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Title: Cluster model analysis of late rectal bleeding after IMRT of prostate cancer: A case-control study

Abstract

Purpose: Cluster models are newly developed normal-tissue complication probability models in which the spatial aspects of radiation-induced injury are taken into account by considering the size of spatially contiguous aggregates of damaged tissue units. The purpose of this study was to test the validity of a two-dimensional cluster model of late rectal toxicity based on maximum cluster size of damage to rectal surface. Methods and Materials: A paired case-control study was performed in which each of 9 patients experiencing Grade 2 or higher late rectal toxicity after intensity-modulated radiation therapy of localized prostate cancer was paired with a patient having a similar rectal dose-surface histogram but free of rectal toxicity. Numeric simulations were performed to determine the distribution of maximum cluster size on each rectal surface for each of many different choices of possible model parameters. Results: Model parameters were found for which patients with rectal toxicity were consistently more likely to have a significantly larger mean maximum cluster size than their matched controls. These parameter values correspond to a 50% probability of tissue-unit damage at doses near 30 Gy. Conclusions: This study suggests that a cluster model based on maximum cluster size of damage to rectal surface successfully incorporatesmore » spatial information beyond that contained in the rectal dose-surface histogram and may therefore provide a useful new tool for predicting rectal normal-tissue complication probability after radiotherapy.« less

Authors:
 [1];  [2];  [3];  [3];  [4];  [2]
  1. Department of Biostatistics and Applied Mathematics, University of Texas M.D. Anderson Cancer Center, Houston, TX (United States). E-mail: sltucker@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:
20793408
Resource Type:
Journal Article
Resource Relation:
Journal Name: International Journal of Radiation Oncology, Biology and Physics; Journal Volume: 64; Journal Issue: 4; Other Information: DOI: 10.1016/j.ijrobp.2005.10.029; PII: S0360-3016(05)02943-3; Copyright (c) 2006 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; CARCINOMAS; CLUSTER MODEL; DAMAGE; INJURIES; PATIENTS; PROSTATE; RADIATION DOSES; RADIOTHERAPY; TOXICITY

Citation Formats

Tucker, Susan L., Zhang Ming, Dong Lei, Mohan, Radhe, Kuban, Deborah, and Thames, Howard D.. Cluster model analysis of late rectal bleeding after IMRT of prostate cancer: A case-control study. United States: N. p., 2006. Web. doi:10.1016/J.IJROBP.2005.1.
Tucker, Susan L., Zhang Ming, Dong Lei, Mohan, Radhe, Kuban, Deborah, & Thames, Howard D.. Cluster model analysis of late rectal bleeding after IMRT of prostate cancer: A case-control study. United States. doi:10.1016/J.IJROBP.2005.1.
Tucker, Susan L., Zhang Ming, Dong Lei, Mohan, Radhe, Kuban, Deborah, and Thames, Howard D.. Wed . "Cluster model analysis of late rectal bleeding after IMRT of prostate cancer: A case-control study". United States. doi:10.1016/J.IJROBP.2005.1.
@article{osti_20793408,
title = {Cluster model analysis of late rectal bleeding after IMRT of prostate cancer: A case-control study},
author = {Tucker, Susan L. and Zhang Ming and Dong Lei and Mohan, Radhe and Kuban, Deborah and Thames, Howard D.},
abstractNote = {Purpose: Cluster models are newly developed normal-tissue complication probability models in which the spatial aspects of radiation-induced injury are taken into account by considering the size of spatially contiguous aggregates of damaged tissue units. The purpose of this study was to test the validity of a two-dimensional cluster model of late rectal toxicity based on maximum cluster size of damage to rectal surface. Methods and Materials: A paired case-control study was performed in which each of 9 patients experiencing Grade 2 or higher late rectal toxicity after intensity-modulated radiation therapy of localized prostate cancer was paired with a patient having a similar rectal dose-surface histogram but free of rectal toxicity. Numeric simulations were performed to determine the distribution of maximum cluster size on each rectal surface for each of many different choices of possible model parameters. Results: Model parameters were found for which patients with rectal toxicity were consistently more likely to have a significantly larger mean maximum cluster size than their matched controls. These parameter values correspond to a 50% probability of tissue-unit damage at doses near 30 Gy. Conclusions: This study suggests that a cluster model based on maximum cluster size of damage to rectal surface successfully incorporates spatial information beyond that contained in the rectal dose-surface histogram and may therefore provide a useful new tool for predicting rectal normal-tissue complication probability after radiotherapy.},
doi = {10.1016/J.IJROBP.2005.1},
journal = {International Journal of Radiation Oncology, Biology and Physics},
number = 4,
volume = 64,
place = {United States},
year = {Wed Mar 15 00:00:00 EST 2006},
month = {Wed Mar 15 00:00:00 EST 2006}
}
  • Purpose: The aim of this study was to determine the risk factors for late gastrointestinal (GI) morbidity after hypofractionated carbon ion radiotherapy (C-ion RT) for prostate cancer. Methods and Materials: Between April 2000 and November 2003, a Phase II clinical trial of C-ion RT with a total dose of 66 GyE in 20 fractions was performed on 175 patients with prostate cancer, and the correlations of clinical and dosimetric parameters with the incidence of late GI toxicity in 172 patients who survived for more than 18 months were investigated. Results: Although no Grade 3-4 late morbidities of the rectum weremore » observed, Grade 1 and 2 morbidities developed in 23 (13%) and 4 (2%) patients, respectively. Dose-volume histogram analysis revealed that the percentage of rectal volume receiving 50% of the prescribed dose (V50) was significantly higher in patients with rectal toxicity than without toxicity (13.2 {+-} 5.6% with toxicity; 11.4 {+-} 4.0% without toxicity, p = 0.046). Multivariate analysis demonstrated that the use of anticoagulation therapy (p = 0.010) and rectal V50 (p = 0.012) were significant risk factors for the occurrence of Grade 1-2 late GI toxicity. Conclusions: Although C-ion RT with hypofractionation yielded favorable results regarding late GI complication, dosimetric parameter was a very important factor in the occurrence of rectal bleeding after C-ion RT as well as photon beam RT. Our results provide useful information for physicians applying charged particle RT in the treatment of prostate cancer.« less
  • Purpose: To evaluate the incidence of Grade 2 or worse rectal bleeding after high-dose-rate (HDR) brachytherapy combined with hypofractionated external-beam radiotherapy (EBRT), with special emphasis on the relationship between the incidence of rectal bleeding and the rectal dose from HDR brachytherapy. Methods and Materials: The records of 100 patients who were treated by HDR brachytherapy combined with EBRT for {>=}12 months were analyzed. The fractionation schema for HDR brachytherapy was prospectively changed, and the total radiation dose for EBRT was fixed at 51 Gy. The distribution of the fractionation schema used in the patients was as follows: 5 Gy xmore » 5 in 13 patients; 7 Gy x 3 in 19 patients; and 9 Gy x 2 in 68 patients. Results: Ten patients (10%) developed Grade 2 or worse rectal bleeding. Regarding the correlation with dosimetric factors, no significant differences were found in the average percentage of the entire rectal volume receiving 30%, 50%, 80%, and 90% of the prescribed radiation dose from EBRT between those with bleeding and those without. The average percentage of the entire rectal volume receiving 10%, 30%, 50%, 80%, and 90% of the prescribed radiation dose from HDR brachytherapy in those who developed rectal bleeding was 77.9%, 28.6%, 9.0%, 1.5%, and 0.3%, respectively, and was 69.2%, 22.2%, 6.6%, 0.9%, and 0.4%, respectively, in those without bleeding. The differences in the percentages of the entire rectal volume receiving 10%, 30%, and 50% between those with and without bleeding were statistically significant. Conclusions: The rectal dose from HDR brachytherapy for patients with prostate cancer may have a significant impact on the incidence of Grade 2 or worse rectal bleeding.« 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 predictors of late rectal toxicity in a prospectively investigated group of patients treated at 70-80 Gy for prostate cancer (1.8-2 Gy fractions) with three-dimensional conformal radiotherapy. Methods and Materials: A total of 1,132 patients were entered into the study between 2002 and 2004. Three types of rectal toxicity, evaluated by a self-administered questionnaire, mainly based on the subjective objective management, analytic late effects of normal tissue system, were considered: stool frequency/tenesmus/pain, fecal incontinence, and bleeding. The data from 506 patients with a follow-up of 24 months were analyzed. The correlation between a number of clinical andmore » dosimetric parameters and Grade 2 or greater toxicity was investigated by univariate and multivariate (MVA) logistic analyses. Results: Of the 1,132 patients, 21, 15, and 30 developed stool frequency/tenesmus/pain, fecal incontinence, and bleeding, respectively. Stool frequency/tenesmus/pain correlated with previous abdominal/pelvic surgery (MVA, p = 0.05, odds ratio [OR], 3.3). With regard to incontinence, MVA showed the volume receiving {>=}40 Gy (V{sub 40}) (p = 0.035, OR, 1.037) and surgery (p = 0.02, OR, 4.4) to be the strongest predictors. V{sub 40} to V{sub 70} were highly predictive of bleeding; V{sub 70} showed the strongest impact on MVA (p = 0.03), together with surgery (p = 0.06, OR, 2.5), which was also the main predictor of Grade 3 bleeding (p = 0.02, OR, 4.2). Conclusions: The predictive value of the dose-volume histogram was confirmed for bleeding, consistent with previously suggested constraints (V{sub 50} <55%, V{sub 60} <40%, V{sub 70} <25%, and V{sub 75} <5%). A dose-volume histogram constraint for incontinence can be suggested (V{sub 40} <65-70%). Previous abdominal/pelvic surgery correlated with all toxicity types; thus, a modified constraint for bleeding (V{sub 70} <15%) can be suggested for patients with a history of abdominal/pelvis surgery, although further validation on a larger population with longer follow-up is needed.« less
  • Purpose: Accurate modeling of rectal complications based on dose-volume histogram (DVH) data are necessary to allow safe dose escalation in radiotherapy of prostate cancer. We applied different equivalent uniform dose (EUD)-based and dose-volume-based normal tissue complication probability (NTCP) models to rectal wall DVHs and follow-up data for 319 prostate cancer patients to identify the dosimetric factors most predictive for Grade {>=} 2 rectal bleeding. Methods and Materials: Data for 319 patients treated at the William Beaumont Hospital with three-dimensional conformal radiotherapy (3D-CRT) under an adaptive radiotherapy protocol were used for this study. The following models were considered: (1) Lyman modelmore » and (2) logit-formula with DVH reduced to generalized EUD (3) serial reconstruction unit (RU) model (4) Poisson-EUD model, and (5) mean dose- and (6) cutoff dose-logistic regression model. The parameters and their confidence intervals were determined using maximum likelihood estimation. Results: Of the patients, 51 (16.0%) showed Grade 2 or higher bleeding. As assessed qualitatively and quantitatively, the Lyman- and Logit-EUD, serial RU, and Poisson-EUD model fitted the data very well. Rectal wall mean dose did not correlate to Grade 2 or higher bleeding. For the cutoff dose model, the volume receiving > 73.7 Gy showed most significant correlation to bleeding. However, this model fitted the data more poorly than the EUD-based models. Conclusions: Our study clearly confirms a volume effect for late rectal bleeding. This can be described very well by the EUD-like models, of which the serial RU- and Poisson-EUD model can describe the data with only two parameters. Dose-volume-based cutoff-dose models performed wor0008.« less