Dr Rimas Lukas (Associate Chief, Neuro-oncology, Malmadi Brain Tumour Institute, Northwestern University, Evanston, IL, USA) highlights the key presentations and advances in the field of neuro-oncology from the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago, IL, USA.
Dr Lukas highlights the use of focused ultrasound to enhance blood–brain barrier permeability, new evidence on the extent of resection in IDH-mutant gliomas and final data from the CATNON trial supporting adjuvant temozolomide in grade 3 astrocytomas. A trial comparing radiotherapy approaches for brain metastases clarified the cognitive benefits of stereotactic radiosurgery, while early data on gamma delta T cell therapy suggested a novel immunotherapeutic direction.
Focused ultrasound to enhance blood–brain barrier permeability in high-grade gliomas
Several studies this year explored the use of focused ultrasound to transiently disrupt the blood–brain barrier and enhance drug delivery in high-grade gliomas.
Dr Graham Woodworth (University of Maryland) presented findings from clinical trial BT008 (Abstract 2009; NCT03551249, NCT03616860), in which external transcranial focused ultrasound was combined with standard-of-care temozolomide. Compared with historical controls, the approach appeared feasible and relatively safe. Although outcomes were generally favourable, the key takeaways were the proof-of-concept nature of the method and its potential to enhance drug delivery across the blood–brain barrier.
Dr Adam Sonabend (Northwestern University) presented complementary work using a cranially implanted ultrasound device (Abstract 2016). Unlike external ultrasound, this implanted platform allows lower-intensity sonication and shorter treatment durations but is limited to fixed treatment areas. It also supports in vivo testing and enables the use of a broader range of therapies, including chemotherapies with poor blood–brain barrier penetration and some immunotherapies.
Collectively, these studies support the safety and practicality of various ultrasound-based approaches. Differences between the approaches – including treatment duration, mobility and drug compatibility – will shape their future utility. Research is ongoing to lend a more thorough understanding of the role of focused ultrasound in the treatment of gliomas, but it has advanced to an ongoing international randomized phase III trial (NCT05902169).
Radiation strategies in brain metastases
Dr Eudocia Lee Aizer (Brigham and Women’s/Dana-Farber Cancer Institute) presented results from a small multicentre phase 3 trial (Abstract 2011) evaluating radiation strategies for patients with 5–20 brain metastases. Patients were randomised to hippocampal avoidance whole-brain radiotherapy (HA-WBRT) with memantine versus stereotactic radiosurgery (SRS).
HA-WBRT with memantine, first validated by the NRG-CC001 trial, demonstrated superior cognitive outcomes compared to traditional WBRT. However, this new trial addressed whether SRS might offer even better cognitive preservation. Dr Aizer’s results suggested that, in appropriately selected patients, SRS may indeed be the preferred approach, with improved cognitive outcomes compared to HA-WBRT.
These findings provide clarity on a long-standing clinical question and may influence future guidelines. The data support greater use of SRS in patients with multiple brain metastases, pending validation and broader community adoption.
Extent of resection in IDH-mutant grade 2 gliomas
Dr Philip Karschnia (University of Erlangen, Germany) presented new data from the RANO-RANOresect group (Abstract 2001), focusing on IDH-mutant grade 2 gliomas. The group has previously published on the importance of extent of surgical resection across multiple glioma subtypes. This study confirmed that greater extent of resection is associated with improved overall survival, extending earlier findings to lower-grade tumors.
In the context of the INDIGO trial and increasing interest in IDH-mutant gliomas, these results are timely. While not a revolutionary conclusion, this is among the strongest data supporting aggressive surgical resection in the upfront setting. It reinforces the role of neurosurgical intervention as a foundational part of management in these patients.
Final results of the CATNON trial
Dr Martin Van Den Bent (Erasmus Cancer Center, Rotterdam, Netherlands) presented the final analysis of the CATNON trial (Abstract 2002), a large, international cooperative study investigating treatment strategies for grade 3 astrocytomas. Originally designed for patients with anaplastic astrocytoma – a category no longer recognised in the latest WHO classification – the trial now informs management of IDH-mutant WHO grade 3 astrocytomas.
The updated analysis, applying current molecular classification, confirmed that adjuvant temozolomide is associated with longer survival in this patient population. These data provide definitive evidence supporting temozolomide as part of standard care, a view that has been widely held but until now lacked confirmatory long-term data.
The study is notable for the persistence of the investigators, who completed a rigorous trial over many years despite evolving classification systems and treatment paradigms.
gamma-delta T cell therapy in glioblastoma: INB-200
Dr Louis Nabors (University of Alabama at Birmingham, AL, USA) presented the phase 1 results of the INB-200 trial (Abstract 2007), investigating the use of engineered gamma-delta (γδ) T cells in glioblastoma. γδ T cells, typically resident in the gut and not naturally found in the central nervous system, were engineered to be resistant to temozolomide through preservation of O6-Methylguanine-DNA methyltransferase (MGMT) activity. This approach allows the cells to persist during concurrent chemotherapy and may support tumour control via local injection and immune activation.
This is a novel immunotherapy concept that differs from conventional CAR T cell approaches. Whereas CAR T cells are typically designed to target specific epitopes, γδ T cells may act more broadly, potentially recognising a wider range of tumour-associated signals. The approach is still early in development but offers an intriguing addition to the landscape of cell-based therapies in glioma.
View full #ASCO25 coverage here!
Disclosures: Rimas Lukas is a consultant for Merck and Novocure. He has received grant/research support from BMS and is a member of the advisory board for Merck and Novocure. He has received honoraria/honorarium from EBSCO, Elsevier and Medlink Neurology. He is a Speaker’s Bureau participant with Merck and Novocure.
This content has been developed independently by Touch Medical Media for touchONCOLOGY. It is not affiliated with the American Society of Clinical Oncology (ASCO). Views expressed are the speaker’s own and do not necessarily reflect the views of Touch Medical Media.
Cite: #ASCO25: Key highlights in neuro-oncology: Focused ultrasound, resection and immunotherapy. touchONCOLOGY. June 18th, 2025.
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