A randomized trial of bevacizumab for newly diagnosed glioblastoma.

BACKGROUND: Concurrent treatment with temozolomide and radiotherapy followed by maintenance temozolomide is the standard of care for patients with newly diagnosed glioblastoma. Bevacizumab, a humanized monoclonal antibody against vascular endothelial growth factor A, is currently approved for recurrent glioblastoma. Whether the addition of bevacizumab would improve survival among patients with newly diagnosed glioblastoma is not known. METHODS: In this randomized, double-blind, placebo-controlled trial, we treated adults who had centrally confirmed glioblastoma with radiotherapy (60 Gy) and daily temozolomide. Treatment with bevacizumab or placebo began during week 4 of radiotherapy and was continued for up to 12 cycles of maintenance chemotherapy. At disease progression, the assigned treatment was revealed, and bevacizumab therapy could be initiated or continued. The trial was designed to detect a 25% reduction in the risk of death and a 30% reduction in the risk of progression or death, the two coprimary end points, with the addition of bevacizumab. RESULTS: A total of 978 patients were registered, and 637 underwent randomization. There was no significant difference in the duration of overall survival between the bevacizumab group and the placebo group (median, 15.7 and 16.1 months, respectively; hazard ratio for death in the bevacizumab group, 1.13). Progression-free survival was longer in the bevacizumab group (10.7 months vs. 7.3 months; hazard ratio for progression or death, 0.79). There were modest increases in rates of hypertension, thromboembolic events, intestinal perforation, and neutropenia in the bevacizumab group. Over time, an increased symptom burden, a worse quality of life, and a decline in neurocognitive function were more frequent in the bevacizumab group. CONCLUSIONS: First-line use of bevacizumab did not improve overall survival in patients with newly diagnosed glioblastoma. Progression-free survival was prolonged but did not reach the prespecified improvement target. (Funded by the National Cancer Institute; ClinicalTrials.gov number, NCT00884741.)

The State of Neuro-Oncology During the COVID-19 Pandemic: A Worldwide Assessment

To assess the impact of the pandemic on the field, we performed an international web-based survey of practitioners, scientists, and trainees from 21 neuro-oncology organizations across 6 continents from April 24 through May 17. Of 582 respondents, 258 (45%) were in the US, and 314 (55%) were international. 80.4% were affiliated with academic institutions. 94% respondents reported changes in clinical practice; 95% reported conversion to telemedicine for at least some appointments. However, almost 10% practitioners felt the need to see patients in person specifically because of billing concerns and perceived institutional pressure. Over 50% believed neuro-oncology patients were at increased risk of contracting COVID-19. 67% practitioners suspended enrollment for at least one clinical trial: 53% suspended phase II and 62% suspended phase III trial enrollment. 71% clinicians feared for their or their families’ safety, specifically because of their clinical duties. 20% percent said they did not have enough PPE to work safely; about the same percentage were unhappy with their institutions’ response to the pandemic. 43% believed the pandemic would negatively affect their academic career, and 52% fellowship program directors were worried about losing funding for their training programs. While 69% respondents reported increased stress, 44% were offered no psychosocial support. 37% had their salary reduced. 36% researchers had to temporarily close their laboratories. In contrast, the pandemic created positive changes in perceived patient and family satisfaction, quality of communication, and use of technology to deliver care and interactions with other practitioners. CONCLUSIONS: The pandemic has altered standard treatment schedules and limited investigational treatment options for patients. In some cases, clinicians felt institutional pressure to continue conducting billable in-person visits when telemedicine visits would have sufficed. A lack of institutional support created anxiety among clinicians and researchers. We make specific recommendations to guide clinical and scientific infrastructure moving forward

Impaired neurocognitive function in glioma patients: from pathophysiology to novel intervention strategies

PURPOSE OF REVIEW: This review succinctly summarizes the recent literature regarding etiological contributors to impaired neurocognitive function (NCF) in adult patients with glioma. A brief overview of intervention and prevention strategies is also provided. RECENT FINDINGS: A majority of patients with glioma exhibit NCF deficits, most frequently in memory and executive functioning. Impairments are often disabling and associated with reduced quality of life and survival. Cause is multifactorial and includes the tumour itself, treatments received and associated comorbidities. Although modern techniques such as brain mapping, dosing modifications and prophylactic medication aim to improve the NCF outcomes following neurosurgical resection and radiation therapy, a sizeable proportion of patients continue to evidence treatment-related NCF declines related to adverse effects to both local and distributed cerebral networks. Numerous patient and tumour characteristics, including genetic markers and sociodemographic factors, influence the pattern and severity of NCF impairment. Some rehabilitative and pharmacologic approaches show promise in mitigating NCF impairment in this population, though benefits are somewhat modest and larger scale intervention studies are needed. SUMMARY: Research regarding NCF in patients with glioma has dramatically proliferated, providing insights into the mechanisms underlying impaired NCF and pointing to potential interventions, though further work is needed

Neurocognitive Changes Associated With Surgical Resection of Left and Right Temporal Lobe Glioma

Abstract BACKGROUND: Little is known regarding the neurocognitive impact of temporal lobe tumor resection. OBJECTIVE: To clarify subacute surgery-related changes in neurocognitive functioning (NCF) in patients with left (LTL) and right (RTL) temporal lobe glioma. METHODS: Patients with glioma in the LTL (n = 45) or RTL (n = 19) completed comprehensive pre- and postsurgical neuropsychological assessments. NCF was analyzed with 2-way mixed design repeated-measures analysis of variance, with hemisphere (LTL or RTL) as an independent between-subjects factor and pre- and postoperative NCF as a within-subjects factor. RESULTS: About 60% of patients with LTL glioma and 40% with RTL lesions exhibited significant worsening on at least 1 NCF test. Domains most commonly impacted included verbal memory and executive functioning. Patients with LTL tumor showed greater decline than patients with RTL tumor on verbal memory and confrontation naming tests. Nonetheless, over one-third of patients with RTL lesions also showed verbal memory decline. CONCLUSION: In patients with temporal lobe glioma, NCF decline in the subacute postoperative period is common. As expected, patients with LTL tumor show more frequent and severe decline than patients with RTL tumor, particularly on verbally mediated measures. However, a considerable proportion of patients with RTL tumor also exhibit decline across various domains, even those typically associated with left hemisphere structures, such as verbal memory. While patients with RTL lesions may show even greater decline in visuospatial memory, this domain was not assessed. Nonetheless, neuropsychological assessment can identify acquired deficits and help facilitate early intervention in patients with temporal lobe glioma

Default mode network connectivity distinguishes chemotherapy-treated breast cancer survivors from controls.

Breast cancer (BC) chemotherapy is associated with cognitive changes including persistent deficits in some individuals. We tested the accuracy of default mode network (DMN) resting state functional connectivity patterns in discriminating chemotherapy treated (C+) from non-chemotherapy (C-) treated BC survivors and healthy controls (HC). We also examined the relationship between DMN connectivity patterns and cognitive function. Multivariate pattern analysis was used to classify 30 C+, 27 C-, and 24 HC, which showed significant accuracy for discriminating C+ from C- (91.23%, P < 0.0001) and C+ from HC (90.74%, P < 0.0001). The C- group did not differ significantly from HC (47.06%, P = 0.60). Lower subjective memory function was correlated (P < 0.002) with greater hyperplane distance (distance from the linear decision function that optimally separates the groups). Disrupted DMN connectivity may help explain long-term cognitive difficulties following BC chemotherapy

Levetiracetam mitigates doxorubicin-induced DNA and synaptic damage in neurons

Neurotoxicity may occur in cancer patients and survivors during or after chemotherapy. Cognitive deficits associated with neurotoxicity can be subtle or disabling and frequently include disturbances in memory, attention, executive function and processing speed. Searching for pathways altered by anti-cancer treatments in cultured primary neurons, we discovered that doxorubicin, a commonly used anti-neoplastic drug, significantly decreased neuronal survival. The drug promoted the formation of DNA double-strand breaks in primary neurons and reduced synaptic and neurite density. Pretreatment of neurons with levetiracetam, an FDA-approved anti-epileptic drug, enhanced survival of chemotherapy drug-treated neurons, reduced doxorubicin-induced formation of DNA double-strand breaks, and mitigated synaptic and neurite loss. Thus, levetiracetam might be part of a valuable new approach for mitigating synaptic damage and, perhaps, for treating cognitive disturbances in cancer patients and survivors