Normal tissue complication probability modeling for late rectal bleeding after conventional or hypofractionated...

To develop a single NTCP model for grade ≥ 2 late rectal bleeding (G2 LRB) after conventional or hypofractionated radiotherapy for prostate cancer.

The development dataset consisted of prostate cancer patients (n = 656) previously randomized to conventional (39 x 2 Gy) or hypofractionated (19 x 3.4 Gy) external beam radiotherapy with N = 89 G2 LRB cases. Candidate predictors were obtained from literature. We fitted five separate logistic regression models to the data, each with one of the following dose parameters as candidate predictors in biological effective dose (BED), assuming α/β = 3 Gy: Equivalent uniform dose (EUD) with n = 0.1, EUD with n = 0.2, the relative volume receiving ≥ 111.9 Gy in BED (V111.9, the equivalent of physical V70 for a conventional schedule), minimum BED to the hottest 0.1 cm³ (D_0.1cm3) or 2 cm³ (D_2cm3). Previous abdominal surgery was included in every model and fractionation schedule was tested as predictor in each model. A sensitivity analysis was performed by varying the α/β-ratio, n and dose-volume cutoff.

The pre-selected candidate dosimetric predictor and previous abdominal surgery were significantly associated with the outcome in all five models. Fractionation schedule was eliminated by the backward scheme in only the EUD (n = 0.1), D_0.1cm3 and D_2cm3-based models. In internal validation these models showed AUC's of 0.64, 0.60 & 0.62, respectively. The sensitivity analyses showed that EUD models with n ≥ 0.15 and / or α/β ≥ 4 Gy failed, and EUD models based on α/β = 2 Gy with n = 0.05-0.2 showed good fits as well.

Our trial data set with different fractionation schedules offered the unique possibility to generate unbiased BED-based models. EUD (n = 0.1), D_0.1cm3 and D_2cm3 performed overall best in predicting G2 LRB; with α/β = 2 Gy equally good models were obtained. External validation is required to confirm our results.