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

• Published in: Physics and imaging in radiation oncology 2021-10, Vol.20, p.62-68
• Main Authors: Pedersen, Jesper, Liang, Xiaoying, Bryant, Curtis, Mendenhall, Nancy, Li, Zuofeng, Muren, Ludvig P.
• Format: Article
• Language: English
• Subjects: Biological modelling; Original; Prostate; Proton therapy
• ISSN: 2405-6316; 2405-6316
• DOI: 10.1016/j.phro.2021.10.004

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. 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. 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). 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.