Can zapping cancer spots delay lung cancer progression?

Copied word for word from the study's registry entry, so the wording is the study team's rather than ours.

Participant Inclusion Criteria (both Part I and Part II) Monitoring Phase * Stage IV NSCLC. Note that patients are eligible for the study if they have received definitive treatment for early stage disease, presuming that they remain candidates for local ablative therapy (LAT). * AJCC 8th Edition Stage IV disease * Has had up to four cycles of standard first-line systemic therapy +/- 3 weeks, defined as: a) platinum-doublet chemotherapy, b) ICI, or c) platinum-doublet chemotherapy + ICI at the baseline ctDNA draw being used for the study. * Patient initiated their ctDNA blood draws during their first 4 cycles of first line systemic therapy +/- 3 weeks (during their first 4 cycles, or up to 3 weeks before/after they have begun/ended their first 4 cycles of systemic therapy * Ten or less metastatic lesions (Note that this criterion includes lesions, not sites: 3 brain metastases = 3 lesions). ° Imaging defining extent of disease should be performed within 4 weeks of ctDNA blood draw 1. PET/CT scan or CT scan of the chest/abdomen/pelvis within 4 weeks of blood draw for ctDNA analysis 2. MRI or CT scan of the brain at baseline, AND within 4 weeks of blood draw for ctDNA analysis (optional, per discretion of treating physician) * All lesions amenable to LAT. o Note that patients who receive local therapy (radiation, surgery, or RFA) prior to enrollment for palliative purposes or to CNS lesions are eligible for enrollment if: a) all other eligibility criteria are met and b) at least one other lesion is amenable to LAT and is RECIST evaluable. All lesions treated for palliative purposes will also be counted towards the total number of lesions. * At least one site of measurable disease * ECOG Performance status 0 - 2. * Age ≥ 18 years. * The participant, or their legally authorized representative (LAR) are able to provide informed consent. * Adequate baseline organ function to allow SBRT to all relevant targets, as determined by the treating radiation oncologist based on lesion location, lesion size, and proximity to relevant organs at risk. Therapeutic Phase - Being Enrolled from Monitoring Phase * Has received at least 2 cycles of treatment, remains on first-line therapy * No evidence of radiographic RECIST 1.1\* progression (as defined above), as measured through the following imaging modalities: * 1\) PET/CT scan or CT scan of the chest/abdomen/pelvis within 4 weeks of blood draw for ctDNA analysis * 2\) MRI or CT scan of the brain at baseline, AND within 4 weeks of blood draw for ctDNA analysis (optional, per discretion of treating physician) * NR-VAF results within 4 weeks of enrollment * All active lesions amenable to LAT ° Note that patients who receive local therapy (radiation, surgery, or RFA) prior to enrollment for palliative purposes or to CNS lesions are eligible for enrollment if: a) all other eligibility criteria are met and b) at least one other lesion is amenable to LAT and is RECIST evaluable. All lesions treated for palliative purposes will also be counted towards the total number of lesions. Female subjects must either be of non-reproductive potential (i.e. post-menopausal by history: \>/= 60 years old and no menses for 1\> year without an alternative medical cause; OR history of hysterectomy, OR history of bilateral tubal ligation, OR history of bilateral oophorectomy) or must have a negative pregnancy test (serum) within 2 weeks or a urine pregnancy test the day of treatment * Note that patients can either be: a) enrolled on the Monitoring Phase, followed by the Therapeutic Phase, or b) enrolled directly on to the Therapeutic Phase if they present for enrollment at the time that the therapeutic phase would be delivered and retrospectively would have met all of the criteria of the monitoring phase. * Example: If a patient has received 2 cycles of systemic therapy and has NR-VAF, then presents to the clinic for enrollment, they can be enrolled on to the Therapeutic Phase if they meet all of the criteria in the Therapeutic Phase and upon evaluating their prior ctDNA/imaging results would have also met the criteria for the Monitoring Phase. * This allowance will substantially increase accrual, as many patients will present after undergoing baseline ctDNA analysis, and does not affect the scientific question that the study addresses. Therapeutic Phase - Being Enrolled Directly into Therapeutic Phase As the criteria below indicate, patients can either be: a) enrolled on the Monitoring Phase, followed by the Therapeutic Phase, or b) enrolled directly on to the Therapeutic Phase if they present for enrollment at the time that the therapeutic phase would be delivered and retrospectively would have met all of the criteria of the monitoring phase. For example, if a patient has received 2 cycles of systemic therapy and has NR-VAF, then presents to the clinic for enrollment, they can be enrolled on to the Therapeutic Phase if they meet all of the criteria in the Therapeutic Phase and upon evaluating their prior ctDNA/imaging results would have also met the criteria for the Monitoring Phase. This allowance will substantially increase accrual, as many patients will present after undergoing baseline ctDNA analysis, and does not affect the scientific question that the study addresses. Inclusion Criteria for Patients Being Enrolled Directly into the Therapeutic Phase * Stage IV NSCLC. Note that patients are eligible for the study if, prior to the development of stage IV disease, they have received definitive treatment for early stage disease, presuming that they remain candidates for local ablative therapy (LAT). * AJCC 8th Edition Stage IV disease * Ten or less metastatic lesions (Note that this criterion includes lesions, not sites: 3 brain metastases = 3 lesions). o Imaging defining extent of disease should be performed within 4 weeks of ctDNA blood draw * All lesions amenable to LAT. * At least one site of measurable disease * Detectable ctDNA * ECOG Performance status 0 - 2. * Age ≥ 18 years. * The participant, or their legally authorized representative (LAR) are able to provide informed consent. * Female subjects must either be of non-reproductive potential (i.e. post-menopausal by history: \>/= 60 years old and no menses for 1\> year without an alternative medical cause; OR history of hysterectomy, OR history of bilateral tubal ligation, OR history of bilateral oophorectomy) or must have a negative pregnancy test (serum) within 2 weeks or a urine pregnancy test the day of treatment. * Adequate baseline organ function to allow SBRT to all relevant targets, as determined by the treating radiation oncologist based on lesion location, lesion size, and proximity to relevant organs at risk. * Patient initiated their ctDNA blood draws during their first 4 cycles of first line systemic therapy +/- 3 weeks (during their first 4 cycles, or up to 3 weeks before/after they have begun/ended their first 4 cycles of systemic therapy. * Has received at least 2 cycles of treatment, remains on first-line therapy * No evidence of radiographic RECIST 1.1\* progression (as defined above), as measured through the following imaging modalities: * 1\) PET/CT scan or CT scan of the chest/abdomen/pelvis within 4 weeks of blood draw for ctDNA analysis * 2\) MRI or CT scan of the brain at baseline, AND within 4 weeks of blood draw for ctDNA analysis (optional, per discretion of treating physician) * NR-VAF results within 4 weeks of enrollment o For patients that do not have detectable ctDNA at enrollment in the monitoring phase, NR-VAF is defined as the emergence of detectable VAF on follow up blood draws * All active lesions amenable to LAT o Note that patients who receive local therapy (radiation, surgery, or RFA) prior to enrollment for palliative purposes or to CNS lesions are eligible for enrollment if: a) all other eligibility criteria are met and b) at least one other lesion is amenable to LAT and is RECIST evaluable. All lesions treated for palliative purposes will also be counted towards the total number of lesions. Exclusion Criteria: * At the time of therapeutic phase enrollment, complete response radiographically (no lesions to target) * Patients with CNS-only disease (due to limited capacity of peripheral blood ctDNA to detect CNS lesions) * Planned treatment by targeted agents (e.g. tyrosine kinase inhibitors) or patient not a candidate for systemic therapy * Serious medical co-morbidities precluding radiotherapy or ablation, determined at the discretion of the treating investigator. * At the time of therapeutic phase enrollment, pregnant or lactating women. * Physical limitation to undergo stereotactic radiotherapy. * Other active malignancy within the last year except for basal cell carcinoma of the skin and in situ malignancy even if without evidence of disease.