The Phase 3 TRIDENT trial enrolled 981 newly diagnosed glioblastoma (GBM) patients to evaluate whether starting Tumor Treating Fields (TTFields) during radiation and temozolomide treatment could improve survival compared with the current approach of starting TTFields after chemoradiation is completed.

The trial did not meet its primary endpoint, with median overall survival of 17.7 months in the early-start group versus 17.5 months in the standard group. However, these results should not be interpreted as a negative study for TTFields itself. Both groups received TTFields; the question being tested was whether starting treatment earlier would provide additional benefit.

One encouraging finding was the long-term survival tail in both groups. Three-year survival rates were 22.5% in the early-start arm and 18.4% in the standard-start arm, which compares favorably with historical outcomes for newly diagnosed GBM. 

While earlier initiation did not significantly improve overall survival in the overall study population, additional analyses may identify patient subgroups that derive greater benefit from earlier treatment. Novocure has not yet released detailed compliance (usage) data, which may provide additional insights when the full results are presented at the ASTRO 2026 Annual Meeting.

Do you know a college student (ages 18–23) whose parent has been diagnosed with or passed away from a primary brain tumor? Our friends at the George Bartol Memorial Scholarship Fund are once again awarding scholarships to students across the United States impacted by a parent’s brain cancer diagnosis.

Eligibility:
- Full-time student at a 2- or 4-year college/university
-Minimum 2.5 GPA
-Ages 18–23

Applications are due by October 1, 2026! To request an application, please message the George Bartol Memorial Scholarship Fund on Facebook! 

 As a friendly reminder, brain tumor patients and caregivers can receive free one-on-one navigation support through the Brain Cancer Support & Solutions Alliance (BCSSA), a program jointly funded by Cancer Commons, Head for the Cure, and the Musella Foundation. You can enroll at diagnosis, recurrence, or anytime in between. We know how difficult the brain tumor journey can be, and we're here to help. To learn more or register, click HERE. 

Researchers in Ireland have reported the first preclinical study of an mRNA vaccine designed specifically to treat neuroblastoma, one of the deadliest childhood cancers.

This vaccine is designed to target Glypican-2 (GPC2), a protein found at high levels on many neuroblastoma cells and also expressed in medulloblastoma and certain other high-grade gliomas. Instead of using traditional lipid nanoparticles for the vaccine, they employed tiny self-assembling peptide nanoparticles called RALA to deliver the mRNA instructions to the immune system.

The vaccine successfully stimulated a strong anti-tumor immune response in lab models, increasing production of several immune signaling molecules, including IFN-γ, IL-2, and TNF-α. In mice with aggressive MYCN-amplified neuroblastoma, the vaccine delayed tumor growth by roughly 10-11 days and reduced tumor volume by ~70% compared with untreated animals.

These results are preclinical, and significant additional work will be needed before human trials can test the safety and efficacy of this vaccine. Nevertheless, we will keep an eye on this promising research.

This Phase 1 GT-20 trial tested a personalized DNA neoantigen vaccine in 9 patients with newly diagnosed MGMT-unmethylated glioblastoma (GBM). Unlike other neoantigen vaccine approaches, GT-20 sequenced multiple regions of each tumor rather than just one and incorporated up to 40 patient-specific neoantigens into each vaccine.

The vaccine was generally well tolerated and generated measurable immune responses in six of seven evaluable patients, with evidence that vaccine-induced T cells entered the tumor microenvironment. The study was not designed to evaluate efficacy, but investigators reported a median overall survival of 16.3 months and a two-year survival rate of 33%. Patients receiving dexamethasone had weaker immune responses, consistent with findings from other immunotherapy studies.

While several neoantigen vaccine programs have successfully generated anti-tumor immune responses in GBM, the key question remains whether those responses can translate into meaningful clinical benefit, either alone or in combination with other therapies.

We’re excited to see these Phase 1 study results now published in Neuro-Oncology Advances.

The drug appeared safe and generally well tolerated, and the median overall survival was about 16 months, which compares favorably to historical outcomes in recurrent glioblastoma. While this is a small, non-randomized trial of only 22 analyzed patients, thes results are encouraging for a Phase 1 study in this setting.

Most patients still followed the expected course of progression over time, but five of the 22 included patients are still alive. Four of those are beyond 18 months, and two of them are at 31 and 39 months since starting treatment with gallium maltolate.

We helped fund an expanded access program for oral gallium maltolate, and we’re encouraged to see it is now expected to open to about 20 additional patients, giving more families access while the research continues.

This signal concerning proton pump inhibitors (PPIs) first emerged from analyses of real-world registry data from the xCures database, which suggested a potential link between PPI use and shorter survival in glioblastoma (GBM) patients. It is a good example of how patient registries and real-world evidence can help identify clinically relevant signals early, often years before they are evaluated or confirmed in larger randomized clinical trial datasets. Now, the association has been independently validated in a large analysis of nearly 3,000 patients from five randomized GBM clinical trials.

The recent study found that patients taking certain PPIs, including omeprazole and pantoprazole, had shorter progression-free and overall survival, even after adjusting for key factors such as age, MGMT status, extent of surgery, and steroid use. Other stomach-protecting medications, such as famotidine (Pepcid), did not show the same association, suggesting the effect may not simply be related to acid suppression.

This does not prove that PPIs cause worse outcomes, but the consistency of the signal across datasets adds to the concern. Since many GBM patients are placed on PPIs automatically when steroids are prescribed, it is reasonable to periodically reassess whether a PPI is truly needed or whether an alternative agent could be used instead.

As always, patients should not stop prescribed medications without discussing it with their medical team.

Researchers in Germany have developed a deep-learning AI system called “Hetairos” that can predict the molecular classification of brain and spinal cord tumors in minutes using standard histology slides. The system was trained on over 11,000 digitized tissue sections from 9,606 patients across 11 centers on four continents, with ground-truth diagnoses based on DNA methylation profiling, which is currently the gold standard for CNS tumor classification. It can distinguish 102 molecular tumor subtypes, covering nearly the full WHO classification spectrum for CNS tumors.

In a head-to-head comparison with five expert neuropathologists across 210 challenging cases, Hetairos achieved significantly higher diagnostic accuracy (68% vs ~30% for humans), and 84% when considering top-three predictions. In prospective testing, it produced molecular subtype predictions in about 12 minutes, compared to roughly 12 days for standard methylation-based diagnostics.

The AI also includes a confidence scoring system, with high-certainty predictions in 50-70% of cases reaching ~87-88% accuracy, and it can narrow broad differential diagnoses into a small number of likely subtypes. Importantly, it highlights the specific tissue regions driving its decisions, improving interpretability and clinical trust.

While this system shows great potential, additional validation in independent cohorts and further regulatory evaluation will be required before it can be approved for routine diagnostic clinical use.

A large 37-year analysis of over 20,000 patients from the Traumatic Brain Injury Model Systems National Database found that a history of traumatic brain injury (TBI) is associated with a 1.75-fold higher risk of death from brain cancer compared to the general population. The risk was especially pronounced in certain subgroups, including patients with gunshot-related TBIs (over 14-fold higher risk) and those with “mild but complicated” injuries. Researchers believe chronic post-injury inflammation may contribute, and while these findings do not prove causation, they suggest TBI may have long-term oncologic as well as neurologic consequences that deserve further study.

A new preclinical study found that blocking a protein called MAGMAS, which helps tumor cells manage energy inside their mitochondria, may make glioblastoma cells more sensitive to temozolomide (TMZ). In laboratory and animal models, inhibiting MAGMAS weakened tumor cell survival and appeared to improve the effect of TMZ, radiation, and tumor treating fields, including in treatment-resistant cells.

This is early-stage research, but it adds to a growing body of evidence suggesting that targeting how tumor cells produce and manage energy may help overcome resistance to standard GBM treatments.

This is an interesting new paper from researchers at Yale, Massachusetts General Hospital, the Weizmann Institute of Science, and the University of Miami.

Using one of the largest longitudinal single-cell datasets in IDH-mutant glioma, the researchers showed that progression can occur through both genetic evolution and cell-state changes. In some tumors, acquired genetic alterations expand proliferative, stem-like cell populations. In others, tumors adopt a mesenchymal-like state associated with immune suppression and poorer outcomes, even without major new genetic changes.

Thus, treatment resistance is not necessarily driven solely by accumulating mutations. Instead, tumors under treatment pressure can evolve toward distinct biological trajectories, including stem-like or more glioblastoma-like programs. Two IDH-mutant gliomas could have similar DNA yet behave very differently because of the cell types and cellular programs active within the tumor. Single-cell sequencing is a powerful tool for capturing these differences, and as our understanding of these evolutionary trajectories improves, it may help identify early warning signs of resistance, predict treatment response, and potentially guide strategies to keep tumors on more treatment-sensitive paths.

In this study, another group of researchers reports a similar idea - that response to therapy in glioblastoma (GBM) may depend just as much on tumor cell state and the surrounding immune environment as on genetic mutations. The study analyzed 181 immune checkpoint inhibitor (ICI)-treated glioblastoma (GBM) samples using bulk DNA and RNA sequencing along with single-nucleus RNA sequencing to understand what predicts response in IDH-wildtype GBM.

The main finding was that the tumor’s baseline cell state, rather than its mutational burden, best predicted outcomes. Tumors with a mesenchymal (MES) subtype had better survival with ICIs compared to non-MES tumors, even though this same subtype did not benefit as much from standard chemoradiation. This MES state was linked to higher immune signaling (HLA class I expression) and more T cell infiltration, consistent with a more inflamed tumor environment. In contrast, overall mutation burden was not predictive, while specific genetic changes such as PDGFRA and CDKN2A were associated with worse outcomes after ICI but not standard therapy.

Long-term analyses suggested that ICI treatment may shift how tumors evolve over time, with selection of resistant subclones and changes away from MES-like states, suggesting that immunotherapy and chemoradiation may push tumors along different evolutionary paths.

The UNITED trial was a single-center phase 2 study testing MRI-guided adaptive radiotherapy for high-grade glioma using a 1.5T MR-Linac. Ninety-eight patients received standard chemoradiation, but with weekly MRI scans used to adjust radiation plans in real time. This allowed doctors to tighten treatment margins around the tumor while still accounting for microscopic spread.

The key concern with this approach had always been whether smaller margins would lead to more “missed” tumor at the edges. In this study, that did not happen. The rate of marginal failure was low (4%), meeting the study’s non-inferiority goal compared with historical outcomes. Treatment was generally well tolerated, with lymphopenia as the most common significant side effect. Overall, these results provide reassuring evidence that MRI-guided adaptive radiotherapy can safely reduce radiation margins in glioma, and support further testing in randomized trials.

A small, prospective pilot study from researchers at the University of Pennsylvania, including the Musella Foundation's Chief Scientific Advisor Dr. Steven Brem, evaluated machine learning-guided personalized precision radiation therapy (PPRT) in newly diagnosed IDH-wildtype glioblastoma (GBM). Twenty patients were enrolled after gross total resection, with efficacy analyses reported for 17 patients. The PPRT used an AI-based model to estimate patterns of microscopic tumor infiltration beyond what was visible on MRI to personalize radiation targeting, followed by standard temozolomide.

Compared with a matched historical control group, PPRT was associated with improved median progression-free survival (24.4 vs 11.6 months) and overall survival (35.4 vs 17.7 months). Treatment was generally well tolerated, with no grade ≥3 acute toxicities, but radiation necrosis was more frequent in the PPRT group. These findings will need further validation in larger studies, but we hope to see the survival gains replicated.

We are happy to share our brain tumor copayment assistance program is now open to new (and renewal) patients! This program can help cover the copay costs for: Optune Gio, Avastin, Temodar, Lomustine, and Modeyso, as well as their generics. If you think you may need help, apply ASAP as the program often closes quickly. Go to braintumorcopays.org for details and to apply.  

Researchers at the American Society for Clinical Oncology (ASCO) 2026 meeting reported results from the Phase 3 ROADS trial, which enrolled 230 patients with newly diagnosed brain metastases requiring surgery and randomized them to receive either GammaTile (115 patients) or standard postoperative stereotactic radiotherapy (115 patients).

GammaTile is a collagen implant containing radioactive cesium-131 seeds that is placed directly into the surgical cavity during tumor removal. Investigators reported that local recurrence occurred in just 1% of GammaTile patients, compared with 12% of patients receiving standard postoperative radiation.

The study also reported improvements in recurrence-free survival and overall survival, with an estimated 61.7% of GammaTile patients alive two years after diagnosis, compared with 35.7% in the control group. Importantly, these benefits were achieved without an increase in serious treatment-related side effects.

 For more neuro-oncology updates from the 2026 ASCO conference (e.g., DOC1021, NeoVax, Nan02, liposomal curcumin, CAR T trials), click HERE. 

Fantastic work from Dr. Rifaquat and colleagues, who showed that carefully matched external control data produced treatment effect estimates nearly identical to those obtained using the randomized control arm of the INSIGhT glioblastoma (GBM) trial. Their findings add to the growing evidence that external controls can, in appropriate scenarios, help reduce the number of patients who must be assigned to traditional control groups while still generating reliable results.

We have long advocated for this approach. Years ago, the Musella Foundation used its brain tumor registry to show that carefully curated and well-matched real-world GBM patient cohorts could approximate outcomes seen in traditional clinical trial control arms. (See HERE) We are very happy to see the neuro-oncology field advancing this concept, as it has great potential to improve the efficiency of clinical trials, increase trial enrollment, and meaningfully benefit patients.

Researchers at the University of Cincinnati and Johns Hopkins reported promising preclinical results for a novel 'NanoMesh' implant designed to deliver multiple anti-cancer drugs directly into the surgical cavity after glioblastoma (GBM) resection. In mouse models, the multi-layered nanofiber device released temozolomide, acriflavine, and PT2385 in a controlled fashion, significantly extending survival. While this technology is still in the preclinical stage, it's an interesting new approach to local drug delivery for GBM. 

This is a great blog post from long-term brain cancer survivor and practicing physician Courtney Burnett, explaining why many survivors continue to talk about and advocate for brain cancer even years after treatment. Her perspective will likely resonate with many survivors and patient families who live daily with the lasting impacts of a brain tumor diagnosis.