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. 

The REGAIN study is a small feasibility/safety trial expected to enroll up to 10 patients with recurrent GBM. The trial is using Alpha DaRT, an investigational alpha-radiation therapy placed directly into the tumor tissue via a minimally invasive stereotactic procedure. Early interim results from the first 3 patients treated in the trial showed two complete MRI responses (using RANO criteria), and the third patient had stable disease with 30% tumor reduction. So far, there has only been one grade 3 adverse event in the trial: a treatment-related seizure with temporary paralysis that resolved with steroids.

While these initial objective imaging responses are exciting, the data should be interpreted cautiously. Longer follow-up will be needed to determine durability of response, survival impact, risks such as radiation necrosis, and whether results can be reproduced in a larger population. More information on the trial can be found HERE. 

This phase 1 trial investigated a personalized neoantigen DNA vaccine (GNOS-PV01) in 9 newly diagnosed MGMT-unmethylated glioblastoma patients. The vaccine was individually designed for each patient using up to 40 tumor-specific neoantigen targets (more than most prior GBM vaccine approaches). No serious treatment-related adverse events were reported. Vaccine-induced immune responses were seen in 8 of 9 patients, and the only non-responder was on steroids. Three of the 9 patients survived beyond 2 years, and 1 patient remains recurrence-free nearly 5 years after diagnosis. The study adds to growing evidence supporting vaccine strategies for GBM and especially supporting multi-target neoantigen vaccines. The Musella Foundation continues working to support the advancement of promising investigational vaccine approaches for brain tumors, with the strong hope that more patients will gain access to these therapies in the near future.

A new study is challenging assumptions about testosterone and glioblastoma (GBM). Some previous preclinical studies suggested testosterone or androgen receptor signaling might promote GBM growth, but many of those studies focused mainly on direct effects of testosterone on tumor cells themselves, often in cell cultures (“cells in a dish”) or simplified tumor models.

Our next educational webinar is tomorrow, Tuesday, May 12, at 7pm ET with Dr. Nicholas Blondin on "Harnessing Oxygen to Fight Brain Tumors." To join, visit virtualtrials.org/webinar. 

Dr. David Nathanson and his team at UCLA are developing an EGFR-targeted drug for glioblastoma (GBM) called KTM-101. About half of GBMs have EGFR alterations, so there have been many attempts to target EGFR, but EGFR-targeted monotherapies have repeatedly disappointed in GBM. Several likely reasons for these failures include poor blood-brain barrier penetration, the heterogeneity and adaptability of GBM tumors, and the ability of tumors to bypass a single blocked pathway or even lose the targeted EGFR alteration over time. We will be watching KTM-101 for further validation in larger studies, and we hope to see EGFR-targeted therapy increasingly explored as one component of rational combination approaches rather than as a stand-alone strategy.