Pathologic and Immunologic Response After Ablative Radiation in Lung Cancer

This is a pilot study to compare pre- and post-SABR core biopsies of stage I NSCLC tumors to identify SABR-induced immune-mediated tumor recognition based on a significant and specific expansion of T-cell clones using a novel T-cell receptor (TCR) sequencing assay. This will be coupled with (1) novel genomic analysis of candidate tumor antigens that may be released from the pre-SABR tumor and (2) functional validation assays to screen post-treatment peripheral blood T-cells for reactivity to these released candidate tumor antigens. In addition, cell-based analysis will be used to identify changes in key T-cell infiltrates into the post-SABR tumor.

Inclusion Criteria: * Written informed consent obtained from the subject prior to performing any protocol-related procedures, including screening evaluations * Age \> 18 year * Confirmed non-small cell lung cancer after initial biopsies * Patient with accessible tumor for biopsy * Patient is to have sufficient initial core biopsy samples for tissue analyses * Stage I lung cancer * Adequate normal organ and marrow function * Patient with tumor amenable to SABR treatment as determined by a radiation oncologist * Subject is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up. * Post-menopausal status or negative urinary or serum pregnancy test for female pre-menopausal subjects. Women will be considered post-menopausal if they have been amenorrheic for 12 months without an alternative medical cause. Exclusion Criteria: * Primary tumors not amenable to serial core biopsies. * Prior thoracic radiation in the region that will be treated by SABR. * Patient may not be receiving any other concurrent investigational agents or chemotherapy. * Patient may not be receiving or received immunotherapy. * Patients may not be on or use steroids within 14 days before radiation, and from the duration of radiation to the time of the post-SABR biopsies and blood samples. * Female patients who are pregnant from screening to completion of SABR