OPTIMISE Lung SABR

This study is for patients who have a lung tumour located near the ribs or chest wall, and who are not suitable for surgery. Currently, these patients are usually treated with Stereotactic Ablative Radiotherapy (SABR). SABR is a precise form of radiotherapy that delivers high doses of radiation to the tumour while protecting surrounding healthy tissue. The standard treatment for these patients currently is 60 Gray (Gy) in 5 treatments (12 Gy each), spread over about 2 weeks. This schedule is thought to reduce the risk of rib fractures and is currently adopted when a patient has a tumour located near the ribs or chest wall. This study is testing whether an alternative investigational treatment schedule, 54 Gy in 3 treatments (18 Gy each) given over about 1 week, is just as safe and effective for these patients. This new approach means patients would need to attend the hospital for two fewer visits. A new method of SABR planning for the alternative treatment schedule makes it possible to direct the radiation dose straight to the tumour while avoiding the ribs and chest wall as much as possible. Because of this planning method, the research team believes the investigational three-treatment schedule will not increase side effects such as rib fractures or chest wall pain compared with the standard five-treatment schedule. SABR is already widely used in many types of cancer. It works by delivering higher doses of radiation over fewer treatment sessions. This can be more effective than conventional external beam radiotherapy where treatment is delivered over 4-6 weeks in some cases and is often more convenient for patients. In this study, patients will be randomly assigned to receive either: Arm 1: Regimen of 60 Gy in 5 treatments over approximately two weeks, or Arm 2: Investigational regimen of 54 Gy in 3 treatments over approximately 1 week. Treatments in both groups are given on weekdays only, with at least forty hours between each session. The technology used in SABR allows very precise targeting of the tumour while protecting nearby healthy organs such as the heart, spinal cord and normal lung tissue. The planning process also accounts for the natural movement of the lungs during breathing. Before each treatment, a cone beam CT scan is used to ensure the patient is in the correct position. The purpose of the study is to see how well each treatment schedule controls lung tumours and what side effects patients experience. It will also explore what factors might influence whether side effects such as rib fractures or chest wall pain occur. The enrolment period is expected to be approximately 3.5 years. Toxicity assessments will be carried out weekly during radiotherapy (RT), at 4 and 8-weeks post-treatment and at 3, 6, 9, 12, 18, 24 months post-treatment and annually thereafter to 5 years post treatment. Translational Sub-Study: (Raman spectroscopic analysis) - Primary aim is to undertake biomarker discovery using label-free Raman spectroscopy coupled with multivariate statistical methods to identify spectral biomarkers that could: 1. Predict response based on individual radiation sensitivity 2. Monitor response based on individual radiation sensitivity