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      Adjuvant vaginal cuff brachytherapy for high-risk, early stage endometrial cancer

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          Abstract

          Purpose

          To report outcomes following adjuvant high-dose-rate vaginal brachytherapy (VBT) with or without chemotherapy for high-intermediate risk (HIR) and high-risk, early stage endometrial cancer as defined in Gynecologic Oncology Group trial 0249.

          Material and methods

          From May 2000 to January 2014, 68 women with HIR and high-risk endometrial cancer underwent surgical staging followed by VBT. Median VBT dose was 21 Gy delivered in three fractions prescribed to 0.5 cm depth. Paclitaxel 175 mg/m 2 and carboplatin area under the curve 6 was administered every 21 days in sequence with VBT. Actuarial survival estimates were calculated using the Kaplan-Meier method.

          Results

          Patient demographics included a median age of 66 years (range: 36-91) and stages IA (49%), IB (38%), and II (13%), respectively. Thirty-one (46%) patients had HIR disease with endometrioid histology, and 33 (48%) patients had serous or clear cell histology. Thirty-seven (54%) patients received a median 3 cycles (range: 3-6) of chemotherapy in addition to VBT, and 65 patients (96%) completed all prescribed therapy. During a median follow up of 33.1 months (range: 4.0-161.7), four patients have recurred, including one vaginal recurrence. The 3-year estimates of vaginal, pelvic, and distant recurrences were 1.9%, 2.4%, and 9.1%, respectively. The 3-year rates of disease-free and overall survival were 87.7% and 93.9%, respectively.

          Conclusions

          Early outcomes with adjuvant VBT with or without chemotherapy demonstrate high rates of vaginal and pelvic control for women with HIR disease. Early vaginal and pelvic relapses in high-risk patients suggest that pelvic external beam radiotherapy is warranted in this subgroup, but additional data from large phase III trials is warranted.

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          Most cited references 34

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          Survival after relapse in patients with endometrial cancer: results from a randomized trial.

          The 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. The 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. The 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. Survival 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 pelvic relapse 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.
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            Prognosis of papillary serous, clear cell, and grade 3 stage I carcinoma of the endometrium.

            The purpose of this study was to evaluate patients with uterine papillary serous carcinoma (UPSC), clear cell (CC), and grade 3 endometrioid (G3) surgically stage I endometrial cancer. The 25th Annual Report (AR) of FIGO was used to identify patients with endometrial cancers who were surgically staged. For comparison, all cancers reported were evaluated with particular interest in patients with stage I UPSC, CC, and G3. Incidence, substage, post-surgical treatment, and survival were identified. Of 5694 endometrial cancer patients reported to the AR, 3996 (70%) were surgically stage I. There were 148 UPSC, 59 CC, and 325 with G3 lesions. UPSC and CC represent 5.2% of all stage I cancers while 8.1% are G3. Although there were greater number of UPSC, CC, and G3 with extrauterine disease, about 50% of UPSC and CC were stage I. This compares to 81% for G1, 68% for G2, and only 42% for G3. There were more IA cancers with UPSC and CC than G3 (22%, 33%, and 17%, respectively). Survival (5 years) for UPSC and CC was 72% and 81%, respectively, compared to 76% for G3 lesions. Postoperative radiation improved survival somewhat (6-8%) but the difference was not significant. UPSC and CC histotypes when diagnosed as stage I have a better survival than commonly perceived and equal to G3 endometrioid cancers. Postoperative radiation improves survival but not significantly so. The role of chemotherapy has not been defined.
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              Long-term outcome and quality of life of patients with endometrial carcinoma treated with or without pelvic radiotherapy in the post operative radiation therapy in endometrial carcinoma 1 (PORTEC-1) trial.

              To determine the long-term outcome and health-related quality of life (HRQL) of patients with endometrial carcinoma (EC) treated with or without pelvic radiotherapy in the Post Operative Radiation Therapy in Endometrial Carcinoma 1 (PORTEC-1) trial. Between 1990 and 1997, 714 patients with stage IC grade 1 to 2 or IB grade 2 to 3 EC were randomly allocated to pelvic external-beam radiotherapy (EBRT) or no additional treatment (NAT). HRQL was evaluated with the Short Form 36-Item (SF-36) questionnaire; subscales from the European Organisation for Research and Treatment of Cancer (EORTC) PR25 module for bowel and bladder symptoms and the OV28 and CX24 modules for sexual symptoms; and demographic questions. Analysis was by intention-to-treat. Median follow-up was 13.3 years. The 15-year actuarial locoregional recurrence rates were 5.8% for EBRT versus 15.5% for NAT (P < .001), and 15-year overall survival was 52% versus 60% (P = .14). Of the 351 patients confirmed to be alive with correct address, 246 (70%) returned the questionnaire. Patients treated with EBRT reported significant (P < .01) and clinically relevant higher rates of urinary incontinence, diarrhea, and fecal leakage leading to more limitations in daily activities. Increased symptoms were reflected by the frequent use of incontinence materials after EBRT (day and night use, 42.9% v 15.2% for NAT; P < .001). Patients treated with EBRT reported lower scores on the SF-36 scales "physical functioning" (P = .004) and "role-physical" (P = .003). EBRT for endometrial cancer is associated with long-term urinary and bowel symptoms and lower physical and role-physical functioning, even 15 years after treatment. Despite its efficacy in reducing locoregional recurrence, EBRT should be avoided in patients with low- and intermediate-risk EC.
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                Author and article information

                Journal
                J Contemp Brachytherapy
                J Contemp Brachytherapy
                JCB
                Journal of Contemporary Brachytherapy
                Termedia Publishing House
                1689-832X
                2081-2841
                05 September 2014
                October 2014
                : 6
                : 3
                : 262-270
                Affiliations
                [1 ]Department of Radiation Oncology, Kimmel Cancer Center, Thomas Jefferson University Hospital
                [2 ]Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, Thomas Jefferson University Hospital
                [3 ]Department of Medical Oncology, Kimmel Cancer Center, Thomas Jefferson University Hospital, Philadelphia, USA
                Author notes
                Address for correspondence: Harriet Belding Eldredge-Hindy, MD, Department of Radiation Oncology, Kimmel Cancer Center, Thomas Jefferson University Hospital, Philadelphia, PA, USA, 111 South 11th Street, Philadelphia, PA 19107, USA. phone: +1 215 503-7554. e-mail: harrieteldredge@ 123456gmail.com
                Article
                23468
                10.5114/jcb.2014.45031
                4200177
                Copyright © 2014 Termedia

                This is an Open Access article distributed under the terms of the Creative Commons Attribution-Noncommercial 3.0 Unported License, permitting all non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

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