Hotspot Stereotactic Ablative Radiotherapy Versus Traditional Stereotactic Ablative Radiotherapy for the Treatment of Early-Stage Non-Small Cell Lung Cancer

Inclusion Criteria:

* Age ≥ 18 years
* Have an Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2
* Diagnosed with T1-3N0 biopsy-proven NSCLC of the lung. Multiple primary lung tumors are allowed; however, each lesion requires histologic confirmation
* Metachronous lung tumors as defined as a new lung lesion in the setting of a historically treated lung cancer are allowed under certain conditions. The previous lung cancer must have been treated greater than 6 months prior to protocol therapy and this cancer must be considered controlled
* Eligible for SABR
* Participants of child-bearing potential must agree to use adequate contraceptive methods (e.g., hormonal or barrier method of birth control; abstinence) prior to study entry. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately
* Participant must understand the investigational nature of this study and sign an Independent Ethics Committee/Institutional Review Board approved written informed consent form prior to receiving any study related procedure

Exclusion Criteria:

* Patients with a history of a prior lung cancer will be excluded only if the previous treatment is within 6 months of the protocol therapy
* Mixed small cell and non-small cell lung cancer
* History of allogeneic organ transplantation
* History of primary immunodeficiency
* Patients must not have undergone prior radiation to overlapping regions of the chest that, in the opinion of the treatment physician, will interfere with protocol treatment
* Active autoimmune disease that has required systemic treatment in the last 2 years. Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment and is allowed
* Known EGFR or ALK mutation
* Past medical history of interstitial lung disease (ILD), drug-induced ILD, radiation pneumonitis which required steroid treatment, or any evidence of clinically active ILD
* Pregnant or nursing female participant
* Unwilling or unable to follow protocol requirements