Treatment of ovarian cancer with surgery, short-course chemotherapy and whole abdominal radiation

Background The primary aim was to induce a high number of pCR in early (FIGO IC, JIB + C)-and advanced (FIGO ffl—IV)—stage ovarian cancer with a surgery plus 4 cycles of cisplatin and meiphalan (PAMP) regimen. The second objective was to prevent relapse with WAR in patients in remission after chemotherapy. Patients and methods 218 eligible patients were treated after staging laparotomy with cisplatin 80 mg/sqm iv. on day 1 and melphalan 12 mg/sqm i.v. on day 2 q 4 weeks. Response was verified by second-look laparotomy. WAR was carried out with the open field technique on a linear accele rator (daily dose: 1.3 Gy, total dose: 29.9 Gy) in patients with pathological or clinicaJ CR or pathological PR with microscopical residual disease. Results 146/218 patients (67%, 95% CI: 61%-73%) responded to PAMIP: 56 (26%) achieved pCR, 24 (11%), cCR, 56 (26%) pPR and 10 (5%) cPR (c=clinical, p=pathological). Multivariate analyses revealed that in advanced stages (92 cases in remission), the achievement of pCR was the most important factor for longer time to failure (TIF) and survival. Only 5 1/118 (43%) patients in remission received WAR Early-stage patients <=55 years were more likely to have WAR than patients older than 55 years (77% vs. 23%; p= 0.02). Advanced-stage patients with cCR were less likely to be irradiated than patients with pCR or pPR (10% vs. 51%; p= 0.003). Toxicity of PAMP was acceptable with 10% of WHO grade 4 hematologic toxicity. Acute hematological toxicity of WAR caused interruption (3 3%) or incompleteness (3 3%) of irradiation in the majority of patients. Conclusions PAMP is an effective treatment for advanced ovarian cancer with a 67% response rate after 4 cycles. For the majority of patients in remission, WAR as a consolidation treatment was hardly feasible. For these patients new treatment modalities to consolidate remission are neede

Follow-up strategies after trimodal treatment for muscle-invasive bladder cancer: a systematic review

PURPOSE: Optimal follow-up strategies following trimodal treatment for muscle invasive bladder cancer play a crucial role in detecting and managing relapse and side-effects. This article provides a comprehensive summary of the patterns and risk factors of relapse, functional outcomes, and follow-up protocols. METHODS: A systematic literature search on PubMed and review of current guidelines and institutional follow-up protocols after trimodal therapy were conducted. RESULTS: Out of 200 identified publications, 43 studies (28 retrospective, 15 prospective) were selected, encompassing 7447 patients (study sizes from 24 to 728 patients). Recurrence rates in the urinary bladder varied between 14-52%; 3-16% were muscle-invasive while 11-36% were non-muscle invasive. Nodal recurrence occurred at 13-16% and distant metastases at 15-35%. After 5 and 10 years of follow-up, around 60-85% and 45-75% of patients could preserve their bladder, respectively. Various prognostic risk factors associated with relapse and inferior survival were proposed, including higher disease stage (> c/pT2), presence of extensive/multifocal carcinoma in situ (CIS), hydronephrosis, multifocality, histological subtypes, incomplete transurethral resection of bladder tumor (TURBT) and incomplete response to radio-chemotherapy. The analyzed follow-up guidelines varied slightly in terms of the number, timing, and types of investigations, but overall, the recommendations were similar. CONCLUSION: Randomized prospective studies should focus on evaluating the impact of specific follow-up protocols on oncological and functional outcomes following trimodal treatment for muscle-invasive bladder cancer. It is crucial to evaluate personalized adaption of follow-up protocols based on established risk factors, as there is potential for improved patient outcomes and resource allocation

Certified reference materials for radionuclides in Bikini Atoll sediment (IAEA-410) and Pacific Ocean sediment (IAEA-412)

The preparation and characterization of certified reference materials (CRMs) for radionuclide content in sediments collected offshore of Bikini Atoll (IAEA-410) and in the open northwest Pacific Ocean (IAEA-412) are described and the results of the certification process are presented. The certified radionuclides include: 40K, 210Pb (210Po), 226Ra, 228Ra, 228Th, 232Th, 234U, 238U, 239Pu, 239+240Pu and 241Am for IAEA-410 and 40K, 137Cs, 210Pb (210Po), 226Ra, 228Ra, 228Th, 232Th, 235U, 238U, 239Pu, 240Pu and 239+240Pu for IAEA-412. The CRMs can be used for quality assurance and quality control purposes in the analysis of radionuclides in sediments, for development and validation of analytical methods and for staff training

European Association of Urology Guidelines Office Rapid Reaction Group: An Organisation-wide Collaborative Effort to Adapt the European Association of Urology Guidelines Recommendations to the Coronavirus Disease 2019 Era

The coronavirus disease 2019 (COVID-19) pandemic is unlike anything seen before by modern science-based medicine. As a scientific society, the European Association of Urology, via the guidelines, section offices, and the European Urology family of journals, we believe that it is important that we try to support urologists in this difficult situation. We aim to do this by providing tools that can facilitate decision making with the goal to minimise the impact and risks for both patients and health professionals delivering urological care, whenever possible, although it is clear that it is not always possible to mitigate them entirely. We hope that these revised recommendations will fill an important urological practice void and assist urologist surgeons across the globe as they do their very best to deal with the crisis of our generation

A compact and cost-effective hard X-ray free-electron laser driven by a high-brightness and low-energy electron beam

We present the first lasing results of SwissFEL, a hard X-ray free-electron laser (FEL) that recently came into operation at the Paul Scherrer Institute in Switzerland. SwissFEL is a very stable, compact and cost-effective X-ray FEL facility driven by a low-energy and ultra-low-emittance electron beam travelling through short-period undulators. It delivers stable hard X-ray FEL radiation at 1-Å wavelength with pulse energies of more than 500 μJ, pulse durations of ~30 fs (root mean square) and spectral bandwidth below the per-mil level. Using special configurations, we have produced pulses shorter than 1 fs and, in a different set-up, broadband radiation with an unprecedented bandwidth of ~2%. The extremely small emittance demonstrated at SwissFEL paves the way for even more compact and affordable hard X-ray FELs, potentially boosting the number of facilities worldwide and thereby expanding the population of the scientific community that has access to X-ray FEL radiation

Abiraterone acetate plus prednisolone with or without enzalutamide for patients with metastatic prostate cancer starting androgen deprivation therapy: final results from two randomised phase 3 trials of the STAMPEDE platform protocol

Background: Abiraterone acetate plus prednisolone (herein referred to as abiraterone) or enzalutamide added at the start of androgen deprivation therapy improves outcomes for patients with metastatic prostate cancer. Here, we aimed to evaluate long-term outcomes and test whether combining enzalutamide with abiraterone and androgen deprivation therapy improves survival. Methods: We analysed two open-label, randomised, controlled, phase 3 trials of the STAMPEDE platform protocol, with no overlapping controls, conducted at 117 sites in the UK and Switzerland. Eligible patients (no age restriction) had metastatic, histologically-confirmed prostate adenocarcinoma; a WHO performance status of 0–2; and adequate haematological, renal, and liver function. Patients were randomly assigned (1:1) using a computerised algorithm and a minimisation technique to either standard of care (androgen deprivation therapy; docetaxel 75 mg/m2 intravenously for six cycles with prednisolone 10 mg orally once per day allowed from Dec 17, 2015) or standard of care plus abiraterone acetate 1000 mg and prednisolone 5 mg (in the abiraterone trial) orally or abiraterone acetate and prednisolone plus enzalutamide 160 mg orally once a day (in the abiraterone and enzalutamide trial). Patients were stratified by centre, age, WHO performance status, type of androgen deprivation therapy, use of aspirin or non-steroidal anti-inflammatory drugs, pelvic nodal status, planned radiotherapy, and planned docetaxel use. The primary outcome was overall survival assessed in the intention-to-treat population. Safety was assessed in all patients who started treatment. A fixed-effects meta-analysis of individual patient data was used to compare differences in survival between the two trials. STAMPEDE is registered with ClinicalTrials.gov (NCT00268476) and ISRCTN (ISRCTN78818544). Findings: Between Nov 15, 2011, and Jan 17, 2014, 1003 patients were randomly assigned to standard of care (n=502) or standard of care plus abiraterone (n=501) in the abiraterone trial. Between July 29, 2014, and March 31, 2016, 916 patients were randomly assigned to standard of care (n=454) or standard of care plus abiraterone and enzalutamide (n=462) in the abiraterone and enzalutamide trial. Median follow-up was 96 months (IQR 86–107) in the abiraterone trial and 72 months (61–74) in the abiraterone and enzalutamide trial. In the abiraterone trial, median overall survival was 76·6 months (95% CI 67·8–86·9) in the abiraterone group versus 45·7 months (41·6–52·0) in the standard of care group (hazard ratio [HR] 0·62 [95% CI 0·53–0·73]; p&lt;0·0001). In the abiraterone and enzalutamide trial, median overall survival was 73·1 months (61·9–81·3) in the abiraterone and enzalutamide group versus 51·8 months (45·3–59·0) in the standard of care group (HR 0·65 [0·55–0·77]; p&lt;0·0001). We found no difference in the treatment effect between these two trials (interaction HR 1·05 [0·83–1·32]; pinteraction=0·71) or between-trial heterogeneity (I2 p=0·70). In the first 5 years of treatment, grade 3–5 toxic effects were higher when abiraterone was added to standard of care (271 [54%] of 498 vs 192 [38%] of 502 with standard of care) and the highest toxic effects were seen when abiraterone and enzalutamide were added to standard of care (302 [68%] of 445 vs 204 [45%] of 454 with standard of care). Cardiac causes were the most common cause of death due to adverse events (five [1%] with standard of care plus abiraterone and enzalutamide [two attributed to treatment] and one (&lt;1%) with standard of care in the abiraterone trial). Interpretation: Enzalutamide and abiraterone should not be combined for patients with prostate cancer starting long-term androgen deprivation therapy. Clinically important improvements in survival from addition of abiraterone to androgen deprivation therapy are maintained for longer than 7 years. Funding: Cancer Research UK, UK Medical Research Council, Swiss Group for Clinical Cancer Research, Janssen, and Astellas