Award Title: Design and evaluation of a novel methodology for stereotactic ablative radiotherapy for lung cancer: reducing treatment side-effects and enabling more patients to benefit from this treatment.
Funder: Department of Health and Social Care

Abstract: Research question: Can the volume of non-cancer tissue receiving a high dose of radiotherapy to moving lung tumours be reduced without adversely affecting treatment outcome?Background: SABR is a new treatment option for >1000 lung cancer patients/year. A major advantage is that the success rate of eradication of tumour mass is reported to be >80% for SABR compared with 30% for conventional radiotherapy. In SABR a more focussed, much higher dose is delivered to the tumour than in conventional radiotherapy.Due to the high doses delivered per treatment, SABR needs to be delivered extremely accurately. X-ray imaging is used to ensure the tumour is correctly targeted and to avoid normal, healthy tissue. This is challenging since lung tumours move due to breathing which may vary because breathing cycles are variable in nature particularly in patients with compromised lung function and who may suffer treatment anxiety. In the UK the approach used to account for tumour motion, is to add a margin around the tumour which ensures the tumour is covered in all positions of the breathing cycle, consequently resulting in a large volume of normal tissue receiving a high radiation dose (increasing radiation side-effects such as pneumonitis/breathlessness). An alternative approach which promises significantly smaller high dose volumes of normal tissue whilst still ensuring effective tumour dose, targets the tumour in the middle of the tumour movement range.Aims and Objectives: I will develop a methodology for implementation of the new treatment approach. I will build on international work by making the method easily usable by other NHS hospitals and by developing a method for validation through actual dose measurement.Method: It will be essential to carefully monitor 3D tumour motion during SABR delivery. This will be achieved by measuring the 3D motion of the patient's chest surface during breathing with a novel approach utilising low cost 3D camera technology (used by my supervisor in a different setting). For 30 patients X-ray CT images measuring internal tumour motion will be combined with chest surface measurements to build patient-specific breathing models that correlate external chest motion with tumour motion during SABR delivery. To evaluate this new method I will take advantage of advancements in the design of physical models of the thorax that allow realistic simulation of 3D tumour motion. Detectors positioned in the thorax model will allow measurement of dose delivered to a moving tumour by SABR plans generated for both treatment approaches. Dose measurements will be analysed and used to calculate parameters proven in the literature to have a direct relation to tumour control and normal tissue complication. This will allow both approaches to be compared.Finally I will explore the potential of developing a clinical trial that compares outcomes from the standard and new approach, as a topic of follow-on funding.Anticipated Impact: Fewer patients will develop severe radiation side-effects. SABR will become a treatment option for an increased number of patients (+15%/year) who are currently excluded due to too high doses to healthy lung tissue or adjacent organs.

Lay Abstract: Aims: To increase the number of patients that benefit from Stereotactic Ablative Radiotherapy (SABR) for lung cancer using new treatment methods that reduce the amount of non-cancer tissue receiving a high radiation dose without effecting treatment outcome.Background: SABR is a treatment for lung cancer which offers major advantages over conventional radiotherapy: a) It is a more precise highly effective treatment with significantly improved treatment outcomes (greater elimination of the cancer cells). b) It is delivered in fewer (3-8) high doses as opposed to many low doses over several weeks. It is favoured by patients, for convenience and reduction of travel costs.Due to the high doses delivered per treatment visit, SABR needs to be delivered extremely accurately to avoid unwanted radiation dose to healthy normal tissue. X-ray imaging is used to ensure this. However, it is complicated by the lung tumour's movement caused by normal breathing which can vary significantly during treatment, particularly in patients with breathing problems (due to their cancer or other diseases) and because they may be anxious. Therefore to avoid missing the tumour, the irradiated volume needs to be larger than the actual tumour.UK standard practice ensures the tumour is targeted by radiation in all positions of the breathing cycle. This results in a lot of normal tissue receiving a high dose which causes side effects (e.g. lung inflammation and breathlessness). To address this, I will design a treatment based on a new approach that targets the tumour at the position it spends most time. This will result in significantly smaller volumes of normal tissue that need to be given a high radiation dose.It would greatly enhance current practice by impacting on current SABR patients since fewer patients would develop severe radiation side-effects. Moreover, SABR would become a viable treatment option for patients who are currently excluded due to too high a risk of complications from unwanted radiation to their healthy tissue.Design and Methods: I will develop a method for safely implementing the new treatment approach. I will build on international work by making the method easily usable by other NHS hospitals and developing necessary testing through dose measurement.To carefully monitor the variability of tumour motion during treatment, a camera will be used to make videos of how the patient's chest moves in 3D. I will draw on my supervisor's experience using this technology to build a complex mathematical model that infers movement of the tumour from movement of the chest. Next, I will take advantage of recent advancements in the design of dummies of the chest and dose detectors. Dose detectors will be positioned inside a dummy to allow measurement of dose delivered to a moving tumour during SABR. I will measure differences between the old and new treatment approach.Finally I will explore the potential development of a clinical trial to start after this project that would compare clinical outcomes between both approaches.Patient and Public Involvement and Dissemination: Patient representatives have already been involved in the writing and development of this proposal. Representatives will participate in bi-annual steering group meetings during which they will provide advice and guidance on patient impact as the study progresses. To ensure the results are disseminated to public and patients, they will be presented through the patient group Independent Cancer Patients' Voice. Additionally, it is planned that this work will produce at least three journal papers alongside presentations at international conferences, and at least one European multidisciplinary meeting.To facilitate early translation to clinical practice, the work will be presented to the UK SABR Consortium, which is responsible for current Lung SABR guidelines.

Research Activity Codes: 6.5 RADIOTHERAPY AND OTHER NON-INVASIVE THERAPIES
Health Categories: CANCER AND NEOPLASMS