Comparing the Safety of a Three- versus Five-Fraction Regimen of Stereotactic Body Radiation Therapy for Treating Early Stage Non-Small Cell Lung Cancer

Inclusion Criteria

• Histological confirmation of non-small cell cancer will not be required as primary goal of this phase II trial is to look at toxicity. However, all primary non-small cell lung cancers otherwise of following types are eligible: squamous cell carcinoma, adenocarcinoma, large cell carcinoma, bronchioalveolar cell carcinoma, or non-small cell carcinoma not otherwise specified. * Tumors need to be determined to be medically inoperable or patient has refused surgery
• Eligible patients must have appropriate staging studies identifying them as specific subsets of American Joint Committee on Cancer (AJCC) stage I or II based on only one of the following combinations of TNM staging: * T1, N0, M0 * T2 (≤ 5 cm), N0, M0
• Patients with hilar or mediastinal lymph nodes ≤ 1cm and no abnormal hilar or mediastinal uptake on PET will be considered N0. Patients with > 1 cm hilar or mediastinal lymph nodes on CT or abnormal PET (including suspicious but non-diagnostic uptake) may still be eligible if directed tissue biopsy of all abnormally identified areas are negative for cancer. All patients with suspicious nodes will be evaluated for mediastinal and hilar staging with bronchoscopy and (if amenable) bronchoscopic biopsy (preferably navigational biopsy and/or endobronchial ultrasound [US] guided biopsy)
• Zubrod (also known as Eastern Cooperative Oncology Group [ECOG]) performance status 0-2 within 4 weeks of study entry. KPS (Karnofsky performance status) will be converted to Zubrod for the purpose of study eligibility
• Women of childbearing potential and male participants must use an effective contraceptive method
• Evaluations required at time of study entry: * History & consult for treatment by a radiation oncologist within 4 weeks of study entry; * Evaluation by a thoracic surgeon (either via clinical examination and/or input at multidisciplinary tumor board) prior to study entry; CT chest within 6 months of study entry (preferably with intravenous contrast, unless medically contraindicated) - to include the entirety of both lungs, the mediastinum, liver, and adrenal glands; primary tumor dimension will be measured on this CT; * Whole body positron emission tomography (PET) scan using FDG with adequate visualization of the primary tumor and draining lymph node basins in the hilar and mediastinal regions within 6 months prior to study entry * At least ONE of either the chest CT or the PET scans MUST be completed within 12 weeks of study entry, however BOTH are required within 6 months of study entry * The CT done with the PET, or the treatment planning CT done at simulation will be allowed if another CT is not completed
• Informed consent signed by the subject and a member of the study team

Exclusion Criteria

• Patients with central tumors. Specifically; central location implies a tumor inside the zone of the proximal bronchial tree defined as a volume 2 cm in all directions around the proximal bronchial tree (carina, right and left main bronchi, right and left upper lobe bronchi, intermedius bronchus, right middle lobe bronchus, lingular bronchus, right and left lower lobe bronchi)
• Evidence of regional or distant metastases after appropriate staging studies
• Synchronous primary NSCLC
• Those with prior malignancy in the past 2 years other than non-melanomatous skin cancer or in situ cancer or thyroid cancer
• Previous lung or mediastinal radiotherapy
• Plans for the patient to receive concomitant antineoplastic therapy (including standard fractionated radiotherapy, chemotherapy, biological therapy, vaccine therapy, and surgery) while on this protocol
• Patients with active systemic, pulmonary or pericardial infection
• Pregnant or lactating women, as treatment involves unforeseeable risks to the embryo or fetus