Stereotactic Radiotherapy for Oligo-Progressive Metastatic Cancer (The STOP Trial)

Inclusion Criteria: * Age 18 or older * Willing to provide informed consent * Histologically confirmed Non-Small Cell Lung Cancer (NSCLC) with metastatic disease detected on imaging. Biopsy of metastasis at some time point prior to enrollment is preferred, but not required. * Eastern Cooperative Oncology Group (ECOG) performance status 0-2 * Life expectancy \> 3 months * Patient has received treatment with systemic therapy (either cytotoxic or targeted, including maintenance therapies) during the past 6 weeks. This most recent systemic therapy agent must have been delivered for a total of at least 3 months, with an initial partial response (PR), complete response (CR) or stable disease (CR) prior to the development of oligo-progressive lesions. * Oligoprogression, defined as Response Evaluation Criteria in Solid Tumors (RECIST)-documented progression in up to 5 individual lesions, with no previous radiation or radiofrequency ablation to those sites. Oligoprogression may be defined as: * Progression of an individual metastasis according to RECIST 1.1 criteria * Unambiguous development of a new metastatic lesion at least 5mm in size * Progressive enlargement of a known metastasis on 2 consecutive imaging studies 2- 3 months apart with a minimum 5mm increase in size from baseline * All sites of oligoprogression can be safely treated * Maximum 3 progressing metastases in any single organ system (i.e. lung, liver, brain, bone), and the total number of metastases must be 5 or less Note for Patients with Brain Metastases: For patients with brain metastases and oligo-progression elsewhere where stereotactic radiation to the brain is deemed to be warranted, this must be specified prior to randomization. If randomized to Standard Arm, patient would receive stereotactic radiation to brain only. If randomized to Experimental Arm, patient would receive stereotactic radiation to brain and to body lesions Exclusion Criteria: * Serious medical comorbidities precluding radiotherapy, such as ataxia-telangiectasia or scleroderma. For patients with oligoprogressive lesions in the lung or thorax, this includes interstitial lung disease * Prior radiotherapy to a site requiring treatment * Malignant pleural effusion * Inability to treat all sites of enlarging, oligoprogressive disease * Clinical or radiological evidence of spinal cord compression or tumor within 3mm of spinal cord on MRI * Any other condition which in the judgment of the investigator would make the patient inappropriate for entry into this study