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Title: Low-grade toxicity after conformal radiation therapy for prostate cancer-impact of bladder volume

Abstract

Purpose: To assess the impact of dose-volume histogram parameters on low-grade toxicity after radiotherapy for prostate cancer. Methods and Materials: Eighty patients have been surveyed prospectively before (time A), at the last day (B), 2 months after (C), and 16 months (median) after (D) radiotherapy (70.2 Gy) using a validated questionnaire (Expanded Prostate Cancer Index Composite). Dose-volume histograms were correlated with urinary and bowel function/bother scores. Results: The initial bladder volume and the percentage of the bladder volume receiving 10%-90% of the prescription dose significantly correlated with urinary function/bother scores (significant cutoff levels found for all dose levels). Pain with urination proved to be mainly an acute problem, subsiding faster for patients with larger bladder volumes and smaller volumes inside particular isodose lines. At time D, persisting problems with smaller initial bladder volumes were a weak stream and an increased frequency of urination. Though bladder volume and planning target volume both independently have an influence on dose-volume histogram parameters for the bladder, bladder volume plays the decisive role for urinary toxicity. Conclusions: The patient's ability to fill the bladder has a major impact on the dose-volume histogram and both acute and late urinary toxicity.

Authors:
 [1];  [2];  [2];  [2];  [2];  [2]
  1. Department of Radiotherapy, RWTH Aachen University, Aachen (Germany). E-mail: mpinkawa@ukaachen.de
  2. Department of Radiotherapy, RWTH Aachen University, Aachen (Germany)
Publication Date:
OSTI Identifier:
20793353
Resource Type:
Journal Article
Resource Relation:
Journal Name: International Journal of Radiation Oncology, Biology and Physics; Journal Volume: 64; Journal Issue: 3; Other Information: DOI: 10.1016/j.ijrobp.2005.09.003; PII: S0360-3016(05)02594-0; Copyright (c) 2006 Elsevier Science B.V., Amsterdam, The 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; PATIENTS; PLANNING; PROSTATE; RADIATION DOSES; RADIOTHERAPY; TOXICITY

Citation Formats

Pinkawa, Michael, Fischedick, Karin, Asadpour, Branka, Gagel, Bernd, Piroth, Marc D., and Eble, Michael J.. Low-grade toxicity after conformal radiation therapy for prostate cancer-impact of bladder volume. United States: N. p., 2006. Web. doi:10.1016/J.IJROBP.2005.0.
Pinkawa, Michael, Fischedick, Karin, Asadpour, Branka, Gagel, Bernd, Piroth, Marc D., & Eble, Michael J.. Low-grade toxicity after conformal radiation therapy for prostate cancer-impact of bladder volume. United States. doi:10.1016/J.IJROBP.2005.0.
Pinkawa, Michael, Fischedick, Karin, Asadpour, Branka, Gagel, Bernd, Piroth, Marc D., and Eble, Michael J.. Wed . "Low-grade toxicity after conformal radiation therapy for prostate cancer-impact of bladder volume". United States. doi:10.1016/J.IJROBP.2005.0.
@article{osti_20793353,
title = {Low-grade toxicity after conformal radiation therapy for prostate cancer-impact of bladder volume},
author = {Pinkawa, Michael and Fischedick, Karin and Asadpour, Branka and Gagel, Bernd and Piroth, Marc D. and Eble, Michael J.},
abstractNote = {Purpose: To assess the impact of dose-volume histogram parameters on low-grade toxicity after radiotherapy for prostate cancer. Methods and Materials: Eighty patients have been surveyed prospectively before (time A), at the last day (B), 2 months after (C), and 16 months (median) after (D) radiotherapy (70.2 Gy) using a validated questionnaire (Expanded Prostate Cancer Index Composite). Dose-volume histograms were correlated with urinary and bowel function/bother scores. Results: The initial bladder volume and the percentage of the bladder volume receiving 10%-90% of the prescription dose significantly correlated with urinary function/bother scores (significant cutoff levels found for all dose levels). Pain with urination proved to be mainly an acute problem, subsiding faster for patients with larger bladder volumes and smaller volumes inside particular isodose lines. At time D, persisting problems with smaller initial bladder volumes were a weak stream and an increased frequency of urination. Though bladder volume and planning target volume both independently have an influence on dose-volume histogram parameters for the bladder, bladder volume plays the decisive role for urinary toxicity. Conclusions: The patient's ability to fill the bladder has a major impact on the dose-volume histogram and both acute and late urinary toxicity.},
doi = {10.1016/J.IJROBP.2005.0},
journal = {International Journal of Radiation Oncology, Biology and Physics},
number = 3,
volume = 64,
place = {United States},
year = {Wed Mar 01 00:00:00 EST 2006},
month = {Wed Mar 01 00:00:00 EST 2006}
}
  • Purpose: Image-guided intensity modulated radiation therapy (IG-IMRT) allows significant dose reductions to organs at risk in prostate cancer patients. However, clinical data identifying the benefits of IG-IMRT in daily practice are scarce. The purpose of this study was to compare dose distributions to organs at risk and acute gastrointestinal (GI) and genitourinary (GU) toxicity levels of patients treated to 78 Gy with either IG-IMRT or 3D-CRT. Methods and Materials: Patients treated with 3D-CRT (n=215) and IG-IMRT (n=260) receiving 78 Gy in 39 fractions within 2 randomized trials were selected. Dose surface histograms of anorectum, anal canal, and bladder were calculated. Identical toxicitymore » questionnaires were distributed at baseline, prior to fraction 20 and 30 and at 90 days after treatment. Radiation Therapy Oncology Group (RTOG) grade ≥1, ≥2, and ≥3 endpoints were derived directly from questionnaires. Univariate and multivariate binary logistic regression analyses were applied. Results: The median volumes receiving 5 to 75 Gy were significantly lower (all P<.001) with IG-IMRT for anorectum, anal canal, and bladder. The mean dose to the anorectum was 34.4 Gy versus 47.3 Gy (P<.001), 23.6 Gy versus 44.6 Gy for the anal canal (P<.001), and 33.1 Gy versus 43.2 Gy for the bladder (P<.001). Significantly lower grade ≥2 toxicity was observed for proctitis, stool frequency ≥6/day, and urinary frequency ≥12/day. IG-IMRT resulted in significantly lower overall RTOG grade ≥2 GI toxicity (29% vs 49%, respectively, P=.002) and overall GU grade ≥2 toxicity (38% vs 48%, respectively, P=.009). Conclusions: A clinically meaningful reduction in dose to organs at risk and acute toxicity levels was observed in IG-IMRT patients, as a result of improved technique and tighter margins. Therefore reduced late toxicity levels can be expected as well; additional research is needed to quantify such reductions.« less
  • Purpose: To determine the potential association between genitourinary (GU) toxicity and planning dose–volume parameters for GU pelvic structures after high-dose intensity modulated radiation therapy in localized prostate cancer patients. Methods and Materials: A total of 268 patients who underwent intensity modulated radiation therapy to a prescribed dose of 86.4 Gy in 48 fractions during June 2004-December 2008 were evaluated with the International Prostate Symptom Score (IPSS) questionnaire. Dose–volume histograms of the whole bladder, bladder wall, urethra, and bladder trigone were analyzed. The primary endpoint for GU toxicity was an IPSS sum increase ≥10 points over baseline. Univariate and multivariate analysesmore » were done by the Kaplan-Meier method and Cox proportional hazard models, respectively. Results: Median follow-up was 5 years (range, 3-7.7 years). Thirty-nine patients experienced an IPSS sum increase ≥10 during follow-up; 84% remained event free at 5 years. After univariate analysis, lower baseline IPSS sum (P=.006), the V90 of the trigone (P=.006), and the maximal dose to the trigone (P=.003) were significantly associated with an IPSS sum increase ≥10. After multivariate analysis, lower baseline IPSS sum (P=.009) and increased maximal dose to the trigone (P=.005) remained significantly associated. Seventy-two patients had both a lower baseline IPSS sum and a higher maximal dose to the trigone and were defined as high risk, and 68 patients had both a higher baseline IPSS sum and a lower maximal dose to the trigone and were defined as low risk for development of an IPSS sum increase ≥10. Twenty-one of 72 high-risk patients (29%) and 5 of 68 low-risk patients (7%) experienced an IPSS sum increase ≥10 (P=.001; odds ratio 5.19). Conclusions: The application of hot spots to the bladder trigone was significantly associated with relevant changes in IPSS during follow-up. Reduction of radiation dose to the lower bladder and specifically the bladder trigone seems to be associated with a reduction in late GU toxicity.« less
  • Purpose: To assess the impact of pretreatment prostate volume on the development of severe acute genitourinary toxicity in patients undergoing intensity-modulated radiation therapy (IMRT) for prostate cancer. Methods and Materials: Between 2004 and 2007, a consecutive sample of 214 patients who underwent IMRT (75.6 Gy) for prostate cancer at two referral centers was analyzed. Prostate volumes were obtained from computed tomography scans taken during treatment simulation. Genitourinary toxicity was defined using the National Cancer Institute Common Terminology Criteria for Adverse Events Version 3.0 guidelines. Acute toxicity was defined as any toxicity originating within 90 days of the completion of radiationmore » therapy. Patients were characterized as having a small or large prostate depending on whether their prostate volume was less than or greater than 50 cm{sup 3}, respectively. Genitourinary toxicity was compared in these groups using the chi-square or Fisher's exact test, as appropriate. Bivariate and multivariate logistic regression analysis was performed to further assess the impact of prostate volume on severe (Grade 3) acute genitourinary toxicity. Results: Patients with large prostates (>50 cm{sup 3}) had a higher rate of acute Grade 3 genitourinary toxicity (p = .02). Prostate volume was predictive of the likelihood of developing acute Grade 3 genitourinary toxicity on bivariate (p = .004) and multivariate (p = .006) logistic regression. Every 27.0 cm{sup 3} increase in prostate volume doubled the likelihood of acute Grade 3 genitourinary toxicity. Conclusions: Patients with larger prostates are at higher risk for the development of severe acute genitourinary toxicity when treated with IMRT for prostate cancer.« less
  • Purpose: To characterize the late genitourinary (GU) and gastrointestinal (GI) toxicity for prostate cancer patients treated with intensity-modulated radiation therapy (IMRT) and propose dose-volume histogram (DVH) guidelines to limit late treatment-related toxicity. Methods and Materials: In this study 296 consecutive men were treated with IMRT for adenocarcinoma of the prostate. Most patients received treatment to the prostate with or without proximal seminal vesicles (90%), to a median dose of 76 Gy. Concurrent androgen deprivation therapy was given to 150 men (51%) for a median of 4 months. Late toxicity was defined by Common Toxicity Criteria version 3.0 as greater thanmore » 3 months after radiation therapy completion. Four groupings of DVH parameters were defined, based on the percentage of rectal or bladder tissue receiving 70 Gy (V{sub 70}), 65 Gy (V{sub 65}), and 40 Gy (V{sub 40}). These DVH groupings, as well as clinical and treatment characteristics, were correlated to maximal Grade 2+ GU and GI toxicity. Results: With a median follow-up of 41 months, the 4-year freedom from maximal Grade 2+ late toxicity was 81% and 91% for GU and GI systems, respectively, and by last follow-up, the rates of Grade 2+ GU and GI toxicity were 9% and 5%, respectively. On multivariate analysis, whole-pelvic IMRT was associated with Grade 2+ GU toxicity and age was associated with Grade 2+ GI toxicity. Freedom from Grade 2+ GI toxicity at 4 years was 100% for men with rectal V{sub 70} {<=}10%, V{sub 65} {<=}20%, and V{sub 40} {<=}40%; 92% for men with rectal V{sub 70} {<=}20%, V{sub 65} {<=}40%, and V{sub 40} {<=}80%; and 85% for men exceeding these criteria (p = 0.13). These criteria were more highly associated with GI toxicity in men aged {>=}70 years (p = 0.07). No bladder dose-volume relationships were associated with the risk of GU toxicity. Conclusions: IMRT is associated with low rates of severe GU or GI toxicity after treatment for prostate cancer. Rectal dose constraints may help limit late GI morbidity.« less
  • Purpose: To give a preliminary report of clinical and treatment factors associated with toxicity in men receiving high-dose radiation therapy (RT) on a phase 3 dose-escalation trial. Methods and Materials: The trial was initiated with 3-dimensional conformal RT (3D-CRT) and amended after 1 year to allow intensity modulated RT (IMRT). Patients treated with 3D-CRT received 55.8 Gy to a planning target volume that included the prostate and seminal vesicles, then 23.4 Gy to prostate only. The IMRT patients were treated to the prostate and proximal seminal vesicles to 79.2 Gy. Common Toxicity Criteria, version 2.0, and Radiation Therapy Oncology Group/Europeanmore » Organization for Research and Treatment of Cancer late morbidity scores were used for acute and late effects. Results: Of 763 patients randomized to the 79.2-Gy arm of Radiation Therapy Oncology Group 0126 protocol, 748 were eligible and evaluable: 491 and 257 were treated with 3D-CRT and IMRT, respectively. For both bladder and rectum, the volumes receiving 65, 70, and 75 Gy were significantly lower with IMRT (all P<.0001). For grade (G) 2+ acute gastrointestinal/genitourinary (GI/GU) toxicity, both univariate and multivariate analyses showed a statistically significant decrease in G2+ acute collective GI/GU toxicity for IMRT. There were no significant differences with 3D-CRT or IMRT for acute or late G2+ or 3+ GU toxicities. Univariate analysis showed a statistically significant decrease in late G2+ GI toxicity for IMRT (P=.039). On multivariate analysis, IMRT showed a 26% reduction in G2+ late GI toxicity (P=.099). Acute G2+ toxicity was associated with late G3+ toxicity (P=.005). With dose–volume histogram data in the multivariate analysis, RT modality was not significant, whereas white race (P=.001) and rectal V70 ≥15% were associated with G2+ rectal toxicity (P=.034). Conclusions: Intensity modulated RT is associated with a significant reduction in acute G2+ GI/GU toxicity. There is a trend for a clinically meaningful reduction in late G2+ GI toxicity with IMRT. The occurrence of acute GI toxicity and large (>15%) volumes of rectum >70 Gy are associated with late rectal toxicity.« less