Risk of Late toxicity in men receiving dose-escalated hypofractionated intensity modulated prostate radiation therapy: Results from a randomized trial

Karen E. Hoffman, K. Ranh Voong, Thomas J. Pugh, Heath Skinner, Lawrence B. Levy, Vinita Takiar, Seungtaek Choi, Weiliang Du, Steven J. Frank, Jennifer Johnson, James Kanke, Rajat J. Kudchadker, Andrew K. Lee, Usama Mahmood, Sean E. McGuire, Deborah A. Kuban

Research output: Contribution to journalArticle

Abstract

Objective To report late toxicity outcomes from a randomized trial comparing conventional and hypofractionated prostate radiation therapy and to identify dosimetric and clinical parameters associated with late toxicity after hypofractionated treatment. Methods and Materials Men with localized prostate cancer were enrolled in a trial that randomized men to either conventionally fractionated intensity modulated radiation therapy (CIMRT, 75.6 Gy in 1.8-Gy fractions) or to dose-escalated hypofractionated IMRT (HIMRT, 72 Gy in 2.4-Gy fractions). Late (≥90 days after completion of radiation therapy) genitourinary (GU) and gastrointestinal (GI) toxicity were prospectively evaluated and scored according to modified Radiation Therapy Oncology Group criteria. Results 101 men received CIMRT and 102 men received HIMRT. The median age was 68, and the median follow-up time was 6.0 years. Twenty-eight percent had low-risk, 71% had intermediate-risk, and 1% had high-risk disease. There was no difference in late GU toxicity in men treated with CIMRT and HIMRT. The actuarial 5-year grade ≥2 GU toxicity was 16.5% after CIMRT and 15.8% after HIMRT (P=.97). There was a nonsignificant numeric increase in late GI toxicity in men treated with HIMRT compared with men treated with CIMRT. The actuarial 5-year grade ≥2 GI toxicity was 5.1% after CIMRT and 10.0% after HIMRT (P=.11). In men receiving HIMRT, the proportion of rectum receiving 36.9 Gy, 46.2 Gy, 64.6 Gy, and 73.9 Gy was associated with the development of late GI toxicity (P<.05). The 5-year actuarial grade ≥2 GI toxicity was 27.3% in men with R64.6Gy ≥ 20% but only 6.0% in men with R64.6Gy < 20% (P=.016). Conclusions Dose-escalated IMRT using a moderate hypofractionation regimen (72 Gy in 2.4-Gy fractions) can be delivered safely with limited grade 2 or 3 late toxicity. Minimizing the proportion of rectum that receives moderate and high dose decreases the risk of late rectal toxicity after this hypofractionation regimen.

Original languageEnglish (US)
Pages (from-to)1074-1084
Number of pages11
JournalInternational Journal of Radiation Oncology Biology Physics
Volume88
Issue number5
DOIs
StatePublished - Apr 1 2014

ASJC Scopus subject areas

  • Radiation
  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Cancer Research

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    Hoffman, K. E., Voong, K. R., Pugh, T. J., Skinner, H., Levy, L. B., Takiar, V., Choi, S., Du, W., Frank, S. J., Johnson, J., Kanke, J., Kudchadker, R. J., Lee, A. K., Mahmood, U., McGuire, S. E., & Kuban, D. A. (2014). Risk of Late toxicity in men receiving dose-escalated hypofractionated intensity modulated prostate radiation therapy: Results from a randomized trial. International Journal of Radiation Oncology Biology Physics, 88(5), 1074-1084. https://doi.org/10.1016/j.ijrobp.2014.01.015