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      Self-assessed bowel toxicity after external beam radiotherapy for prostate cancer - predictive factors on irritative symptoms, incontinence and rectal bleeding

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          Abstract

          Background

          The aim of the study was to evaluate self-assessed bowel toxicity after radiotherapy (RT) for prostate cancer. In contrast to rectal bleeding, information concerning irritative symptoms (rectal urgency, pain) and incontinence after RT has not been adequately documented and reported in the past.

          Methods

          Patients (n = 286) have been surveyed prospectively before (A), at the last day (70.2-72.0 Gy; B), a median time of two (C) and 16 months after RT (D) using a validated questionnaire (Expanded Prostate Cancer Index Composite). Bowel domain score changes were analyzed and patient-/dose-volume-related factors tested for a predictive value on three separate factors (subscales): irritative symptoms, incontinence and rectal bleeding.

          Results

          Irritative symptoms were most strongly affected in the acute phase, but the scores of all subscales remained slightly lower at time D in comparison to baseline scores. Good correlations (correlation indices >0.4; p < 0.001 for all) were found between irritative and incontinence function/bother scores at times B-D, suggesting the presence of an urge incontinence for the majority of patients who reported uncontrolled leakage of stool. Planning target volume (PTV), haemorrhoids and stroke in past history were found to be independent predictive factors for rectal bleeding at time D. Chronic renal failure predisposed for lower irritative scores at time D. Paradoxically, patients with greater rectum volumes inside higher isodose levels presented with higher quality of life scores in the irritative and incontinence subscales.

          Conclusion

          PTV and specific comorbidities are important predictive factors on adverse bowel quality of life changes after RT for prostate cancer. However, greater rectum volumes inside high isodose levels have not been found to be associated with lower quality of life scores.

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          Most cited references39

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          Long-term results of the M. D. Anderson randomized dose-escalation trial for prostate cancer.

          To report the long-term results of a randomized radiotherapy dose escalation trial for prostate cancer. From 1993 to 1998, a total of 301 patients with stage T1b to T3 prostate cancer were accrued to a randomized external beam dose escalation trial using 70 Gy versus 78 Gy. The median follow-up is now 8.7 years. Kaplan-Meier analysis was used to compute rates of prostate-specific antigen (PSA) failure (nadir + 2), clinical failure, distant metastasis, disease-specific, and overall survival as well as complication rates at 8 years post-treatment. For all patients, freedom from biochemical or clinical failure (FFF) was superior for the 78-Gy arm, 78%, as compared with 59% for the 70-Gy arm (p = 0.004, and an even greater benefit was seen in patients with initial PSA >10 ng/ml (78% vs. 39%, p = 0.001). The clinical failure rate was significantly reduced in the 78-Gy arm as well (7% vs. 15%, p = 0.014). Twice as many patients either died of prostate cancer or are currently alive with cancer in the 70-Gy arm. Gastrointestinal toxicity of grade 2 or greater occurred twice as often in the high dose patients (26% vs. 13%), although genitourinary toxicity of grade 2 or greater was less (13% vs. 8%) and not statistically significantly different. Dose-volume histogram analysis showed that the complication rate could be significantly decreased by reducing the amount of treated rectum. Modest escalation in radiotherapy dose improved freedom from biochemical and clinical progression with the largest benefit in prostate cancer patients with PSA >10 ng/ml.
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            Development and validation of the expanded prostate cancer index composite (EPIC) for comprehensive assessment of health-related quality of life in men with prostate cancer.

            Health-related quality of life (HRQOL) is an increasingly important endpoint in prostate cancer care. However, pivotal issues that are not fully assessed in existing HRQOL instruments include irritative urinary symptoms, hormonal symptoms, and multi-item scores quantifying bother between urinary, sexual, bowel, and hormonal domains. We sought to develop a novel instrument to facilitate more comprehensive assessment of prostate cancer-related HRQOL. Instrument development was based on advice from an expert panel and prostate cancer patients, which led to expanding the 20-item University of California-Los Angeles Prostate Cancer Index (UCLA-PCI) to the 50-item Expanded Prostate Index Composite (EPIC). Summary and subscale scores were derived by content and factor analyses. Reliability and validity were assessed by test-retest correlation, Cronbach's alpha coefficient, interscale correlation, and EPIC correlation with other validated instruments. Test-retest reliability and internal consistency were high for EPIC urinary, bowel, sexual, and hormonal domain summary scores (each r >/=0.80 and Cronbach's alpha >/=0.82) and for most domain-specific subscales. Correlations between function and bother subscales within domains were high (r >0.60). Correlations between different primary domains were consistently lower, indicating that these domains assess distinct HRQOL components. EPIC domains had weak to modest correlations with the Medical Outcomes Study 12-item Short-Form Health Survey (SF-12), indicating rationale for their concurrent use. Moderate agreement was observed between EPIC domains relevant to the Functional Assessment of Cancer Therapy Prostate module (FACT-P) and the American Urological Association Symptom Index (AUA-SI), providing criterion validity without excessive overlap. EPIC is a robust prostate cancer HRQOL instrument that complements prior instruments by measuring a broad spectrum of urinary, bowel, sexual, and hormonal symptoms, thereby providing a unique tool for comprehensive assessment of HRQOL issues important in contemporary prostate cancer management.
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              Update of Dutch multicenter dose-escalation trial of radiotherapy for localized prostate cancer.

              To update the analysis of the Dutch dose-escalation trial of radiotherapy for prostate cancer. A total of 669 patients with localized prostate cancer were randomly assigned to receive 68 or 78 Gy. The patients were stratified by age, institution, use of neoadjuvant or adjuvant hormonal therapy, and treatment group. The primary endpoint was freedom from failure (FFF), with failure defined as clinical or biochemical failure. Two definitions of biochemical failure were used: the American Society for Therapeutic Radiology and Oncology definition (three consecutive increases in prostate-specific antigen level) and the Phoenix definition (nadir plus 2 microe secondary endpoints were freedom from clinical failure, overall survival, and genitourinary and gastrointestinal toxicity. After a median follow-up of 70 months, the FFF using the American Society for Therapeutic Radiology and Oncology definition was significantly better in the 78-Gy arm than in the 68-Gy arm (7-year FFF rate, 54% vs. 47%, respectively; p = 0.04). The FFF using the Phoenix definition was also significantly better in the 78-Gy arm than in the 68-Gy arm (7-year FFF rate, 56% vs. 45%, respectively; p = 0.03). However, no differences in freedom from clinical failure or overall survival were observed. The incidence of late Grade 2 or greater genitourinary toxicity was similar in both arms (40% and 41% at 7 years; p = 0.6). However, the cumulative incidence of late Grade 2 or greater gastrointestinal toxicity was increased in the 78-Gy arm compared with the 68-Gy arm (35% vs. 25% at 7 years; p = 0.04). The results of our study have shown a statistically significant improvement in FFF in prostate cancer patients treated with 78 Gy but with a greater rate of late gastrointestinal toxicity.
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                Author and article information

                Journal
                Radiat Oncol
                Radiation Oncology (London, England)
                BioMed Central
                1748-717X
                2009
                21 September 2009
                : 4
                : 36
                Affiliations
                [1 ]Department of Radiation Oncology, RWTH Aachen University, Pauwelsstrasse 30, 52072 Aachen, Germany
                Article
                1748-717X-4-36
                10.1186/1748-717X-4-36
                2753361
                19772568
                8c3a890f-b5e8-4b73-ae31-2fcae2b1c2a5
                Copyright © 2009 Pinkawa et al; licensee BioMed Central Ltd.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 13 July 2009
                : 21 September 2009
                Categories
                Research

                Oncology & Radiotherapy
                Oncology & Radiotherapy

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