Local Consolidative Radiotherapy for Oligoprogressive in Non-small Cell Lung Carcinoma

Inclusion Criteria:

* Histologically confirmed diagnosis of non-small cell lung cancer.
* Have completed at least 4 cycles of a first line systemic therapy regimen for metastatic disease that includes a PD-1 axis targeted agent prior to progression. (Patients may be on maintenance/consolidation anti PD-1 axis therapy or have completed maintenance anti PD-1 axis therapy within the last 3 months at the time of progression).
* Initial response of stable disease (SD), partial response (PR) or complete response (CR) in at least one lesion prior to progression as defined by RECIST v1.1 criteria.
* Oligoprogressive disease in 4 or fewer lesions (Progression of the primary tumor and/or regional lymph nodes will be counted as one lesion)
* CNS lesions will not count towards the 4 or fewer progressive lesions if they are all able to be treated with stereotactic radiosurgery.
* Progression by RECIST v1.1 criteria or by PET/CT criteria will be considered progressive disease. Both are not required to determine progressive disease.

Progression for study entry will be defined as by a modified RECIST v1.1 criteria, including: Development of a new lesion; increase in the longest diameter (shortest diameter for lymph node lesions) of any individual lesion by 20% above nadir and a minimal increase of 5 mm.

* In cases of PET/CT, the criteria for progression of PET/CT are: Any individual FDG avid lesion with an uptake greater than twice that of the surrounding tissue on the attenuation corrected image. Any individual FDG avid lesion with greater than 30% increase in 18F-FDG SUV peak, with greater than 0.8 SUV units increase in tumor SUV from the nadir or the pre-enrollment PET/CT in pattern typical of tumor and not of infection/treatment effect per the treating investigator. Visible increase in the extent of 18F-FDG uptake of any lesion by 20% in the longest diameter and an absolute increase of at least 5mm that is not consistent with treatment effect and/or infection per the treating investigator. No more than the following number of progressing lesions in any one organ (including any lesions previously treated with radiation therapy). Less than or equal to four (4) lung lesions (including primary and mediastinal lymph nodes as one lesion). Less than or equal to three (3) liver lesions. Less than or equal to three (3) cumulative vertebral lesions
* At least one non-progressing lesion, which may not have undergone prior definitive local therapy.
* All progressive lesions must be amenable to definitive radiation therapy as determined by the treating radiation oncologist.
* Age of 18 years or greater.
* ECOG Performance Status of 0-2.
* Negative serum or urine pregnancy test within 2 weeks of the date of enrollment
* for women of child-bearing potential.
* Ability to understand and the willingness to sign an IRB-approved informed consent document (either directly or via a legally authorized representative).
* If EGFR and/or ALK status is unknown, the patient is eligible.

Exclusion Criteria:

* Inability to safely treat all progressive lesions with definitive radiation therapy as determined by the treating radiation oncologist
* Patients may not be receiving any other investigational anti-cancer agents.
* Progressive disease in the CNS only.
* Known targetable EGFR mutation or EML4-ALK fusion.
* Progressive cutaneous metastases.
* Progressive disease involving the esophagus, stomach, or intestines.
* Malignant pleural or pericardial effusion at the time of oligoprogression.
* Thoracentesis/thoracoscopic biopsy for a stable or asymptomatic pleural effusion is not required unless the effusion is hypermetabolic on PET/CT or if there are active pleural based metastatic lesions at the time of oligoprogression.
* Effusions that are too small for thoracentesis/pericardiocentesis are considered resolved for the purposes of trial eligibility.
* Pregnant women are excluded from this study because radiation therapy has known potential for teratogenic or abortifacient effects.
* Uncontrolled intercurrent illness including, but not limited to ongoing or active infection requiring intravenous antibiotics, symptomatic congestive heart failure, unstable angina pectoris, unstable cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements as determined by the treating physician.