Stereotactic Ablative Radiotherapy for Oligometastatic Non-small Cell Lung Cancer

Registration Inclusion criteria 1. Patient ≥ 18 years 2. Histologically or cytologically confirmed NSCLC. 3. Staging with FDG PET-CT whole body scan and MRI brain within 45 days prior to registration (but prior to commencement of first cycle of SACT). \[Note: Brain CT with IV contrast can be performed instead (within 45 days prior to registration). However, if brain metastases are evident on the brain CT then a brain MRI must be performed prior to randomisation, i.e. the Brain CT is sufficient for registration into the trial but not for randomisation if it is positive for brain metastases, in which case a brain MRI must be performed\] 4. ECOG performance status 0 to 1 (prior to commencement of first cycle of SACT). 5. Patient presenting with primary disease +/- lymph nodes and synchronous oligometastatic disease (1-5 lesions in up to a maximum of 3 organs). 6. Patient is deemed fit to receive four cycles of systemic anti-cancer therapy, according to local guidelines and assessment. 7. Patient is deemed fit to receive radical RT (either conventional RT or SABR) to primary disease +/- lymph node and SABR/SRS to 1-5 metastases according to local guidelines and assessment. 8. Primary tumour +/- lymph node suitable for radical RT (either conventional RT or SABR). 9. 1-5 metastatic lesions in up to a maximum of 3 organs, assessable according to RECIST v1.1 and all of which are suitable for SABR/SRS (only one site of metastasis or primary tumour needs to be measurable according to RECIST v1.1). i. If brain metastasis present, the NHS commissioning guidelines need to be met for intracranial SRS (≤20 cc) (or equivalent for Wales, Scotland \& Northern Ireland in line with standard of care). ii. Lymph nodes included in the N1-3 categories of the IASLC 2009 staging criteria are treated in the conventional radiotherapy volume and are not counted as metastases. iii. Lymph nodes not included in the N1-3 categories of the IASLC 2009 staging criteria, e.g. pelvic lymph nodes, are counted as metastases. iv. For bone metastases pre-SABR stabilisation should be considered as clinically appropriate. This does not exclude the patient from the study. 10. Acceptable lung function for radical lung radiotherapy as assessed according to local policy. Note: Potential thoracic sub-study patients will need to complete pulmonary function tests pre-randomisation 11. No relevant co-morbidities, including UIP pulmonary fibrosis and connective tissue disorders. Additional inclusion Information Patients with lung cancer and an additional malignant nodule are difficult to categorise, and the current stage classification rules are unclear. Such patients should be evaluated by the local multidisciplinary team to determine whether the additional lesion represents a second primary lung cancer or an additional tumour nodule corresponding to the dominant cancer. The SARON TMG will accept local MDM decisions on this and will centrally review all baseline imaging retrospectively Registration Exclusion Criteria 1. Patient has had palliative radiotherapy to any tumour site prior to registration or requires palliative radiotherapy prior to randomisation. 2. Presence of an actionable molecular aberration. 3. Patients currently receiving VEGF inhibitors. 4. One or more metastases previously treated with alternative ablative treatment.Note: Surgical ablation (partial or total excision biopsy) is permitted for palliative or diagnostic purposes (e.g. for molecular analysis). Treatment for any residual disease/tumour bed will be at the discretion of treating clinician/MDT. Resected/ablated metastases will count towards the total number of metastases. 5. Patient has received any previous treatment for this NSCLC malignancy. 6. Patients who present with brain metastasis only and no sites of extra cranial metastatic disease i.e. the presence of more than 4 brain metastases is an exclusion criterion. 7. Metastasis in sites where normal radiotherapy OAR constraints cannot be met. 8. Brain metastasis within the brainstem. 9. Patients who have more than five sites of metastases in up to 3 organs prior to trial registration. 10. Primary tumour or metastases causing direct invasion or high clinical suspicion of direct invasion of the wall of a major blood vessel, oesophagus, trachea, proximal bronchial tree, stomach, intestines or mesenteric lymph nodes or cutaneous metastases or diffuse serosal metastases. 11. Malignant pleural or pericardial effusion. 12. Bilateral adrenal metastases. 13. History of prior malignant tumour likely to interfere with the protocol treatment, (patients without evidence of disease for at least 1 year or a non-melanoma skin tumour or early cervical cancer are eligible). 14. Women who are pregnant or breast feeding. 15. Stage III disease with extensive nodal disease not treatable in radical radiotherapy field. 16. Leptomeningeal disease Eligibility Criteria for Randomisation Following cycle 2 of induction SACT, patients must meet the following eligibility criteria for randomisation: * No confirmed disease progression on post-cycle 2 CT scan (according to RECIST v1.1) * Patients with up to 5 metastases at the time of registration but less than 5 visible after induction SACT are still eligible for randomisation. * Patients with no visible metastases following 2 cycles of induction of SACT are eligible for randomisation. If randomised to the Investigational Arm, these patients will receive RT upon relapse of metastases (patients who experience progression with new metastases are not eligible for randomisation or for trial treatment). * Patients with complete response of the lung primary +/- lymph nodes following 2 cycles of induction SACT are eligible for randomisation. Patients randomised to the Investigational Arm, should receive conventional RT to the pre-SACT involved nodal stations and to any scar residuum at the primary site. * Patients who progress following 2 cycles of induction of SACT cannot be randomised. Only overall survival data will be collected for these patients. * ECOG Performance Status 0-2. * Continued suitability for trial treatment as deemed by the treating clinician. * Continues to meet all registration eligibility criteria, as detailed in section 6.4.1 (with the exception of ECOG status).