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Modeling precision genomic-based radiation dose response in rectal cancer.

Zhigang YuanMarissa FrazerKamran A AhmedSyeda Mahrukh Hussnain NaqviMichael J SchellSeth FelderJulian SanchezSophie DessureaultIman ImaniradRichard D KimJavier F Torres-RocaSarah E HoffeJessica M Frakes
Published in: Future oncology (London, England) (2020)
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.
Keyphrases
  • rectal cancer
  • locally advanced
  • copy number
  • neoadjuvant chemotherapy
  • physical activity
  • mental health
  • randomized controlled trial
  • squamous cell carcinoma
  • open label
  • dna methylation