Normal tissue complication probability models for prospectively scored late rectal and urinary morbidity after proton therapy of prostate cancer

BACKGROUND AND PURPOSE: Photons and protons have fundamentally different properties, i.e. protons have a reduced dose bath but a higher relative biological effectiveness. Photon-based normal tissue complication probability (NTCP) models may therefore not immediately be applicable to proton therapy (PT). The aim was to derive parameters of the Lyman-Kutcher-Burman (LKB) NTCP model using prospectively recorded late morbidity data from PT, focusing on rectal morbidity and prostate cancer. MATERIALS AND METHODS: Prospectively collected data were available for 1151 prostate cancer patients treated with passive scattering PT and prescribed target doses of 78–82 Gy (RBE = 1.1) in 2 Gy fractions. Morbidity data (CTCAE v3.0) consisted of two alternative late grade 2 rectal bleeding endpoints: Medical Grade2A (GR2A) and procedural Grade2B (GR2B), as well as late grade 3 + urinary morbidity. GR2A + 2B were observed in 156/1047 patients (15%), GR2B in 45/1047 patients (4%), and urinary grade 3 + in 51/1151 patients (4%). LKB NTCP model parameters (D50, m, and n) were derived by maximum likelihood estimation. RESULTS: For the rectum/rectal wall the volume parameter n was low (0.07–0.14) for both GR2A + 2B and GR2B, as was the m parameter (range: 0.16–0.20). For the bladder/bladder wall both parameters were high (n-range: 0.20–0.36; m-range: 0.32–0.36). D50 parameters were higher for GR2B of the rectum/rectal wall (95.9–98.0 Gy) and bladder/bladder wall (118.1–119.9 Gy), but lower for GR2A2B (71.7–73.6 Gy). CONCLUSION: PT specific LKB NTCP model parameters were derived from a population of more than 1000 patients. The D50 parameter differed for all structures and endpoints and deviated from typical photon-based LKB model values.