Daily vs. Non-Daily SBRT for NSCLC

Inclusion Criteria:

* ≥ 18 years of age (no upper age limit).
* A diagnosis of non-small cell lung cancer, T1-2 N0 M0 either with histologic confirmation or with documented interval growth of the index lesion on two interval computed tomography (CT) chest scans and an SUVmax of the lesion ≥ 3.0 on a pretreatment PET scan.
* Patient must be deemed medically inoperable or refuse surgery.
* Radiographic evaluation of the mediastinum and distant sites with a CT scan of the chest and PET scan.
* For T2b N0 patients, radiographic evaluation of the brain with magnetic resonance imaging (MRI) of the brain unless the patient has contraindications to an MRI scan (in which case a CT scan of the head is necessary).
* For central T1 N0 and all T2 N0 patients, pathologic sampling (either via endobronchial ultrasound-guided biopsy \[EBUS\] or mediastinoscopy) of mediastinal lymph nodes is required.
* ECOG Performance Status 0-2.
* For women of childbearing potential, negative pregnancy test within 2 weeks prior to SBRT treatment.
* Patients must be deemed able to comply with the treatment plan and follow-up schedule.
* Patients must provide specific informed consent prior to study entry.
* Women of childbearing potential and male participants who are sexually active must use adequate contraception during treatment and for 6 weeks following treatment.

Exclusion Criteria:

* Prior history of radiation therapy to the thorax that would likely increase the risk of serious complications from the radiotherapy delivered on this protocol.
* Prior history of lung cancer.
* Currently taking disease-modifying rheumatoid drugs (DMRDs).
* Severe, active co-morbidity, defined as follows:
* Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration.
* Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects. Note, however, that coagulation parameters are not required for entry into this protocol.
* Prior organ transplant.
* Systemic lupus.
* Psoriatic arthritis.
* Known to be HIV positive. HIV-positive patients are known to have worse clinical outcomes, especially for local, regional, and distant cancer control. This poorer prognosis is thought to be secondary to a compromised immune system.