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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 
 JOURNAL OF NEUROSURGERY, Vol.134(2) : 475-483, 2021-02 
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AU = arbitrary unit ; BBB = blood-brain barrier ; BBBD = disruption of the BBB ; GBM = glioblastoma ; GRE = gradient echo ; MB = microbubble ; MRgFUS = MR-guided focused ultrasound ; P-gp = P-glycoprotein 1 ; TMZ = temozolomide ; blood-brain barrier ; focused ultrasound ; glioblastoma ; magnetic resonance imaging ; oncology ; surgical technique
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.Clinical trial registration no.: NCT03712293 (clinicaltrials.gov).
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1. College of Medicine (의과대학) > Dept. of Neurosurgery (신경외과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Radiology (영상의학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Urology (비뇨의학교실) > 1. Journal Papers
Yonsei Authors
Kim, Myung Ji(김명지)
Rha, Koon Ho(나군호) ORCID logo https://orcid.org/0000-0001-8588-7584
Park, So Hee(박소희)
Chang, Won Seok(장원석) ORCID logo https://orcid.org/0000-0003-3145-4016
Chang, Jin Woo(장진우) ORCID logo https://orcid.org/0000-0002-2717-0101
Jung, Hyun Ho(정현호)
Choi, Hyun Seok(최현석) ORCID logo https://orcid.org/0000-0003-4999-8513
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