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BACKGROUND. Advanced MRI-based neuroimaging techniques, such as perfusion and spectroscopy, have been increasingly incorporated into routine follow-up protocols in patients treated for high-grade glioma (HGG), to help differentiate tumor progression from treatment effect. However, these techniques' influence on clinical management remains poorly understood. OBJECTIVE. The purpose of this article was to evaluate the impact of MRI-based advanced neuroimaging on clinical decision-making in patients with HGG after treatment. METHODS. This prospective study, performed at a comprehensive cancer center from March 1, 2017, to October 31, 2020, included adult patients treated by chemoradiation for WHO grade 4 diffuse glioma who underwent MRI-based advanced neuroimaging (comprising multiple perfusion imaging sequences and spectroscopy) to further evaluate findings on conventional MRI equivocal for tumor progression versus treatment effect. The ordering neurooncologists completed surveys before and after each advanced neuroimaging session. The percent of episodes of care with a change between the intended and actual management plan on the surveys conducted before and after advanced neuroimaging, respectively, was computed and compared with a published percent using the Wald test for independent samples proportions. RESULTS. The study included 63 patients (mean age, 54.6 ± 12.9 [SD] years; 36 women, 27 men) who underwent 70 advanced neuroimaging sessions. Ordering neurooncologists' intended and actual management plans on the surveys completed before and after advanced neuroimaging, respectively, differed in 44% (31/70; 95% CI: 33-56%) of episodes, which differed from the published frequency of 8.5% (5/59) ( p < .001). These management plan changes included selection of a different plan for six of eight episodes with an intended plan to enroll patients in a clinical trial, 12 of 19 episodes with an intended plan to change chemotherapeutic agents, four of eight episodes with an intended plan of surgical intervention, and one of two episodes with an intended plan of reirradiation. The ordering neurooncologists found advanced neuroimaging to be helpful in 93% (65/70; 95% CI: 87-99%) of episodes. CONCLUSION. Neurooncologists' management plans changed in a substantial fraction of adult patients with HGG who underwent advanced neuroimaging to further evaluate conventional MRI findings equivocal for tumor progression versus treatment effect. CLINICAL IMPACT. The findings support incorporation of advanced neuroimaging into HGG posttreatment monitoring protocols.

Purpose: Bevacizumab has evolved as an integral treatment option for patients with high-grade gliomas. Little is known about clinical risk factors that predispose patients with high-grade gliomas receiving bevacizumab to VTE or ICH. We sought to characterize the clinical risk factors associated with risk of either event., Methods: In this multi-institutional retrospective study, we first evaluated patients with high-grade gliomas who were treated with bevacizumab at University of Texas MD Anderson Cancer Center from 2015-2021. We compared clinical and treatment-related factors among three cohorts: those who developed VTE, ICH, or neither. We further compared survival outcomes of these patients from the time of bevacizumab initiation. Then to further confirm our results in a non-cancer center hospital setting we evaluated patients from two Ascension Seton Hospitals in Austin, Texas which are affiliated with Dell Medical School at the University of Texas at Austin from 2017-2022., Results: We found that the presence of cerebral macrobleeding, defined as a magnetic susceptibility of > 1 cm 3 on magnetic resonance imaging, was highly associated with risk of developing ICH after initiation of bevacizumab. Development of ICH was significantly associated with poorer survival outcomes. We did not find a statistically significant effect of VTE on survival after bevacizumab initiation., Conclusion: In order to stratify the risk for developing ICH before the initiation of bevacizumab, we recommend to assess for the presence of cerebral macrobleeding as it is associated with ICH development., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Aim: To ascertain the maximum tolerated dose (MTD)/maximum feasible dose (MFD) of WP1066 and p-STAT3 target engagement within recurrent glioblastoma (GBM) patients. Patients & methods: In a first-in-human open-label, single-center, single-arm 3 + 3 design Phase I clinical trial, eight patients were treated with WP1066 until disease progression or unacceptable toxicities. Results: In the absence of significant toxicity, the MFD was identified to be 8 mg/kg. The most common adverse event was grade 1 nausea and diarrhea in 50% of patients. No treatment-related deaths occurred; 6 of 8 patients died from disease progression and one was lost to follow-up. Of 8 patients with radiographic follow-up, all had progressive disease. The longest response duration exceeded 3.25 months. The median progression-free survival (PFS) time was 2.3 months (95% CI: 1.7 months-NA months), and 6-month PFS (PFS6) rate was 0%. The median overall survival (OS) rate was 25 months (95% CI: 22.5 months-NA months), with an estimated 1-year OS rate of 100%. Pharmacokinetic (PK) data demonstrated that at 8 mg/kg, the T 1/2 was 2-3 h with a dose dependent increase in the C max . Immune monitoring of the peripheral blood demonstrated that there was p-STAT3 suppression starting at a dose of 1 mg/kg. Conclusion: Immune analyses indicated that WP1066 inhibited systemic immune p-STAT3. WP1066 had an MFD identified at 8 mg/kg which is the target allometric dose based on prior preclinical modeling in combination with radiation therapy and a Phase II study is being planned for newly diagnosed MGMT promoter unmethylated glioblastoma patients.

Background: Reports suggest that phosphatidylinositol 3-kinase pathway alterations confer increased risk of progression and poor prognosis in oligodendroglioma, IDH-mutant, and 1p/19q-codeleted molecular oligodendrogliomas (mODG). However, factors that affect prognosis in mODG have not been thoroughly studied. In addition, the benefits of adjuvant radiation and temozolomide (TMZ) in mODGs remain to be determined., Objective: To evaluate the role of PIK3CA mutations in mODGs., Methods: One hundred seven mODGs (2008-2019) diagnosed at 2 institutions were included. A retrospective review of clinical characteristics, molecular alterations, treatments, and outcomes was performed., Results: The median age was 37 years, and 61 patients (57%) were male. There were 64 (60%) World Health Organization (WHO) grade 2 and 43 (40%) WHO grade 3 tumors. Eighty-two patients (77%) were stratified as high risk (age 40 years or older and/or subtotal resection per Radiation Treatment Oncology Group-9802). Gross-total resection was achieved in 47 patients (45%). Treatment strategies included observation (n = 15), TMZ (n = 11), radiation (n = 13), radiation/TMZ (n = 62), and others (n = 6). Our results show a benefit of TMZ vs observation in progression-free survival (PFS). No difference in PFS or overall survival (OS) was observed between radiation and radiation/TMZ. PIK3CA mutations were detected in 15 (14%) mODG, and shorter OS was observed in PIK3CA-mutant compared with PIK3CA wild-type mODGs (10.7 years vs 15.1 years, P = .009). WHO grade 3 tumors showed a shorter PFS, but no significant difference in OS was observed between WHO grades., Conclusion: Our findings suggest that mODGs harboring PIK3CA mutations have worse OS. Except for an advantage in PFS with TMZ treatment, adjuvant TMZ, radiation, or a combination of the two showed no significant improvement in OS., (Copyright © Congress of Neurological Surgeons 2022. All rights reserved.)

Immunotherapy has changed the landscape of treatment of many solid and hematological malignancies and is at the forefront of cancer breakthroughs. Several circumstances unique to the central nervous system (CNS) such as limited space for an inflammatory response, difficulties with repeated sampling, corticosteroid use for management of cerebral edema, and immunosuppressive mechanisms within the tumor and brain parenchyma have posed challenges in clinical development of immunotherapy for intracranial tumors. Nonetheless, the success of immunotherapy in brain metastases (BMs) from solid cancers such as melanoma and non-small cell lung cancer (NSCLC) proves that the CNS is not an immune-privileged organ and is capable of initiating and regulating immune responses that lead to tumor control. However, the development of immunotherapeutics for the most malignant primary brain tumor, glioblastoma (GBM), has been challenging due to systemic and profound tumor-mediated immunosuppression unique to GBM, intratumoral and intertumoral heterogeneity, and lack of stably expressed clonal antigens. Here, we review recent advances in the field of immunotherapy for neuro-oncology with a focus on BM, GBM, and rare CNS cancers., (© 2021. The Author(s), under exclusive license to Springer Nature Switzerland AG.)