Clinical and dosimetric predictors of late rectal toxicity after conformal radiation for localized prostate cancer: Results of a large multicenter observational study (original) (raw)
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International Journal of Radiation Oncology Biology Physics, 2000
Purpose: The purpose of this paper is to use the outcome of a dose escalation protocol for three-dimensional conformal radiation therapy (3D-CRT) of prostate cancer to study the dose-response for late rectal toxicity and to identify anatomic, dosimetric, and clinical factors that correlate with late rectal bleeding in multivariate analysis. Methods and Materials: Seven hundred forty-three patients with T1c-T3 prostate cancer were treated with 3D-CRT with prescribed doses of 64.8 to 81.0 Gy. The 5-year actuarial rate of late rectal toxicity was assessed using Kaplan-Meier statistics. A retrospective dosimetric analysis was performed for patients treated to 70.2 Gy (52 patients) or 75.6 Gy (119 patients) who either exhibited late rectal bleeding (RTOG Grade 2/3) within 30 months after treatment (i.e., 70.2 Gy-13 patients, 75.6 Gy-36 patients) or were nonbleeding for at least 30 months (i.e., 70.2 Gy-39 patients, 75.6 Gy-83 patients). Univariate and multivariate logistic regression was performed to correlate late rectal bleeding with several anatomic, dosimetric, and clinical variables. Results: A dose response for > Grade 2 late rectal toxicity was observed. By multivariate analysis, the following factors were significantly correlated with > Grade 2 late rectal bleeding for patients prescribed 70.2 Gy: 1) enclosure of the outer rectal contour by the 50% isodose on the isocenter slice (i.e., Iso50) (p < 0.02), and 2) smaller anatomically defined rectal wall volume (p < 0.05). After 75.6 Gy, the following factors were significant: 1) smaller anatomically defined rectal wall volume (p < 0.01), 2) higher rectal D max (p < 0.01), 3) enclosure of rectal contour by Iso50 (p < 0.01), 4) patient age (p ؍ 0.02), and 5) history of diabetes mellitus (p ؍ 0.04). In addition to these five factors, acute rectal toxicity was also significantly correlated (p ؍ 0.05) with late rectal bleeding when patients from both dose groups were combined in multivariate analysis. Conclusion: A multivariate logistic regression model is presented which describes the probability of developing late rectal bleeding after conformal irradiation of prostate cancer. Late rectal bleeding correlated with factors which may indicate that a greater fractional volume of rectal wall was exposed to high dose, such as smaller rectal wall volume, inclusion of the rectum within the 50% isodose on the isocenter slice, and higher rectal D max .
International Journal of Radiation Oncology Biology Physics, 2008
Purpose: Assessing the predictors of late rectal toxicity after high-dose conformal radiotherapy for prostate cancer. Methods: One thousand one hundred thirty-two patients entered a prospective observational multicentric study; late rectal toxicity was evaluated by a self-reported questionnaire. Results concerning bleeding and faecal incontinence of 718/1132 patients with a complete follow-up at 36 months were analysed. The correlation between a number of clinical-dosimetric parameters and moderate/severe toxicity was investigated by univariate and multivariate logistic analyses. Results: Fifty-two (7.2%) and 57/718 (7.9%) patients were scored as moderate/severe bleeders and faecal incontinents, respectively; 19/57 incontinent patients showed persistent incontinence at 36 months. Bleeding was mainly correlated with V75 Gy while severe bleeding was mainly correlated with the previous abdominal/pelvic surgery; a different rectal dose-volume relationship in the two groups of patients (with/without surgery) was found. Moderate/severe acute toxicity was weakly correlated to late bleeding. The best predictor of faecal incontinence was acute toxicity (OR = 4 and 7 for chronic and actuarial incontinence, respectively). Conclusion: The application of rectal dose-volume constraints limited the incidence of rectal bleeding. The risk of bleeding may be further reduced by limiting V75 Gy < 5% and, in the case of patients previously submitted to abdominal/pelvic surgery, V70 Gy < 15-20%. Faecal incontinence seems to be mainly a consequential effect after acute toxicity.
International Journal of Radiation Oncology Biology Physics, 1998
Purpose: To investigate whether Dose-Volume Histogram (DVH) parameters can be used to identify risk groups for developing late gastrointestinal (GI) and genitourinary (GU) complications after conformal radiotherapy for prostate cancer. Methods and Materials: DVH parameters were analyzed for 130 patients with localized prostate cancer, treated with conformal radiotherapy in a dose-escalating protocol (70-78 Gy, 2 Gy per fraction). The incidence of late (>6 months) GI and GU complications was classified using the RTOG/EORTC and the SOMA/LENT scoring system. In addition, GI complications were divided in nonsevere and severe (requiring one or more laser treatments or blood transfusions) rectal bleeding. The median follow-up time was 24 months. We investigated whether rectal and bladder wall volumes, irradiated to various dose levels, correlated with the observed actuarial incidences of GI and GU complications, using volume as a continuous variable. Subsequently, for each dose level in the DVH, the rectal wall volumes were dichotomized using different volumes as cutoff levels. The impact of the total radiation dose, and the maximum radiation dose in the rectal and bladder wall was analyzed as well. Results: The actuarial incidence at 2 years for GI complications >Grade II was 14% (RTOG/EORTC) or 20% (SOMA/LENT); for GU complications >Grade III 8% (RTOG/EORTC) or 21% (SOMA/LENT). Neither for GI complications >Grade II (RTOG/EORTC or SOMA/LENT), nor for GU complications >Grade III (RTOG/ EORTC or SOMA/LENT), was a significant correlation found between any of the DVH parameters and the actuarial incidence of complications. For severe rectal bleeding (actuarial incidence at 2 years 3%), four consecutive volume cutoff levels were found, which significantly discriminated between high and low risk. A trend was observed that a total radiation dose > 74 Gy (or a maximum radiation dose in the rectal wall >75 Gy) resulted in a higher incidence of severe rectal bleeding (p ؍ 0.07). Conclusions: These data show that dose escalation up to 78 Gy, using a conformal technique, is feasible. However, these data have also demonstrated that the incidence of severe late rectal bleeding is increased above certain dose-volume thresholds.
Australasian Radiology, 2007
This study investigates the rate of late rectal and urinary toxicity from three-dimensional conformal radiation therapy (3DCRT) for localized prostate cancer. The influence of neoadjuvant androgen deprivation (AD) on toxicity rates was also examined. A total of 402 men at Liverpool and Westmead hospitals received radical 3DCRT for localized prostate cancer between 1999 and 2003. Patients received either 70 Gy or 74 Gy, according to their prognostic risk grouping and or date of commencing radiation therapy (RT). Late rectal and urinary toxicity data were collected prospectively using Radiation Therapy Oncology Group/European Organisation for Research and Treatment of Cancer criteria. The median follow up of this cohort was 43.5 months. At 36 months, the cumulative incidence of grade 2 rectal and urinary toxicities was 6.7 and 17.5%, respectively. Peak prevalence of late urinary toxicity occurred at 36 months (9.5%), although late rectal toxicity was highest at 12 months (2.9%) from completion of 3DCRT. The use of AD did not cause additional late toxicities. Patients receiving 74 Gy did not experience significantly worse toxicities than the group receiving 70 Gy.
Radiotherapy and …, 2004
Purpose: To investigate the relation between acute toxicity and irradiated volume in the organs at risk during three-dimensional conformal radiation therapy for prostate cancer. Methods and materials: From January to December 2001, we treated 132 prostate cancer patients to a prescribed target dose of 70 Gy. Twenty-six patients (20%) received irradiation to the prostate only (Group P), 86 patients (65%) had field arrangements encompassing the prostate and seminal vesicles (Group PSV) while 20 (15%) received modified pelvic fields (Group MPF). A four-field conformal box technique was used. Acute toxicity according to the RTOG scoring system was prospectively recorded throughout the course of treatment. Results: Overall, radiation was well tolerated with 11%, 16% and 35% Grade 2 gastro-intestinal (GI) toxicity and 19%, 34% and 35% Grade 2 or higher genito-urinary (GU) toxicity in Groups P, PSV and MPF, respectively. In univariate and multivariate analyses treatment group was a significant predictor for Grade 2 or higher acute morbidity. In multivariate logistic regression, the rectum dose-volume histogram parameters were correlated to the incidence of acute Grade 2 GI toxicity, with the fractional volumes receiving more than 37-40 Gy and above 70 Gy showing the statistically strongest correlation. The fractional bladder volume receiving more than 14-27 Gy showed the statistically strongest correlation with acute GU toxicity. Conclusions: 3D-CRT radiation therapy to 70 Gy for prostate cancer was well tolerated. Only two of the 132 patients in the cohort experienced acute bladder toxicity Grade 3, none had Grade 3 rectal toxicity. Uni-and multivariate analyses indicated that the volume treated was a significant factor for the incidence of Grade 2 or higher acute morbidity.
International Journal of Radiation Oncology Biology Physics, 2007
Purpose: To find predictors for rectal and intestinal acute toxicity in patients with prostate cancer treated with >70 Gy conformal radiotherapy. Methods and Materials: Between July 2002 and March 2004, 1,132 patients were entered into a cooperative study (AIROPROS01-02). Toxicity was scored using the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer scale and by considering the changes (before and after treatment) of the scores of a self-administered questionnaire on rectal/intestinal toxicity. The correlation with a number of parameters was assessed by univariate and multivariate analyses. Concerning the questionnaire, only moderate/ severe complications were considered. Results: Of 1,132 patients, 1,123 were evaluable. Of these patients, 375, 265, and 28 had Grade 1, 2, and 3 Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer toxicity, respectively. The mean rectal dose was the most predictive parameter (p ؍ 0.0004; odds ratio, 1.035) for Grade 2 or worse toxicity, and the use of anticoagulants/antiaggregants (p ؍ 0.02; odds ratio, 0.63) and hormonal therapy (p ؍ 0.04, odds ratio, 0.65) were protective. The questionnaire-based scoring revealed that a greater mean rectal dose was associated with a greater risk of bleeding; larger irradiated volumes were associated with frequency, tenesmus, incontinence, and bleeding; hormonal therapy was protective against frequency and tenesmus; hemorrhoids were associated with a greater risk of tenesmus and bleeding; and diabetes associated highly with diarrhea. Conclusion: The mean rectal dose correlated with acute rectal/intestinal toxicity in three-dimensional conformal radiotherapy for prostate cancer, and hormonal therapy and the use of anticoagulants/antiaggregants were protective. According to the moderate/severe injury scores on the self-assessed questionnaire, several clinical and dose-volume parameters were independently predictive for particular symptoms.
International Journal of Radiation Oncology*Biology*Physics, 2010
Purpose: To analyze the correlation between acute and late injury in 973 prostate cancer patients treated with radiotherapy and to evaluate the effect of patient-, tumor-, and treatment-related variables on toxicity. Methods and Materials: Of the 973 patients, 542 and 431 received definitive or postprostatectomy radiotherapy, respectively. Three-dimensional conformal radiotherapy included a six-field technique and two-dynamic arc therapy. Toxicity was classified according to the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer criteria. The correlation between acute and late toxicity (incidence and severity) was assessed. Results: Multivariate analysis showed that age #65 years (p = .06) and use of the three-dimensional, six-field technique (p <.0001) correlated significantly with greater acute rectal toxicity. The three-dimensional, six-field technique (p = .0002), dose >70 Gy (p = .014), and radiotherapy duration (p = .05) correlated with greater acute urinary toxicity. Acute rectal toxicity (p <.0001) was the only factor that correlated with late rectal injury on multivariate analysis. Late urinary toxicity correlated with acute urinary events (p <.0001) and was inversely related to the use of salvage radiotherapy (p = .018). A highly significant correlation was found between the incidence of acute and late events for both rectal (p <.001) and urinary (p <.001) reactions. The severity of acute toxicity (Grade 2 or greater) was predictive for the severity of late toxicity for both rectal and urinary events (p <.001). Conclusion: The results of our study have shown that the risk of acute reactions depends on both patientrelated (age) and treatment-related (dose, technique) factors. Acute toxicity was an independent significant predictor of late toxicity. These findings might help to predict and prevent late radiotherapy-induced complications. Ó 2010 Elsevier Inc.
Tumori
Rectal and urinary toxicities are the principal limiting factors in delivering a high target dose to patients affected by prostate cancer. The verification of such toxicity is an important step before starting a dose-escalation program. The present observational study reports on the acute and late rectal and urinary toxicity in relation with dose-volume parameters in 104 patients with localized prostate cancer treated with 3-dimensional conformal radiation therapy. One hundred and four patients with stage T1b-T3b prostate cancer were treated with three-dimensional conformal radiation therapy to a total dose of 74 Gy, 2 Gy per fraction. Rigid dose constraints were applied for rectum and bladder. Acute and late rectal and urinary toxicities were analyzed also in relation to dose-volume histograms. Biochemical relapse-free survival was defined according to the American Society of Therapeutic Radiation Oncology (ASTRO) criteria and to the RTOG-ASTRO Phoenix Consensus Conference Recommen...