Physics and Imaging in Radiation Oncology 23 (2022) 97–102 Available online 16 July 2022 2405-6316/© 2022 The Authors. Published by Elsevier B.V. on behalf of European Society of Radiotherapy & Oncology. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). Original Research Article Dose-volume analysis of planned versus accumulated dose as a predictor for late gastrointestinal toxicity in men receiving radiotherapy for high-risk prostate cancer Ashley L.K Ong a, b, * , Kellie Knight b , Vanessa Panettieri b, c , Mathew Dimmock b, d , Jeffrey K.L Tuan a , Hong Qi Tan a , Caroline Wright b a National Cancer Centre Singapore, Division of Radiation Oncology, Singapore b Monash University, Department of Medical Imaging and Radiation Sciences, Clayton, Australia c Alfred Hospital, Alfred Health Radiation Oncology, Melbourne, Australia d Keele University, School of Allied Health Professions, Staffordshire, UK A R T I C L E INFO Keywords: Accumulated dose Predictive model Gastrointestinal toxicity High-risk prostate Volumetric image-guidance ABSTRACT Background and purpose: Signifcant dose deviations have been reported between planned (D P ) and accumulated (D A ) dose in prostate radiotherapy. This study aimed to develop multivariate analysis (MVA) models associating Grade 1 and 2 gastrointestinal (GI) toxicity with clinical and D P or D A dosimetric variables separately. Materials and methods: Dose volume (DV) metrics were compared between D A and D P for 150 high-risk prostate cancer patients. MV models were generated from signifcant clinical and dosimetric variables (p < 0.05) at univariate level. Dose-based-region of interest (DB-ROI) metrics were included. Model performance was measured, and additional subgroup analysis were performed. Results: Rectal D A demonstrated a higher intermediate-high dose (V 30-65 Gy and DB-ROI at 15–50 mm) compared to D P . Conversely, at the very high dose region, rectal D A (V 75 Gy and DB-ROI at 5–10 mm) were signifcantly lower. In MVA, rectal DB-ROI at 10 mm was predictive for Grade ≥ 1 GI toxicity for D A and D P . Age, rectal D A for D 0.03 cc , and rectal D P for DB-ROI 10 mm were predictors for Grade 2 GI toxicity. Subgroup analysis revealed that patients ≥ 72 years old and a rectal D A of ≥ 78.2 Gy were highly predictive of Grade 2 GI toxicity. Conclusions: The dosimetric impact of a higher dose rectal dose in D A due to volumetric changes was minimal and was not predictive of detrimental clinical toxicity apart from rectal D 0.03 cc ≥ 78.2 Gy for Grade 2 GI toxicity. The use of the DB-ROI method can provide equivalent predictive power as the DV method in toxicity prediction. 1. Introduction External beam radiotherapy combined with androgen deprivation therapy is the recommended clinical management for locally advanced high-risk prostate cancer (HR-PCa) [1]. As prostate cancer exhibits a low α/β value (1.5 Gy) which is comparable to that of late responding tissues [2], there’s a shift towards the use of dose escalation and hypofractio- nated regimens to improve the overall therapeutic ratio [3,4]. This is especially critical for HR-PCa because of the high likelihood of mutation to a lethal phenotype that could reduce the biochemical and local con- trol rate [5]. However, the drawback of these treatment schemes is often associated with a decline in patients’ quality of life as the incidence of reported gastrointestinal (GI) toxicity remains signifcant despite the use of advanced radiotherapy technologies [6,7]. Signifcant volumetric variations of the organs at risk (OARs) that could affect the actual delivered dose during prostate RT have been reported [8,9]. Small cohort studies demonstrated signifcant dose dif- ferences between accumulated dose (D A ) obtained from either daily megavoltage computed tomography (MVCT) or repeated CT scans and planned dose (D P ) [10,11]. Majority of the large cohort studies focusing on the correlations between the rectal dose with the risk of late GI complications were mainly based on the dose distributions obtained with three-dimensional conformal radiation therapy (3D-CRT) tech- niques [12,13]. Although some work has been done on evaluating the risk of GI toxicity with D A generated based on patients’ cone-beam computed tomography (CBCT) scans, they were mainly performed on * Corresponding author at: National Cancer Centre Singapore, Division of Radiation Oncology, 11 Hospital Crescent, Singapore 169610, Singapore. Email address: ashley.ong.l.k@nccs.com.sg (A.L.K. Ong) Contents lists available at ScienceDirect Physics and Imaging in Radiation Oncology journal homepage: www.sciencedirect.com/journal/physics-and-imaging-in-radiation-oncology https://doi.org/10.1016/j.phro.2022.07.001 Received 20 March 2022; Received in revised form 2 July 2022; Accepted 6 July 2022