How to Improve SBRT Outcomes in NSCLC: From Pre-Clinical Modeling to Successful Clinical Translation

SIMPLE SUMMARY: Despite major research and clinical efforts, lung cancer remains the leading cause of cancer-related death. Stereotactic body radiotherapy (SBRT) has emerged as a major treatment modality for lung cancer in the last decade. Additional research is needed to elucidate underlying mechanisms of resistance and to develop improved therapeutic strategies. Clinical progress relies on accurate preclinical modelling of human disease in order to yield clinically meaningful results; however, successful translation of pre-clinical research is still lagging behind. In this review, we summarize the major clinical developments of radiation therapy for non-small-cell lung cancer (NSCLC), and we discuss the pre-clinical research models at our disposal, highlighting ongoing translational challenges and future perspectives. ABSTRACT: Despite major research and clinical efforts, lung cancer remains the leading cause of cancer-related death. While the delivery of conformal radiotherapy and image guidance of stereotactic body radiotherapy (SBRT) have revolutionized the treatment of early-stage non-small-cell lung cancer (NSCLC), additional research is needed to elucidate underlying mechanisms of resistance and identify novel therapeutic combinations. Clinical progress relies on the successful translation of pre-clinical work, which so far has not always yielded expected results. Improved clinical modelling involves characterizing the preclinical models and selecting appropriate experimental designs that faithfully mimic precise clinical scenarios. Here, we review the current role of SBRT and the scope of pre-clinical armamentarium at our disposal to improve successful clinical translation of pre-clinical research in the radiation oncology of NSCLC.