Modeling precision genomic-based radiation dose response in rectal cancer

Future Oncol. 2020 Oct;16(30):2411-2420. doi: 10.2217/fon-2020-0060. Epub 2020 Jul 20.

Abstract

Aim: Genomic-based risk stratification to personalize radiation dose in rectal cancer. Patients & methods: We modeled genomic-based radiation dose response using the previously validated radiosensitivity index (RSI) and the clinically actionable genomic-adjusted radiation dose. Results: RSI of rectal cancer ranged from 0.19 to 0.81 in a bimodal distribution. A pathologic complete response rate of 21% was achieved in tumors with an RSI <0.31 at a minimal genomic-adjusted radiation dose of 29.76 when modeling RxRSI to the commonly prescribed physical dose of 50 Gy. RxRSI-based dose escalation to 55 Gy in tumors with an RSI of 0.31-0.34 could increase pathologic complete response by 10%. Conclusion: This study provides a theoretical platform for development of an RxRSI-based prospective trial in rectal cancer.

Keywords: chemoradiation therapy; genomic-adjusted radiation dose; pathologic response; radiosensitivity; rectal cancer.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Combined Modality Therapy / methods
  • Dose-Response Relationship, Radiation
  • Female
  • Gene Expression Profiling
  • Genomics* / methods
  • Humans
  • Male
  • Middle Aged
  • Neoplasm Grading
  • Neoplasm Metastasis
  • Neoplasm Staging
  • Odds Ratio
  • Precision Medicine* / methods
  • Radiation Tolerance / genetics
  • Radiotherapy Dosage*
  • Rectal Neoplasms / diagnosis
  • Rectal Neoplasms / genetics*
  • Rectal Neoplasms / mortality
  • Rectal Neoplasms / radiotherapy*
  • Transcriptome
  • Treatment Outcome