Current Landscape and Future Prospects of Radiation Sensitizers for Malignant Brain Tumors: A Systematic Review.

Usman Beg, Brianna Michelle Snyder, Sarosh Irfan Madhani, Nima Hamidi, Varun Padmanaban, Leonard C Tuanquin, Timothy J Kruser, James Connor, Alireza Mansouri

Journal: World neurosurgery 2021;151():e839-e856

PMID: 33974987

Full Text on Elsevier Science View on PubMed

Abstract

BACKGROUND

Radiation therapy (RT) is the cornerstone of management of malignant brain tumors, but its efficacy is limited in hypoxic tumors. Although numerous radiosensitizer compounds have been developed to enhance the effect of RT, progress has been stagnant. Through this systematic review, we provide an overview of radiosensitizers developed for malignant brain tumors, summarize their safety and efficacy, and evaluate areas for possible improvement.

METHODS

Following PRISMA guidelines, PubMed, EMBASE, Cochrane, and Web of Science were searched using terminology pertaining to radiosensitizers for brain tumor RT. Articles reporting clinical evidence of nonantineoplastic radiosensitizers with RT for malignant central nervous system tumors were included. Data of interest were presumed mechanism of action, median overall survival (OS), progression-free survival (PFS), and adverse events.

RESULTS

Twenty-two unique radiosensitizers were identified. Only 2/22 agents (fluosol with oxygen, and efaproxiral) showed improvement in OS in patients with glioblastoma and brain metastasis, respectively. A larger study was not able to confirm the latter. Improved PFS was reported with use of metronidazole, sodium glycididazole, and chloroquine. There was a wide range of toxicities, which prompted change of schedule or complete discontinuation of 9 agents.

CONCLUSIONS

Progress in radiosensitizers for malignant CNS tumors has been limited. Only 2 radiosensitizers have shown limited improvement in survival. Alternative strategies such as synthetic drug design, based on a mechanism of action that is independent of crossing the blood-brain barrier, may be necessary. Use of drug development strategies using new technologies to overcome past challenges is necessary.

Address: Midwestern University Arizona College of Osteopathic Medicine, Glendale, Arizona, USA.; Aga Khan University, Karachi, Pakistan.; Penn State Health Milton S. Hershey Medical Center, Hershey, Pennsylvania, USA.; Penn State Cancer Institute, Hershey, Pennsylvania, USA.; Turville Bay Radiation Oncology Center, Madison, Wisconsin, USA.; Penn State Cancer Institute, Hershey, Pennsylvania, USA; Penn State Department of Neurosurgery, Hershey, Pennsylvania, USA.; Penn State Cancer Institute, Hershey, Pennsylvania, USA; Penn State Department of Neurosurgery, Hershey, Pennsylvania, USA. Electronic address: [email protected].

DOI: 10.1016/j.wneu.2021.04.134