Cluster model analysis of late rectal bleeding after IMRT of prostate cancer: a case-control study.

Cluster models are newly developed normal-tissue complication probability models in which the spatial aspects of radiation-induced injury are taken into account by considering the size of spatially contiguous aggregates of damaged tissue units. The purpose of this study was to test the validity of a two-dimensional cluster model of late rectal toxicity based on maximum cluster size of damage to rectal surface. A paired case-control study was performed in which each of 9 patients experiencing Grade 2 or higher late rectal toxicity after intensity-modulated radiation therapy of localized prostate cancer was paired with a patient having a similar rectal dose-surface histogram but free of rectal toxicity. Numeric simulations were performed to determine the distribution of maximum cluster size on each rectal surface for each of many different choices of possible model parameters. Model parameters were found for which patients with rectal toxicity were consistently more likely to have a significantly larger mean maximum cluster size than their matched controls. These parameter values correspond to a 50% probability of tissue-unit damage at doses near 30 Gy. This study suggests that a cluster model based on maximum cluster size of damage to rectal surface successfully incorporates spatial information beyond that contained in the rectal dose-surface histogram and may therefore provide a useful new tool for predicting rectal normal-tissue complication probability after radiotherapy.