The final 2017 issue of Neuro-Oncology Practice offers a number of wonderful reviews and interesting survey results that provide us an opportunity to reflect on our clinical trial designs, clinical practice, and the opportunities and benefits of collaborating in biobanking and other efforts to address the pressing clinical questions facing us and our patients. We are also presented data from small, well-characterized cohorts of patients describing the impacts of tumors and our treatments on disease and functional outcomes.
Taylor et al. review a number of common clinical trial endpoints in therapeutic clinical trials of patients with glioma. The review attends to issues in both high-grade and lower-grade glioma populations including overall survival, progression-free survival, response rates, neurocognitive function, quality of life, biomarker-driven clinical trials (e.g., bucket or basket trials), and the use of adaptive designs. The authors define these approaches, provide interpretable examples, and describe remaining challenges we face including the impact of salvage therapy on overall survival, pseudoresponse and pseudoprogression, new emerging radiographic criteria, molecular heterogeneity in glioma, the need for concurrent control arms, and fundamentally what endpoints are clearly necessary to identify clinical benefit in patients with brain tumor.
Although brain tumors are rare diseases, there is still a relatively large volume of clinical trials, often without clarion signals, that can make it challenging to summarize how such findings impact clinical practice. Lukas et al. provide a concise summary of what they have referred to as “pivotal therapeutic trials” (temozolomide, bevacizumab, implanted BCNU wafers, tumor treating fields, and PCV), offering a perspective on the relevant clinical question addressed in these studies and remaining issues for the next series of pivotal trials.
In recent years there has been increased discussion and compelling evidence of the value of large databanks. Ostrom et al. offer a roadmap of how to develop a neuro-oncology biobank in an era where increasingly detailed biomarker/biospecimen data are being generated and evaluated to enhance the provision of precision medicine. The discussion of issues related to this process range from fundamental aspects of consenting, obtaining biospecimens, storing materials, accessing materials, clinically annotating materials, collaboration within and between centers, and new ethical challenges encountered as a result of NIH and journal policies related to data that comes from these biospecimens.
Dallabona et al. report neuropsychological findings from a small cohort of patients with high-grade glioma who were carefully studied and closely followed longitudinally before and after surgery. A more novel aspect of this manuscript is identifying reduction in mass effect as a strong correlate of improved cognitive function after surgery, and increased age as a risk factor for decreased cognitive function after surgery. Importantly, models including radiographic and demographic variables still generally accounted for 50% or less of the variance in outcome, encouraging us to continue striving to identify such predictors of patient outcome.
The management of lower-grade glioma remains a matter of debate with wide variability in clinical practice. Mandonnet et al. report results from a survey concerning practice patterns at centers within the European Low-Grade Glioma Network (ELGGN). The service identified areas of ongoing inconsistency in clinical practice concerning diverse clinical management issues, including cognitive assessment, imaging, intraoperative management and assessment, postoperative assessment of patient outcomes, use of biomarkers, and adjuvant treatment practice patterns. The ELGGN identified three pressing clinical questions that they argue require a low-grade glioma database, rather than randomized clinical trials, to address.
In an era of increasing attention to health care costs and quality outcomes Wasilewski et al. report on single institutions experience regarding the nature, frequency, and consequences of acute care visits in newly diagnosed adult patients with glioblastoma. Acute care visits were frequent, with disease-related factors (i.e., seizure) being the most common precipitating event, and admission being associated with an increased risk for higher level of care upon discharge. They offer a number of clinical and practical recommendations for patient communication and management that may prevent some acute care visits, decrease health care utilization/costs, and empower patients and caregivers. These provide a rich set of considerations that are amenable to clinical trial research.
Finally, Rhome et al. report on the efficacy and toxicity of fractionated stereotactic radiosurgery in patients with acromegaly associated with pituitary tumors from a small cohort of patients who were followed longitudinally at a single center. They report and compare their radiographic, biochemical, and toxicity outcomes with those obtained after systematically reviewing the published literature available on this topic.