Purpose: This systematic review focused on rare histological types of corpus uteri malignancy, including uterine carcinosarcoma (UCS), uterine clear cell carcinoma (UCCC), and uterine papillary serous carcinoma (UPSC), and it is proposed to assist with clinical decision-making. Adjuvant treatment decisions must be made based on available evidences. We mainly investigated the role of vaginal interventional radiotherapy (VIRt) in UCS, UCCC, and UPSC managements. Material and methods: A systematic research using PubMed and Cochrane library was conducted to identify full articles evaluating the efficacy of VIRt in early-stage UPSC, UCCC, and UCS. A search in ClinicalTrials.gov was performed in order to detect ongoing or recently completed trials as well as in PROSPERO for ongoing or recently completed systematic reviews. Survival outcomes and toxicity rates were obtained. Results: All studies were retrospective. For UCS, the number of evaluated patients was 432. The 2- to 5-year average local control (LC) was 91% (range, 74.2-96%), disease-free survival (DFS) 88% (range, 82-94%), overall survival (OS) 79% (range, 53.8-84.3%), the average 5-year cancer-specific survival (CSS) was 70% (range, 70-94%), and G3-G4 toxicity was 0%. For UCCC, the number of investigated patients was 335 (UCCC - 124, mixed - 211), with an average 5-year LC of 100%, DFS of 83% (range, 82-90%), OS of 93% (range, 83-100%), and G3-G4 toxicity of 0%. For UPSC, the number of examined patients was 1,092 (UPSC - 866, mixed - 226). The average 5-year LC was 97% (range, 87.1-100%), DFS 84% (range, 74.7-95.6%), OS 93% (range, 71.9-100%), CSS 89% (range, 78.9-94%), and G3-G4 toxicity was 0%. Conclusions: These data suggest that in adequately selected early-stage UPSC and UCCC patients, VIRt alone may be suitable in women who underwent surgical staging and received adjuvant chemotherapy. In early-stage UCS, a multidisciplinary therapeutic approach has to be planned, considering high-rate of pelvic and distant relapses.

Purpose To evaluate clinical outcomes in patients with localized prostate cancer (LPC) treated with 3D conformal high-dose-rate (HDR) brachytherapy (BT) as monotherapy. Material and methods From March 2004 to November 2017, 277 men with LPC underwent 3D conformal HDR-BT as monotherapy, with a temporary implant. The dose prescription was: 38 Gy in 4 fractions (149 patients), 27 Gy in 2 fractions (41 patients), and 19-20 Gy in a single fraction (87 patients). Biochemical progression-free survival (bPFS), progression-free survival (PFS), and cancer-specific survival (CSS) were calculated. Acute and late genitourinary (GU) and gastrointestinal (GI) toxicity assessment were performed using Common Terminology Criteria for Adverse Events v5.0. Results The mean age was 67 (range, 47-81) years. Overall, 145 patients were low-risk, 116 intermediate-risk, and 16 high-risk prostate cancer. After a median follow-up of six years (range, 6-160 months), bPFS, PFS, and CSS were 81%, 96%, and 97%, respectively. Dose prescription, initial prostate specific antigen (iPSA) ≥ 9,5 ng/ml, and high-risk disease resulted in prognostic factors regarding bPFS. Only G2-G3 acute or late GI and GU toxicities were observed. Conclusions HDR-BT as monotherapy is a valid and safe treatment modality for localized prostate cancer. After a long follow-up, patients receiving 19-20 Gy in a single fraction had a lower biochemical control rate compared to patients receiving 38 Gy in 4 fractions or 27 Gy in 2 fractions. Randomized prospective trials with a longer follow-up are necessary to confirm our results, and define total doses and dose per fraction for HDR-BT in patients with LPC.

PURPOSE:Serous adenocarcinoma (uterine serous carcinoma - USC) is a rare and aggressive histologic subtype of endometrial cancer, with a high-rate of recurrence and poor prognosis. The adjuvant treatment for stage I patients is unclear. The purpose of this study was to evaluate the outcomes of stage I USC treated exclusively with chemotherapy plus vaginal brachytherapy (VBT).MATERIAL AND METHODS:A systematic research using PubMed, Scopus, and Cochrane library was conducted to identify full articles evaluating the efficacy of VBT in patients with stage I USC. A search in ClinicalTrials.gov was performed in order to detect ongoing or recently completed trials, and in PROSPERO for searching ongoing or recently completed systematic reviews.RESULTS:All studies were retrospective and 364 of evaluated patients were found. The average local control was 97.5% (range, 91-100%), the disease free-survival was 88% (range, 82-94%), the overall survival was 93% (range, 72-100%), the specific cancer survival was 89.4% (range, 84.8-94%), and the G3-G4 toxicity was 0-8%.CONCLUSIONS:These data support the concept that in adequately selected patients, VBT alone may be a suitable radiotherapy technique in women with stage I USC who underwent surgical staging and received adjuvant chemotherapy.

Women with high-risk endometrial cancer (HREC) are at increased risk of recurrence. The PORTEC-3 trial investigated the benefit of adjuvant chemotherapy during and after radiation therapy (CTRT) versus pelvic radiation therapy alone (RT) for women with HREC. In the present analysis we updated outcomes, focusing on patterns of recurrence, and survival and on results for serous cancers. Women with HREC (FIGO-stage I grade 3 with deep myometrial invasion and/or LVSI; stage II or III; or serous/ clear cell histology) were randomized (1:1) to CTRT (two cycles of cisplatin 50 mg/m2 in week 1&4 of RT, followed by four cycles of carboplatin AUC5 and paclitaxel 175 mg/m2 at 3-week intervals) or RT alone (48.6 Gy in 1.8 Gy fractions). The co-primary endpoints were overall survival (OS) and failure-free survival (FFS). Secondary endpoints vaginal, pelvic, and distant recurrence were analyzed according to first site of recurrence. The Kaplan-Meier method, log-rank test, and Cox regression analysis were used according to intention-to-treat, and competing risk methods for FFS and recurrence. Analysis of the primary endpoints was adjusted for the stratification factors (participating group, lymphadenectomy, stage of cancer and histological type). PORTEC-3 is registered with ISRCTN (ISRCTN14387080) and ClinicalTrials.gov (NCT00411138). Six hundred eighty-six women were enrolled between 2006 and 2013; 26 were excluded for immediate informed consent withdrawal or ineligibility, leaving 660 patients in the final analysis, 330 CTRT and 330 RT. Median follow-up was 72.6 months (IQR 59.9-85.6). 5-year OS was 81.4% vs 76.1% for CTRT vs RT [HR 0.70, 95% CI 0.51-0.97, p=0.034], and 5-year FFS was 76.5% vs 69.1% [HR 0.70, 95% CI 0.52-0.94, p=0.016]. Women with serous cancers had significantly lower OS compared with other histologies (62.0% vs 81.9% at 5 years), while 5-year OS for serous cancer was 71.4% with CTRT vs 52.8% with RT [HR 0.48, 95% CI 0.24-0.96, p=0.037], and 5-year FFS was 59.7% vs 47.9% [HR 0.42, 95% CI 0.22-0.80, p=0.008]. For women with stage III disease an absolute 5-year OS improvement of 10% (HR 0.63, 95% CI 0.41-0.99, p=0.043) and FFS improvement of 12.5% at (HR 0.61 (95% CI 0.42-0.89, p=0.011) was found with CTRT. Distant metastases were the first site of recurrence in the majority of patients, 21.4% (CTRT) vs 29.1% (RT) (p=0.047), and most patients received chemotherapy for recurrence. Survival after recurrence was 1.2 vs 1.4 years (p=0.7). Pelvic control was high in both arms with isolated vaginal or pelvic recurrence in only 1.2%. This updated analysis with median FU of 6 years showed a significantly improved OS and FFS with combined adjuvant chemotherapy and radiation therapy for HREC. The largest improvement was found for women with stage III and/or serous cancers. Shared decision making remains essential to weigh the costs and benefits for individual patients.

The role and identity of the general practitioner (GP) in the frame of primary care have significantly changed. The article of Livio Garattini and Anna Padula [1] compares the main traditional characteristics and recent tendencies of primary care in the English and Italian National Health Services. Through a comparative analysis the authors ask for more patient-centered primary care, recommending an holistic approach to patients and full access to services. Continuing the debate opened by these authors we emphasize once more the need to think over a person-centered model of primary care, reporting also some considerations that emerged from a recent survey conducted by the Social Healthcare Academy, PoliS Lombardia, Regional Institute for Policy Support.

Background Although women with endometrial cancer generally have a favourable prognosis, those with high-risk disease features are at increased risk of recurrence. The PORTEC-3 trial was initiated to investigate the benefit of adjuvant chemotherapy during and after radiotherapy (chemoradiotherapy) versus pelvic radiotherapy alone for women with high-risk endometrial cancer. Methods PORTEC-3 was an open-label, international, randomised, phase 3 trial involving 103 centres in six clinical trials collaborating in the Gynaecological Cancer Intergroup. Eligible women had high-risk endometrial cancer with FIGO 2009 stage I, endometrioid-type grade 3 with deep myometrial invasion or lymph-vascular space invasion (or both), endometrioid-type stage II or III, or stage I to III with serous or clear cell histology. Women were randomly assigned (1: 1) to receive radiotherapy alone (48.6 Gy in 1.8 Gy fractions given on 5 days per week) or radiotherapy and chemotherapy (consisting of two cycles of cisplatin 50 mg/m(2) given during radiotherapy, followed by four cycles of carboplatin AUC5 and paclitaxel 175 mg/m (2)) using a biased-coin minimisation procedure with stratification for participating centre, lymphadenectomy, stage of cancer, and histological type. The co-primary endpoints were overall survival and failure-free survival. We used the Kaplan-Meier method, log-rank test, and Cox regression analysis for final analysis by intention to treat and adjusted for stratification factors. The study was closed on Dec 20, 2013, after achieving complete accrual; follow-up is ongoing. PORTEC-3 is registered with ISRCTN, number ISRCTN14387080, and ClinicalTrials. gov, number NCT00411138. Findings 686 women were enrolled between Nov 23, 2006, and Dec 20, 2013. 660 eligible patients were included in the final analysis, of whom 330 were assigned to chemoradiotherapy and 330 were assigned to radiotherapy. Median follow-up was 60.2 months (IQR 48.1-73.1). 5-year overall survival was 81.8% (95% CI 77.5-86.2) with chemoradiotherapy versus 76.7% (72.1-81.6) with radiotherapy (adjusted hazard ratio [HR] 0.76, 95% CI 0.54-1.06; p= 0.11); 5-year failure-free survival was 75 . 5% (95% CI 70.3-79.9) versus 68.6% (63.1-73.4; HR 0.71, 95% CI 0.53-0.95; p= 0.022). Grade 3 or worse adverse events during treatment occurred in 198 (60%) of 330 who received chemoradiotherapy versus 41 (12%) of 330 patients who received radiotherapy (p< 0.0001). Neuropathy (grade 2 or worse) persisted significantly more often after chemoradiotherapy than after radiotherapy (20 [8%] women vs one [1%] at 3 years; p< 0.0001). Most deaths were due to endometrial cancer; in four patients (two in each group), the cause of death was uncertain. One death in the radiotherapy group was due to either disease progression or late treatment complications; three deaths (two in the chemoradiotherapy group and one in the radiotherapy group) were due to either intercurrent disease or late treatment-related toxicity. Interpretation Adjuvant chemotherapy given during and after radiotherapy for high-risk endometrial cancer did not improve 5-year overall survival, although it did increase failure-free survival. Women with high-risk endometrial cancer should be individually counselled about this combined treatment. Continued follow-up is needed to evaluate long-term survival.

5502 Background: Women with high-risk endometrial cancer (HREC) are at increased risk of distant metastasis and endometrial cancer-related death. The randomized PORTEC-3 intergroup trial was initiated to investigate the benefit of adjuvant chemotherapy during and after radiotherapy (CTRT) versus pelvic radiotherapy (RT) alone for women with HREC. Methods: Women with HREC (FIGO stage I grade 3 with deep myometrial invasion and/or LVSI; stage II or III; or serous/clear cell histology) were randomly allocated (1:1) to RT (48.6 Gy in 1.8 Gy fractions) or CTRT (two cycles of cisplatin 50 mg/m² in week 1 and 4 of RT, followed by four cycles of carboplatin AUC5 and paclitaxel 175 mg/m² at 3-week intervals) with stratification for participating center, lymphadenectomy, stage, and histological type. The co-primary endpoints were overall survival (OS) and failure-free survival (FFS). The Kaplan-Meier method, log-rank test and Cox regression analysis were used for final analysis according to intention-to-treat. PORTEC-3 is registered with ISRCTN (ISRCTN14387080) and ClinicalTrials.gov (NCT00411138). Results: 686 women were enrolled between 2006 and 2013. 26 women were excluded; 13 withdrew consent early and 13 were ineligible, which left 660 patients in the analysis, with a median follow up time of 60.2 months (IQR 47.1–72.9): 330 CTRT and 330 RT. Three- and five-year OS for CTRT vs. RT was 84.4% versus 83.9%, and 81.8% versus 76.7%; overall HR 0.79 [95% CI 0.57-1.12, p=0.183]. Three-year FFS was 79.7% (CTRT) versus 71.8% (RT), and at 5 years 75.5% versus 68.9%, overall HR for FFS 0.77 [0.58-1.03, p=0.078]. Patients with stage III EC had lower 5-year FFS and OS compared to stage I-II (FFS 63.9% vs 78.9%, p<0.001, and OS 74.3% vs 83.1%, p=0.003). They also had greatest benefit of CTRT: 5-year FFS for stage III was 69.3% for CTRT vs 58.0% for RT [95% CI 0.45-0.97, p=0.032], and 5-year OS for stage III was 78.7 % vs 69.8% (p=0.114). Conclusions: Adjuvant chemotherapy given during and after pelvic radiotherapy for treatment of HREC did not significantly improve 5-year FFS and OS, compared with RT alone. For women with stage III EC FFS was however significantly improved with CTRT by 11% at 5 years. Follow-up will continue to evaluate long-term outcomes. Clinical trial information: NCT00411138.

Background About 15% of patients with endometrial cancer have high-risk features and are at increased risk of distant metastases and endometrial cancer-related death. We designed the PORTEC-3 trial to investigate the benefit of adjuvant chemoradiotherapy compared with radiotherapy alone for women with high-risk endometrial cancer.Methods PORTEC-3 was a multicentre, open-label, randomised, international trial. Women with high-risk endometrial cancer were randomly allocated (1: 1) to radiotherapy alone (48.6 Gy) in 1.8 Gy fractions five times a week or chemoradiotherapy (two cycles concurrent cisplatin 50 mg/m(2) and four adjuvant cycles of carboplatin area under the curve [AUC] 5 and paclitaxel 175 mg/m(2)) using a biased coin minimisation procedure with stratification for participating centre, lymphadenectomy, stage of cancer, and histological type. The primary endpoints of the PORTEC-3 trial were overall survival and failure-free survival analysed in the intention-to-treat population. This analysis focuses on 2-year toxicity and health-related quality of life as secondary endpoints; analysis was done according to treatment received. Health-related quality of life was assessed with the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) the cervix cancer module and chemotherapy and neuropathy subscales of the ovarian cancer module at baseline, after radiotherapy and at 6, 12, 24, 36, and 60 months after randomisation. Adverse events were graded with Common Terminology Criteria for Adverse Events version 3.0. The study was closed on Dec 20, 2013, after achieving complete accrual, and follow-up remains ongoing for the primary outcomes analysis. This trial is registered with ISRCTN.com, number ISRCTN14387080, and with ClinicalTrials.gov, number NCT00411138.Findings Between Sept 15, 2006, and Dec 20, 2013, 686 women were randomly allocated in the PORTEC-3 trial. Of these, 660 met eligibility criteria, and 570 (86%) were evaluable for health-related quality of life. Median follow-up was 42.3 months (IQR 25.8-55.1). At completion of radiotherapy and at 6 months, EORTC QLQ-C30 functioning scales were significantly lower (worse functioning) and health-related quality of life symptom scores higher (worse symptoms) for the chemoradiotherapy group compared with radiotherapy alone, improving with time. At 12 and 24 months, global health or quality of life was similar between groups, whereas physical functioning scores remained slightly lower in patients who received chemoradiotherapy compared with patients who received radiotherapy alone. At 24 months, 48 (25%) of 194 patients in the chemoradiotherapy group reported severe tingling or numbness compared with 11 (6%) of 170 patients in the radiotherapy alone group (p<0.0001). Grade 2 or worse adverse events were found during treatment in 309 (94%) of 327 patients in the chemoradiotherapy group versus 145 (44%) of 326 patients in the radiotherapy alone group, and grade 3 or worse events were found in 198 (61%) of 327 patients in the chemoradiotherapy group versus 42 (13%) of 326 patients in the radiotherapy alone group (p<0.0001), with most of the grade 3 adverse events being haematological (45%). At 12 and 24 months, no significant differences in grade 3 or worse adverse events were found between groups; only grade 2 or higher sensory neuropathy adverse events persisted at 24 months (25 [10%] of 240 patients in the chemoradiotherapy group vs one [<1%] of 247 patients in the radiotherapy alone group; p<0.0001).Interpretation Despite the increased physician and patient-reported toxicities, this schedule of adjuvant chemotherapy given during and after radiotherapy in patients with high-risk endometrial cancer is feasible, with rapid recovery after treatment, but with persistence of patient-reported sensory neurological symptoms in 25% of patients. We await the analysis of primary endpoints before final conclusions are made. Copyright (C) The Author(s). Published by Elsevier Ltd.

A 79-year-old man presented with progressive dyspnea, gradually worsening over a period of several weeks. His past medical history included hypertension, chronic hepatitis C without cirrhosis, ischemic stroke occurred at the age of 68 and chronic obstructive pulmonary disease (COPD) caused by long-term cigarette smoking. The patient was alert and oriented and not in acute distress. The physical examination of the chest revealed decreased breath sounds at the bases of the lungs, without crackles or wheezes. Heart sounds were regular without murmurs. The respiration rate was normal. Extremities had no cyanosis, clubbing or oedema. The 12-lead electrocardiogram showed sinus rhythm with normal heart rate and non-specific T wave changes in D1, D2 and V5-V6. The chest radiograph revealed bilateral hilar prominence. Baseline peripheral capillary oxygen saturation (SpO2) measured by standard pulse oximetry was 89%. A face mask was placed, delivering oxygen at 6 L/min. The subsequent arterial blood gas analysis provided information on the following parameters: pH 7.41, PaCO2 34 mmHg, PaO2 64 mmHg, SaO2 91%. The full blood examination was normal, except for elevated C-reactive protein (50 mL/L, normal range < 10 mg/L) and D-dimer (782 ng/mL, normal range ≤ 270 ng/mL). A pulmonary embolism was suspected and a computed tomography pulmonary angiogram was then performed. No filling defects within the lumen of the pulmonary arterial branches were detected, neither were pleural effusion or pulmonary inflammatory infiltrates. A transthoracic echocardiogram (TTE) showed normal left ventricular ejection fraction, grade I diastolic dysfunction, normal heart valves, normal pulmonary pressure (systolic pulmonary artery pressure of 27 mmHg) and moderate enlargement of the ascending aorta (sinuses of Valsalva diameter of 49 mm). The patient was treated with a standard therapy for the acute exacerbation of COPD. Serum inflammatory markers progressively decreased. Nevertheless, episodes of dyspnea, central cyanosis and fluctuating hypoxia persisted. In clinostatism, SpO2 was 90% breathing ambient air. In the orthostatic position, it decreased to 70% with face mask delivering 10 L/min oxygen. The patient became cyanotic, but breath and heart sounds remained unremarkable in both supine and standing positions. A right-to-left shunt was suspected. A TTE and a transcranial Doppler ultrasound with agitated saline contrast showed a mild right-to-left shunt across the interatrial septum (Figure 1A). Contrast-enhanced echocardiography and contrast-enhanced transcranial Doppler ultrasound in both supine and sitting position were then performed. At 60 degrees incline, there was a dramatic shunt increase (Figure 1B). The patient underwent a 2D and 3D transesophageal echocardiography (TEE) in both supine and sitting position. It showed an aneurismal interatrial septum with patent foramen ovale (PFO) (Figure 1C & D). After the intravenous injection of agitated saline, the TEE documented a small right-to-left shunting across the PFO in the supine position. However, the TEE showed larger PFO size associated with significant shunt increasing in the upright position. The patient underwent successful percutaneous PFO closure with GORE® HELEX® Septal Occluder (W.L. Gore & Associates, Flagstaff, Arizona, USA). Subsequent right heart catheterisation demonstrated normal pulmonary pressures. The patient experienced progressive relief from dyspnea. Before discharge arterial saturation was 95% breathing room air without orthodeoxia. A strict clinical and echocardiographic follow-up was scheduled. Figure 1. Transthoracic and transesophageal echocardiographic images. Platypnea-orthodeoxia (POS) is a rare clinical syndrome characterized by dyspnea and deoxygenation in the sitting or upright position, relieved by the assumption of the supine position. Two conditions must coexist to cause POS: an anatomical defect (i.e., the interatrial communication) and a functional component that cause right-to-left shunt. The physiopathological explanation is still under debate. As matter of fact, the POS is characterized by dynamic right-to-left shunting in the absence of pulmonary hypertension. In 2002 this paradox has been described as “water flowing uphill”.[1] The possible mechanism could be an extrinsic compression of the right atrium, causing an increase of the atrial filling pressure and a right-to-left shunting across the atrial septum in the upright position.[3],[4] Positional modification of the atrial septum due to a different anatomical relationship of the inferior caval vein (IVC) with PFO or atrial septal defect may also cause a right-to-left shunting in the standing posture.[5] In the case presented, why a significant right-to-left shunting developed in a 79-year-old man with PFO? The PFO was apparently an “innocent bystander” during childhood, youth and adulthood of the patient. An ischemic stroke occurred when he was 68 years old. It can't be ruled out that the PFO may have played a role in the etiology of the ischemic stroke. However, at that time hypertension and cigarette smoking were assumed to be responsible for this. Subsequently, the PFO was proved “guilty” in old age. The association between POS and a number of conditions causing distortion of the interatrial septum has been described: kyphoscoliosis, pneumonectomy, aortic aneurysm or elongation.[6] The patient had a moderate enlargement of the ascending aorta that may have altered the intra-cardiac anatomical relationships stretching the right atrial septum. The co-existing atrial septal aneurysm could have caused a “spinnaker effect” redirecting the IVC flow through the PFO. As matter of fact, it is assumed that a prominent Eustachian valve could become redirected to the foramen ovale guiding the blood directly from the IVC to the foramen in elderly.[7] The proper diagnosis of POS may be difficult because the symptoms are non-specific. However, the POS should be considered in patients with unexplained dyspnea and deoxygenation related to postural changes. The most readily available and non-invasive diagnostic method is supine and upright contrast TTE.[8] TTE imaging in standing position is technically more difficult than in the standard left lateral one. Assessment of the anatomical correlation by TEE should be performed if an intra-cardiac shunt is detected.[9] The detection of this rare clinical syndrome has important therapeutic implications. Surgical or transcatheter percutaneous approaches to close atrial septal defect or PFO may be considered.[10] Percutaneous closure of PFO has been proposed as the treatment of choice for patients with POS.[11] However, there are no randomized controlled studies assessing the effectiveness of PFO closure in patients aged 75 years or older. Our case suggests that the diagnosis of POS is challenging in older patients complaining dyspnea. Percutaneous closure of PFO can be feasible, safe and effective in elderly with POS, comorbidities and frailty. Figure 2. Intracardiac echocardiographic image showing the GORE® HELEX® Septal Occluder device placement through the PFO.

5501 Background: PORTEC-3 is an intergroup trial investigating survival improvement with adjuvant chemotherapy given during and after pelvic RT (CTRT) versus RT alone (RT) for women with high-risk endometrial cancer (HR-EC). Primary endpoints are overall and failure free survival, secondary endpoints toxicity and health-related quality of life (HRQL). Accrual was completed Dec 2013. Toxicity and 2-year HRQL results are presented. Methods: 686 women with HR-EC were allocated to RT (48.6 Gy in 1.8 Gy fractions) or CTRT (2 cycles of cisplatin 50 mg/m2 during RT, followed by 4 cycles of carboplatin AUC5 and paclitaxel 175 mg/m2). Adverse events (AE) were graded using CTCAEv3.0. HRQL was evaluated using EORTC QLQ-C30 and symptom scales from CX 24 and OV28 at baseline, after RT and at 6-12 month follow up (FU) intervals. Results: 674 patients met eligibility criteria, and 572 (85%) were evaluable for HRQL. Median FU was 30 months. Rates of AE were significantly higher for CTRT vs RT. During RT, grade ≥ 2 AE were found in 79 vs 44%, and grade ≥ 3 in 36 vs 13% of patients, both p < 0.001. During FU, any grade ≥ 3 AE were reported in 67% (CTRT) vs 32% (RT), especially hematologic (32 vs 8%), neurologic (10 vs 2%) and GI AE (14 vs 5%, all p < 0.001). AE decreased over time; at 1 yr differences for CTRT vs RT were only significant for grade ≥ 2 neurologic (12 vs 1%, p < 0.001) and musculoskeletal AE (3 vs 0%, p = 0.015). Rates of any grade ≥2 and ≥3 AE were 47 vs 39% (p=0.06) and 12 vs 8% (ns). At 2 years, grade ≥2 neurologic AE persisted (10 vs 2%, p<0.001) without differences in grade ≥ 3 AE. QLQC30 functioning scores were lower and HRQL symptom scores were higher for CTRT vs RT after RT and at 6 months, improving with time. At 1 and 2 years, small (mean 5-6 points) but significant differences in physical, role, emotional and social functioning remained. Most striking differences at 2 years were tingling/numbness (24 vs 7%, p < 0.001) and weakness arm/legs (14 vs 9%, p < 0.001). Conclusions: CTRT for high-risk endometrial cancer causes significantly higher AE and symptom ratings and reduced HRQL during and after treatment as compared with RT, but with recovery over time, without differences in grade ≥ 3 AE at 2 years. Clinical trial information: NCT00411138.