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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. 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/m2 given during radiotherapy, followed by four cycles of carboplatin AUC5 and paclitaxel 175 mg/m2) 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. 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. 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. Dutch Cancer Society, Cancer Research UK, National Health and Medical Research Council Project Grant and Cancer Australia, L'Agenzia Italiana del Farmaco, and Canadian Cancer Society Research Institute.

Postoperative radiotherapy for International Federation of Gynaecology and Obstetrics (FIGO) stage-1 endometrial carcinoma is a subject of controversy due to the low relapse rate and the lack of data from randomised trials. We did a multicentre prospective randomised trial to find whether postoperative pelvic radiotherapy improves locoregional control and survival for patients with stage-1 endometrial carcinoma Patients with stage-1 endometrial carcinoma (grade 1 with deep [≥50%] myometrial invasion, grade 2 with any invasion, or grade 3 with superficial [<50%] invasion) were enrolled. After total abdominal hysterectomy and bilateral salpingo-oophorectomy, without lymphadenectomy, 715 patients from 19 radiation oncology centres were randomised to pelvic radiotherapy (46 Gy) or no further treatment. The primary study endpoints were locoregional recurrence and death, with treatment-related morbidity and survival after relapse as secondary endpoints. Analysis was done according to the intention-to-treat principle. Of the 715 patients, 714 could be evaluated. The median duration of follow-up was 52 months. 5-year actuarial locoregional recurrence rates were 4% in the radiotherapy group and 14% in the control group (p<0·001). Actuarial 5-year overall survival rates were similar in the two groups: 81% (radiotherapy) and 85% (controls), p=0·31. Endometrial-cancer-related death rates were 9% in the radiotherapy group and 6% in the control group (p=0·37). Treatment-related complications occurred in 25% of radiotherapy patients, and in 6% of the controls (p<0·0001). Two-thirds of the complications were grade 1. Grade 3–4 complications were seen in eight patients, of which seven were in the radiotherapy group (2%). 2-year survival after vaginal recurrence was 79%, in contrast to 21% after pelvic recurrence or distant metastases. Survival after relapse was significantly (p=0·02) better for patients in the control group. Multivariate analysis showed that for locoregional recurrence, radiotherapy and age below 60 years were significant favourable prognostic factors. Postoperative radiotherapy in stage-1 endometrial carcinoma reduces locoregional recurrence but has no impact on overall survival. Radiotherapy increases treatment-related morbidity. Postoperative radiotherapy is not indicated in patients with stage-1 endometrial carcinoma below 60 years and patients with grade-2 tumours with superficial invasion.

MiStent is a drug-eluting stent with a fully absorbable polymer coating containing and embedding a microcrystalline form of sirolimus into the vessel wall. It was developed to overcome the limitation of current durable polymer drug-eluting stents eluting amorphous sirolimus. The clinical effect of MiStent sirolimus-eluting stent compared with a durable polymer drug-eluting stents has not been investigated in a large randomised trial in an all-comer population. We did a randomised, single-blind, multicentre, phase 3 study (DESSOLVE III) at 20 hospitals in Germany, France, Netherlands, and Poland. Eligible participants were any patients aged at least 18 years who underwent percutaneous coronary intervention in a lesion and had a reference vessel diameter of 2·50–3·75 mm. We randomly assigned patients (1:1) to implantation of either a sirolimus-eluting bioresorbable polymer stent (MiStent) or an everolimus-eluting durable polymer stent (Xience). Randomisation was done by local investigators via web-based software with random blocks according to centre. The primary endpoint was a non-inferiority comparison of a device-oriented composite endpoint (DOCE)—cardiac death, target-vessel myocardial infarction, or clinically indicated target lesion revascularisation—between the groups at 12 months after the procedure assessed by intention-to-treat. A margin of 4·0% was defined for non-inferiority of the MiStent group compared with the Xience group. All participants were included in the safety analyses. This trial is registered with ClinicalTrials.gov, number NCT02385279. Between March 20, and Dec 3, 2015, we randomly assigned 1398 patients with 2030 lesions; 703 patients with 1037 lesions were assigned to MiStent, of whom 697 received the index procedure, and 695 patients with 993 lesions were asssigned to Xience, of whom 690 received the index procedure. At 12 months, the primary endpoint had occurred in 40 patients (5·8%) in the sirolimus-eluting stent group and in 45 patients (6·5%) in the everolimus-eluting stent group (absolute difference −0·8% [95% CI −3·3 to 1·8], pnon-inferiority=0·0001). Procedural complications occurred in 12 patients (1·7%) in the sirolimus-eluting stent group and ten patients (1·4%) in the everolimus-eluting stent group; no clinical adverse events could be attributed to these dislodgements through a minimum of 12 months of follow-up. The rate of stent thrombosis, a safety indicator, did not differ between groups and was low in both treatment groups. The sirolimus-eluting bioabsorbable polymer stent was non-inferior to the everolimus-eluting durable polymer stent for a device-oriented composite clinical endpoint at 12 months in an all-comer population. MiStent seems a reasonable alternative to other stents in clinical practice. The European Cardiovascular Research Institute, Micell Technologies (Durham, NC, USA), and Stentys (Paris, France).

PurposeTo provide insight into the current use and results of ultrasound-facilitated catheter-directed thrombolysis (USAT) in patients with high-risk pulmonary embolism (PE).IntroductionSystemic thrombolysis is an effective treatment for hemodynamically unstable, high-risk PE, but is associated with bleeding complications. USAT is thought to reduce bleeding and is therefore advocated in patients with high-risk PE and contraindications for systemic thrombolysis.MethodsWe conducted a retrospective cohort study of all patients who underwent USAT for high-risk PE in the Netherlands from 2010 to 2017. Characteristics and outcomes were analyzed. Primary outcomes were major (including intracranial and fatal) bleeding and all-cause mortality after 1 month. Secondary outcomes were all-cause mortality and recurrent venous thromboembolism within 3 months.Results33 patients underwent USAT for high-risk PE. Major bleeding occurred in 12 patients (36%, 95% CI 22–53), including 1 intracranial and 3 fatal bleeding. All-cause mortality after 1 month was 48% (16/33, 95% CI 31–66). All-cause mortality after 3 months was 50% (16/32, 95% CI 34–66), recurrent venous thromboembolism occurred in 1 patient (1/32, 3%, 95% CI 1–16).ConclusionsThis study was the first to describe characteristics and outcomes after USAT in a study population of patients with high-risk PE only, an understudied population. Although USAT is considered a relatively safe treatment option, our results illustrate that at least caution is needed in critically ill patients with high-risk PE. Further research in patients with high-risk PE is warranted to guide patient selection.