Optimise Lung SABR: testing 3-fraction vs 5-fraction radiotherapy for peripheral NSCLC

Inclusion Criteria:

1. Written informed consent obtained prior to any study-specific procedures.
2. ≥ 18 years of age.
3. Life expectancy \>6 months.
4. ECOG (Eastern Cooperative Oncology Group) performance status of 0-2.
5. Histological diagnosis (biopsy or cytology) or radiological diagnosis (tumour which meets definition of 'measurable' per RECIST criteria and eligible for local ablative therapy per multi-disciplinary team (MDT) recommendations) of either:

   (i) Primary Non-Small Cell Lung Cancer (squamous cell carcinoma, adenocarcinoma, large cell): T1-T2 N0 M0 tumour (AJCC 8th edition) and selected T3 and T4 N0M0 which has only one lesion (a co-existing lesion unlikely to interfere with treatment or assessment of outcomes is permitted) to be treated for the purpose of the study OR (ii) Single pulmonary oligometastatic lesion to be treated for the purpose of the study.

   (Note: for (i) and (ii), a co-existing lesion(s) unlikely to interfere with treatment or assessment of outcomes is (are) permitted).
6. Patients with peripherally located tumours, defined as tumours not fulfilling the UK 2022 SABR Consortium Consensus optimal 3 fraction constraints for Chest wall (0.1 cc \<36.9 Gy) or (30 cc \< 30 Gy), with standard Planning Target Volume (PTV) coverage due to the proximity of their tumour to the chest wall , but which are predicted to meet the CTRIAL-IE 24-15 OPTIMISE Lung SABR Study dose volume constraints with dose escalation optimised to the Gross Tumour Volume (GTV).
7. Inoperable (as per MDT) or patient refuses surgery.
8. People of childbearing potential must not be pregnant or lactating and must be prepared to take adequate contraception methods during treatment. People whose partners are of child-bearing potential must be prepared to take adequate contraception methods during treatment.
9. Absence of psychological, familial, sociological, or geographical condition, or psychiatric illness/social situation potentially hampering compliance with the study protocol and follow-up schedule

Exclusion Criteria:

1. Known co-existing or prior malignancy within the last 5 years (except for adequately treated basal cell carcinoma which is likely to interfere with treatment or assessment of outcomes.
2. Evidence of regional (nodal) or distant metastases or metastatic pleural effusion for patients with primary NSCLC.
3. Malignant spinal canal involvement.
4. Patients with syndromes or conditions associated with increased radiosensitivity.
5. Idiopathic pulmonary fibrosis / usual interstitial pneumonia.
6. Chemotherapy and/or other targeted therapy administered within 3 months prior to study radiotherapy (RT) or planned for \<6 weeks following RT for patients with primary NSCLC, or within 1 week prior to study RT or planned within 1 week following RT for patients with an oligometastatic lesion.
7. Any previous RT to the thorax or mediastinum (excluding previous breast or Chest Wall RT) which is likely to interfere with treatment or assessment of outcomes.
8. Any tumour not clinically definable on the treatment planning CT scan (e.g. surrounding consolidation or atelectasis).
9. Patients unable to undergo 4-Dimensional Computed Tomography (4DCT scan).
10. Uncontrolled intercurrent illness that is likely to interfere with treatment or assessment of outcomes.
11. Evidence of any other significant clinical disorder or laboratory finding that makes it undesirable for the patient to participate in the study, or if it is felt by the research/ medical team that the patient may not be able to comply with the protocol.