Multivariate normal tissue complication probability models for rectal and bladder morbidity in prostate cancer patients treated with proton therapy.

BACKGROUND AND PURPOSE

Normal tissue complication probability (NTCP) models applied for model-based patient selection to proton therapy (PT) have usually been derived using dose/volume histogram (DVH) parameters from photon-based radiotherapy. This study aimed to derive PT-specific multivariate NTCP models that also accounted for the spatial dose distribution (rectum only) as well as non-dose/volume related factors.

MATERIALS AND METHODS

The study included rectum and bladder DVHs, 2D rectal dose maps and relevant patient/treatment characteristics from 1151 prostate cancer cases treated with PT. Prospectively scored Grade 2 late rectal bleeding (CTCAE v3.0, also procedural interventions separately) (n = 156 (15%)) and Grade 3+ GU morbidity (n = 51 (4%)) were entered into a multivariate logistic regression analysis. Model evaluation included assessment of the area under the receiver operating characteristic curve (AUC).

RESULTS

Anticoagulant use was a dominant predictor, chosen in four of the six rectum models and in the bladder model. Age was a dominant predictor in all procedural only rectum models while prostate volume, bladder D5% and V75Gy were predictors in the bladder model. The selection frequency of the dose/volume predictors varied widely, where the percentage of the anterior rectum surface receiving >=75 Gy was the most robust. AUC values ranged from 0.58 to 0.70 across all models, with no clear difference between the DVH- and spatial-based models for the rectum.

CONCLUSION

Anticoagulant use and age were the most prominent predictors in the NTCP models. V75Gy of the rectal wall and the bladder was a predictor in the DVH-based models of the rectum and bladder respectively.