Dina Randazzo

Recurrent Glioblastoma Treated with Recombinant Poliovirus

BACKGROUND The prognosis of patients with recurrent World Health Organization (WHO) grade IV malignant glioma is dismal, and there is currently no effective therapy. We conducted a dose‐finding and toxicity study in this population of patients, evaluating convection‐enhanced, intratumoral delivery of the recombinant nonpathogenic polio–rhinovirus chimera (PVSRIPO). PVSRIPO recognizes the poliovirus receptor CD155, which is widely expressed in neoplastic cells of solid tumors and in major components of the tumor microenvironment. METHODS We enrolled consecutive adult patients who had recurrent supratentorial WHO grade IV malignant glioma, confirmed on histopathological testing, with measurable disease (contrast‐enhancing tumor of ≥1 cm and ≤5.5 cm in the greatest dimension). The study evaluated seven doses, ranging between 107 and 1010 50% tissue‐culture infectious doses (TCID50), first in a dose‐escalation phase and then in a dose‐expansion phase. RESULTS From May 2012 through May 2017, a total of 61 patients were enrolled and received a dose of PVSRIPO. Dose level ‐1 (5.0×107 TCID50) was identified as the phase 2 dose. One dose‐limiting toxic effect was observed; a patient in whom dose level 5 (1010 TCID50) was administered had a grade 4 intracranial hemorrhage immediately after the catheter was removed. To mitigate locoregional inflammation of the infused tumor with prolonged glucocorticoid use, dose level 5 was deescalated to reach the phase 2 dose. In the dose‐expansion phase, 19% of the patients had a PVSRIPO‐related adverse event of grade 3 or higher. Overall survival among the patients who received PVSRIPO reached a plateau of 21% (95% confidence interval, 11 to 33) at 24 months that was sustained at 36 months. CONCLUSIONS Intratumoral infusion of PVSRIPO in patients with recurrent WHO grade IV malignant glioma confirmed the absence of neurovirulent potential. The survival rate among patients who received PVSRIPO immunotherapy was higher at 24 and 36 months than the rate among historical controls. (Funded by the Brain Tumor Research Charity and others; ClinicalTrials.gov number, NCT01491893.)

Pineal Region Glioblastoma, a Case Report and Literature Review

Introduction Pineal region glioblastoma multiforme (GBM) is a rare disease entity with a generally poor prognosis. We present a case of a patient with an unresectable pineal region GBM treated with chemoradiation with favorable outcome. Case background A 65-year-old patient who was presented with visual symptoms was found to have a pineal region tumor on imaging. A stereotactic biopsy showed a World Health Organization Grade IV GBM, O-6-methylguanine-DNA methyltransferase (MGMT) promoter methylated, isocitrate dehydrogenase 1 and 2 wild type. The patient was treated with radiotherapy with concurrent temozolomide, followed by adjuvant temozolomide. Disease progression occurred at 58 weeks post-biopsy, which prompted the initiation of bevacizumab. The patient was alive and functioning well as of his last follow up, 166 weeks from the initial biopsy. Discussion On our review of the literature, 24 cases of pineal region GBM have been reported. The median reported survival for these previously reported cases was 6 months (range, 2–24 months). This patient has the longest overall survival reported to date for a patient with this diagnosis. This is the first patient in the literature with pineal region GBM who has been reported to have MGMT promoter methylation. Concluding remarks Although pineal region GBM is a rare disease entity with a generally poor prognosis, long-term survival is achievable for select patients. MGMT promoter methylation may potentially have prognostic value. Favorable control of recurrent disease with the use of bevacizumab is possible.

Psychosocial distress and its effects on the health-related quality of life of primary brain tumor patients

All cancer patients experience distress from the diagnosis, the effects of the disease or the treatment. Clinically significant distress decreases overall quality of life and the recognition of distress with prompt intervention is essential. The National Comprehensive Cancer Network distress thermometer (NCCN-DT) is a validated measuring tool that has been utilized in the primary brain tumor population to detect psychologic distress thereby provoking a referral process to the appropriate support system. Brain tumor patients commonly reported emotional and physical distress encompassing: fatigue, fears, memory and concentration and worry. More research is needed to identify the stressors of all primary brain tumor patients and their caretakers and integrate appropriate interventions to improve health-related quality of life in both groups.

Adjunctive perampanel for glioma-associated epilepsy

Glioma-associated epilepsy is associated with excessive glutamate signaling. We hypothesized that perampanel, an amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-type glutamate receptor antagonist, would treat glioma-related epilepsy. We conducted a single-arm study of adjunctive perampanel for patients with focal-onset glioma-associated seizures. The most common related adverse events were fatigue and dizziness. Three out of 8 participants had self-reported seizure reduction and an additional 3 reported improved control. Of these 6, 5 had isocitrate dehydrogenase 1 mutant gliomas. We conclude that perampanel is safe for patients with glioma-related focal-onset epilepsy. Further study into the association between AMPA signaling, IDH1 status and seizures is warranted.