Advances in the field of developing biomarkers for re-irradiation: a how-to guide to small, powerful data sets and artificial intelligence.

Introduction: Patient selection remains challenging as the clinical use of re-irradiation (re-RT) increases. Re-RT data is limited to retrospective studies and small prospective single-institution reports, resulting in small, heterogenous data sets. Validated prognostic and predictive biomarkers are derived from large-volume studies with long-term follow-up. This review aims to examine existing re-RT publications and available data sets and discuss strategies using artificial intelligence (AI) to approach small data sets to optimize the use of re-RT data. Methods: Re-RT publications were identified where associated public data was present. The existing literature on small data sets to identify biomarkers was also explored. Results: Publications with associated public data were identified, with glioma and nasopharyngeal cancers emerging as the most common tumor sites where the use of re-RT was the primary management approach. Existing and emerging AI strategies have been used to approach small data sets including data generation, augmentation, discovery, and transfer learning. Conclusions: Further data is needed to generate adaptive frameworks, improve the collection of specimens for molecular analysis, and improve the interpretability of results in re-RT data.