articles+ search results

Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Adult, Brain Neoplasms, Clinical Trials, Phase II as Topic, Clinical Trials, Phase III as Topic, Drug Delivery Systems, Humans, Pharmaceutical Preparations, Neurosciences, Oncology & Carcinogenesis, and Oncology and carcinogenesis

Biomedical and Clinical Sciences, Clinical Sciences, Oncology and Carcinogenesis, Neurosciences, Behavioral and Social Science, Patient Safety, Clinical Research, Cancer, Clinical Trials and Supportive Activities, Brain Disorders, Evaluation of treatments and therapeutic interventions, 6.5 Radiotherapy and other non-invasive therapies, Activities of Daily Living, Adolescent, Adult, Brain Neoplasms, Cognition Disorders, Disease Progression, Disease-Free Survival, Dose Fractionation, Radiation, Female, Follow-Up Studies, Humans, Intention to Treat Analysis, Magnetic Resonance Imaging, Male, Metastasectomy, Middle Aged, Neoplasm Recurrence, Local, Quality of Life, Radiosurgery, Radiotherapy, Adjuvant, Survival Rate, Young Adult, Oncology & Carcinogenesis, and Oncology and carcinogenesis

BackgroundWhole brain radiotherapy (WBRT) is the standard of care to improve intracranial control following resection of brain metastasis. However, stereotactic radiosurgery (SRS) to the surgical cavity is widely used in an attempt to reduce cognitive toxicity, despite the absence of high-level comparative data substantiating efficacy in the postoperative setting. We aimed to establish the effect of SRS on survival and cognitive outcomes compared with WBRT in patients with resected brain metastasis.MethodsIn this randomised, controlled, phase 3 trial, adult patients (aged 18 years or older) from 48 institutions in the USA and Canada with one resected brain metastasis and a resection cavity less than 5·0 cm in maximal extent were randomly assigned (1:1) to either postoperative SRS (12-20 Gy single fraction with dose determined by surgical cavity volume) or WBRT (30 Gy in ten daily fractions or 37·5 Gy in 15 daily fractions of 2·5 Gy; fractionation schedule predetermined for all patients at treating centre). We randomised patients using a dynamic allocation strategy with stratification factors of age, duration of extracranial disease control, number of brain metastases, histology, maximal resection cavity diameter, and treatment centre. Patients and investigators were not masked to treatment allocation. The co-primary endpoints were cognitive-deterioration-free survival and overall survival, and analyses were done by intention to treat. We report the final analysis. This trial is registered with ClinicalTrials.gov, number NCT01372774.FindingsBetween Nov 10, 2011, and Nov 16, 2015, 194 patients were enrolled and randomly assigned to SRS (98 patients) or WBRT (96 patients). Median follow-up was 11·1 months (IQR 5·1-18·0). Cognitive-deterioration-free survival was longer in patients assigned to SRS (median 3·7 months [95% CI 3·45-5·06], 93 events) than in patients assigned to WBRT (median 3·0 months [2·86-3·25], 93 events; hazard ratio [HR] 0·47 [95% CI 0·35-0·63]; p

Clinical Trials and Supportive Activities, Neurosciences, Comparative Effectiveness Research, Clinical Research, Academies and Institutes, Biomedical Research, Clinical Trials as Topic, Guidelines as Topic, Humans, Neurosurgery, Neurosurgical Procedures, Research Design, Workshop Participants, Clinical trials, Effectiveness research, Equipoise, Randomized controlled trial, Registry, Clinical Sciences, and Neurology & Neurosurgery

This workshop addressed challenges of clinical research in neurosurgery. Randomized controlled clinical trials (RCTs) have high internal validity, but often insufficiently generalize to real-world practice. Observational studies are inclusive but often lack sufficient rigor. The workshop considered possible solutions, such as (1) statistical methods for demonstrating causality using observational data; (2) characteristics required of a registry supporting effectiveness research; (3) trial designs combining advantages of observational studies and RCTs; and (4) equipoise, an identified challenge for RCTs. In the future, advances in information technology potentially could lead to creation of a massive database where clinical data from all neurosurgeons are integrated and analyzed, ending the separation of clinical research and practice and leading to a new "science of practice."