Daily vs. Non-Daily SBRT for NSCLC

The purpose of this study is to determine if treatment with stereotactic body radiotherapy
(SBRT) on non-consecutive days will improve the chance of curing non-small cell lung cancer
compared to treatment with SBRT on consecutive days. In either case, the dose of radiation is
the same. Non-consecutive treatments will be at least 40 hours apart and no more than 100
hours apart. The total course of treatment will be 8-12 days. Consecutive treatments will be
daily over 4-5 days within one calendar week. The total course of treatment will be 4-5 days.

The study team will assess if DNA from the tumor can be found in the blood to determine which
patients respond quickest to radiotherapy. These results will not be made available to
participants and will not change treatment.

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.