A comparison of dose–volume constraints derived using peak and longitudinal definitions of late rectal toxicity (original) (raw)
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Physics and Imaging in Radiation Oncology
Background and purpose: Significant dose deviations have been reported between planned (D P) and accumulated (D A) dose in prostate radiotherapy. This study aimed to develop multivariate analysis (MVA) models associating Grade 1 and 2 gastrointestinal (GI) toxicity with clinical and D P or D A dosimetric variables separately. Materials and methods: Dose volume (DV) metrics were compared between D A and D P for 150 high-risk prostate cancer patients. MV models were generated from significant clinical and dosimetric variables (p < 0.05) at univariate level. Dose-based-region of interest (DB-ROI) metrics were included. Model performance was measured, and additional subgroup analysis were performed. Results: Rectal D A demonstrated a higher intermediate-high dose (V 30-65 Gy and DB-ROI at 15-50 mm) compared to D P. Conversely, at the very high dose region, rectal D A (V 75 Gy and DB-ROI at 5-10 mm) were significantly lower. In MVA, rectal DB-ROI at 10 mm was predictive for Grade ≥ 1 GI toxicity for D A and D P. Age, rectal D A for D 0.03 cc , and rectal D P for DB-ROI 10 mm were predictors for Grade 2 GI toxicity. Subgroup analysis revealed that patients ≥ 72 years old and a rectal D A of ≥ 78.2 Gy were highly predictive of Grade 2 GI toxicity. Conclusions: The dosimetric impact of a higher dose rectal dose in D A due to volumetric changes was minimal and was not predictive of detrimental clinical toxicity apart from rectal D 0.03 cc ≥ 78.2 Gy for Grade 2 GI toxicity. The use of the DB-ROI method can provide equivalent predictive power as the DV method in toxicity prediction.
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, 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.
Physics in Medicine and Biology, 2009
Many studies have been performed to assess correlations between measures derived from dose-volume histograms and late rectal toxicities for radiotherapy of prostate cancer. The purpose of this study was to quantify correlations between measures describing the shape and location of the dose distribution and different outcomes. The dose to the rectal wall was projected on a two-dimensional map. In order to characterize the dose distribution, its centre of mass, longitudinal and lateral extent, and eccentricity were calculated at different dose levels. Furthermore, the dosesurface histogram (DSH) was determined. Correlations between these measures and 7 clinically-relevant rectal-toxicity endpoints were quantified by maximally selected standardised Wilcoxon rank statistics. The analysis was performed using data from the RT01 prostate radiotherapy trial. For some endpoints the shape of the dose distribution is more strongly correlated with the outcome than simple DSHs. Rectal bleeding was most strongly correlated with lateral extent of the dose distribution. For loose stools the strongest correlations were found for longitudinal extent; proctitis was most strongly correlated with DSH. For the other endpoints no statistically-significant correlations could be found. The strengths of the correlations between the shape of the dose distribution and
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.
Frontiers in Oncology
Background and purposeNormal tissue complication probability (NTCP) parameters derived from traditional 3D plans may not be ideal in defining toxicity outcomes for modern radiotherapy techniques. This study aimed to derive parameters of the Lyman-Kutcher-Burman (LKB) NTCP model using prospectively scored clinical data for late gastrointestinal (GI) and genitourinary (GU) toxicities for high-risk prostate cancer patients treated using volumetric-modulated-arc-therapy (VMAT). Dose-volume-histograms (DVH) extracted from planned (DP) and accumulated dose (DA) were used.Material and methodsDP and DA obtained from the DVH of 150 prostate cancer patients with pelvic-lymph-nodes irradiation treated using VMAT were used to generate LKB-NTCP parameters using maximum likelihood estimations. Defined GI and GU toxicities were recorded up to 3-years post RT follow-up. Model performance was measured using Hosmer-Lemeshow goodness of fit test and the mean area under the receiver operating character...
OMICS Journal of Radiology
Purpose: Intensity Modulated Radiation Therapy (IMRT) allows for significant dose reductions to organs at risk in prostate cancer patients. However, the accurate delivery of IMRT plans can be compromised by patient positioning errors. The purpose of this study was to determine if the modeling of grade ≥ 2 acute rectal toxicity could be used to monitor the quality of IMRT protocols. Materials and Methods: 79 patients treated with Image and Fiducial Markers Guided IMRT (FMIGRT) and 302 patients treated with trans-abdominal ultrasound guided IMRT (USGRT) was selected for this study. Treatment plans were available for the FMIGRT group, and hand recorded dosimetric indices were available for both groups. We modeled toxicity in the FMIGRT group using the Lyman Kutcher Burman (LKB) and Univariate Logistic Regression (ULR) models, and we modeled toxicity in USGRT group using the ULR model. We performed Receiver Operating Characteristics (ROC) analysis on all of the models and compared the Area under the ROC curve (AUC) for the FMIGRT and the USGRT groups. Results: The observed Incidence of grade ≥ 2 rectal toxicity was 20% in FMIGRT patients and 54% in USGRT patients. LKB model parameters in the FMIGRT group were TD 50 =56.8 Gy, slope m=0.093, and exponent n=0.131. The most predictive indices in the ULR model for the FMIGRT group were D 25% and V 50 Gy. AUC for both models in the FMIGRT group was similar (AUC=0.67). The FMIGRT URL model predicted less than a 37% incidence of grade ≥ 2 acute rectal toxicity in the USGRT group. A fit of the ULR model to USGRT data did not yield a predictive model (AUC=0.5). This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
International Journal of Radiation Oncology*Biology*Physics, 2008
Purpose: Although several institutions have reported rectal dose constraints according to threshold toxicity, the plethora of trials has resulted in multiple, confusing dose-volume histogram recommendations. A set of standardized, literature-based constraints for patients undergoing whole pelvic radiotherapy (RT) for prostate cancer would help guide the practice of prostate RT. The purpose of this study was to develop these constraints, demonstrate that they are achievable, and assess the corresponding rectal toxicity. Methods and Materials: An extensive literature search identified eight key studies relating dose-volume histogram data to rectal toxicity. A correction factor was developed to address differences in the anatomic definition of the rectum across studies. The dose-volume histogram constraints recommended by each study were combined to generate the constraints. The data from all patients treated with definitive intensity-modulated RT were then compared against these constraints. Acute rectal toxicity was assessed. Results: A continuous, proposed rectal dose-constraint curve was generated. Intensity-modulated RT not only met this constraint curve, but also was able to achieve at least 30-40% lower dose to the rectum. The preliminary clinical results were also positive: 50% of patients reported no acute bowel toxicity, 33% reported Grade 1 toxicity, and 17% reported Grade 2 toxicity. No patients reported Grade 3-4 acute rectal toxicity. Conclusions: In this study, we developed a set of proposed rectal dose constraints. This allowed for volumetric assessment of the dose-volume relationship compared with single dose-volume histogram points. Additional research will be performed to validate this threshold as a class solution for rectal dose constraints. Ó 2008 Elsevier Inc.
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.