Stereotactic Body Radiation Therapy in Treating Patients with Stage IV Oncogene-Driven Non-small Cell Lung Cancer Receiving Selected Targeted Therapy

Inclusion Criteria

• Participants must have histologically or cytologically confirmed non-small cell lung cancer (NSCLC) with any actionable mutation or translocation in epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), or c-ros oncogene 1 (ROS1)
• Documented history of clinical stage IV (any T, any N, M1a/b) disease as per American Joint Committee on Cancer (AJCC) staging system 7th edition
• Participants must be within 6 months of initiating TKI treatment with a traditional TKI such as erlotinib, gefitinib, afatinib or crizotinib, which specifically targets the actionable mutation their tumor harbors; participants receiving TKIs typically associated with a long PFS, such as first-line osimertinib or alectinib, should be within 12 months of TKI treatment; other TKIs are acceptable with approval of study principal investigator (PI)
• Participants must have stable or responding systemic disease to TKI (no evidence of progression) on the most recent staging studies; the required staging studies are: (1) a re-staging computed tomography (CT) scan of the chest +/- abdomen with intravenous (IV) contrast (unless medically contraindicated) within 2 months of study enrollment; and (2) in patients with known brain metastasis, or to investigate patients with new onset of neurologic symptoms that may suggest metastasis to the brain, brain magnetic resonance imaging (MRI) with gadolinium, or head CT scan with IV contrast will be required within 2 months of study enrollment; the complete extent of the current residual systemic disease must be deemed amenable to SBRT as per review of imaging studies by a radiation oncologist involved in this trial; this will be based on the following criteria: * Lung: 1-3 lesions (including the primary) of maximum size 5 cm in longest diameter; a minimum size 1 cm in the longest diameter is recommended; (patients with a malignant pleural effusion prior to the start of TKI therapy will be considered eligible for SBRT if there is complete radiographic resolution of the effusion while on systemic therapy) * Spine: bone lesions must be limited to the spine; a maximum of 2 spinal metastases will be considered for SBRT, with each site spanning 1-3 vertebral bodies; a minimum size of 1 cm in longest diameter is recommended; SBRT may target sclerotic lesions that persist following TKI therapy * Gastrointestinal (GI): 1-4 liver metastases of maximum size 5 cm in longest diameter and/or 1-2 adrenal metastases of maximum 4 cm size in longest diameter; a minimum size of 1 cm in longest diameter is recommended * In addition: * Central nervous system (CNS): 1-4 brain metastases of maximum size 3cm in longest diameter; however, these should be treated with standard-of-care stereotactic radiosurgery (SRS) and will not be defined as target lesions for purposes of this protocol; there is no minimum size requirement for treatment of brain lesions but small foci of potential disease (1-4 mm size) detected on high-resolution MRI may not be clinically relevant and do not count towards the maximum number of 4 brain metastases as per the treating radiation oncologist’s discretion and in line with institutional practice * A maximum number of 5 target lesions outside the brain, excluding the lung primary, is recommended to ensure that enrollment is limited to patients with low-burden disease and that treatments can be delivered within the specified time frame; this is not an absolute requirement as situations may exist when more than 5 metastatic targets are appropriate in the treating radiation oncologist’s clinical judgment, for example when nearby lesions can be included in a single treatment field
• History of prior radiation therapy to brain or skeleton is allowed, but should have occurred > 2 months from enrollment
• Life expectancy of greater than 6 months
• Eastern Cooperative Oncology Group (ECOG) performance status =< 2
• Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study treatment; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately
• Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria

• Subjects deemed to have residual hilar or mediastinal lymph node disease (defined as nodal size > 1 cm in short-axis diameter on CT scan); nonmalignant etiologies for enlarged lymph nodes may be evaluated per standard clinical practice
• Participants who have received prior radiation therapy to anatomical sites other than brain or skeleton
• Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
• Patients who are pacemaker or defibrillator-dependent
• Pregnant or lactating women; female subjects of childbearing potential must indicate to their physician that there is not a possibility of being pregnant at the time of enrollment or have a negative pregnancy test prior to the initiation of radiation therapy