Late rectal bleeding following combined x-ray and proton high dose irradiation for patients with stages T3–T4 prostate carcinoma (original) (raw)
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International Journal of Radiation Oncology*Biology*Physics, 2007
Purpose: The purpose of this article was to investigate how exceeding specified rectal wall dose-volume constraints impacts on the risk of late rectal bleeding by using radiobiologic calculations. Methods and Materials: Dose-volume histograms (DVH) of the rectal wall of 250 patients with prostate cancer were analyzed. All patients were treated by three-dimensional conformal radiation therapy, receiving mean target doses of 80 Gy. To study the main features of the patient population, the average and the standard deviation of the distribution of DVHs were generated. The mean dose , generalized equivalent uniform dose formulation (gEUD), modified equivalent uniform dose formulation (mEUD) 0 , and normal tissue complication probability (NTCP) distributions were also produced. The DVHs set was then binned into eight classes on the basis of the exceeding or the fulfilling of three dose-volume constraints: V 40 ؍ 60%, V 50 ؍ 50%, and V 70 ؍ 25%. Comparisons were made between them by , gEUD, mEUD 0 , and NTCP. Results: The radiobiologic calculations suggest that late rectal toxicity is mostly influenced by V 70 . The gEUD and mEUD 0 are risk factors of toxicity always concordant with NTCP, inside each DVH class. The mean dose, although a reliable index, may be misleading in critical situations. Conclusions: Both in three-dimensional conformal radiation therapy and particularly in intensity-modulated radiation therapy, it should be known what the relative importance of each specified dose-volume constraint is for each organ at risk. This requires a greater awareness of radiobiologic properties of tissues and radiobiologic indices may help to gradually become aware of this issue. © 2007 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 ...
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.
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 .
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, 2007
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 model 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 worse.
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.