Epicure: a European epidemiological study of patients with an advanced or metastatic Urothelial Carcinoma (UC) having progressed to a platinum-based chemotherapy

Background: Platinum-based systemic chemotherapy is considered the backbone for management of advanced urothelial carcinomas. However there is a lack of real world data on the use of such chemotherapy regimens, on patient profiles and on management after treatment failure. Methods: Fifty-one randomly selected physicians from 4 European countries registered 218 consecutive patients in progression or relapse following a first platinum-based chemotherapy. Patient characteristics, tumor history and treatment regimens, as well as the considerations of physicians on the management of urothelial carcinoma were recorded. Results: A systemic platinum-based regimen had been administered as the initial chemotherapy in 216 patients: 15 in the neoadjuvant setting, 61 in adjuvant therapy conditions, 137 in first-line advanced setting and 3 in other conditions. Of these patients, 76 (35 %) were initially considered as cisplatin-unfit, mainly because of renal impairment (52 patients). After platinum failure, renal impairment was observed in 44 % of patients, ECOG Performance Status ≥ 2 in 17 %, hemoglobinemia 30 % patients). The most frequent all-settings second anticancer therapy regimen was vinflunine (70 % of single-agent and 42 % of all subsequent treatments), the main reasons evoked by physicians (>1 out of 4) being survival benefit, safety and phase III evidence. Conclusion: In this daily practice experience, a majority of patients with urothelial carcinoma previously treated with a platinum-based therapy received a second chemotherapy regimen, most often a single agent after an initial chemotherapy in the advanced setting and preferably a cytotoxic combination after a neoadjuvant or adjuvant chemotherapy. Performance Status and prior response to chemotherapy were the main drivers of further treatment decisions

PSA Kinetics as Prognostic Markers of Overall Survival in Patients with Metastatic Castration-Resistant Prostate Cancer Treated with Abiraterone Acetate

Background: Abiraterone acetate (AA) is widely used in the treatment of patients with metastatic castration-resistant prostate cancer (mCRPC). However, a significant percentage of patients will still progress, highlighting the need to identify patients more likely to benefit from AA. Parameters linked to prostate-specific antigen (PSA) kinetics are promising prognostic markers. We have examined clinical and PSA-related factors potentially asso- ciated with overall survival (OS) in patients treated with AA. Methods: Between 2011 and 2014, 104 patients with mCRPC treated with AA after progression to docetaxel at centers of the Catalan Institute of Oncology were included in this retrospective study. Patients were assessed monthly. Baseline characteristics and vari- ables related to PSA kinetics were included in univariate and multivariate analyses of OS. Results: Median OS was 16.4 months (range 12.4-20.6) for all patients. The univariate analysis identified the following baseline characteristics as significantly associated with OS: ECOG PS, location of metastases, time between starting androgen deprivation therapy and starting AA, time between stopping docetaxel treatment and starting AA, neutrophil- lymphocyte ratio (NLR), alkaline phosphatase levels, and PSA levels. Factors related to PSA kinetics associated with longer OS were PSA response >50%, early PSA response (>30% decline at four weeks), PSA decline >50% at week 12, PSA nadir 140 days, the combination of PSA nadir and time to PSA nadir, and low end-of- treatment PSA levels. The multivariate analysis identified ECOG PS (HR 37.46; p<0.001), NLR (HR 3.7; p<0.001), early PSA response (HR 1.22; p=0.002), and time to PSA nadir (HR 0.39; p=0.002) as independent prognostic markers. Conclusion: Our results indicate an association between PSA kinetics, especially early PSA response, and outcome to AA after progression to docetaxel. Taken together with other factors, lack of an early PSA response could identify patients who are unlikely to benefit from AA and who could be closely monitored with a view to offering alternative therapies

Bone sarcomas: ESMO–EURACAN–GENTURIS–ERN PaedCan Clinical Practice Guideline for diagnosis, treatment and follow-up

Production costs have been covered by ESMO from central funds

Sarcoma classification by DNA methylation profiling

Sarcomas are malignant soft tissue and bone tumours affecting adults, adolescents and children. They represent a morphologically heterogeneous class of tumours and some entities lack defining histopathological features. Therefore, the diagnosis of sarcomas is burdened with a high inter-observer variability and misclassification rate. Here, we demonstrate classification of soft tissue and bone tumours using a machine learning classifier algorithm based on array-generated DNA methylation data. This sarcoma classifier is trained using a dataset of 1077 methylation profiles from comprehensively pre-characterized cases comprising 62 tumour methylation classes constituting a broad range of soft tissue and bone sarcoma subtypes across the entire age spectrum. The performance is validated in a cohort of 428 sarcomatous tumours, of which 322 cases were classified by the sarcoma classifier. Our results demonstrate the potential of the DNA methylation-based sarcoma classification for research and future diagnostic applications

Ramucirumab plus docetaxel versus placebo plus docetaxel in patients with locally advanced or metastatic urothelial carcinoma after platinum-based therapy (RANGE): a randomised, double-blind, phase 3 trial

Few treatments with a distinct mechanism of action are available for patients with platinum-refractory advanced or metastatic urothelial carcinoma. We assessed the efficacy and safety of treatment with docetaxel plus either ramucirumab-a human IgG1 VEGFR-2 antagonist-or placebo in this patient population

Gastrointestinal stromal tumours: ESMO-EURACAN-GENTURIS Clinical Practice Guidelines for diagnosis, treatment and follow-up

Gastrointestinal stromal tumours (GISTs) are malignant mesenchymal tumours with a variable clinical behaviour, marked by differentiation towards the interstitial cells of Cajal.1 GISTs belong to the family of soft tissue sarcomas (STSs) but are treated separately due to their peculiar histogenesis, clinical behaviour and specific therapy. This European Society for Medical Oncology (ESMO)–European Reference Network for Rare Adult Solid Cancers (EURACAN)–European Reference Network for Genetic Tumour Risk Syndromes (GENTURIS) Clinical Practice Guideline (CPG) will cover GISTs while other STSs are covered in the ESMO–EURACAN–European Reference Network for Paediatric Oncology (ERN PaedCan)–GENTURIS STS CPG.Peer reviewe

Evaluation of a quality improvement intervention to reduce anastomotic leak following right colectomy (EAGLE): pragmatic, batched stepped-wedge, cluster-randomized trial in 64 countries

Background Anastomotic leak affects 8 per cent of patients after right colectomy with a 10-fold increased risk of postoperative death. The EAGLE study aimed to develop and test whether an international, standardized quality improvement intervention could reduce anastomotic leaks. Methods The internationally intended protocol, iteratively co-developed by a multistage Delphi process, comprised an online educational module introducing risk stratification, an intraoperative checklist, and harmonized surgical techniques. Clusters (hospital teams) were randomized to one of three arms with varied sequences of intervention/data collection by a derived stepped-wedge batch design (at least 18 hospital teams per batch). Patients were blinded to the study allocation. Low- and middle-income country enrolment was encouraged. The primary outcome (assessed by intention to treat) was anastomotic leak rate, and subgroup analyses by module completion (at least 80 per cent of surgeons, high engagement; less than 50 per cent, low engagement) were preplanned. Results A total 355 hospital teams registered, with 332 from 64 countries (39.2 per cent low and middle income) included in the final analysis. The online modules were completed by half of the surgeons (2143 of 4411). The primary analysis included 3039 of the 3268 patients recruited (206 patients had no anastomosis and 23 were lost to follow-up), with anastomotic leaks arising before and after the intervention in 10.1 and 9.6 per cent respectively (adjusted OR 0.87, 95 per cent c.i. 0.59 to 1.30; P = 0.498). The proportion of surgeons completing the educational modules was an influence: the leak rate decreased from 12.2 per cent (61 of 500) before intervention to 5.1 per cent (24 of 473) after intervention in high-engagement centres (adjusted OR 0.36, 0.20 to 0.64; P &lt; 0.001), but this was not observed in low-engagement hospitals (8.3 per cent (59 of 714) and 13.8 per cent (61 of 443) respectively; adjusted OR 2.09, 1.31 to 3.31). Conclusion Completion of globally available digital training by engaged teams can alter anastomotic leak rates. Registration number: NCT04270721 (http://www.clinicaltrials.gov)