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BackgroundTreatment options for unresectable new and recurrent glioblastoma remain limited. Laser ablation has demonstrated safety as a surgical approach to treating primary brain tumors. The LAANTERN prospective multicenter registry (NCT02392078) data were analyzed to determine clinical outcomes for patients with new and recurrent IDH wild-type glioblastoma.MethodsDemographics, intraprocedural data, adverse events, KPS, health economics, and survival data were prospectively collected and then analyzed on IDH wild-type newly diagnosed and recurrent glioblastoma patients who were treated with laser ablation at 14 US centers between January 2016 and May 2019. Data were monitored for accuracy. Statistical analysis included individual variable summaries, multivariable differences in survival, and median survival numbers.ResultsA total of 29 new and 60 recurrent IDH wild-type WHO grade 4 glioblastoma patients were treated. Positive MGMT promoter methylation status was present in 5/29 of new and 23/60 of recurrent patients. Median physician-estimated extent of ablation was 91%-99%. Median overall survival (OS) was 9.73 months (95% confidence interval: 5.16, 15.91) for newly diagnosed patients and median post-procedure survival was 8.97 months (6.94, 12.36) for recurrent patients. Median OS for newly diagnosed patients receiving post-LITT chemo/radiation was 16.14 months (6.11, not reached). Factors associated with improved survival were MGMT promoter methylation, adjuvant chemotherapy within 12 weeks, and tumor volume

Glioblastoma is the most common primary malignant brain tumor in adults and is associated with poor survival. The Ivy Foundation Early Phase Clinical Trials Consortium conducted a randomized, multi-institution clinical trial to evaluate immune responses and survival following neoadjuvant and/or adjuvant therapy with pembrolizumab in 35 patients with recurrent, surgically resectable glioblastoma. Patients who were randomized to receive neoadjuvant pembrolizumab, with continued adjuvant therapy following surgery, had significantly extended overall survival compared to patients that were randomized to receive adjuvant, post-surgical programmed cell death protein 1 (PD-1) blockade alone. Neoadjuvant PD-1 blockade was associated with upregulation of T cell- and interferon-γ-related gene expression, but downregulation of cell-cycle-related gene expression within the tumor, which was not seen in patients that received adjuvant therapy alone. Focal induction of programmed death-ligand 1 in the tumor microenvironment, enhanced clonal expansion of T cells, decreased PD-1 expression on peripheral blood T cells and a decreasing monocytic population was observed more frequently in the neoadjuvant group than in patients treated only in the adjuvant setting. These findings suggest that the neoadjuvant administration of PD-1 blockade enhances both the local and systemic antitumor immune response and may represent a more efficacious approach to the treatment of this uniformly lethal brain tumor.

We sought to compare the tumor profiles of brain metastases from common cancers with those of primary tumors and extracranial metastases in order to identify potential targets and prioritize rational treatment strategies. Tumor samples were collected from both the primary and metastatic sites of nonsmall cell lung cancer, breast cancer and melanoma from patients in locations worldwide, and these were submitted to Caris Life Sciences for tumor multiplatform analysis, including gene sequencing (Sanger and next-generation sequencing with a targeted 47-gene panel), protein expression (assayed by immunohistochemistry) and gene amplification (assayed by in situ hybridization). The data analysis considered differential protein expression, gene amplification and mutations among brain metastases, extracranial metastases and primary tumors. The analyzed population included: 16,999 unmatched primary tumor and/or metastasis samples: 8,178 nonsmall cell lung cancers (5,098 primaries; 2,787 systemic metastases; 293 brain metastases), 7,064 breast cancers (3,496 primaries; 3,469 systemic metastases; 99 brain metastases) and 1,757 melanomas (660 primaries; 996 systemic metastases; 101 brain metastases). TOP2A expression was increased in brain metastases from all 3 cancers, and brain metastases overexpressed multiple proteins clustering around functions critical to DNA synthesis and repair and implicated in chemotherapy resistance, including RRM1, TS, ERCC1 and TOPO1. cMET was overexpressed in melanoma brain metastases relative to primary skin specimens. Brain metastasis patients may particularly benefit from therapeutic targeting of enzymes associated with DNA synthesis, replication and/or repair.

Herein, we report a case of a collision tumor involving a multinodular and vacuolating neuronal tumor (MVNT) and a diffuse astrocytoma. A collision tumor between these two entities has not previously been reported. The patient is a 35‐year‐old woman who presented with new‐onset hearing loss and ringing in her right ear. Magnetic resonance imaging identified a non‐enhancing mass involving the gray matter and subcortical white matter of the left middle frontal gyrus. Additionally, tiny clustered nodules were noted along the underlying subcortical ribbon and superficial subcortical white matter of the left superior frontal gyrus. The patient underwent a left frontal craniotomy and complete resection of the mass. Histologic examination of the resected specimen demonstrated a collision tumor consisting of a diffuse astrocytoma (isocitrate dehydrogenase [IDH] mutant, central nervous system [CNS] World Health Organization [WHO] grade 2) and an MVNT, with the latter demonstrating characteristic morphologic and immunohistochemical features. [ABSTRACT FROM AUTHOR]

Background We observed rapid tumor progression following COVID-19 infection among patients with glioblastoma and sought to systematically characterize their disease course in a retrospective case–control study. Methods Using an institutional database, we retrospectively identified a series of COVID-19-positive glioblastoma cases and matched them by age and sex 1:2 to glioblastoma controls who had a negative COVID-19 test during their disease course. Demographic and clinical data were analyzed. Hyperprogression was defined using modified response evaluation criteria in solid tumors criteria. Time to progression and overall survival were estimated using the Kaplan–Meier method. Results Thirty-two glioblastoma cases with positive COVID-19 testing were matched to 64 glioblastoma controls with negative testing; age, sex, and molecular profiles did not differ between groups. Progression events occurred in 27 cases (84%) and 46 controls (72%). Of these, 14 cases (52%) presented with multifocal disease or leptomeningeal disease at progression compared with 10 controls (22%; P  = .0082). Hyperprogression was identified in 13 cases (48%) but only 4 controls (9%; P  = .0001). Cases had disease progression at a median of 35 days following COVID-19 testing, compared with 164 days for controls (P  = .0001). Median survival from COVID-19 testing until death was 8.3 months for cases but 17 months for controls (P  = .0016). Median overall survival from glioblastoma diagnosis was 20.7 months for cases and 24.6 months for controls (P  = .672). Conclusions Patients with glioblastoma may have accelerated disease progression in the first 2 months after COVID-19 infection. Infected patients should be monitored vigilantly. Future investigations should explore tumor-immune microenvironment changes linking tumor progression and COVID-19. [ABSTRACT FROM AUTHOR]

Background Burnout is a syndrome characterized by emotional exhaustion, depersonalization, and a reduced sense of accomplishment, which commonly arises from chronic workplace stress in the medical field. Given the higher risk of burnout in younger age groups reported in some studies, the Society for Neuro-Oncology (SNO) Young Investigator (YI) and Wellness Committees combined efforts to examine burnout in the SNO YI membership to better understand and address their needs. Methods We distributed an anonymous online survey to SNO members in 2019. Only those meeting the definition of a YI were asked to complete the survey. The survey consisted of questions about personal and professional characteristics as well as the validated Maslach Burnout Inventory-Human Services Survey (MBI-HSS) questionnaire. Statistical analyses included descriptive statistics, univariate and multivariate analyses, and incorporation of previously defined burnout profiles. Results Data were analyzed for 173 participants who self-identified as YI. Measures of burnout showed that YI members scored higher on emotional exhaustion and depersonalization compared to normative population but similar to those in a prior SNO general membership survey. With respect to burnout profiles, 30% of YI respondents classified as overextended and 15% as burnout. Organizational challenges were the most common contributors to stress. Conclusions Similar to results from a previous survey completed by general SNO membership, the prevalence of burnout among neuro-oncology clinical and research YI is high, and is mainly characterized by overextension, warranting interventions at institutional and organizational levels. [ABSTRACT FROM AUTHOR]

Purpose Burnout is a psychological occupational syndrome defined by the Maslach Burnout Inventory (MBI) as emotional exhaustion, depersonalization, and a low sense of personal accomplishment. We sought to characterize the prevalence of burnout among early-career medical oncologists at The University of Texas MD Anderson Cancer Center (MDACC). Methods For this institutional review board–approved study, an electronic survey was developed for Assistant Professors in the MDACC Division of Cancer Medicine. All participants were involved directly in patient care. Our survey included questions assessing self-reported burnout, nine questions validated in the abbreviated MBI, and 31 questions to assess potential contributors to burnout. Each question was scaled 1-5, with higher scores associated with higher burnout. Descriptive statistics were used to estimate the prevalence of burnout, and logistic regression analyses were performed to identify contributing factors. Results Among 86 Assistant Professors, 56 (65%) responded to the survey. The mean duration on faculty was 3.1 years. The mean clinical effort was 67% (range, 19-95). Fifty-four percent of respondents self-reported symptoms of burnout including 21% indicating severe burnout. Using the MBI, sentiments of being emotionally drained (54%), fatigued facing another day on the job (45%), and becoming more callous (30%) were especially notable. Twenty-five percent of respondents exhibited severe emotional exhaustion, which was more prevalent (P < .0001) than depersonalization (6%) or lack of personal accomplishment (17%). Conclusion Burnout exists with high prevalence among early-career medical oncologists, with emotional exhaustion being the most common manifestation of burnout. Interventions focusing on reducing emotional exhaustion are needed to reduce burnout among early-career medical oncologists. [ABSTRACT FROM AUTHOR]