Int J Radiat Oncol Biol Phys
Tucker S, Dong L, Michalski J, Bosch W, Winter K, Cox J, Purdy J, Mohan R
Department of Bioinformatics and Computational Biology, University of Texas M. D. Anderson Cancer Center, Houston, TX.
PURPOSE: To investigate whether the volumes of rectum exposed to intermediate doses, from 30 to 50 Gy, contribute to the risk of Grade ≥2 late rectal toxicity among patients with prostate cancer receiving radiotherapy. METHODS AND MATERIALS: Data from 1009 patients treated on Radiation Therapy Oncology Group protocol 94-06 were analyzed using three approaches. First, the contribution of intermediate doses to a previously published fit of the Lyman-Kutcher-Burman (LKB) normal tissue complication probability (NTCP) model was determined. Next, the extent to which intermediate doses provide additional risk information, after taking the LKB model into account, was investigated. Third, the proportion of rectum receiving doses higher than a threshold, VDose, was computed for doses ranging from 5 to 85 Gy, and a multivariate Cox proportional hazards model was used to determine which of these parameters were significantly associated with time to Grade ≥2 late rectal toxicity. RESULTS: Doses <60 Gy had no detectable impact on the fit of the LKB model, as expected on the basis of the small estimate of the volume parameter (n = 0.077). Furthermore, there was no detectable difference in late rectal toxicity among cohorts with similar risk estimates from the LKB model but with different volumes of rectum exposed to intermediate doses. The multivariate Cox proportional hazards model selected V75 as the only value of VDose significantly associated with late rectal toxicity. CONCLUSIONS: There is no evidence from these data that intermediate doses influence the risk of Grade ≥2 late rectal toxicity. Instead, the critical doses for this endpoint seem to be ≥75 Gy. It is hypothesized that cases of Grade ≥2 late rectal toxicity occurring among patients with V75 less than approximately 12% may be due to a "background" level of risk, likely due mainly to biological factors.