Update on glioma biotechnology

© 2020 Elsevier B.V. Neuro-oncological research is at the forefront of the rising cancer therapy market, as evidenced by its growing revenue and the multitude of clinical trials investigating innovative treatment approaches. The Feinstein Institute for Medical Research, in conjunction with the Department of Neurosurgery at Lenox Hill Hospital and the Zucker School of Medicine at Hofstra / Northwell, sponsored The Brain Tumor Biotech Summit in New York City in June 2019. The aim of the Summit was to provide a forum that encourages collaboration between cancer specialists, biotechnology and pharmaceutical industry leaders, and the investment community in order to promote innovation and advance emerging therapies for brain tumors. Areas highlighted during the Summit included immunotherapy, precision medicine, and novel applications and experimental treatments such as receptor targeting, methods for improved drug delivery, and innovative intraoperative techniques and technologies. This review synthesizes the recent breakthroughs in brain tumor research as presented at The Brain Tumor Biotech Summit

superselective intraarterial cerebral infusion of cetuximab with blood brain barrier disruption combined with stupp protocol for newly diagnosed glioblastoma

© 2018 Old City Publishing, Inc. We describe the first case of a novel treatment for a newly diagnosed glioblastoma (GBM) using superselective intraarterial cerebral infusion (SIACI) of cetuximab after osmotic disruption of the blood-brain barrier (BBB) with mannitol. A 51year-old female underwent craniotomy for removal of a right frontal GBM. Pathology confirmed EGFR amplification, and she underwent three treatments of SIACI of cetuximab to the tumor site. The first treatment was given within a week of starting standard of care chemoradiation (Stupp protocol), which is a combination of radiation treatment (2 Gy per/ day x 30 days, total of 60 Gy) and oral temozolomide (75 mg/ m2). The second and third SIACI of cetuximab were administered 3 and 6 months later, while the patient continued on maintenance temozolomide. Post-radiation changes on MRI were stable, and there were no signs of recurrence at 4 and 6 months post-resection. Herein, we detail the technical aspects of this novel treatment paradigm and suggest that SIACI of cetuximab after BBB disruption using mannitol, combined with the standard of care chemoradiation therapy, may be an effective treatment method for newly diagnosed EGFR amplified glioblastoma

Rechallenging Recurrent Glioblastoma with Intra-Arterial Bevacizumab with Blood Brain–Barrier Disruption Results in Radiographic Response

© 2019 Elsevier Inc. Background: High-dose bevacizumab delivered via super selective intra-arterial cerebral infusion (SIACI) is one promising clinical trial combination for patients with glioblastoma (GBM). Although both continuous intravenous and intra-arterial administration of bevacizumab, and rechallenge with intravenous bevacizumab, have demonstrated improved survival, this is the first description of rechallenging GBM with SIACI of bevacizumab. Case Description: We report a case of a 43-year-old woman with recurrent GBM who had received treatment from 3 clinical trials, including a rechallenge with SIACI of bevacizumab. First, she enrolled into a phase I/II trial for patients newly diagnosed with GBM (NCT01811498) and received 3 doses of SIACI bevacizumab over 180 days in addition to standard of care chemotherapy and radiation. Following progression, as indicated on her magnetic resonance imaging scan, she consented for a separate clinical trial for her disease and received 2 cycles of temozolomide with an investigational agent. The patient was removed from the study on tumor progression. Subsequently, she was rechallenged with SIACI of bevacizumab via a third clinical trial (NCT01269853) and then completed 3 intravenous infusions. After completing the third trial, her magnetic resonance imaging scan demonstrated improvement based on Response Assessment In Neuro-Oncology criteria. Conclusions: This is the first report to highlight the effect of rechallenging a patient with SIACI of bevacizumab following disease progression after initial bevacizumab treatment and subsequent alternate clinical trial failure. There is a need to conduct further clinical trials to evaluate the benefits of rechallenge with SIACI versus intravenous bevacizumab for GBM and further explore theories of bevacizumab resistance

Vascularized Temporoparietal Fascial Flap: A Novel Surgical Technique to Bypass the Blood-Brain Barrier in Glioblastoma

© 2020 Elsevier Inc. Background: The major difficulty in treating glioblastoma stems from the intrinsic privileged nature of the brain. This complicates therapy, as many traditionally potent chemotherapeutics cannot access their target sites in the brain. Several techniques have been investigated to overcome this barrier and facilitate drug delivery. However, these techniques have inherent shortcomings related to the delivery system, the drug itself, or its bioactivity. Periosteal flaps and temporoparietal fascial flaps (TPFFs) are widely used options because they have predictable vasculature and a wide rotational arc. These flaps are not restricted by the blood-brain barrier, as they derive their vascular supply from branches of the external carotid artery, which can be readily identified with Doppler ultrasound. We hypothesized that transposition of a vascularized TPFF to the walls of a resected tumor surgical cavity may bring autologous tissue not restricted by the blood-brain barrier in close vicinity of the resected tumor bed microenvironment. This offers a nonselective, long-lasting gateway to target the residual tumor cells nesting in the brain adjacent to the tumor. Case Description: A 47-year-old, right-handed woman with newly diagnosed multifocal glioblastoma underwent excision of the tumor and TPFF placement. This illustrative case report represents the first case of the use of this novel surgical technique with radiologic follow-up. Conclusions: The blood-brain barrier is identified as a major barrier for effective drug delivery in glioblastoma. This study demonstrates the feasibility of the TPFF technique to bypass this barrier and help facilitate the goal of improving drug delivery