Paediatric Solid Tumour Biology and Therapeutics Group

Scientists have successfully used real-time MRI to demonstrate that swallowing causes minimal motion of the larynx, known as the voice box, in people undergoing a radiotherapy session for cancer in this part of the body. This finding supports the rationale for radiotherapy techniques that focus irradiation on as small a target area as possible. These techniques aim to destroy cancerous cells while also minimising damage to the surrounding tissues.

For this study, the researchers focused on a type of head and neck cancer called early-stage glottic cancer (ESGC), which affects the middle region inside the larynx.

Their work has validated the process of measuring motion during radiotherapy, which could be expanded to other areas affecting the head and neck. For example, future research could assess whether treatment margins need to be adjusted to account for movements of the tongue.

The findings could also lead to better patient outcomes in the long-term. Although short-term outcomes are generally positive for people who receive radiotherapy for ESGC, this treatment can harm the carotid arteries, which are located close by. This damage increases the person’s risk of having a stroke one or two decades later. Reducing the target volume for radiotherapy would prevent much of this damage, potentially reducing the frequency of stroke in years to come.

Researchers at The Institute of Cancer Research, London, and The Royal Marsden NHS Foundation Trust led the study, which was funded by Cancer Research UK. The findings were published in the journal Advances in Radiation Oncology.

Balancing safety and effectiveness

Radiotherapy is an effective treatment, but it destroys healthy cells as well as cancerous ones. This can lead to short-term side effects, which may include dry mouth, tooth decay and gum sores when the treatment is aimed at the head and neck area. It can also cause long-term effects, such as scarring, nerve problems and even another cancer.

These risks mean that many treatment centres have switched from conventional three-dimensional conformal radiotherapy (3D-CRT) radiotherapy to more conformal radiotherapy, which better shapes the radiation beams to match the tumour in an attempt to spare the surrounding tissue. The forms of this advanced approach that are more conformal than 3D-CRT include intensity-modulated radiation therapy (IMRT) and volumetric modulated arc therapy (VMAT).

However, strategies to spare healthy tissue from radiation must be balanced against the need to destroy the cancerous cells. If radiotherapy does not target the whole of the tumour, cancer cells will remain, and the person will be at increased risk of disease recurrence.

For this reason, clinicians factor in small internal movements of the body when determining the target area for irradiation. They add a safety margin around the edge of the tumour to create an expanded area known as the internal target volume (ITV). Targeting the ITV helps ensure that even if the tumour moves slightly during the treatment session, the radiation can still destroy it.

In some cases, the ITV will account for respiratory motions. In others, radiographers may either ask the patient to hold their breath during treatment or only deliver the radiation at certain points within the person’s breathing cycle.

For cancers of the head and neck, swallowing motions can also temporarily affect the position of the tumour. Until now, there has been little research into whether these movements are significant enough to warrant adding larger safety margins to the treatment volume.

Cine-MRI can inform treatment planning

For this study, the team had access to the MR Linac Unit based at the Sutton site of the ICR and The Royal Marsden. This ground-breaking machine can simultaneously perform MRI scans and deliver radiotherapy to patients. It allowed them to visualise and measure movements of the vocal cords, which surround the glottis, and other nearby structures, including the bone at the front of the neck and the circle of cartilage around the windpipe. They chose to focus on the extent of these movements in the vertical plane, meaning from head to toe.

The researchers recorded these measurements at the start, middle and end of treatment in 15 patients with ESGC who were receiving radiotherapy to the laryngeal area. They found that, on average, swallowing caused up to 2.48 cm of movement to the laryngeal structures. However, the patients swallowed a maximum of one time per minute, and each swallow lasted only 1.5 seconds. In addition, the average rate of swallowing decreased over the course of the treatment. Based on these findings, the team deemed the swallow-related motions “clinically insignificant”.

Despite this, when measuring the radiation delivered to the target area, the scientists used a “worst-case estimate”. They looked at the dose that reached the farthest edge of the target area, which is where the tumour would likely be during a swallow. They found that more than 95 per cent of the prescribed dose treated this region, meaning that the treatment remained effective despite swallowing.

In the next part of the study, the researchers checked the dose delivery to organs at risk, including the thyroid glands and carotid arteries. They compared treatment plans for 3D-CRT, which targeted the whole larynx, with those for IMRT, which targeted only the ITV. They also looked at two types of VMAT plans – one that targeted the whole larynx and one that was adapted to treat the ITV.

Overall, IMRT and the adapted VMAT technique delivered significantly lower mean doses to the organs at risk than 3D-CRT and non-adapted VMAT. This confirms that smaller target areas are, as would be expected, best for limiting damage to healthy tissue.

“We can make evidence-based decisions”

First author Dr Amit Gupta, Clinical Oncology Consultant in Head and Neck at the Mount Vernon Cancer Centre in London, who carried out the work when he was a Clinical Research Fellow at the ICR and The Royal Marsden, said:

“By investigating the measurement of motion using a new platform, our planning study has demonstrated that it’s possible to deliver conformal radiotherapy safely in ESGC. Other studies have looked at laryngeal motion using MRI before, but they have not had access to MR-Linac. With this technology, we were able to visualise the movement of the voice box. The degree of motion we could see, even when patients were at rest, was astonishing. Encouragingly, our findings were consistent with previous research, confirming the strength of our real-time approach.

“The clinical insignificance of swallow-related motions is good news for patients, as it means we can spare critical organs at risk, including the carotid arteries. We hope that in the longer term, we will be able to further reduce the irradiated volume by removing the ITV completely.”

Senior author Dr Kee Howe Wong, Consultant Clinical Oncologist at The Royal Marsden, said:

“Incorporating motion analysis as part of the planning process is really important in radiotherapy. Traditionally, it has not been considered in head and neck cancer. Now that we can visualise motion in real time using MR-Linac, we can make evidence-based decisions to help us treat the cancer as effectively as possible while also sparing nearby organs.”

Professor Kevin Harrington, Head of the Division of Radiotherapy and Imaging at the ICR, also worked on the study. He said:

“Our work has confirmed that accounting for resting motion in an ITV is sufficient, which supports a move towards more conformal target volumes that can significantly reduce the risk of damage to vital organs. By sparing the carotid arteries and thyroid gland, we can help more patients avoid conditions affecting the flow of blood to the brain.”