Evidence map›Paper›PMID 41308679›Full record

Trial reportThe Lancet. Oncology2025

Microbubble-enhanced transcranial focused ultrasound with temozolomide for patients with high-grade glioma (BT008NA): a multicentre, open-label, phase 1/2 trial.

Graeme F Woodworth, Pavlos Anastasiadis, Ahmad Ozair, Jeremi Chabros, Chetan Bettegowda, Chixiang Chen, Jakob V E Gerstl, Christopher Douville, Rania A Mekary, Timothy R Smith and 29 more

Abstract readClinical Trial, Phase IIClinical Trial, Phase IMulticenter Study
PubMed Full text at PMC Publisher
In one paragraph

Trial report in The Lancet. Oncology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
27citing papers in PubMed, 2 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

27 citing papers in PubMed, 2 syntheses or guidelines pooled it.

  1. Pooled it
  2. Pooled it
  3. Accelerating discovery: Transformative clinical trial models in neuro-oncology.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026
    Review
  4. Inhibiting glioma cell invasion by sequential photo-sonodynamic therapy.Photochemical & photobiological sciences : Official journal of the European Photochemistry Association and the European Society for Photobiology · 2026
    Article
  5. Next-generation therapeutics for glioblastoma: Challenges and future directions.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026
    Review
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

39 authors.

Graeme F WoodworthDepartment of Neurosurgery, University of Maryland School of Medicine, Baltimore, MD, USA; Brain Tumor Program, University of Maryland Marlene and Stewart Greenebaum Comprehensive Cancer Center, Baltimore, MD, USA; Department of Diagnostic Radiology and Nuclear Medicine, University of Maryland School of Medicine, Baltimore, MD, USA. Electronic address: gwoodworth@som.umaryland.edu.
Pavlos AnastasiadisDepartment of Neurosurgery, University of Maryland School of Medicine, Baltimore, MD, USA; Brain Tumor Program, University of Maryland Marlene and Stewart Greenebaum Comprehensive Cancer Center, Baltimore, MD, USA; Department of Diagnostic Radiology and Nuclear Medicine, University of Maryland School of Medicine, Baltimore, MD, USA.
Ahmad OzairDepartment of Neurosurgery, University of Maryland School of Medicine, Baltimore, MD, USA; Brain Tumor Program, University of Maryland Marlene and Stewart Greenebaum Comprehensive Cancer Center, Baltimore, MD, USA; Montreal Neurological Institute and Hospital, McGill University, Montreal, QC, Canada.
Jeremi ChabrosComputational Neuroscience Outcomes Center, Department of Neurosurgery, Brigham and Women's Hospital, Boston, MA, USA; Harvard T H Chan School of Public Health, Harvard University, Boston, MA, USA.
Chetan BettegowdaSidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Chixiang ChenDepartment of Neurosurgery, University of Maryland School of Medicine, Baltimore, MD, USA; Department of Epidemiology and Public Health, University of Maryland School of Medicine, Baltimore, MD, USA.
Jakob V E GerstlComputational Neuroscience Outcomes Center, Department of Neurosurgery, Brigham and Women's Hospital, Boston, MA, USA; Department of Neurosurgery, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
Christopher DouvilleSidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Rania A MekaryDepartment of Neurosurgery, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA; School of Pharmacy, Massachusetts College of Pharmacy and Health Sciences University, Boston, MA, USA.
Timothy R SmithComputational Neuroscience Outcomes Center, Department of Neurosurgery, Brigham and Women's Hospital, Boston, MA, USA; Department of Neurosurgery, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
Ying MengHarquail Centre for Neuromodulation, Sunnybrook Health Sciences Centre, Toronto, ON, Canada; Division of Neurosurgery, Department of Surgery, Temerty Faculty of Medicine, University of Toronto, Toronto, ON, Canada.
Cynthia HawkinsHarquail Centre for Neuromodulation, Sunnybrook Health Sciences Centre, Toronto, ON, Canada; Division of Neurosurgery, Department of Surgery, Temerty Faculty of Medicine, University of Toronto, Toronto, ON, Canada.
Christopher B PopleHarquail Centre for Neuromodulation, Sunnybrook Health Sciences Centre, Toronto, ON, Canada; Division of Neurosurgery, Department of Surgery, Temerty Faculty of Medicine, University of Toronto, Toronto, ON, Canada.
Agessandro AbrahaoHarquail Centre for Neuromodulation, Sunnybrook Health Sciences Centre, Toronto, ON, Canada.
Maheleth LlinasHarquail Centre for Neuromodulation, Sunnybrook Health Sciences Centre, Toronto, ON, Canada.
Chinthaka HeynHarquail Centre for Neuromodulation, Sunnybrook Health Sciences Centre, Toronto, ON, Canada.
Adomas BuneviciusDepartment of Neurology, Columbia University, New York, NY, USA.
Ali R RezaiDepartment of Neuroradiology, Rockefeller Neuroscience Institute, West Virginia University, Morgantown, WV, USA; Department of Neurosurgery, Rockefeller Neuroscience Institute, West Virginia University, Morgantown, WV, USA.
Anna J S BallDepartment of Neurosurgery, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
Kaitlyn HenryDepartment of Neurosurgery, University of Maryland School of Medicine, Baltimore, MD, USA; Brain Tumor Program, University of Maryland Marlene and Stewart Greenebaum Comprehensive Cancer Center, Baltimore, MD, USA.
Arjun SahgalDivision of Neurosurgery, Sunnybrook Health Sciences Centre, Toronto, ON, Canada.
Erickson TorioDepartment of Neurosurgery, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
Haoyu RenDepartment of Mathematics and Statistics, University of Maryland, Baltimore, MD, USA.
Haroon AhmadDepartment of Neurosurgery, University of Maryland School of Medicine, Baltimore, MD, USA; Brain Tumor Program, University of Maryland Marlene and Stewart Greenebaum Comprehensive Cancer Center, Baltimore, MD, USA.
Harshit AroraDepartment of Neurosurgery, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
Howard EisenbergDepartment of Neurosurgery, University of Maryland School of Medicine, Baltimore, MD, USA.
James PerryHarquail Centre for Neuromodulation, Sunnybrook Health Sciences Centre, Toronto, ON, Canada.
Jeffrey S CarpenterDepartment of Neuroradiology, Rockefeller Neuroscience Institute, West Virginia University, Morgantown, WV, USA.
Kullervo HynynenPhysical Sciences Platform, Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, Toronto, ON, Canada; Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada.
Lily C PhamDepartment of Neurosurgery, University of Maryland School of Medicine, Baltimore, MD, USA; Brain Tumor Program, University of Maryland Marlene and Stewart Greenebaum Comprehensive Cancer Center, Baltimore, MD, USA.
Mary Beth AnketellDepartment of Neurosurgery, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
Mary Jane Lim-FatHarquail Centre for Neuromodulation, Sunnybrook Health Sciences Centre, Toronto, ON, Canada; Division of Neurosurgery, Sunnybrook Health Sciences Centre, Toronto, ON, Canada.
Zhiyuan XuDepartment of Neuroradiology, Rockefeller Neuroscience Institute, West Virginia University, Morgantown, WV, USA.
Christopher P CifarelliDepartment of Neurosurgery, Rockefeller Neuroscience Institute, West Virginia University, Morgantown, WV, USA.
Jason P SheehanDepartment of Neurological Surgery, University of Virginia, Charlottesville, VA, USA.
Nathan J McDannoldDepartment of Radiology, Brigham and Women's Hospital, Boston, MA, USA; Department of Radiology, Harvard Medical School, Boston, MA, USA.
Dheeraj GandhiDepartment of Neurosurgery, University of Maryland School of Medicine, Baltimore, MD, USA; Department of Diagnostic Radiology and Nuclear Medicine, University of Maryland School of Medicine, Baltimore, MD, USA.
Alexandra J GolbyDepartment of Neurosurgery, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA; Department of Radiology, Brigham and Women's Hospital, Boston, MA, USA; Department of Radiology, Harvard Medical School, Boston, MA, USA.
Nir LipsmanHarquail Centre for Neuromodulation, Sunnybrook Health Sciences Centre, Toronto, ON, Canada; Division of Neurosurgery, Department of Surgery, Temerty Faculty of Medicine, University of Toronto, Toronto, ON, Canada; Hurvitz Brain Sciences Research Program, Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, Toronto, ON, Canada.

Funding

Johns Hopkins Institute for Clinical and Translational ResearchUM1TR004926 · NCATS · JOHNS HOPKINS UNIVERSITY · PI STEPHEN N. DAVIS, Daniel Ernest Ford · 2024 to 2026
$28.5M
MRgFUS-enabled non-invasive interrogation of malignant glioma via circulating tumor DNAR21NS113016 · NINDS · JOHNS HOPKINS UNIVERSITY · PI BETTEGOWDA, CHETAN, WOODWORTH, GRAEME F · 2019 to 2019
$454k
NCATS NIH HHS UM1 TR004926NINDS NIH HHS R21 NS113016
6 · The paper itself

Abstract

backgroundBrain-infiltrating tumour cells from high-grade glioma remain shielded from drug treatments by the blood-brain barrier, leading to inevitable recurrence. Microbubble-enhanced transcranial focused ultrasound (MB-FUS) enables controlled blood-brain barrier opening (BBBO), permitting localised drug delivery. We aimed to assess safety and feasibility of MB-FUS plus standard-of-care chemotherapy for individuals with high-grade glioma.

methodsBT008NA was an open-label, single-arm, phase 1/2 trial conducted at five sites in the USA and Canada (part of the ReFOCUSED Consortium). Key eligibility criteria were participants with newly diagnosed high-grade glioma (glioblastoma as per WHO 2016 classification), aged 18-80 years, with normal organ function, a baseline Karnofsky Performance Status score of 70 or higher, who had received maximal safe resection and 6-week chemoradiotherapy and were to start standard-of-care monthly adjuvant temozolomide chemotherapy (150 mg/m

findingsBetween Oct 16, 2018, and March 9, 2022, we enrolled 34 participants, all evaluable for prespecified primary and secondary endpoints, with a mean age of 51·5 years (SD 13·0) and median follow-up 44·5 months (95% CI 34·9-57·3). By self-reporting, 18 (53%) participants were female and 16 (47%) male, 28 (82%) were White, and 34 (100%) were non-Hispanic. 176 adverse events were captured: 54 (31%) chemotherapy-related, 10 (6%) disease-related, 87 (49%) related to undergoing MB-FUS (40 [46%] grade 1, 46 [53%] grade 2, and one [1%] grade 3), and 25 (14%) unrelated. Two (1%) of the adverse events were grade 5 (disease-related deaths), three (2%) grade 4 (temozolomide-related haematological abnormalities), and eight (5%) grade 3 (three [2%] temozolomide-related, one [1%] MB-FUS-related, three [2%] disease-related, and one [1%] unrelated); these occurred across seven (21%) of 34 participants. No treatment-related deaths occurred during the trial. BBBO was visualised in all treatments. Median overall survival was 31·3 months (95% CI 21·1-not reached) and median progression-free survival was 13·5 months (9·9-26·9) with patient-specific disease courses found concordant with trajectories of MB-FUS-enriched plasma cell-free DNA.

interpretationMB-FUS plus temozolomide is a safe combinatorial therapeutic approach for individuals with high-grade glioma, with the potential to improve survival and enable non-invasive plasma biomarker-based disease surveillance (sono-liquid biopsy), warranting randomised controlled trials.

fundingNational Institutes of Health and Insightec.

Indexed as

Antineoplastic Agents, AlkylatingBrain NeoplasmsGliomaMicrobubblesTemozolomideAdolescentAdultAgedAged, 80 and overFemaleHumansMaleMiddle AgedNeoplasm GradingYoung AdultAntineoplastic Agents, AlkylatingTemozolomide

Identifiers

PMID41308679
PMCPMC12757104

What Socratic holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.