Safety and feasibility of multiple blood-brain barrier disruptions for the treatment of glioblastoma in patients undergoing standard adjuvant chemotherapy

So Hee Park, Myung Ji Kim, Hyun Ho Jung, Won Seok Chang, Hyun Seok Choi, Itay Rachmilevitch, Eyal Zadicario, Jin Woo Chang

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48 Citations (Scopus)


OBJECTIVE Glioblastoma (GBM) remains fatal due to the blood-brain barrier (BBB), which interferes with the delivery of chemotherapeutic agents. The purpose of this study was to evaluate the safety and feasibility of repeated disruption of the BBB (BBBD) with MR-guided focused ultrasound (MRgFUS) in patients with GBM during standard adjuvant temozolomide (TMZ) chemotherapy. METHODS This study was a prospective, single-center, single-arm study. BBBD with MRgFUS was performed adjacent to the tumor resection margin on the 1st or 2nd day of the adjuvant TMZ chemotherapy at the same targets for 6 cycles. T2*-weighted/gradient echo (GRE) MRI was performed immediately after every sonication trial, and comprehensive MRI was performed at the completion of all sonication sessions. Radiological, laboratory, and clinical evaluations were performed 2 days before each planned BBBD. RESULTS From September 2018, 6 patients underwent 145 BBBD trials at various locations in the brain. The authors observed gadolinium-enhancing spots at the site of BBBD on T1-weighted MRI in 131 trials (90.3%) and 93 trials (64.1%) showed similar spots on T2*-weighted/GRE MRI. When the 2 sequences were combined, BBBD was observed in 134 targets (92.4%). The spots disappeared on follow-up MRI. There were no imaging changes related to BBBD and no clinical adverse effects during the 6 cycles. CONCLUSIONS This study is the first in which repetitive MRgFUS was performed at the same targets with a standard chemotherapy protocol for malignant brain tumor. BBBD with MRgFUS was performed accurately, repeatedly, and safely. Although a longer follow-up period is needed, this study allows for the possibility of other therapeutic agents that previously could not be used due to the BBB.

Original languageEnglish
Pages (from-to)475-483
Number of pages9
JournalJournal of neurosurgery
Issue number2
Publication statusPublished - 2021 Feb

Bibliographical note

Funding Information:
This study was supported by a grant from the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (grant no. HI19C0060). We would like to thank Jung Il Lee, MD (Samsung Medical Center), Jeong Hoon Kim, MD (Asan Medical Center), and Jong Hee Chang, MD (Severance Hospital), for their help in recruiting the patients. We would also like to thank Eun Jung Kweon, RN, for her great assistance in this study.

Publisher Copyright:
©AANS 2021, except where prohibited by US copyright law

All Science Journal Classification (ASJC) codes

  • Surgery
  • Clinical Neurology


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