Neuro-oncology practice最新文献

Background: Primary central nervous system tumors are a leading cause of death and disability amongst pediatric cancer patients. Akron Children's Hospital published data in 2018 on response time for brain tumor diagnosis and implemented components of an established program to decrease diagnostic delays and thereby reduce tumor- and treatment-related morbidities. This study evaluates if there was an improvement in the total diagnostic interval (TDI, time from symptom onset to diagnosis) after provider education. During the study, the COVID-19 pandemic forced alterations in care delivery. The impact this had on the TDI was also assessed.

Methods: A retrospective chart review was performed, and patients were separated into 2008-2017 (historical) and 2018-2021 (posteducation) groups to assess the effect of educational interventions on TDI. The posteducation cohort was analyzed separately to assess the impact of COVID-19 pandemic.

Results: The 85 patients studied in the post-education group showed a median TDI of 31 days. Though not statistically significant (P = .939), this represents an 11-day decrease in median TDI compared to the historical group (42 days). In addition, the posteducation group showed an increase in the average number of healthcare provider visits (HCP, 2.4 historical to 3.2 posteducation, P = .009). The pre-COVID-19 group (median TDI 43.5 days) did not differ statistically from the post-COVID-19 group (30-day median TDI).

Conclusion: The nonsignificant decrease in TDI and concurrent increase in HCP visits after implementation of education suggests a potential gap amongst providers in working-up primary CNS tumors. These results will influence expansion of education to further improve TDI.

Background: Social determinants of health (SDOHs)-specifically those related to rurality, health care accessibility, and income-may play as-yet-unidentified roles in prognosis for glioma patients, and their impact on access to clinical trials is important to understand. We examined SDOHs of patients enrolled in glioma clinical trials and evaluate disparities in trial participation and outcomes between rural and urban patients.

Methods: We retrospectively identified patients enrolled in glioma clinical trials at Huntsman Cancer Institute (HCI) from May 2012 to May 2022 to evaluate clinical trial participation. We used multivariable models to evaluate SDOHs and geographic information system mapping to assess representation across Utah's counties. We utilized the most recent 10-year datasets of patients treated for glioma at HCI and from the Utah Cancer Registry to analyze survival and incidence, respectively.

Results: A total of 570 participants (68 trials) resided in Utah, 84.4% from urban counties, 13.5% from rural counties, and 2.1% from frontier (least-populous) counties. Nineteen counties (65.5%) were underrepresented in trials (enrolled participants vs. eligible), 1 (3.5%) was represented in a near-1:1 ratio, and 9 (31.0%) were overrepresented. Counties with greater enrollment had greater population densities, highest per-capita income, and proximity to HCI. Among patients treated at HCI, patients from rural/frontier counties had equivalent survival with urban patients across nearly all glioma types, including glioblastomas, despite underrepresentation in clinical trials.

Conclusions: By highlighting disparities in clinical trial enrollment, our results can support efforts to improve recruitment in underrepresented regions, which can assist providers in delivering equitable care for all patients.

Background: 5-aminolevulinic acid (5-ALA) fluorescence-guided resection increases the percentage of complete CNS tumor resections and improves the progression-free survival of IDH-wildtype glioblastoma patients. A small subset of IDH-wildtype glioblastoma shows no 5-ALA fluorescence. An explanation for these cases is missing. In this study, we used DNA methylation profiling to further characterize non-fluorescent glioblastomas.

Methods: Patients with newly diagnosed and recurrent IDH-wildtype glioblastoma that underwent surgery were analyzed. The intensity of intraoperative 5-ALA fluorescence was categorized as non-visible or visible. DNA was extracted from tumors and genome-wide DNA methylation patterns were analyzed using Illumina EPIC (850k) arrays. Furthermore, 5-ALA intensity was measured by flow cytometry on human gliomasphere lines (BT112 and BT145).

Results: Of 74 included patients, 12 (16.2%) patients had a non-fluorescent glioblastoma, which were compared to 62 glioblastomas with 5-ALA fluorescence. Clinical characteristics were equally distributed between both groups. We did not find significant differences between DNA methylation subclasses and 5-ALA fluorescence (P = .24). The distribution of cells of the tumor microenvironment was not significantly different between the non-fluorescent and fluorescent tumors. Copy number variations in EGFR and simultaneous EGFRvIII expression were strongly associated with 5-ALA fluorescence since all non-fluorescent glioblastomas were EGFR-amplified (P < .01). This finding was also demonstrated in recurrent tumors. Similarly, EGFR-amplified glioblastoma cell lines showed no 5-ALA fluorescence after 24 h of incubation.

Conclusions: Our study demonstrates an association between non-fluorescent IDH-wildtype glioblastomas and EGFR gene amplification which should be taken into consideration for recurrent surgery and future studies investigating EGFR-amplified gliomas.

Background: Recurrent gliomas are therapeutically challenging diseases with few treatment options available. One area of potential therapeutic vulnerability is the presence of targetable oncogenic fusion proteins.

Methods: To better understand the clinical benefit of routinely testing for fusion proteins in adult glioma patients, we performed a retrospective review of 647 adult patients with glioma who underwent surgical resection at our center between August 2017 and May 2021 and whose tumors were analyzed with an in-house fusion transcript panel.

Results: Fifty-two patients (8%) were found to harbor a potentially targetable fusion with 11 (21%) of these patients receiving treatment with a fusion-targeted inhibitor. The targetable genes found to be involved in a fusion included FGFR3, MET, EGFR, NTRK1, NTRK2, BRAF, ROS1, and PIK3CA.

Conclusions: This analysis demonstrates that routine clinical testing for gene fusions identifies a diverse repertoire of potential therapeutic targets in adult patients with glioma and can offer rational therapeutic options for patients with recurrent disease.

AbstractGlioma patients carry the burden of having both a progressive neurological disease and cancer, and may face a variety of symptoms, including depression and anxiety. These symptoms are highly prevalent in glioma patients (median point prevalence ranging from 16-41% for depression and 24-48% for anxiety when assessed by self-report questionnaires) and have a major impact on health-related quality of life and even overall survival time. A worse overall survival time for glioma patients with depressive symptoms might be due to tumor progression and/or its supportive treatment causing depressive symptoms, an increased risk of suicide or other (unknown) factors. Much is still unclear about the etiology of depressive and anxiety symptoms in glioma. These psychiatric symptoms often find their cause in a combination of neurophysiological and psychological factors, such as the tumor and/or its treatment. Although these patients have a particular idiosyncrasy, standard treatment guidelines for depressive and anxiety disorders apply, generally recommending psychological and pharmacological treatment. Only a few nonpharmacological trials have been conducted evaluating the efficacy of psychological treatments (eg, a reminiscence therapy-based care program) in this population, which significantly reduced depressive and anxiety symptoms. No pharmacological trials have been conducted in glioma patients specifically. More well-designed trials evaluating the efficacy of nonpharmacological treatments for depressive and anxiety disorders in glioma are urgently needed to successfully treat psychiatric symptoms in brain tumor patients and to improve (health-related) quality of life.