Patient-reported urinary incontinence after radiotherapy for prostate cancer: Quantifying the dose–effect

Cozzarini, C.; Rancati, T.; Palorini, F.; Avuzzi, B.; Garibaldi, E.; Balestrini, Damiano; Cante, Domenico; Muñoz, Fernándo; Franco, Pierfrancesco; Girelli, G.; Sini, C.; Vavassori, V.; Valdagni, Riccardo; Fiorino, Claudio

doi:10.1016/j.radonc.2017.07.029

Cited by 25 publications

(25 citation statements)

References 28 publications

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“…Repeating the analyses using a considerably lower α/β value, i.e. 0.8Gy, [18], did neither result in any identified dose-response relationship for late GU toxicity or Pollakiuria. Thus, these results suggest that mitigation of late GU toxicity likely requires identification of the associated critical structure(s) [9,19] rather than focusing on the bladder.…”

Section: Discussionmentioning

confidence: 87%

Tolerance doses for late adverse events after hypofractionated radiotherapy for prostate cancer on trial NRG Oncology/RTOG 0415

Thor

Deasy

Paulus

et al. 2019

Radiotherapy and Oncology

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Purpose/Objective: Hypofractionated radiotherapy (HRT) regimens for prostate cancer are emerging, but tolerance doses for late adverse events are scarce. The purpose of this study is to define dose-volume predictors for late gastrointestinal and genitourinary (GI and GU) toxicities after HRT in the multi-center NRG/RTOG 0415 low-risk prostate cancer trial (N=521). Material/methods: Treatment in the studied HRT arm was delivered as 70Gy at 2.5Gy/fraction with 3D-CRT/IMRT (N=108/413). At a median follow-up of 5.9 years, the crude late ≥Grade 2 GI and GU toxicities were 19% and 29%, respectively. For modeling, the complete HRT cohort was randomly split into training and validation (70% and 30%; preserved toxicity rates). Within training, dose-response modeling was based on dose-volume cut-points (EQD2Gy; bladder/ rectum: α/β=6Gy/3Gy), age, acute ≥Grade 2 toxicity, and treatment technique using univariate and multivariate logistic regression on bootstrapping (UVA and MVA). Candidate predictors were determined at p≤0.05, and the selected MVA models were explored on validation where model generalizability was judged if the area under the receiver-operating curve in validation (AUC validation) was within AUC training ±SD with p≤0.05, and with an Hosmer-Lemeshow p-value (p HL)>0.05. Results: Three candidate predictors were suggested for late GI toxicity: the minimum dose to the hottest 5% rectal volume (D5%[Gy]), the absolute rectal volume <35Gy, and acute GI toxicity (AUC=0.59-0.63; p=0.02-0.04). The two generalizable MVA models, i.e.. D5%[Gy] with or without acute GI toxicity (AUC validation =0.64. 0.65; p=0.01, 0.03; p HL =0.45-0.56), suggest that reducing late GI toxicity from 20% to 10% would require reducing D5%[Gy] from ≤65Gy to ≤62Gy (logistic function argument: 17+(0.24D5%[Gy])). Acute GU toxicity showed only a trend to predict late GU toxicity (AUC training =0.57; p=0.07). Conclusion: Uate GI toxicity, following moderate HRT for low-risk prostate cancer, increases with higher doses to small rectal volumes. This work provides quantitative evidence that limiting small rectal dose 'hotspots' in clinical practice of such HRT regimens is likely to further reduce the associated rates of GI toxicity.

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Section: Discussionmentioning

confidence: 87%

Tolerance doses for late adverse events after hypofractionated radiotherapy for prostate cancer on trial NRG Oncology/RTOG 0415

Thor

Deasy

Paulus

et al. 2019

Radiotherapy and Oncology

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“…Although acute toxicities were assessed, this study was limited to a short follow up and did not account for the impact of pretreatment clinical procedures which may have been a contributing factor. For instance, previous transurethral resection of the prostate (TURP) is one of the main independent predictors for late urinary incontinence elicited from a multivariate-analysis by Cozarini et al [22]. Moving forward, this study has suggested a minimum threshold of bladder-filling and volume to minimise intra-fraction motion.…”

Section: Limitations and Future Directionsmentioning

confidence: 82%

Reduction of intra-fraction prostate motion – Determining optimal bladder volume and filling for prostate radiotherapy using daily 4D TPUS and CBCT

Pang

Knight

Hussain

et al. 2018

Technical Innovations & Patient Support in Radiation Oncolo

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Background and purpose: Inconsistent bladder and rectal volumes have been associated with motion uncertainties during prostate radiotherapy. This study investigates the impact of these volumes to determine the optimal bladder volume. Materials and methods: 60 patients from two Asian hospitals were recruited prospectively. 1887 daily cone-beam computed tomography (CBCT) images were analysed. Intra-fraction motion of the prostate was monitored real-time using a four-dimension transperineal ultrasound (4D TPUS) Clarity Ò system. The impact of planned bladder volume, adequacy of daily bladder filling, and rectum volume on mean intra-fraction motion of the prostate was analysed. Patients' ability to comply with the full bladder hydration protocol and level of frustration was assessed using a questionaire. Acute side effects were assessed using the Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 and quality of life (QoL) assessed using the International Prostate Symptom Score (IPSS). Results: The mean (SD) bladder and rectum volumes achieved during daily treatment were 139.7 cm 3 (82.4 cm 3) and 53.3 cm 3 (18 cm 3) respectively. Mean (SD) percentage change from planned CT volumes in bladder volume was reduced by 8.2% (48.7%) and rectum volume was increased by 12.4% (42.2%). Linear Mixed effect model analysis revealed a reduction in intra-fraction motion in both the Sup/Inf (p = 0.008) and Ant/Post (p = 0.0001) directions when the daily bladder was filled between 82 and 113% (3rd Quartiles) of the planned CT volumes. A reduction in intra-fraction motion of the prostate in the Ant/Post direction (z-plane) (p = 0.03) was observed when the planned bladder volume was greater than 200 ml. Patients complied well with the hydration protocol with minimal frustration (mean (SD) scores of 2.1 (1.4) and 1.8 (1.2) respectively). There was a moderate positive correlation (0.496) between mean bladder volume and IPSS reported post-treatment urinary straining (p = 0.001). Conclusions: A planned bladder volume >200 cm 3 and daily filling between 82 and 113%, reduced intrafraction motion of the prostate. The hydration protocol was well tolerated.

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“…DUE-01 is a prospective multi-centre cohort study which enrolled 539 patients with localized prostate cancer treated with radical radiotherapy between 2010 and 2014 [23,24]; no patient had a prostatectomy. Twenty-seven patients were withdrawn before radiotherapy.…”

Section: Patients and Endpointsmentioning

confidence: 99%

Patterns in ano-rectal dose maps and the risk of late toxicity after prostate IMRT

et al. 2019

Self Cite

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The aim of this work was to determine how the spatial pattern of dose in the ano-rectal wall is related to late gastro-intestinal toxicity for prostate cancer patients treated with mainly IMRT. Patients and methods: Patients from the DUE-01 multicentre study with patient-reported (prospective) follow-up and available dosimetric data were included. Conventionally fractionated patients received 74-80 Gy and hypofractionated patients received 65-75.2 Gy. A large majority of the patients were treated with intensity-modulated radiotherapy (IMRT). Dose-surface maps (DSMs) for the anal canal and rectum as a single structure, and for the anal canal and the rectum separately, were co-registered rigidly in two dimensions and, for the patients with and without toxicity, respectively, the mean value of the dose in each pixel was calculated. A pixel-wise t-test was used to highlight the anatomical areas where there was a significant difference between the 'mean dose maps' of each group. Univariate models were also fitted to a range of spatial parameters. The endpoints considered were a mean grade !1 late fecal incontinence and a maximum grade !2 late rectal bleeding. Results: Twenty-six out of 213 patients had fecal incontinence, while 21/225 patients had rectal bleeding. Incontinence was associated with a higher dose in the caudal region of the anal canal; the most relevant spatial parameter was the lateral extent of the low and medium isodoses (5-49 Gy in EQD2). Bleeding was associated with high isodoses reaching the posterior rectal wall. The spatial dose parameters with the highest AUC value (.69) were the lateral extent of the 60-70 Gy isodoses. Conclusions: To avoid fecal incontinence it is important to limit the portion of the anal canal irradiated. Our analysis confirms that rectal bleeding is a function of similar spatial dose parameters for patients treated with IMRT, compared to previous studies on patients treated with three-dimensional conformal radiotherapy.

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Patient-reported urinary incontinence after radiotherapy for prostate cancer: Quantifying the dose–effect

Cited by 25 publications

References 28 publications

Tolerance doses for late adverse events after hypofractionated radiotherapy for prostate cancer on trial NRG Oncology/RTOG 0415

Tolerance doses for late adverse events after hypofractionated radiotherapy for prostate cancer on trial NRG Oncology/RTOG 0415

Reduction of intra-fraction prostate motion – Determining optimal bladder volume and filling for prostate radiotherapy using daily 4D TPUS and CBCT

Patterns in ano-rectal dose maps and the risk of late toxicity after prostate IMRT

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