37 research outputs found
Review of the Role of the Brain in Chemotherapy-Induced Peripheral Neuropathy
Chemotherapy-induced peripheral neuropathy (CIPN) is a common, debilitating, and dose-limiting side effect of many chemotherapy regimens yet has limited treatments due to incomplete knowledge of its pathophysiology. Research on the pathophysiology of CIPN has focused on peripheral nerves because CIPN symptoms are felt in the hands and feet. However, better understanding the role of the brain in CIPN may accelerate understanding, diagnosing, and treating CIPN. The goals of this review are to (1) investigate the role of the brain in CIPN, and (2) use this knowledge to inform future research and treatment of CIPN. We identified 16 papers using brain interventions in animal models of CIPN and five papers using brain imaging in humans or monkeys with CIPN. These studies suggest that CIPN is partly caused by (1) brain hyperactivity, (2) reduced GABAergic inhibition, (3) neuroinflammation, and (4) overactivation of GPCR/MAPK pathways. These four features were observed in several brain regions including the thalamus, periaqueductal gray, anterior cingulate cortex, somatosensory cortex, and insula. We discuss how to leverage this knowledge for future preclinical research, clinical research, and brain-based treatments for CIPN
A randomized controlled phase III study of VB-111 combined with bevacizumab vs bevacizumab monotherapy in patients with recurrent glioblastoma (GLOBE).
BackgroundOfranergene obadenovec (VB-111) is an anticancer viral therapy that demonstrated in a phase II study a survival benefit for patients with recurrent glioblastoma (rGBM) who were primed with VB-111 monotherapy that was continued after progression with concomitant bevacizumab.MethodsThis pivotal phase III randomized, controlled trial compared the efficacy and safety of upfront combination of VB-111 and bevacizumab versus bevacizumab monotherapy. Patients were randomized 1:1 to receive VB-111 1013 viral particles every 8 weeks in combination with bevacizumab 10 mg/kg every 2 weeks (combination arm) or bevacizumab monotherapy (control arm). The primary endpoint was overall survival (OS), and secondary endpoints were objective response rate (ORR) by Response Assessment in Neuro-Oncology (RANO) criteria and progression-free survival (PFS).ResultsEnrolled were 256 patients at 57 sites. Median exposure to VB-111 was 4 months. The study did not meet its primary or secondary goals. Median OS was 6.8 versus 7.9 months in the combination versus control arm (hazard ratio, 1.20; 95% CI: 0.91-1.59; P = 0.19) and ORR was 27.3% versus 21.9% (P = 0.26). A higher rate of grades 3-5 adverse events was reported in the combination arm (67% vs 40%), mainly attributed to a higher rate of CNS and flu-like/fever events. Trends for improved survival with combination treatment were seen in the subgroup of patients with smaller tumors and in patients who had a posttreatment febrile reaction.ConclusionsIn this study, upfront concomitant administration of VB-111 and bevacizumab failed to improve outcomes in rGBM. Change of treatment regimen, with the lack of VB-111 monotherapy priming, may explain the differences from the favorable phase II results.Clinical trials registrationNCT02511405
The utility of body FDG PET in staging primary central nervous system lymphoma
18F-Fluorodeoxyglucose (FDG) PET has become an important tool in the management of non-Hodgkin’s lymphoma (NHL), but its role in the evaluation of primary CNS lymphoma (PCNSL) has not been established. We investigated the ability of body FDG PET to detect systemic disease in the staging and restaging of PCNSL. The records of 166 PCNSL patients seen at Memorial Sloan-Kettering Cancer Center were examined. Forty-nine patients who underwent body FDG PET for staging of PCNSL were identified. Clinical data were reviewed to determine FDG PET results and their influence on therapy. Body FDG PET disclosed a systemic site of malignancy in 15% of patients. NHL was found in 11% of all patients, 7% of patients at diagnosis, and 27% of patients at CNS relapse. Four percent had a second systemic neoplasm. Workup with conventional staging did not reveal systemic disease, and in 8% of patients, body FDG PET was the only abnormal diagnostic exam suggestive of lymphoma. FDG PET findings altered patient treatment and resulted in additional chemotherapy, surgery, or radiotherapy. Our findings suggest that FDG PET may be more sensitive than conventional body staging and may disclose higher rates of concomitant systemic disease at PCNSL diagnosis. Body FDG PET may be an important noninvasive adjunct to conventional PCNSL staging, and its utility should be evaluated prospectively
Clinical neuro-oncology for the neurologist.
Purpose of reviewNeuro-oncologic patients are routinely encountered in clinical practice. Neuro-oncology is a rapidly evolving field, so understanding the most classic paradigms and contemporary advances will optimize patient care.Recent findingsWe discuss the recent reclassification of tumors via molecular characteristics as it applies to direct clinical practice and review the contemporary standard of care for infiltrating gliomas, meningiomas, brain metastases, and CNS lymphoma.SummaryWe provide a straightforward primer on neuro-oncology with a focus on the brain tumors most commonly encountered by the adult neurologist and a clear emphasis on clinically relevant points including those which have recently become incorporated into our standard management. We cite key reviews to allow interested readers an opportunity to gain a more comprehensive understanding of specific topics
Epid-07. Access to Glioblastoma Clinical Trials for Rural Patients in the United States from 2010–2020
Background:
Patients in rural communities have less access to optimal cancer care and clinical trials. For GBM, access to experimental therapies, and consideration of a clinical trial is embedded in national guidelines. Still, the availability of clinical trials to rural communities, representing 20% of the US population, has not been described.
Methods:
We queried ClinicalTrials.gov for glioblastoma interventional treatment trials opened between 1/2010 and 1/2020 in the United States. We created a Structured Query Language database and leveraged Google application programming interfaces (API) Places to find name and street addresses for the sites, and Google’s Geocode API to determine the county location. Counties were classified by US Department of Agriculture Rural-Urban Continuum Codes (RUCC 1–3 = urban and RUCC 4–9 = rural). We used z-ratios for rural-urban statistical comparisons.
Results:
We identified 406 interventional treatment trials for GBM at 1491 unique sites. 8.7% of unique sites were in rural settings. Rural sites opened an average of 1.7 trials/site and urban sites 2.8 trials/site from 1/2010–1/2020. Rural sites offered more phase II trials (63% vs 57%, p= 0.03) and fewer phase I trials (22% vs 28%, p= 0.01) than urban sites. Rural locations were more likely to offer federally-sponsored trials (p< 0.002). There were no investigator-initiated or single-institution trials offered at rural locations, and only 1% of industry trials were offered rurally.
Discussion:
Clinical trials for GBM were rarely open in rural areas, and were more dependent on federal funding. Clinical trials are likely difficult to access for rural patients, and this has important implications for the generalizability of research as well as how we engage the field of neuro-oncology and patient advocacy groups in improving patient access to trials. Increasing the number of clinical trials in rural locations may enable more rural patients to access and enroll in GBM studies
HCP-16POPULATION-BASED SURVIVAL RATES FROM HIGH GRADE GLIOMA (HGG) ARE NOT IMPROVED BY INCREASED CHEMOTHERAPY USE
A state-of-the-art review and guidelines for tumor treating fields treatment planning and patient follow-up in glioblastoma.
Tumor treating fields (TTFields) are an integral treatment modality in the management of glioblastoma and extend overall survival when combined with maintenance temozolomide in newly diagnosed patients. Complexities exist regarding correct selection of imaging sequences with which to perform TTFields treatment planning. Guidelines are warranted first, to facilitate treatment planning standardization across medical disciplines and institutions, to ensure optimal TTFields delivery to the tumor and peritumoral brain zone while maximizing patient safety, and also to mitigate the risk of premature cessation of a potentially beneficial treatment. This summary guideline outlines methods for starting patients on TTFields, for monitoring patient response to therapy and provides a framework for evaluating when therapy should be re-planned, based on the extent of sequential imaging changes
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A state-of-the-art review and guidelines for tumor treating fields treatment planning and patient follow-up in glioblastoma.
Tumor treating fields (TTFields) are an integral treatment modality in the management of glioblastoma and extend overall survival when combined with maintenance temozolomide in newly diagnosed patients. Complexities exist regarding correct selection of imaging sequences with which to perform TTFields treatment planning. Guidelines are warranted first, to facilitate treatment planning standardization across medical disciplines and institutions, to ensure optimal TTFields delivery to the tumor and peritumoral brain zone while maximizing patient safety, and also to mitigate the risk of premature cessation of a potentially beneficial treatment. This summary guideline outlines methods for starting patients on TTFields, for monitoring patient response to therapy and provides a framework for evaluating when therapy should be re-planned, based on the extent of sequential imaging changes
Top Ten Tips Palliative Care Clinicians Should Know When Caring for Patients with Brain Cancer
The diagnosis of an aggressive, primary brain tumor is life altering for those affected and too often portends a poor prognosis. Despite decades of research, neither a cure nor even a therapy that reliably and dramatically prolongs survival has been found. Fortunately, there are a number of treatments that may prolong the life of select brain tumor patients although the symptom burden can sometimes be high. This article brings together neuro-oncologists, neurologists, and palliative care (PC) physicians to help shine a light on these diseases, their genetics, treatment options, and the symptoms likely to be encountered both from the underlying illness and its treatment. We hope to increase the understanding that PC teams have around these illnesses to improve care for patients and families