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Title: Investigation of bladder dose and volume factors influencing late urinary toxicity after external beam radiotherapy for prostate cancer

Abstract

Background: We sought to identify the bladder dose-volume factors associated with an increased risk of late urinary toxicity among prostate cancer patients treated with radiotherapy. Methods and Materials: This retrospective analysis included data from 128 prostate cancer patients treated on protocol with 2 Gy/fraction to 46 Gy followed by a boost to 78 Gy. The endpoint for this analysis was Grade 1 or greater late genitourinary (GU) toxicity occurring within two years of treatment. The Lyman-Kutcher-Burman, mean dose, threshold dose, and hottest volume models were fitted to the toxicity data using the maximum likelihood method. Results: Model fits based on dose-volume histograms tended to fit the toxicity data better than models based on dose-wall histograms. The hottest volume (hotspot) model was found to be the best-fitting model investigated. The best fit was for the hottest 2.9% of bladder (95% CI, 1.1-6.8%). This model has an area under the receiver operating characteristic curve of 0.74. The hotspot model separated the patients into clinically meaningful subgroups with {approx}25% of the patients who received <78 Gy to the hottest 2.9% of bladder had GU toxicity at eight years compared with {approx}50% when the dose was {>=}78 Gy (p = 0.002). Conclusion: This providesmore » the first evidence supporting that bladder 'hotspots' are related to GU toxicity within two years after external beam radiotherapy for prostate cancer. Confirming data are needed from other investigators. Particular attention should be given to hotspots higher than 78 Gy in bladder in radiation treatment planning.« less

Authors:
 [1];  [2];  [3];  [4];  [4];  [4];  [3];  [2];  [3];  [4]
  1. Department of Radiation Oncology, University of Texas M. D. Anderson Cancer Center, Houston, TX (United States). E-mail: mrcheung@mdanderson.org
  2. Department of Biostatistics and Applied Mathematics, University of Texas M. D. Anderson Cancer Center, Houston, TX (United States)
  3. Department of Radiation Physics, University of Texas M. D. Anderson Cancer Center, Houston, TX (United States)
  4. Department of Radiation Oncology, University of Texas M. D. Anderson Cancer Center, Houston, TX (United States)
Publication Date:
OSTI Identifier:
20944763
Resource Type:
Journal Article
Resource Relation:
Journal Name: International Journal of Radiation Oncology, Biology and Physics; Journal Volume: 67; Journal Issue: 4; Other Information: DOI: 10.1016/j.ijrobp.2006.10.042; PII: S0360-3016(06)03388-8; Copyright (c) 2007 Elsevier Science B.V., Amsterdam, Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
62 RADIOLOGY AND NUCLEAR MEDICINE; BLADDER; CARCINOMAS; HEALTH HAZARDS; MAXIMUM-LIKELIHOOD FIT; PATIENTS; PLANNING; PROSTATE; RADIOTHERAPY; THRESHOLD DOSE; TOXICITY

Citation Formats

Cheung, M. Rex, Tucker, Susan L., Dong Lei, Crevoisier, Renaud de, Lee, Andrew K., Frank, Steven, Kudchadker, Rajat J., Thames, Howard, Mohan, Radhe, and Kuban, Deborah. Investigation of bladder dose and volume factors influencing late urinary toxicity after external beam radiotherapy for prostate cancer. United States: N. p., 2007. Web. doi:10.1016/j.ijrobp.2006.10.042.
Cheung, M. Rex, Tucker, Susan L., Dong Lei, Crevoisier, Renaud de, Lee, Andrew K., Frank, Steven, Kudchadker, Rajat J., Thames, Howard, Mohan, Radhe, & Kuban, Deborah. Investigation of bladder dose and volume factors influencing late urinary toxicity after external beam radiotherapy for prostate cancer. United States. doi:10.1016/j.ijrobp.2006.10.042.
Cheung, M. Rex, Tucker, Susan L., Dong Lei, Crevoisier, Renaud de, Lee, Andrew K., Frank, Steven, Kudchadker, Rajat J., Thames, Howard, Mohan, Radhe, and Kuban, Deborah. Thu . "Investigation of bladder dose and volume factors influencing late urinary toxicity after external beam radiotherapy for prostate cancer". United States. doi:10.1016/j.ijrobp.2006.10.042.
@article{osti_20944763,
title = {Investigation of bladder dose and volume factors influencing late urinary toxicity after external beam radiotherapy for prostate cancer},
author = {Cheung, M. Rex and Tucker, Susan L. and Dong Lei and Crevoisier, Renaud de and Lee, Andrew K. and Frank, Steven and Kudchadker, Rajat J. and Thames, Howard and Mohan, Radhe and Kuban, Deborah},
abstractNote = {Background: We sought to identify the bladder dose-volume factors associated with an increased risk of late urinary toxicity among prostate cancer patients treated with radiotherapy. Methods and Materials: This retrospective analysis included data from 128 prostate cancer patients treated on protocol with 2 Gy/fraction to 46 Gy followed by a boost to 78 Gy. The endpoint for this analysis was Grade 1 or greater late genitourinary (GU) toxicity occurring within two years of treatment. The Lyman-Kutcher-Burman, mean dose, threshold dose, and hottest volume models were fitted to the toxicity data using the maximum likelihood method. Results: Model fits based on dose-volume histograms tended to fit the toxicity data better than models based on dose-wall histograms. The hottest volume (hotspot) model was found to be the best-fitting model investigated. The best fit was for the hottest 2.9% of bladder (95% CI, 1.1-6.8%). This model has an area under the receiver operating characteristic curve of 0.74. The hotspot model separated the patients into clinically meaningful subgroups with {approx}25% of the patients who received <78 Gy to the hottest 2.9% of bladder had GU toxicity at eight years compared with {approx}50% when the dose was {>=}78 Gy (p = 0.002). Conclusion: This provides the first evidence supporting that bladder 'hotspots' are related to GU toxicity within two years after external beam radiotherapy for prostate cancer. Confirming data are needed from other investigators. Particular attention should be given to hotspots higher than 78 Gy in bladder in radiation treatment planning.},
doi = {10.1016/j.ijrobp.2006.10.042},
journal = {International Journal of Radiation Oncology, Biology and Physics},
number = 4,
volume = 67,
place = {United States},
year = {Thu Mar 15 00:00:00 EDT 2007},
month = {Thu Mar 15 00:00:00 EDT 2007}
}
  • Purpose: To investigate the development of gastrointestinal (GI) toxicity, genitourinary (GU) toxicity, erectile dysfunction, and International Prostate Symptom Score (IPSS) resolution in a cohort of patients treated with external-beam radiotherapy (EBRT) followed by a brachytherapy pulsed dose rate (PDR) boost. Methods and Materials: Between 2002 and 2008, 110 patients were treated with 46-Gy EBRT followed by PDR brachytherapy (24.96-28.80 Gy). The investigated outcome variables, GI toxicity, GU toxicity, erectile dysfunction, and IPSS were prospectively scored at several time points during follow-up. Association between time (as continuous and categorical variable) and the outcome variables was assessed using generalized linear models. Results:more » No statistically significant association was found between time (continuous) and GI toxicity (odds ratio [OR], 0.97; 95% confidence interval [CI], 0.89-1.06), GU toxicity (OR, 0.97; 95% CI, 0.91-1.03), erectile dysfunction (OR, 1.06; 95% CI, 0.99-1.11), and IPSS (-0.11; 95% CI, -0.41-0.20). Also, no statistically significant association was found between these variables and time as a categorical variable. GU toxicity was associated with IPSS resolution (OR, 1.16; 95% CI, 1.09-1.24). Posttreatment IPSS was associated with pretreatment IPSS (0.52; 95% CI, 0.25-0.79). Conclusions: No accumulation of high-grade toxicity over time could be established for a group of patients treated with EBRT and PDR brachytherapy for prostate cancer, probably because high-grade late toxicity resolves with time. Also, differences in IPSS values among patients are smaller after treatment than before treatment.« less
  • Purpose: To evaluate the severity of genitourinary (GU) toxicity in high-dose-rate (HDR) brachytherapy combined with hypofractionated external beam radiotherapy (EBRT) for prostate cancer and to explore factors that might affect the severity of GU toxicity. Methods and Materials: A total of 100 Japanese men with prostate cancer underwent {sup 192}Ir HDR brachytherapy combined with hypofractionated EBRT. Mean (SD) dose to 90% of the planning target volume was 6.3 (0.7) Gy per fraction of HDR. After 5 fractions of HDR treatment, EBRT with 10 fractions of 3 Gy was administrated. The urethral volume receiving 1-15 Gy per fraction in HDR brachytherapymore » (V1-V15) and the dose to at least 5-100% of urethral volume in HDR brachytherapy (D5-D100) were compared between patients with Grade 3 toxicity and those with Grade 0-2 toxicity. Prostate volume, patient age, and International Prostate Symptom Score were also compared between the two groups. Results: Of the 100 patients, 6 displayed Grade 3 acute GU toxicity, and 12 displayed Grade 3 late GU toxicity. Regarding acute GU toxicity, values of V1, V2, V3, and V4 were significantly higher in patients with Grade 3 toxicity than in those with Grade 0-2 toxicity. Regarding late GU toxicity, values of D70, D80, V12, and V13 were significantly higher in patients with Grade 3 toxicity than in those with Grade 0-2 toxicity. Conclusions: The severity of GU toxicity in HDR brachytherapy combined with hypofractionated EBRT for prostate cancer was relatively high. The volume of prostatic urethra was associated with grade of acute GU toxicity, and urethral dose was associated with grade of late GU toxicity.« less
  • Purpose: To identify factors predictive for chronic urinary toxicity secondary to high-dose adaptive three-dimensional conformal radiation. Methods and Materials: From 1999 to 2002, 331 consecutive patients with clinical Stage II-III prostate cancer were prospectively treated (median dose, 75.6 Gy). The bladder was contoured, and the bladder wall was defined as the outer 3 mm of the bladder solid volume. Toxicity was quantified according to the National Cancer Institute Common Toxicity Criteria 2.0. Median follow-up was 1.6 years. Results: The 3-year rates of Grade {>=}2 and Grade 3 chronic urinary toxicity were 17.0% and 3.6%, respectively. Prostate volume, confidence-limited patient-specific planningmore » target volume, bladder wall volume, and acute urinary toxicity were all found to be accurate predictors for chronic urinary toxicity. The volume of bladder wall receiving {>=}30 Gy (V30) and {>=}82 Gy (V82), along with prostate volume, were all clinically useful predictors of Grade {>=}2 and Grade 3 chronic urinary toxicity and chronic urinary retention. Both Grade {>=}2 (p = 0.001) and Grade 3 (p = 0.03) acute urinary toxicity were predictive for the development of Grade {>=}2 (p = 0.001, p = 0.03) and Grade 3 (p = 0.05, p < 0.001) chronic urinary toxicity. On Cox multivariate analysis the development of acute toxicity was independently predictive for the development of both Grade {>=}2 and Grade 3 chronic urinary toxicity. Conclusions: Acute urinary toxicity and bladder wall dose-volume endpoints are strong predictors for the development of subsequent chronic urinary toxicity. Our recommendation is to attempt to limit the bladder wall V30 to <30 cm{sup 3} and the V82 to <7 cm{sup 3} when possible. If bladder wall information is not available, bladder solid V30 and V82 may be used.« less
  • Purpose: To evaluate the Vienna Rectoscopy Score (VRS) as a feasible and effective tool for detecting and classifying pathologic changes in the rectal mucosa after radiotherapy (RT) for prostate cancer, and, also, to correlate its findings with the European Organization for Research and Treatment of Cancer (EORTC)/Radiation Therapy Oncology Group (RTOG) score for late rectal toxicity. Methods and Materials: A total of 486 patients with localized prostate cancer underwent external-beam RT up to 70 or 74 Gy within an Austrian-German prospective multicenter trial. In 166 patients, voluntary rectal sigmoidoscopy was performed before and at 12 and/or 24 months after RT.more » Pathologic findings such as telangiectasia, congested mucosa, and ulcers were graded (Grades 0-3) and summarized according to the VRS. Late rectal side effects (EORTC/RTOG) were documented and correlated with the corresponding VRS. Results: Before RT, 99% had a VRS score of 0. The median follow-up was 40 months. Overall, a late rectal side effects grade or score 1-3 was detected in 43% by EORTC/RTOG compared with 68% by VRS (p < 0.05). Grades 0, 1, 2, and 3 late rectal side effects were found using EORTC/RTOG in 57%, 11%, 28%, and 3%, respectively; the corresponding percentages were 32%, 22%, 32%, and 14% for a VRS of 0, 1, 2, and 3, respectively. A significant coherence between the VRS and EORTC/RTOG was found (p < 0.01). Conclusions: The VRS is a feasible and effective tool for describing and classifying pathologic findings in the rectal mucosa after RT within a multicenter trial. The VRS and EORTC/RTOG showed a high coherence. However the VRS was significantly more sensitive.« less
  • Purpose: To assess the impact of prostate volume on health-related quality of life (HRQOL) before and at different intervals after radiotherapy for prostate cancer. Methods and Materials: A group of 204 patients was surveyed prospectively before (Time A), at the last day (Time B), 2 months after (Time C), and 16 months (median) after (Time D) radiotherapy, with a validated questionnaire (Expanded Prostate Cancer Index Composite). The group was divided into subgroups with a small (11-43 cm{sup 3}) and a large (44-151 cm{sup 3}) prostate volume. Results: Patients with large prostates presented with lower urinary bother scores (median 79 vs.more » 89; p = 0.01) before treatment. Urinary function/bother scores for patients with large prostates decreased significantly compared to patients with small prostates due to irritative/obstructive symptoms only at Time B (pain with urination more than once daily in 48% vs. 18%; p < 0.01). Health-related quality of life did not differ significantly between both patient groups at Times C and D. In contrast to a large prostate, a small initial bladder volume (with associated higher dose-volume load) was predictive for lower urinary bother scores both in the acute and late phase; at Time B it predisposed for pollakiuria but not for pain. Patients with neoadjuvant hormonal therapy reached significantly lower HRQOL scores in several domains (affecting only incontinence in the urinary domain), despite a smaller prostate volume (34 cm{sup 3} vs. 47 cm{sup 3}; p < 0.01). Conclusions: Patients with a large prostate volume have a great risk of irritative/obstructive symptoms (particularly dysuria) in the acute radiotherapy phase. These symptoms recover rapidly and do not influence long-term HRQOL.« less