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Purpose: To assess the impact of dose escalation of radiotherapy on quality of life (QoL) in prostate cancer patients. Patients and Methods: Three hundred prostate cancer patients participating in the Dutch randomized trial (CKTO 69-10) comparing 68 Gy with 78 Gy were the subject of this analysis. These patients filled out the SF-36 QoL questionnaire before radiotherapy (baseline) and 6, 12, 24, and 36 months thereafter. Changes in QoL over time of ≥10 points were considered clinically relevant. Repeated-measures regression analyses were applied to estimate and test the QoL changes over time, the differences between the two arms, and for association with a number of covariates. Results: At 3-year follow-up, the summary score physical health was 73.2 for the 68-Gy arm vs. 71.6 for the 78-Gy arm (p = 0.81), and the summary score mental health was 76.7 for the 68-Gy arm vs. 76.1 for the 78-Gy arm (p = 0.97). Statistically significant (p < 0.01) deterioration in QoL scores over time was registered in both arms in six scales. The deterioration over time was more pronounced in the high-dose arm for most scales. However, clinically relevant deterioration (>10 points) was seen for only two scales. None of the tested covariates were significantly correlated with QoL scores. Conclusion: Dose escalation did not result in significant deterioration of QoL in prostate cancer patients. In both randomization arms, statistically significant decreases in QoL scores over time were seen in six scales. The deterioration of QoL was more pronounced in the physical than in the mental health domain and in some scales more in the high- than in the low-dose arm, but the differences between arms were not statistically significant. [ABSTRACT FROM AUTHOR]

Purpose: To update the analysis of the Dutch dose-escalation trial of radiotherapy for prostate cancer. Patients and Methods: 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 μg/L). The secondary endpoints were freedom from clinical failure, overall survival, and genitourinary and gastrointestinal toxicity. Results: 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). Conclusion: 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. [Copyright &y& Elsevier]

Purpose: In 2000, the results of the multicenter Post Operative Radiation Therapy in Endometrial Carcinoma (PORTEC) trial were published. This trial included 714 Stage I endometrial carcinoma patients randomly assigned to postoperative pelvic radiotherapy (RT) or no further treatment, excluding those with Stage IC, Grade 3, or Stage IB, Grade 1 lesions. Radiotherapy significantly decreased the risk of locoregional recurrence (4% vs. 14%), without affecting overall survival. In this report the long-term outcome and results with central pathology review are presented. Methods and Materials: The slides of 569 patients (80%) could be obtained for pathology review. Median follow-up for patients alive was 97 months. Analysis was done according to the intention-to-treat principle. The primary study endpoints were locoregional recurrence and death. Results: Ten-year locoregional relapse rates were 5% (RT) and 14% (controls; p < 0.0001), and 10-year overall survival was 66% and 73%, respectively (p = 0.09). Endometrial cancer related death rates were 11% (RT) and 9% (controls; p = 0.47). Pathology review showed a substantial shift from Grade 2 to Grade 1, but no significant difference for Grade 3. When cases diagnosed at review as Grade 1 with superficial myometrial invasion were excluded from the analysis, the results remained essentially the same, with 10-year locoregional recurrence rates of 5% (RT) and 17% (controls; p < 0.0001). Conclusions: In view of the significant locoregional control benefit, radiotherapy remains indicated in Stage I endometrial carcinoma patients with high-risk features for locoregional relapse. [Copyright &y& Elsevier]

: ObjectiveThe aim of this study was to determine the rates of local control and survival after relapse in patients with stage I endometrial cancer treated in the multicenter randomized PORTEC trial.: MethodsThe PORTEC trial included 715 patients with stage 1 endometrial cancer, either grade 1 or 2 with deep (>50%) myometrial invasion or grade 2 or 3 with <50% invasion. In all cases an abdominal hysterectomy was performed, without lymphadenectomy. After surgery, patients were randomized to receive pelvic RT (46 Gy) or no further treatment.: ResultsThe analysis was done by intention-to-treat. A total of 714 patients were evaluated. At a median follow-up of 73 months, 8-year actuarial locoregional recurrence rates were 4% in the RT group and 15% in the control group (P < 0.0001). The 8-year actuarial overall survival rates were 71 (RT group) and 77% (control group, P = 0.18). Eight-year rates of distant metastases were 10 and 6% (P = 0.20). The majority of the locoregional relapses were located in the vagina, mainly in the vaginal vault. Of the 39 patients with isolated vaginal relapse, 35 (87%) were treated with curative intent, usually with external RT and brachytherapy, and surgery in some. A complete remission (CR) was obtained in 31 of the 35 patients (89%), and 24 patients (77%) were still in CR after further follow-up. Five patients subsequently developed distant metastases, and 2 had a second vaginal recurrence. The 3-year survival after first relapse was 51% for patients in the control group and 19% in the RT group (P = 0.004). The 3-year survival after vaginal relapse was 73%, in contrast to 8 and 14% after pelvic and distant relapse (P < 0.001). At 5 years, the survival after vaginal relapse was 65% in the control group compared to 43% in the RT group.: ConclusionSurvival after relapse was significantly better in the patient group without previous RT. Treatment for vaginal relapse was effective, with 89% CR and 65% 5-year survival in the control group, while there was no difference in survival between patients with pelvicrelapse and those with distant metastases. As pelvic RT was shown to improve locoregional control significantly, but without a survival benefit, its use should be limited to those patients at sufficiently high risk (15% or over) for recurrence in order to maximize local control and relapse-free survival. [ABSTRACT FROM AUTHOR]

Purpose: To compare acute and late gastrointestinal (GI) and genitourinary (GU) side effects in prostate cancer patients randomized to receive 68 Gy or 78 Gy. Methods and materials: Between June 1997 and February 2003, 669 prostate cancer patients were randomized between radiotherapy with a dose of 68 Gy and 78 Gy, in 2 Gy per fraction and using three-dimensional conformal radiotherapy. All T stages with prostate-specific antigen (PSA) <60 ng/mL were included, except any T1a and well-differentiated T1b-c tumors with PSA ≤4 ng/mL. Stratification was done for four dose–volume groups (according to the risk of seminal vesicles [SV] involvement), age, hormonal treatment (HT), and hospital. The clinical target volume (CTV) consisted of the prostate with or without the SV, depending on the estimated risk of SV invasion. The CTV–planning target volume (PTV) margin was 1 cm for the first 68 Gy and was reduced to 0.5 cm (0 cm toward the rectum) for the last 10 Gy in the 78 Gy arm. Four Dutch hospitals participated in this Phase III trial. Evaluation of acute and late toxicity was based on 658 and 643 patients, respectively. For acute toxicity (<120 days), the Radiation Therapy Oncology Group (RTOG) scoring system was used and the maximum score was reported. Late toxicity (>120 days) was scored according to the slightly adapted RTOG/European Organization for Research and Treatment of Cancer (EORTC) criteria. Results: The median follow-up time was 31 months. For acute toxicity no significant differences were seen between the two randomization arms. GI toxicity Grade 2 and 3 was reported as the maximum acute toxicity in 44% and 5% of the patients, respectively. For acute GU toxicity, these figures were 41% and 13%. No significant differences between both randomization arms were seen for late GI and GU toxicity, except for rectal bleeding requiring laser treatment or transfusion (p = 0.007) and nocturia (p = 0.05). The 3-year cumulative risk of late RTOG/EORTC GI toxicity grade ≥2 was 23.2% for 68 Gy, and 26.5% for 78 Gy (p = 0.3). The 3-year risks of late RTOG/EORTC GU toxicity grade ≥2 were 28.5% and 30.2% for 68 Gy and 78 Gy, respectively (p = 0.3). Factors related to acute GI toxicity were HT (p < 0.001), a higher dose–volume group (p = 0.01), and pretreatment GI symptoms (p = 0.04). For acute GU toxicity, prognostic factors were: pretreatment GU symptoms (p < 0.001), HT (p = 0.003), and prior transurethral resection of the prostate (TURP) (p = 0.02). A history of abdominal surgery (p < 0.001) and pretreatment GI symptoms (p = 0.001) were associated with a higher incidence of late GI grade ≥2 toxicity, whereas HT (p < 0.001), pretreatment GU symptoms (p < 0.001), and prior TURP (p = 0.006) were prognostic factors for late GU grade ≥2. Conclusions: Raising the dose to the prostate from 68 Gy to 78 Gy resulted in higher incidences of acute and late GI and GU toxicity, but these differences were not significant, except for late rectal bleeding requiring treatment and late nocturia. Other factors than the studied dose levels appeared to be important in predicting toxicity after radiotherapy, especially previous surgical interventions (abdominal surgery or TURP), hormonal therapy, and the presence of pretreatment symptoms. [Copyright &y& Elsevier]

Purpose: To identify dosimetric parameters derived from anorectal, rectal, and anal wall dose distributions that correlate with different late gastrointestinal (GI) complications after three-dimensional conformal radiotherapy for prostate cancer. Methods and Materials: In this analysis, 641 patients from a randomized trial (68 Gy vs. 78 Gy) were included. Toxicity was scored with adapted Radiation Therapy Oncology Group/European Organization for the Research and Treatment of Cancer (RTOG/EORTC) criteria and five specific complications. The variables derived from dose–volume histogram of anorectal, rectal, and anal wall were as follows: % receiving ≥5–70 Gy (V5–V70), maximum dose (Dmax), and mean dose (Dmean). The anus was defined as the most caudal 3 cm of the anorectum. Statistics were done with multivariate Cox regression models. Median follow-up was 44 months. Results: Anal dosimetric variables were associated with RTOG/EORTC Grade ≥2 (V5–V40, Dmean) and incontinence (V5–V70, Dmean). Bleeding correlated most strongly with anorectal V55–V65, and stool frequency with anorectal V40 and Dmean. Use of steroids was weakly related to anal variables. No volume effect was seen for RTOG/EORTC Grade ≥3 and pain/cramps/tenesmus. Conclusion: Different volume effects were found for various late GI complications. Therefore, to evaluate the risk of late GI toxicity, not only intermediate and high doses to the anorectal wall volume should be taken into account, but also the dose to the anal wall. [Copyright &y& Elsevier]