Radiotherapy to the primary tumour for newly diagnosed, metastatic prostate cancer (STAMPEDE): a randomised controlled phase 3 trial.

BACKGROUND: Based on previous findings, we hypothesised that radiotherapy to the prostate would improve overall survival in men with metastatic prostate cancer, and that the benefit would be greatest in patients with a low metastatic burden. We aimed to compare standard of care for metastatic prostate cancer, with and without radiotherapy. METHODS: We did a randomised controlled phase 3 trial at 117 hospitals in Switzerland and the UK. Eligible patients had newly diagnosed metastatic prostate cancer. We randomly allocated patients open-label in a 1:1 ratio to standard of care (control group) or standard of care and radiotherapy (radiotherapy group). Randomisation was stratified by hospital, age at randomisation, nodal involvement, WHO performance status, planned androgen deprivation therapy, planned docetaxel use (from December, 2015), and regular aspirin or non-steroidal anti-inflammatory drug use. Standard of care was lifelong androgen deprivation therapy, with up-front docetaxel permitted from December, 2015. Men allocated radiotherapy received either a daily (55 Gy in 20 fractions over 4 weeks) or weekly (36 Gy in six fractions over 6 weeks) schedule that was nominated before randomisation. The primary outcome was overall survival, measured as the number of deaths; this analysis had 90% power with a one-sided α of 2·5% for a hazard ratio (HR) of 0·75. Secondary outcomes were failure-free survival, progression-free survival, metastatic progression-free survival, prostate cancer-specific survival, and symptomatic local event-free survival. Analyses used Cox proportional hazards and flexible parametric models, adjusted for stratification factors. The primary outcome analysis was by intention to treat. Two prespecified subgroup analyses tested the effects of prostate radiotherapy by baseline metastatic burden and radiotherapy schedule. This trial is registered with ClinicalTrials.gov, number NCT00268476. FINDINGS: Between Jan 22, 2013, and Sept 2, 2016, 2061 men underwent randomisation, 1029 were allocated the control and 1032 radiotherapy. Allocated groups were balanced, with a median age of 68 years (IQR 63-73) and median amount of prostate-specific antigen of 97 ng/mL (33-315). 367 (18%) patients received early docetaxel. 1082 (52%) participants nominated the daily radiotherapy schedule before randomisation and 979 (48%) the weekly schedule. 819 (40%) men had a low metastatic burden, 1120 (54%) had a high metastatic burden, and the metastatic burden was unknown for 122 (6%). Radiotherapy improved failure-free survival (HR 0·76, 95% CI 0·68-0·84; p<0·0001) but not overall survival (0·92, 0·80-1·06; p=0·266). Radiotherapy was well tolerated, with 48 (5%) adverse events (Radiation Therapy Oncology Group grade 3-4) reported during radiotherapy and 37 (4%) after radiotherapy. The proportion reporting at least one severe adverse event (Common Terminology Criteria for Adverse Events grade 3 or worse) was similar by treatment group in the safety population (398 [38%] with control and 380 [39%] with radiotherapy). INTERPRETATION: Radiotherapy to the prostate did not improve overall survival for unselected patients with newly diagnosed metastatic prostate cancer. FUNDING: Cancer Research UK, UK Medical Research Council, Swiss Group for Clinical Cancer Research, Astellas, Clovis Oncology, Janssen, Novartis, Pfizer, and Sanofi-Aventis.

Factors involved in treatment preference in patients with renal cancer: pazopanib versus sunitinib.

The last decade has seen a surge in the treatment options for metastatic renal cell carcinoma and life expectancies are now approaching 3 years from diagnosis. There is some suggestion that, for now at least, we may have reached a plateau in efficacy. Patients are often stable and on treatment for years rather than months. Attention has therefore shifted to a focus on patient preference rather than reported frequency of toxicities. The standard first-line treatment for metastatic clear-cell renal cancer is either sunitinib or pazopanib. The COMPARZ trial has shown that sunitinib and pazopanib have similar efficacy. The PISCES trial, with its unique design, has evaluated patient preference between pazopanib and sunitinib. This review explores the factors involved in treatment preference in patients with renal cancer and in particular the choice between pazopanib and sunitinib.

Biliary cystadenocarcinoma with superficial spread to the extrahepatic bile duct.

We report a case of biliary cystadenocarcinoma of the liver with superficial spread to the extrahepatic bile duct. Preoperative endoscopic retrograde cholangiography revealed communication between a 4.5-cm cyst in segment 4 of the liver and the bile duct. From the findings obtained by peroral cholangioscopy and intraoperative cholangioscopy, the granular mucosa in the bile duct was diagnosed as superficially spreading cancer. The right posterior segmental bile duct and the right anterior segmental bile duct were resected at the point where the spread of cancer was no longer traceable and left lobectomy plus caudate lobectomy was carried out. This achieved radical resection, leaving the resected margin of the bile duct free from cancer. Histopathologically, well-differentiated papillary adenocarcinoma was found on the inner surface of the cyst, and the cancer had superficially spread from the cyst to the extrahepatic bile duct via the 2.5-mm diameter communication between the cyst and bile duct. The cancer was limited only to the mucosal layer all over the lesion. When performing radical surgery for biliary cystadenocarcinoma, it is recommended that cholangioscopy be performed to examine whether the cancer has superficial spread to the extrahepatic bile duct or not. Bile duct resection should be carried out, depending on the extent of the superficial spread, so that the resected margin of the bile duct is free from cancer.

[Multicenter study of cardiac events and anesthetic management of patients with ischemic heart diseases undergoing noncardiac surgery].

We designed a joint research project to investigate the incidence of ischemic heart diseases in patients undergoing noncardiac surgery and to define the risk of perioperative cardiac complications in these patients. Of the 8358 surgical patients in the 8 departments of anesthesiology between March 1997 and June 1997, 328 (3.9%) had ischemic heart diseases. Among the 328 patients, 54 (16.4%) developed perioperative cardiac events, including myocardial infarction (3 patients) and either lethal or potentially dangerous dysrhythmias (51 patients). Preoperative cardiac assessments were performed while the anesthetic techniques including intensive monitoring and perioperative prophylactic therapy were also employed. Patients with ischemic heart diseases received various types of preoperative evaluation to identify the degree of coronary artery disease and to assess the overall cardiac function. The patients were monitored using a multilead electrocardiogram, an arterial line, a central venous catheter, a pulmonary artery catheter, and by transesophageal echocardiography intraoperatively. Therapeutically, isosorbide, nitroglycerin, beta-blockers, calcium channel blockers, and/or nicorandil were administered to prevent perioperative ischemia. So far, no generally accepted management strategies have been established in patients with cardiovascular disorders based on large-scale outcome trials in Japan. Therefore, nationwide large multicenter trials are awaited with interest in order to establish helpful guidelines to improve the perioperative management and to reduce ischemia in cardiac patients undergoing noncardiac surgery.

Identification of producer and biological activities of new antibiotics, mimosamycin and chlorocarcins.

A strain of Streptomyces, No. 314 identified as a Streptomyces lavendulae produced under a novel condition of culture, four new antibiotics, mimosamycin and chlorocarcins A, B, and C. Among the components of chlorocarcin complex, chlorocarcin A was found to be most biologically active. This antibiotic inhibited the growth of Staphylococcus aureus FDA 209P and Corynebacterium diphtheriae at the concentrations of 0.1 and 0.003 mcg/ml, respectively. Chlorocarcin A also exhibited antitumor activity on EHRLICH carcinoma, ascitic and solid forms, and mouse leukemia L1210. Mimosamycin proved to be mainly active on Mycobacterium tuberculosis and inactive on the experimental murine tumors.