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Purpose: To explore current variations in the use of primary radiotherapy (RT) in a region with two RT departments with adjacent referral areas, one in the eastern and one in the western sector of the southern region of the Netherlands. Methods and Materials: We calculated the proportion of 147,588 patients with newly diagnosed cancer between 1988 and 2006 in the southern Netherlands who received primary RT. Especially for breast and rectal cancer patients we studied primary RT use according to stage (breast cancer) and age and separately for the eastern and western sectors. Results: The number of patients with new diagnoses receiving primary RT increased from 1,668 patients in 1988 to 2,971 patients in 2006, with the proportion of the overall patients receiving RT remaining more or less unchanged (±30%). However, only 20% of elderly patients (75+ years) received primary RT. Over time, more patients with prostate and rectal cancer, fewer patients with lung and bladder cancer or Hodgkin''s lymphoma, and, recently, more patients with cervical or endometrial cancer received RT. The proportion of patients with most other tumor types treated with RT remained more or less unchanged. The total RT rate was slightly higher for patients in the eastern sector. Of particular note, patients with breast or rectal cancer in the eastern sector were significantly more likely to receive primary RT than were their counterparts in the western sector (odds ratio = 1.4, 95% confidence interval =1.4–1.5, and odds ratio = 1.4, 95% confidence interval = 1.3–1.6, respectively). Conclusions: Although the number of RT-treated patients increased substantially during 1988 to 2006, the proportion remained essentially unchanged. In addition, large variations were found in referral rates for RT, especially in later years, between the eastern and the western sectors of the region. [Copyright &y& Elsevier]

Purpose: While patients with early-stage Hodgkin lymphoma (HL) have an excellent outcome with combined treatment, the radiation therapy (RT) dose and treatment with chemotherapy alone remain questionable. This noninferiority trial evaluates the feasibility of reducing the dose or omitting RT after chemotherapy.Methods and Materials: Patients with untreated supradiaphragmatic HL without risk factors (age ≥ 50 years, 4 to 5 nodal areas involved, mediastinum-thoracic ratio ≥ 0.35, and erythrocyte sedimentation rate ≥ 50 mm in first hour without B symptoms or erythrocyte sedimentation rate ≥ 30 mm in first hour with B symptoms) were eligible for the trial. Patients in complete remission after chemotherapy were randomized to no RT, low-dose RT (20 Gy in 10 fractions), or standard-dose involved-field RT (36 Gy in 18 fractions). The limit of noninferiority was 10% for the difference between 5-year relapse-free survival (RFS) estimates. From September 1998 to May 2004, 783 patients received 6 cycles of epirubicin, bleomycin, vinblastine, and prednisone; 592 achieved complete remission or unconfirmed complete remission, of whom 578 were randomized to receive 36 Gy (n=239), 20 Gy of involved-field RT (n=209), or no RT (n=130).Results: Randomization to the no-RT arm was prematurely stopped (≥20% rate of inacceptable events: toxicity, treatment modification, early relapse, or death). Results in the 20-Gy arm (5-year RFS, 84.2%) were not inferior to those in the 36-Gy arm (5-year RFS, 88.6%) (difference, 4.4%; 90% confidence interval [CI] -1.2% to 9.9%). A difference of 16.5% (90% CI 8.0%-25.0%) in 5-year RFS estimates was observed between the no-RT arm (69.8%) and the 36-Gy arm (86.3%); the hazard ratio was 2.55 (95% CI 1.44-4.53; P<.001). The 5-year overall survival estimates ranged from 97% to 99%.Conclusions: In adult patients with early-stage HL without risk factors in complete remission after epirubicin, bleomycin, vinblastine, and prednisone chemotherapy, the RT dose may be limited to 20 Gy without compromising disease control. Omitting RT in these patients may jeopardize the treatment outcome. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the very long-term results of the randomized Post Operative Radiation Therapy in Endometrial Carcinoma (PORTEC)-1 trial for patients with Stage I endometrial carcinoma (EC), focusing on the role of prognostic factors for treatment selection and the long-term risk of second cancers. Patients and Methods: The PORTEC trial (1990–1997) included 714 patients with Stage IC Grade 1–2 or Stage IB Grade 2–3 EC. After surgery, patients were randomly allocated to external-beam pelvic radiotherapy (EBRT) or no additional treatment (NAT). Analysis was by intention to treat. Results: 426 patients were alive at the date of analysis. The median follow-up time was 13.3 years. The 15-year actuarial locoregional recurrence (LRR) rates were 6% for EBRT vs. 15.5% for NAT (p < 0.0001). The 15-year overall survival was 52% vs. 60% (p = 0.14), and the failure-free survival was 50% vs. 54% (p = 0.94). For patients with high-intermediate risk criteria, the 15-year overall survival was 41% vs. 48% (p = 0.51), and the 15-year EC-related death was 14% vs. 13%. Most LRR in the NAT group were vaginal recurrences (11.0% of 15.5%). The 15-year rates of distant metastases were 9% vs. 7% (p = 0.25). Second primary cancers had been diagnosed over 15 years in 19% of all patients, 22% vs. 16% for EBRT vs. NAT (p = 0.10), with observed vs. expected ratios of 1.6 (EBRT) and 1.2 (NAT) compared with a matched population (p = NS). Multivariate analysis confirmed the prognostic significance of Grade 3 for LRR (hazard ratio [HR] 3.4, p = 0.0003) and for EC death (HR 7.3, p < 0.0001), of age >60 (HR 3.9, p = 0.002 for LRR and 2.7, p = 0.01 for EC death) and myometrial invasion >50% (HR 1.9, p = 0.03 and HR 1.9, p = 0.02). Conclusions: The 15-year outcomes of PORTEC-1 confirm the relevance of HIR criteria for treatment selection, and a trend for long-term risk of second cancers. EBRT should be avoided in patients with low- and intermediate-risk EC. [ABSTRACT FROM AUTHOR]

Abstract: Objectives: Routine lymphadenectomy (LA) in early stage endometrial cancer does not improve survival. However, in the absence of lymph node metastasis, radiotherapy (RT) could be withheld and hence could result in less morbidity. Our aim was to evaluate health related quality of life (HRQL) in endometrial cancer survivors that received routine pelvic LA without RT compared to no LA, but RT in the presence of risk factors. Methods: Stage I–II endometrial cancer survivors diagnosed between 1999 and 2007 were selected from the Eindhoven Cancer Registry. Survivors completed the SF-36 and the EORTC-QLQ-EN24. ANCOVA and multiple linear regression analyses were applied. Results: 742 (77%) of the endometrial cancer survivors returned a completed questionnaire. 377 (51%) had received no LA nor RT (LA−RT−), 198 (27%) had received LA+RT−, 153 (21%) LA−RT+ and 14 patients (2%) had received both. LA+ women reported as higher lymphedema symptom scores (25 vs. 20, p=0.04). Women who were treated with RT reported higher gastrointestinal symptom scores vs. those who did not (23 vs. 16, p=0.04). HRQL scales were comparable between all four treatment groups. Conclusion: Despite distinct symptom patterns among women who received LA or RT, no clinically relevant differences in HRQL were observed when compared to women not receiving adjuvant therapy. Using LA to tailor adjuvant pelvic radiotherapy and prevent over-treatment in low-risk patients cannot be recommended. [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]