Phase II study of border zone stereotactic radiosurgery with bevacizumab in patients with recurrent or progressive glioblastoma multiforme.

PURPOSE: Recurrent glioblastoma is universally fatal with limited effective treatment options. The aim of this phase 2 study of Border Zone SRS plus bevacizumab was to evaluate OS in patients with recurrent GBM. METHODS: Patients with histologically confirmed GBM with recurrent disease who had received prior first-line treatment with fractionated radiotherapy and chemotherapy and eligible for SRS were enrolled. Bevacizumab 10 mg/kg was given day -1, day 14, and then every 14 days until disease progression. 1-14 days before BZ-SRS procedure, patients underwent brain MRI /MRS. MRS with measurement of choline-to-N-acetyl aspartate index (CNI) area ≥ 3 was targeted for SRS. RESULTS: From 2015-2017, sixteen of planned 40 patients were enrolled. The median age was 62 (range, 48-74Y). 3/16 (0.188) participants experienced grade 2 toxicity. No AREs were reported. The mOS was 11.73 months compared to 8.74 months (P = 0.324) from date of SRS for the BZ-SRS and institutional historical controls, respectively. PFS-6 and OS-6 were 31.2% (p = 0.00294) and 81.2%(p = 0.058), respectively. Of 13 evaluable for best response: 1 CR (p = 0.077), 4 PR (p = 0.308), 7 SD (p = 0.538), and 1 PD (p = 0.077). 11/16 participants had MRS scans with an estimated probability that MRS changes a treatment plan of 0 (0, 0.285). CONCLUSION: BZ-SRS with bevacizumab was feasible and well tolerated. There is no significant survival benefit using BZ-SRS with bevacizumab compared to institutional historical controls. Secondary analysis revealed a trend toward improved PFS-6, but not OS-6 after BZ-SRS. MRS scans did not result in changes to SRS treatment plans.

Immunotherapy associated central nervous system complications in primary brain tumors.

Advances clarifying the genetics and function of the immune system within the central nervous system (CNS) and brain tumor microenvironment have led to increasing momentum and number of clinical trials using immunotherapy for primary brain tumors. While neurological complications of immunotherapy in extra-cranial malignancies is well described, the CNS toxicities of immunotherapy in patients with primary brain tumors with their own unique physiology and challenges are burgeoning. This review highlights the emerging and unique CNS complications associated with immunotherapy including checkpoint inhibitors, oncolytic viruses, adoptive cell transfer/chimeric antigen receptor (CAR) T cell and vaccines for primary brain tumors, as well as reviews modalities that have been currently employed or are undergoing investigation for treatment of such toxicities.

Major Genetic Motifs in Pituitary Adenomas: A Practical Literature Update.

BACKGROUND: The literature includes many studies examining the genetic abnormalities that influence pituitary adenomas (PAs). We aimed to state the collective knowledge on the genetic underpinnings of PAs by organizing, summarizing, and consolidating the literature to serve as a comprehensive review for scientists and clinicians of the most up-to-date information underlying the genetic landscape of PAs. METHODS: The PubMed and Google Scholar databases were searched using multiple key words and combined Medical Subject Headings terms; only articles published in English between January 2000 and January 2022 were included. Articles in which the focus did not relate to genetics, that included mainly anecdotal evidence, or that were single case studies were eliminated. RESULTS: PAs are one of the most common intracranial neoplasms. However, the genetic underpinnings for these tumors are not yet fully elucidated. There are several categories of PAs: clinically significant versus not clinically significant, functional versus nonfunctional, and germline-derived versus sporadic origin. Each of these disease subcategories is characterized by unique genetic aberrations. Recently, more genes and other types of genetic aberrations have been identified as possible causes of PAs, such as copy number variations and altered levels of microRNAs. CONCLUSIONS: This review serves to consolidate and summarize the literature discussing the genetic motifs of PAs to help physicians and scientists deliver patient-centered therapies.

Supratentorial lymphocytic inflammation with parenchymal perivascular enhancement responsive to steroids: A case report and literature review.

BACKGROUND: Chronic Lymphocytic Inflammation with Pontine Perivascular Enhancement Responsive to Steroids is a rare disorder that presents with subacute brainstem symptoms such as ataxia, facial paresthesias, and episodic diplopia, thought to be due to a T-cell medicated perivascular inflammatory process. A supratentorial variant, Supratentorial Lymphocytic Inflammation with Parenchymal Perivascular Enhancement Responsive to Steroids (SLIPPERS), has been described in only three patients. CASE DESCRIPTION: A 71-year-old male presented with word-finding difficulties, confusion, and left leg weakness. Radiographic workup demonstrated multiple supratentorial ring-enhancing lesions. PET/CT demonstrated hypermetabolism and susceptibility-weighted imaging demonstrated a hemorrhagic component. Frozen pathology revealed a predominately T-cell and monocyte inflammatory infiltrate. He demonstrated interval improvement to dexamethasone therapy, but then demonstrated worsening of his symptoms following discontinuation. CONCLUSION: Given his dramatic response to corticosteroids, he was diagnosed with SLIPPERS. SLIPPERS is an underrecognized diagnostic entity to consider in patients with ring-enhancing lesions and can present with hypermetabolic lesions on PET/CT.

Retrospective study of nivolumab for patients with recurrent high grade gliomas.

INTRODUCTION: Patients with recurrent high-grade gliomas (HGG) have limited treatment options. HGG utilize the PD-1 pathway to evade immune responses. Checkpoint inhibitors have demonstrated safety and clinical activity in patients with recurrent glioblastoma. We explored the efficacy of nivolumab in recurrent HGG with a primary objective of progression free survival (PFS) and overall survival (OS). METHODS: We retrospectively analyzed HGG patients treated with nivolumab in our institution. We included patients with advanced HGG who received nivolumab at their oncologist's decision. Patients received nivolumab 3 mg/kg every 2 weeks until confirmed progression, intolerable toxicity, death, or physician decision. Radiographic assessments were performed every 8 weeks. RESULTS: Between April 2015 and October 2017, 50 HGG patients received nivolumab. 43 patients received nivolumab with bevacizumab. 44 patients were bevacizumab refractory and 7 patients received nivolumab monotherapy. All had received prior radiation and chemotherapy. 39 adverse events (AEs) were noted [most commonly fatigue (16%) and constipation (10%)]. 4 (8%) patients experienced grade 3-4 AEs. 36 (72%) patients experienced stable disease (SD) at the 2-month assessment. Median duration of SD was 4.3 months (5.1 months in the bevacizumab naïve, 3.8 months in the bevacizumab refractory). Median PFS was 4.3 months (95% CI 3.5-5.3); median OS was 6.5 months (95% CI 6.0-8.8). CONCLUSION: Treatment with nivolumab therapy was associated with a manageable safety profile. In a subset of patients, there was disease stabilization in heavily pre-treated recurrent HGG.