Patients ≥ 65 years had a worse outcome in comparison to younger patients. Late vaginal, rectal and bladder toxicities were similar in the three groups, although an increase of severe late small bowel toxicity led to IMRT in patients ≥ 80 years. Further larger studies are needed including quality of life analysis in patients ≥ 80 years.

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The top ranked genes by magnitude of change at week 5 included MUC2, PARP10 and PIK3CA. Pathway analysis of these top ranked genes mapped to key radiation response pathways including regulation of the G1/S transition. Conclusion:We validated this method of performing serial WES over the course of CRT in 2 independent prospective patient cohorts, highlighting the robustness of our novel noninvasive technique. This allowed for the identification of a panel of potential genes involved in CRT resistance. Future directions include examination of dynamic changes in copy number variation, indels, and tumor mutational burden towards a comprehensive analysis of clinically relevant drivers of CRT resistance. This may allow future targeted treatment for patients with a radioresistant genetic profile, or concurrent targeted therapy for tumors with actionable mutations.

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