and no lesions faded at 3 months. In contrast, in all patients who progressed at 3 months by PSA/RECIST criteria (n = 8) bone lesions showed a mixed pattern with some lesions increasing and others decreasing in density. CONCLUSION: The incidence of flare response of metastatic bone disease evident at 3-month post-treatment CT in patients with prostate cancer undergoing systemic treatment is 8%. In patients with falling PSA and stable/responding soft tissue disease at 3 months an increase in bone sclerosis in the absence of fading bone metastases can be interpreted as flare and is likely to represent a response..

OBJECTIVES: To establish normal bone marrow values of apparent diffusion coefficient (ADC) over an age range, compare them with metastatic and myelomatous involvement, to establish reproducibility and to optimise b values. METHODS: The ADCs of bone marrow in 7 volunteers (mean age 29.7 years), 34 volunteers (mean age 63.3 years) and 43 patients with metastatic and myelomatous involvement (mean age 65.5 years) were measured. In 9 volunteers diffusion weighted MRI was repeated within 7 days. b values were derived to optimise contrast between normal and pathological marrow. RESULTS: The mean ADC of bone marrow in younger volunteers was significantly higher than that of older volunteers. The coefficient of reproducibility was 14.8%. The ADC mean of metastatic and myeloma bone disease was 1054 + / -456 x 10⁻⁶mm²s⁻¹. An ADC threshold of 655 × 10(-6) mm(2)s(-1) separated normal and abnormal marrow with a sensitivity and specificity of 90% and 93% respectively. Contrast between normal and abnormal marrow was optimal at b = 1389 smm(-2). CONCLUSION: The reproducibility of ADC measurements in bone is equivalent to published data for soft tissue with a high sensitivity and specificity for separating abnormal from age matched normal bone marrow. A b value of around 1,400 smm(-2) is optimal for imaging bone marrow..

PURPOSE: To prospectively evaluate apparent diffusion coefficient (ADC) histograms in the prediction of chemotherapy response in patients with metastatic ovarian or primary peritoneal cancer. MATERIALS AND METHODS: Research ethics committee approval and patient written informed consent were obtained. Diffusion-weighted (DW) magnetic resonance (MR) imaging was performed through the abdomen and pelvis before and after one and three cycles of chemotherapy in 42 women (mean age, 63.0 years ± 11.4 [standard deviation]) with newly diagnosed or recurrent disease. Reproducibility and intra- and interobserver agreement of ADC calculations were assessed. Per-patient weighted ADC histograms were generated at each time point from pixel ADCs from five or fewer target lesions. Mean ADC, percentiles (10th, 25th, 50th, 75th, 90th), skew, kurtosis, and their change were analyzed according to histologic grade, primary versus recurrent disease status, and response, determined with integrated biochemical and morphologic criteria, with a linear mixed model. Areas under receiver operating characteristic curve (AUCs) for combinations of parameters were calculated with linear discriminant analysis. RESULTS: Coefficients of variation for repeat measurements and for within and between observers were 4.8%, 11.4%, and 13.7%, respectively. Grade and disease status did not significantly affect histogram parameters. Pretreatment ADCs were not predictive of response. In responders, all ADCs increased after the first and third cycle (P < .001), while skew and kurtosis decreased after the third (P < .001 and P = .006, respectively); however, in nonresponders, no parameter changed significantly. Percentage change of the 25th percentile performed best in identifying response (AUC = 0.82 and 0.83 after first and third cycle, respectively), whereas combination of parameters did not improve accuracy. CONCLUSION: An early increase of ADCs and later decrease of skew and kurtosis characterize chemotherapy response. Quantitative DW MR imaging can aid in early monitoring of treatment efficacy in patients with advanced ovarian cancer..

OBJECTIVES: To determine whether changes in ADC of bone metastases secondary to prostate carcinoma are significantly different in responders compared with progressors on chemotherapy. METHODS: Twenty-six patients with known bone metastases secondary to prostate carcinoma underwent diffusion-weighted MRI of the lumbar spine and pelvis at baseline and 12 weeks following chemotherapy. RECIST assessment of staging CT and PSA taken at the same time points were used to classify patients as responders, progressors or stable. ADC (from b = 0,50,100,250,500,750 smm⁻²) and ADC(slow) (from b = 100,250,500,750 smm⁻²) were calculated for up to 5 lesions per patient. RESULTS: Mean ADC/ADC(slow) in lesions from responders and progressors showed a significant increase. Although the majority of lesions demonstrated an ADC/ADC(slow) rise, some lesions in both responders and progressors demonstrated a fall in ADC beyond the limits of reproducibility. CONCLUSIONS: Mean ADC is not an appropriate measure of response in bone metastases. The heterogeneity of changes in ADC is likely to be related to the composition of bone marrow with changes that have opposing effects on ADC..

PURPOSE: Selective tumor cell cytotoxicity can be achieved through a synthetic lethal strategy using poly(ADP)-ribose polymerase (PARP) inhibitor therapy in BRCA1/2 mutation carriers in whom tumor cells have defective homologous recombination (HR) DNA repair. Platinum-based chemotherapy responses correlate with HR DNA repair capacity. Olaparib is a potent, oral PARP inhibitor that is well tolerated, with antitumor activity in BRCA1/2 mutation carriers. PATIENTS AND METHODS: Patients with BRCA1/2-mutated ovarian cancer were treated with olaparib within a dose-escalation and single-stage expansion of a phase I trial. Antitumor activity was subsequently correlated with platinum sensitivity. RESULTS: Fifty patients were treated: 48 had germline BRCA1/2 mutations; one had a BRCA2 germline sequence change of unknown significance, and another had a strong family history of BRCA1/2-associated cancers who declined mutation testing. Of the 50 patients, 13 had platinum-sensitive disease, 24 had platinum-resistant disease, and 13 had platinum-refractory disease (according to platinum-free interval). Twenty (40%; 95% CI, 26% to 55%) achieved Response Evaluation Criteria in Solid Tumors (RECIST) complete or partial responses and/or tumor marker (CA125) responses, and three (6.0%) maintained RECIST disease stabilization for more than 4 months, giving an overall clinical benefit rate of 46% (95% CI, 32% to 61%). Median response duration was 28 weeks. There was a significant association between the clinical benefit rate and platinum-free interval across the platinum-sensitive, resistant, and refractory subgroups (69%, 45%, and 23%, respectively). Post hoc analyses indicated associations between platinum sensitivity and extent of olaparib response (radiologic change, P = .001; CA125 change, P = .002). CONCLUSION: Olaparib has antitumor activity in BRCA1/2 mutation ovarian cancer, which is associated with platinum sensitivity..

PURPOSE: The principal objective of this trial was to evaluate the antitumor activity of abiraterone acetate, an oral, specific, irreversible inhibitor of CYP17 in docetaxel-treated patients with castration-resistant prostate cancer (CRPC). PATIENTS AND METHODS: In this multicenter, two-stage, phase II study, abiraterone acetate 1,000 mg was administered once daily continuously. The primary end point was achievement of a prostate-specific antigen (PSA) decline of > or = 50% in at least seven of 35 patients. Per an attained phase II design, more than 35 patients could be enrolled if the primary end point was met. Secondary objectives included: PSA declines of > or = 30% and > or = 90%; rate of RECIST (Response Evaluation Criteria in Solid Tumors) responses and duration on study; time to PSA progression; safety and tolerability; and circulating tumor cell (CTC) enumeration. RESULTS: Docetaxel-treated patients with CRPC (N = 47) were enrolled. PSA declines of > or = 30%, > or = 50% and > or = 90% were seen in 68% (32 of 47), 51% (24 of 47), and 15% (seven of 47) of patients, respectively. Partial responses (by RECIST) were reported in eight (27%) of 30 patients with measurable disease. Median time to PSA progression was 169 days (95% CI, 113 to 281 days). The median number of weeks on study was 24, and 12 (25.5%) of 47 patients remained on study > or = 48 weeks. CTCs were enumerated in 34 patients; 27 (79%) of 34 patients had at least five CTCs at baseline. Eleven (41%) of 27 patients had a decline from at least five to less than 5 CTCs, and 18 (67%) of 27 had a > or = 30% decline in CTCs after starting treatment with abiraterone acetate. Abiraterone acetate was well tolerated. CONCLUSION: Abiraterone acetate has significant antitumor activity in post-docetaxel patients with CRPC. Randomized, phase III trials of abiraterone acetate are underway to define the future role of this agent..

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Diffusion Weighted Magnetic Resonance Imaging (DW-MRI) combined with conventional MRI can provide a whole body assessment of metastatic bone disease, improved lesion detection compared to other imaging techniques and a direct quantitative assessment of treatment response. In bone marrow, the presence of fat and bone trabeculae and their changing contributions with disease progression and response to treatment present unique challenges for data acquisition and image interpretation. This article discusses these challenges and reviews the potential of DW-MRI to provide a biomarker of response in metastatic bone disease..

INTRODUCTION: Ultra Short TE MRI allows signal to be detected from tissues with a very short T2.The aims of this study were to optimize a 2D UTE MRI sequence for imaging and quantification of sclerotic bone metastases, establish T2* values of sclerotic components and investigate the feasibility of using the method to assess changes in T2* of sclerotic metastases and their relation to attenuation values in patients on treatment. METHODS: Twenty-two subjects were recruited in 3 cohorts. Cohort 1 was used to optimize the 2-D UTE sequence, cohort 2 was used to establish T2* measurements using a range of TEs and cohort 3 was used to assess T2* changes with treatment response and relate them to changes on electron density as measured by CT Hounsfield Units. RESULTS: Sagittal 2D UTE MRI of the lumbar spine is feasible demonstrating short T2 components in normal volunteers. In patients with bone metastases secondary to prostate carcinoma T2* can be measured and mean T2* of sclerotic metastases measured with TEs of 0.07, 0.27, 0.47 and 0.67 ms was 8.5 ms.T2* shortened by 20.0% in responders and increased by 24.4% in progressors. DISCUSSION: The significant linear relationship between percentage change in T2* as derived from UTE MRI and percentage change in HU from corresponding CT studies is indirect evidence that they are measuring effects of the same process.If the relationship between T2* and electron density holds true in further studies it offers potential for MR guided radiotherapy planning as well as attenuation correction for PET/MRI..

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BACKGROUND: There is growing interest in diffusion weighted magnetic resonance imaging (MRI) of cervical carcinoma but normal uterine appearances and effects of the oral contraceptive pill (OCP) have not been described. PURPOSE: To establish apparent diffusion coefficient (ADC) values for normal regions of uterus, determine the effect of the OCP on these values, and compare them with ADCs from cervical cancer. MATERIAL AND METHODS: Twenty-seven premenopausal women (19 taking the OCP) with cervical intraepithelial neoplasia (CIN) were studied with T2W and diffusion weighted MRI (DW-MRI). Regions of interest were drawn on ADC maps by visual matching with T2W images on different zones of the uterus and values compared between women not taking and taking the OCP. A further group of 25 women with clinically obvious tumors of the cervix were also studied with T2W and DW-MRI and ADC values of tumor were compared with ADC values of cervical epithelium and stroma. RESULTS: The ADC values of adjacent zones of the uterus and cervix were significantly different from one another (P<0.001). The junctional zone was seen as a band of restricted diffusion between endometrium and outer myometrium. The ADC value of the junctional zone of the uterus was significantly greater (P<0.001) in patients taking the OCP than those patients not taking the OCP. There was no significant affect of the OCP on the ADC values of other uterine zones. CONCLUSION: The zonal anatomy of the uterus is well demonstrated by DW-MRI with hormonal effects secondary to the OCP affecting junctional zone alone. ADC of cervical tumor is significantly different to cervical epithelium and stroma indicating a role in cervical cancer detection and local staging..

Malignancy presenting during pregnancy is rare. When it does, there are important considerations and challenges for the radiologist. The physiological changes of pregnancy may mask signs and symptoms of malignancy leading to delayed presentation. Endocrine and physiological changes during pregnancy can interact with tumour biology to alter the behaviour and patterns of growth of certain tumours. The timing and choice of imaging technique pose potential risks to the foetus, but this must be weighed against the risks to both mother and foetus of inadequate investigation or misdiagnosis. This review outlines the general principles and approach to imaging the pregnant patient with suspected malignancy, following which there is a more detailed discussion of the effects of pregnancy on tumour biology and presentation of specific tumours. Imaging strategies are discussed for the different entities, and where possible, evidence-based imaging recommendations are made..

PURPOSE: It has been postulated that castration-resistant prostate cancer (CRPC) commonly remains hormone dependent. Abiraterone acetate is a potent, selective, and orally available inhibitor of CYP17, the key enzyme in androgen and estrogen biosynthesis. PATIENTS AND METHODS: This was a phase I/II study of abiraterone acetate in castrate, chemotherapy-naive CRPC patients (n = 54) with phase II expansion at 1,000 mg (n = 42) using a two-stage design to reject the null hypothesis if more than seven patients had a prostate-specific antigen (PSA) decline of > or = 50% (null hypothesis = 0.1; alternative hypothesis = 0.3; alpha = .05; beta = .14). Computed tomography scans every 12 weeks and circulating tumor cell (CTC) enumeration were performed. Prospective reversal of resistance at progression by adding dexamethasone 0.5 mg/d to suppress adrenocorticotropic hormone and upstream steroids was pursued. RESULTS: A decline in PSA of > or = 50% was observed in 28 (67%) of 42 phase II patients, and declines of > or = 90% were observed in eight (19%) of 42 patients. Independent radiologic evaluation reported partial responses (Response Evaluation Criteria in Solid Tumors) in nine (37.5%) of 24 phase II patients with measurable disease. Decreases in CTC counts were also documented. The median time to PSA progression (TTPP) on abiraterone acetate alone for all phase II patients was 225 days (95% CI, 162 to 287 days). Exploratory analyses were performed on all 54 phase I/II patients; the addition of dexamethasone at disease progression reversed resistance in 33% of patients regardless of prior treatment with dexamethasone, and pretreatment serum androgen and estradiol levels were associated with a probability of > or = 50% PSA decline and TTPP on abiraterone acetate and dexamethasone. CONCLUSION: CYP17 blockade by abiraterone acetate results in declines in PSA and CTC counts and radiologic responses, confirming that CRPC commonly remains hormone driven..

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Imaging bone metastases from prostate cancer presents several challenges. The lesions are usually sclerotic and appear late on the conventional X-ray. Bone scintigraphy is the mainstay of lesion detection, but is often not suitable for assessment of treatment response, particularly because of a 'flare' phenomenon after therapy. Magnetic resonance imaging is increasingly used in assessment, and newer techniques allow quantitation. In addition to (18)F-fluorodeoxyglucose ((18)FDG), newer PET isotopes are also showing promise in lesion detection and response assessment. This article reviews the available imaging modalities for evaluating prostatic bony metastases, and links them to the underlying pathological changes within bone lesions..

The potential for curative resection of recurrent rectal cancer and the recognized benefits of palliative resection have led to increased numbers of patients being referred for MRI assessment. This study assesses the use of MRI to provide a roadmap of tumour recurrence to allow for appropriate surgical planning. Differentiation of recurrent rectal cancer from post-surgical and post-radiotherapy changes on MR proved particularly problematic when assessing the pelvic sidewalls. Areas of uncertainty on imaging, therefore, need to be discussed on a case by case basis regarding the decision to proceed to curative or explorative surgery..

PURPOSE: To establish apparent diffusion coefficients (ADCs) of invasive cervical carcinoma compared with nontumor cervical epithelium and determine sensitivity and specificity of diffusion-weighted (DW) magnetic resonance (MR) imaging used in conjunction with T2-weighted MR imaging to help detect invasive cervical carcinoma in patients with stage Ia and Ib1 disease. MATERIALS AND METHODS: Local research ethics committee approval was obtained with written consent from each subject. Group 1 comprised patients (mean age, 38.7 years +/- 13.2 [standard deviation]) with histologically confirmed cervical intraepithelial neoplasia (CIN) found on smear (n = 20) or stage Ib1 cervical tumors (n = 18). Patients were imaged with endovaginal T2-weighted fast spin-echo and single-shot DW echo-planar MR imaging of the cervix. ADCs from invasive cervical carcinoma and nontumor regions were compared within (t test) and between (U test) patients. A derived threshold ADC level indicative of invasive cervical carcinoma was used with T2-weighted imaging by two independent observers to identify possible invasive cervical carcinoma in group 2, patients with suspected disease (n = 21; mean age, 42.0 years +/- 16.4). Surgical specimens were the reference standard. Interobserver agreement was assessed. RESULTS: In group 1, ADCs from cervical carcinoma (757 x 10(-6) mm(2)/sec +/- 110) and adjacent epithelium (1331 x 10(-6) mm(2)/sec +/- 159) or CIN (1291 x 10(-6) mm(2)/sec +/- 156) were significantly different (P < .0001). In group 2, respective sensitivity and specificity to help detect invasive cervical carcinoma on T2-weighted images were 55.6% and 75% for observer 1 and 66.7% and 41.7% for observer 2, and 88.9% and 66.7% for observer 1 and 77.8% and 58.3% for observer 2 when ADC maps with a threshold level of 1100 x 10(-6) mm(2)/sec were added. Interobserver agreement was fair (kappa = 0.37) for T2-weighted images alone and good (kappa = 0.80) with ADC included. CONCLUSION: ADCs from invasive cervical carcinoma are significantly lower than those from nontumor epithelium; good interobserver agreement by using T2-weighted and DW MR imaging makes this technique potentially useful to help detect early-stage disease..

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OBJECTIVE: To describe the use of MR imaging and efficacy of ultrasound-guided steroid injection in the diagnosis and management of athletes with clinical posteromedial impingement of the ankle. DESIGN AND PATIENTS: A retrospective analysis of imaging findings on MR was undertaken in nine elite athletes with clinical posteromedial ankle impingement. MR studies from six professional athletes with posterolateral pain were also reviewed as an imaging control group. The two reviewing radiologists were blinded to the clinical details and the proportion of control and study subjects. The nine study athletes also underwent diagnostic ultrasound and ultrasound-guided injection of steroid and anaesthetic into the posteromedial capsular abnormality. Follow-up was by telephone interview. RESULTS: Posteromedial capsular thickening was seen only in athletes with posteromedial impingement (7/9). Posteromedial synovitis was present in all athletes with posteromedial impingement; however, posterior and posterolateral synovitis was also seen in these athletes. Mild posteromedial synovitis was present in two control athletes. Ultrasound identified abnormal posteromedial soft tissue thickening deep to tibialis posterior between the medial malleolus and talus in all nine athletes. After injection all athletes returned to their previous level of sport, with eight of the nine not experiencing any residual or recurrent symptoms. CONCLUSION: If MR imaging excludes significant coexistent abnormality, ultrasound can localise posteromedial soft tissue abnormality and guide injection therapy, allowing return to athletic activity without surgical intervention..

Despite apparent curative resection of rectal carcinoma, local recurrence rates of between 3 and 32% have been reported. For those patients, radical surgical resection offers the only hope of cure. We present a review of the magnetic resonance imaging (MRI) findings and contraindications to curative surgery demonstrated using imaging..

Endometrial cancer is the second most common gynaecological malignancy. The usual presentation with post-menopausal bleeding results in an early diagnosis in most cases and thus there is opportunity for cure. Magnetic resonance (MR) imaging is pivotal in the decision-making process regarding treatment options. We present a review of the magnetic resonance (MR) findings to illustrate its role in the staging of endometrial cancer..

We report a case of a 33-year-old female presenting with right sided abdominal pain, a right iliac fossa mass and right hydronephrosis. The mass was subsequently shown to represent an isolated desmoid tumour compromising the adjacent ureter. The patient had no predisposing factors for this pathology. This is an uncommon occurrence and we discuss the imaging features and differential diagnosis..

The surface and bulk properties of novel methacrylate polymers prepared by gelling poly(ethyl methacrylate) (PEMA) powder with different ratios of tetrahydrofurfuryl methacrylate (THFMA) and hydroxyethyl methacrylate (HEMA) monomers were investigated. The water adsorption and desorption characteristics of these polymers were measured in water and phosphate buffered saline (PBS). The desorption diffusion coefficients were higher than the adsorption coefficients in both water and PBS. Linear relationships between the equilibrium mass of water taken up and the mass of water desorbed with the concentration of HEMA in the polymer were established. Polymer surfaces were analysed using scanning electron microscopy (SEM) and atomic force microscopy (AFM). Surface features varied with polymer composition; during hydration only selective areas of the surface hydrated indicating a heterogeneous surface. Contact angle data showed no trend between the different polymers indicating that contact angles are not an acceptable method of assessing hydrophobicity/wettability of a material which does not have a homogeneous surface. The effect of these bulk and surface characteristics on biological interactions were examined using bovine chondrocytes and human osteoblast (HOB) cell cultures. Cell attachment decreased when HEMA was present in the copolymer..

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