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Predictive modelling for late rectal and urinary toxicities after prostate radiotherapy using planned and delivered dose.

Knight, K; Panettieri, V; Dimmock, M; Tuan, JKL; Tan, HQ; Wright, C; Ong, ALK

Predictive modelling for late rectal and urinary toxicities after prostate radiotherapy using planned and delivered dose. Thumbnail


K Knight

V Panettieri

JKL Tuan

HQ Tan

C Wright



BACKGROUND AND PURPOSE: Normal tissue complication probability (NTCP) parameters derived from traditional 3D plans may not be ideal in defining toxicity outcomes for modern radiotherapy techniques. This study aimed to derive parameters of the Lyman-Kutcher-Burman (LKB) NTCP model using prospectively scored clinical data for late gastrointestinal (GI) and genitourinary (GU) toxicities for high-risk prostate cancer patients treated using volumetric-modulated-arc-therapy (VMAT). Dose-volume-histograms (DVH) extracted from planned (DP) and accumulated dose (DA) were used. MATERIAL AND METHODS: DP and DA obtained from the DVH of 150 prostate cancer patients with pelvic-lymph-nodes irradiation treated using VMAT were used to generate LKB-NTCP parameters using maximum likelihood estimations. Defined GI and GU toxicities were recorded up to 3-years post RT follow-up. Model performance was measured using Hosmer-Lemeshow goodness of fit test and the mean area under the receiver operating characteristics curve (AUC). Bootstrapping method was used for internal validation. RESULTS: For mild-severe (Grade =1) GI toxicity, the model generated similar parameters based on DA and DP DVH data (DA-D50:71.6 Gy vs DP-D50:73.4; DA-m:0.17 vs DP-m:0.19 and DA/P-n 0.04). The 95% CI for DA-D50 was narrower and achieved an AUC of >0.6. For moderate-severe (Grade =2) GI toxicity, DA-D50 parameter was higher and had a narrower 95% CI (DA-D50:77.9 Gy, 95% CI:76.4-79.6 Gy vs DP-D50:74.6, 95% CI:69.1-85.4 Gy) with good model performance (AUC>0.7). For Grade =1 late GU toxicity, D50 and n parameters for DA and DP were similar (DA-D50: 58.8 Gy vs DP-D50: 59.5 Gy; DA-n: 0.21 vs DP-n: 0.19) with a low AUC of<0.6. For Grade =2 late GU toxicity, similar NTCP parameters were attained from DA and DP DVH data (DA-D50:81.7 Gy vs DP-D50:81.9 Gy; DA-n:0.12 vs DP-n:0.14) with an acceptable AUCs of >0.6. CONCLUSIONS: The achieved NTCP parameters using modern RT techniques and accounting for organ motion differs from QUANTEC reported parameters. DA-D50 of 77.9 Gy for GI and DA/DP-D50 of 81.7-81.9 Gy for GU demonstrated good predictability in determining the risk of Grade =2 toxicities especially for GI derived D50 and are recommended to incorporate as part of the DV planning constraints to guide dose escalation strategies while minimising the risk of toxicity.


Knight, K., Panettieri, V., Dimmock, M., Tuan, J., Tan, H., Wright, C., & Ong, A. (2022). Predictive modelling for late rectal and urinary toxicities after prostate radiotherapy using planned and delivered dose. Frontiers in oncology, 1084311 - ?.

Acceptance Date Nov 30, 2022
Publication Date Dec 16, 2022
Journal Frontiers Oncology
Print ISSN 2234-943X
Publisher Frontiers Media
Pages 1084311 - ?
Keywords normal tissue complication probability (NTCP), Lyman-Kutcher-Burman (LKB) model, accumulated dose, high-risk prostate cancer, image-guided radiotherapy (IGRT), late toxicity complications
Publisher URL
Additional Information © 2022 Ong, Knight, Panettieri, Dimmock, Tuan, Tan and Wright. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.