Late rectal and bladder toxicity following radiation therapy for prostate cancer: Predictive factors and treatment results (original) (raw)
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Reporting Late Rectal Toxicity in Prostate Cancer Patients Treated With Curative Radiation Treatment
International Journal of Radiation Oncology*Biology*Physics, 2008
Purpose: Long-term rectal toxicity is a concern for patients with prostate cancer treated with curative radiation. However, comparing results of late toxicity may not be straightforward. This article reviews the complexity of reporting long-term side effects by using data for patients treated in our institution with hypofractionated irradiation. Methods and Materials: Seventy-two patients with localized prostate cancer treated with hypofractionated radiotherapy alone to a dose of 66 Gy in 22 fractions were prospectively assessed for late rectal toxicity according to the Common Toxicity Criteria, Version 3, scoring system. Ninety percent of patients had more than 24 months of follow-up. Results are compared with data published in the literature. Results: We found an actuarial incidence of Grade 2 or higher late rectal toxicity of 27% at 30 months and a crude incidence of Grade 2 or higher late rectal toxicity of 18%. This was mostly severe toxicity documented during follow-up. The incidence of Grade 3 rectal toxicity at the last visit was 3% compared with 13% documented at any time during follow-up. Conclusion: Comparison of late toxicity after radiotherapy in patients with prostate cancer must be undertaken with caution because many factors need to be taken into consideration. Because accurate assessment of late toxicity in the evaluation of long-term outcome after radiotherapy in patients with localized prostate cancer is essential, there is a need to develop by consensus guidelines for assessing and reporting late toxicity in this group of patients. Ó 2008 Elsevier Inc.
Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology, 2014
To define rectal dose volume constraints (DVC) to prevent ⩾grade2 late rectal toxicity (LRT) after intensity modulated radiotherapy (IMRT) for prostate cancer (PC). Six hundred thirty-seven PC patients were treated with primary (prostate median dose: 78Gy) or postoperative (prostatic bed median dose: 74Gy (adjuvant)-76Gy (salvage)) IMRTwhile restricting the rectal dose to 76Gy, 72Gy and 74Gy respectively. The impact of patient characteristics and rectal volume parameters on ⩾grade2 LRT was determined. DVC were defined to estimate the 5% and 10% risk of developing ⩾grade2 LRT. The 5-year probability of being free from ⩾grade2 LRT, non-rectal blood loss and persisting symptoms is 88.8% (95% CI: 85.8-91.1%), 93.4% (95% CI: 91.0-95.1%) and 94.3% (95% CI: 92.0-95.9%) respectively. There was no correlation with patient characteristics. All volume parameters, except rectal volume receiving ⩾70Gy (R70), were significantly correlated with ⩾grade2 LRT. To avoid 10% and 5% risk of ⩾grade2 LRT ...
Radiotherapy and Oncology, 2011
Background and purpose: To fit an NTCP model including clinical risk factors to late rectal toxicities after radiotherapy for prostate cancer. Methods and materials: Data of 669 patients were considered. The probability of late toxicity within 36 months (bleeding and incontinence) was fitted with the original and a modified Logit-EUD model, including clinical factors by fitting a subset specific TD 50 s: the ratio of TD 50 s with and without including the clinical variable was the dose-modifying factor (D mod ). Results: Abdominal surgery (surg) was a risk factor for G2-G3 bleeding, reflecting in a TD 50 = 82.7 Gy and 88.4 Gy for patients with and without surg (D mod = 0.94; 0.90 for G3 bleeding); acute toxicity was also an important risk factor for G2-G3 bleeding (D mod = 0.93). Concerning incontinence, surg and previous diseases of the colon were the clinical co-factors. D mod (surg) and D mod (colon) were 0.50 and 0.42, respectively for chronic incontinence and 0.73 and 0.64, respectively for mean incontinence score P1. Bestfit n values were 0.03-0.05 and 1 for bleeding and incontinence, respectively. The inclusion of clinical factors always improved the predictive value of the models. Conclusions: The inclusion of predisposing clinical factors improves NTCP estimation; the assessment of other clinical and genetic factors will be useful to reduce parameter uncertainties.
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.
Brachytherapy, 2010
PURPOSE: To describe the rate of gastrointestinal (GI) toxicity after prostate brachytherapy and describe how external beam radiation therapy (EBRT) may influence the association of rectal dosee volume histogram (DVH) parameters with rectal toxicity. METHODS AND MATERIALS: One hundred ten patients with prostate cancer were treated with I-125 brachytherapy alone (n 5 62, 144 Gy) or as a boost (n 5 48, 108 Gy) after 45-Gy EBRT. CT-based dosimetry was performed a median of 29 days after implantation. GI toxicity was evaluated by Radiation Therapy Oncology Group criteria. Median followup was 41 months. RESULTS: Eleven patients developed Grade 2 þ GI toxicity. Men treated with EBRT had an increased risk of GI toxicity, with freedom from Grade 2þ toxicity of 82% vs. 91% for implant alone, but this difference was not statistically significant ( p 5 0.3044). Of the DVH parameters analyzed, only the rectal volume receiving the prescription dose (rV 100% ) was associated with late Grade 2 þ GI toxicity. Men with rV 100% > 0.05 cc had a 4-year freedom from Grade 2þ toxicity of 77% vs. 100% for those with an rV 100% !0.05 cc ( p 5 0.0248). However, this relationship was only significant for the subset of patients treated with EBRT, where men with rV 100% > 0.05 cc had a 26% risk of Grade 2þ toxicity compared with 0% for rV 100% !0.05 cc. Additional DVH parameters, including dose to the hottest 0.1 cc ( p 5 0.0199), 1% ( p 5 0.0086), and 3% ( p 5 0.0043), were also associated with GI toxicity but only in men treated with EBRT. CONCLUSIONS: Supplemental EBRT may lower the threshold for rectal toxicity after prostate brachytherapy. Morbidity can be minimized by observing rectal constraints. Ó
Radiotherapy and Oncology, 2010
Purpose/objective: Whole pelvis irradiation with IMRT (WPRT-IMRT) after prostatectomy is efficient in reducing acute toxicity: however, a number of patients still experience moderate acute bowel toxicity. Materials and methods: Ninety-six patients treated with WPRT-IMRT after prostatectomy with adjuvant or salvage intent were analysed. A number of parameters were individually recovered, including the DVHs of the intestinal cavity outside PTV and of the loops referred to both the WPRT phase and the whole treatment. Correlation between clinical-dosimetric parameters and acute bowel toxicity was investigated by logistic analyses. Best predictive cut-off values for continuous variables were assessed by ROC curves. Results: 15/96 (15.6%) Patients experienced grade 2 toxicity (no grade 3). Best dose-volume predictors were the fraction of loops receiving more than 45, 50 and 55 Gy (respectively, V45TL P 50 cc, V50TL P 13 cc, V55TL P 3 cc; p-values ranging from 0.005 to 0.027). Age, GU acute toxicity, rectal acute toxicity and time between prostatectomy and IMRT were also predictors of acute bowel toxicity. Multivariate analysis showed that the most predictive independent parameters were age (OR: 1.13; 95%CI: 1.02-1.25; p = 0.021) and V50TL (P13 cc, OR: 8.2; 95%CI: 1.7-40; p = 0.009). Conclusions: The risk of moderate acute uGI toxicity during WPRT-IMRT for post-operatively treated patients increases with age; the risk is substantially reduced in patients with small overlap between PTV and loops.
International Journal of Radiation Oncology*Biology*Physics, 2011
Background and purpose: To fit an NTCP model including clinical risk factors to late rectal toxicities after radiotherapy for prostate cancer. Methods and materials: Data of 669 patients were considered. The probability of late toxicity within 36 months (bleeding and incontinence) was fitted with the original and a modified Logit-EUD model, including clinical factors by fitting a subset specific TD 50 s: the ratio of TD 50 s with and without including the clinical variable was the dose-modifying factor (D mod ). Results: Abdominal surgery (surg) was a risk factor for G2-G3 bleeding, reflecting in a TD 50 = 82.7 Gy and 88.4 Gy for patients with and without surg (D mod = 0.94; 0.90 for G3 bleeding); acute toxicity was also an important risk factor for G2-G3 bleeding (D mod = 0.93). Concerning incontinence, surg and previous diseases of the colon were the clinical co-factors. D mod (surg) and D mod (colon) were 0.50 and 0.42, respectively for chronic incontinence and 0.73 and 0.64, respectively for mean incontinence score P1. Bestfit n values were 0.03-0.05 and 1 for bleeding and incontinence, respectively. The inclusion of clinical factors always improved the predictive value of the models. Conclusions: The inclusion of predisposing clinical factors improves NTCP estimation; the assessment of other clinical and genetic factors will be useful to reduce parameter uncertainties.
Strahlentherapie und Onkologie, 2006
Purpose: To compare late rectal toxicity rates after three-dimensional conformal radiotherapy to the prostate alone (P-3D-CRT) and whole-pelvis intensity-modulated radiotherapy along with a prostate boost (WP-IMRT/PB) to the same nominal total dose to the prostate. Patients and Methods: 68 patients treated with conformal radiotherapy to the prostate only to 76 Gy at the National Institute for Cancer Research, Genoa, Italy, represented the first group (P-3D-CRT). The second group consisted of 45 patients treated at the University of Texas Medical Branch (UTMB), Galveston, TX, USA, with IMRT covering the pelvic nodes and seminal vesicles to 54 Gy at 1.8 Gy per fraction and the prostate to 60 Gy in the same 30 fractions. A separate phase boosted the prostate to 76 Gy (WP-IMRT/PB). Major aspects of planning were remarkably similar at both institutions leaving the inclusion or not of pelvic nodes as the main treatment-related difference between the two groups. Late rectal toxicity was prospectively scored according to the RTOG scale. All patients have a 12-month minimum follow-up, and mean follow-up, similar in both groups, is 25.9 months (SD [standard deviation]: 8.4 months). Results: At 2 years, the estimated cumulative incidence of grade 2 late rectal toxicity is 6% ± 4% for WP-IMRT/PB and 21.2% ± 6% for P-3D-CRT (p = 0.06). The difference became significant (HR [hazard ratio] = 0.1, 95% CI [confidence interval]: 0.0-0.6; p = 0.01) at multivariate analysis. None of the patients developed grade 3+ toxicity. Conclusion: Despite the larger treated volume, WP-IMRT/PB allows more rectal sparing than P-3D-CRT.
Radiotherapy and Oncology, 2009
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, 2012
Rectal toxicity was assessed by patient reporting in a prospective observational study of 586 prostate cancer patients treated by high-dose 3DCRT. Two main patterns for fecal incontinence were seen: the first is consequent Purpose: To model late fecal incontinence after high-dose prostate cancer radiotherapy (RT) in patients accrued in the AIROPROS (prostate working group of the Italian Association of Radiation Oncology) 0102 trial using different endpoint definitions. Methods and Materials: The self-reported questionnaires (before RT, 1 month after RT, and every 6 months for 3 years after RT) of 586 patients were available. The peak incontinence (P_INC) and two longitudinal definitions (chronic incontinence [C_INC], defined as the persistence of Grade 1 or greater incontinence after any Grade 2-3 event; and mean incontinence score [M_INC], defined as the average score during the 3-year period after RT) were considered. The correlation between the clinical/dosimetric parameters (including rectal doseevolume histograms) and P_INC (Grade 2 or greater), C_INC, and M_INC of !1 were investigated using International Journal of biology physics www.redjournal.org e.0003 against p Z .02). Nomograms for the two longitudinal definitions were derived. Conclusions: The longitudinal definitions of fecal incontinence (C_INC and M_INC !1) were helpful in accounting for both the persistence and the severity of the incontinence. A significant fraction of peak events was consequential to acute incontinence, and a longer duration of symptoms mainly depended on the rectal dose bath (percentage of rectal volume receiving >40 Gy), and pretreatment clinical factors. Ó 2012 Elsevier Inc.