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

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.

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Work Title Current Landscape and Future Prospects of Radiation Sensitizers for Malignant Brain Tumors: A Systematic Review
Access
Open Access
Creators
  1. Usman Beg
  2. Brianna Michelle Snyder
  3. Sarosh Irfan Madhani
  4. Nima Hamidi
  5. Varun Padmanaban
  6. Leonard C. Tuanquin
  7. Timothy J. Kruser
  8. James Connor
  9. Alireza Mansouri
Keyword
  1. Brain tumor
  2. Chemotherapy
  3. Glioblastoma
  4. Metastasis
  5. Radiosensitizer
  6. Radiosurgery
  7. Radiotherapy
License CC BY-NC-ND 4.0 (Attribution-NonCommercial-NoDerivatives)
Work Type Article
Publisher
  1. World Neurosurgery
Publication Date July 5, 2021
Publisher Identifier (DOI)
  1. https://doi.org/10.1016/j.wneu.2021.04.134
Deposited August 02, 2022

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Version 1
published

  • Created
  • Added MANUSCRIPT_UPLOAD_REVISED_marked.docx
  • Added Creator U Beg
  • Added Creator B M Snyder
  • Added Creator S I Madhani
  • Added Creator N Hamidi
  • Added Creator V Padmanaban
  • Added Creator Leonard C. Tuanquin
  • Added Creator T J Kruser
  • Added Creator James R Connor
  • Added Creator Alireza Mansouri
  • Added Creator S Alireza Mansouri
  • Published
  • Updated Keyword, Publication Date Show Changes
    Keyword
    • Brain tumor, Chemotherapy, Glioblastoma, Metastasis, Radiosensitizer, Radiosurgery, Radiotherapy
    Publication Date
    • 2021-07-01
    • 2021-07-05
  • Updated Work Title Show Changes
    Work Title
    • Current Landscape and Future Prospects of Radiation Sensitizers for Malignant Brain Tumors: A Systematic Review.
    • Current Landscape and Future Prospects of Radiation Sensitizers for Malignant Brain Tumors: A Systematic Review
  • Deleted Creator S Alireza Mansouri
  • Renamed Creator Usman Beg Show Changes
    • U Beg
    • Usman Beg
  • Renamed Creator Brianna Michelle Snyder Show Changes
    • B M Snyder
    • Brianna Michelle Snyder
  • Renamed Creator Sarosh Irfan Madhani Show Changes
    • S I Madhani
    • Sarosh Irfan Madhani
  • Renamed Creator Nima Hamidi Show Changes
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    • Nima Hamidi
  • Renamed Creator Varun Padmanaban Show Changes
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    • Varun Padmanaban
  • Renamed Creator Timothy J. Kruser Show Changes
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    • Timothy J. Kruser
  • Renamed Creator James Connor Show Changes
    • James R Connor
    • James Connor