Our next webinar is this Thursday, August 13th at 7pm ET. The topic is "Multi-antigen T-cell therapy in pediatric brain tumors" with Dr. Eugene Hwang. To join, visit virtualtrials.org/webinar.  

A randomized phase III trial from the Netherlands compared an ultra-short radiation schedule (6 treatments of 6 Gy over 2 weeks) with standard radiation for newly diagnosed glioblastoma (30 treatments of 2 Gy over 6 weeks). Both groups received concurrent temozolomide followed by adjuvant temozolomide.

The study enrolled only 135 of the planned 474 patients due to slow recruitment. Even so, the results were concerning. Median overall survival was 13 months with the 2-week schedule versus 21 months with the standard schedule. The 6 × 6 Gy regimen also produced more radiation necrosis or pseudoprogression (47.8% vs 16.2%), and patients receiving the ultra-short treatment were more likely to require dexamethasone later.

It's worth noting that these results do not mean that all shortened radiation schedules are inferior. The Perry regimen, for example, uses 40 Gy in 15 treatments over 3 weeks and is an established option for selected older patients who may not be ideal candidates for the standard 6-week course. However, this study suggests that compressing radiation into just 6 very high-dose treatments is not advised for the general newly diagnosed GBM population.

A recent University of Miami study looked at 44 patients with butterfly high-grade gliomas (tumors that cross the corpus callosum and involve both sides of the brain). These tumors can be difficult to safely remove with resection surgery.

In the study, 29 patients received laser interstitial thermal therapy (LITT) and 15 had biopsy alone. Median overall survival was 14.9 months with LITT versus 4.9 months with biopsy, and median progression-free survival was 4.7 verses 2.5 months. The researchers reported that larger tumors were harder to ablate completely with LITT, but surprisingly, the amount of tumor ablated or left behind was not associated with survival. Patients whose functional status remained stable or improved after LITT tended to live longer.

While this study was not a comparison between LITT versus conventional resection surgery, it is worth noting the 14.9-month survival with LITT falls within the range typically reported in previous studies of open resection for butterfly gliomas (roughly 7-15 months). 

While this was a small retrospective study, the results support further study of LITT as a minimally invasive option for selected patients with butterfly gliomas.

One of the biggest challenges after GBM treatment is figuring out whether a new or growing area on an MRI is real tumor growth or treatment effect such as pseudoprogression or radiation necrosis. Conventional MRI cannot reliably distinguish the two in a large portion of cases, often estimated at 30-40%.

Researchers assessed the literature to see how this problem is being addressed, including implementation of the RANO 2.0 guidelines. RANO (Response Assessment in Neuro-Oncology) is an international group that develops standardized guidelines for interpreting brain tumor scans, and its RANO 2.0 guidelines were published in 2023. Based on their review, the authors propose a tiered approach for distinguishing tumor growth from treatment effect: starting with RANO 2.0 MRI assessment, then move to advanced/perfusion MRI, then to amino-acid PET, then to biopsy when necessary. They emphasize that this is a potential framework, not yet a validated recommendation. 

For patients, the practical takeaway is that when an MRI is unclear, there are increasingly more tools available to help determine what is really happening, including perfusion and amino-acid PET (and also fractional tumor burden mapping, which we've covered previously), but none can yet guarantee a definitive answer. 

Researchers at the University of Michigan found that ZFTA-RELA fusion ependymoma (which make up most supratentorial ependymomas) tumor cells produce unusually high levels of itaconate, a substance normally made by immune cells. The tumor appears to use itaconate to help keep the ZFTA-RELA cancer-driving gene switched on, creating a cycle that helps the tumor grow. The researchers also found that the tumor changes the way it uses glutamine, a nutrient that helps provide the building blocks needed to make itaconate.

These discoveries have helped identify potential treatment targets. In mouse models, blocking either glutamine metabolism, the enzyme ACOD1 that makes itaconate, or related signaling pathways slowed tumor growth. Combining these treatments worked even better.

While this research is still preclinical, the University of Michigan team is now working with the Pediatric Neuro-Oncology Consortium (PNOC) to develop a clinical trial based on this research. We will keep an eye out and hope to see the trial open soon!

Registration is now open for the 5th Annual BrainStorm Summit, taking place September 16-18, 2026 in McLean, Virginia. The Summit brings together pediatric brain tumor families, researchers, clinicians, advocates, nonprofit organizations, and industry partners for three days of collaboration, education, research updates, and networking. With dedicated programming for children, teens, young adults, and adults, the event is designed to foster meaningful connections and advance progress against pediatric brain tumors. Learn more, register, and reserve discounted hotel accommodations at brainstormsummit.org. 

This recent review article nicely summarizes the current state of glioblastoma treatment and emerging therapeutic strategies. While it does not present new clinical data, it comprehensively covers standard therapy, immunotherapy, precision medicine, novel drug delivery approaches, and new approaches to clinical trials.

We are proud to announce that a new, updated edition of our Brain Tumor Guide for the Newly Diagnosed is now available! You can view it online HERE or order a free printed copy HERE. 

Our copay program has recently closed to new and renewal applications. We will reopen again when we are able to raise more funds. Of course, we will continue to pay claims for those who have an active grant. This program is funded entirely by donations earmarked for this purpose; if you'd like to make a donation towards this program, go to virtualtrials.org/donate and select 'Co-payment Assistance Fund' when you make a donation!  

Preliminary Phase 2 results suggest that BPM31510, an investigational intravenous mitochondrial therapy, may improve outcomes in newly diagnosed glioblastoma (GBM) when added to standard radiation and temozolomide. BPM31510 is designed to deliver very high levels of oxidized CoQ10 into tissues, including the brain, where it may disrupt tumor metabolism, increase oxidative stress, and trigger cancer cell death. The treatment is given together with vitamin K1 to reduce coagulation-related side effects. 

In this single-arm Phase 2 trial, BPM31510 was given with standard chemoradiation and temozolomide. Among 39 evaluable patients, median overall survival was 19.3 months. The most encouraging results were seen in the 24 patients with MGMT-unmethylated tumors, where median overall survival reached 29.3 months. It is not yet known whether or why MGMT-unmethylated patients appeared to benefit more, and these results need confirmation in larger randomized studies. Final results from all enrolled patients are expected later this year.

A Phase 1 trial from Children's National in Washington, DC tested an experimental autologous (patient-derived), non-genetically engineered T-cell therapy targeting WT1, PRAME, and survivin in children with aggressive brain tumors. The study enrolled 11 children with newly diagnosed DIPG and 22 with recurrent non-brainstem brain tumors who received the treatment. The therapy was generally well tolerated, but there was one potentially treatment-related death from tumor swelling in a child with DIPG, which led to a study protocol change. Median overall survival in the DIPG group was 13.7 months. Among the patients with recurrent non-brainstem tumors, three patients (14%) remain disease-free for 31.8-51.6 months without additional treatment, including one patient who had a complete MRI response. The three long-term survivors had recurrent medulloblastoma, anaplastic ependymoma, and high-grade glioma. While this study was designed mainly to assess safety rather than efficacy, the results support further investigation of this personalized T-cell approach. 

Researchers at Northwestern have identified a biological pathway that may help explain why some glioblastoma (GBM) patients respond to immunotherapy while many do not. Using CRISPR-based screening in mouse models, they found that activation of the MAPK/RAF-MEK-ERK signaling pathway made tumors more recognizable to the immune system and improved responses to immune checkpoint inhibitors such as anti-PD-1 and anti-CTLA-4 therapies.

The findings build on earlier observations that rare BRAF and PTPN11 mutations, which activate MAPK signaling, were more common among the small number of GBM patients who had exceptional responses to immunotherapy. The researchers found that MAPK/ERK activation increases inflammatory signals, promotes T-cell infiltration into tumors, and may help immune cells recognize and attack cancer cells.

The team cautions that MAPK activation is necessary but not sufficient for immunotherapy response; in other words, some patients with this pathway activation still do not respond. If validated in human studies, MAPK/ERK activity could become a biomarker to help identify which GBM patients are most likely to benefit from immunotherapies.

Researchers at Northwestern have identified a biological pathway that may help explain why some glioblastoma (GBM) patients respond to immunotherapy while many do not. Using CRISPR-based screening in mouse models, they found that activation of the MAPK/RAF-MEK-ERK signaling pathway made tumors more recognizable to the immune system and improved responses to immune checkpoint inhibitors such as anti-PD-1 and anti-CTLA-4 therapies.

The findings build on earlier observations that rare BRAF and PTPN11 mutations, which activate MAPK signaling, were more common among the small number of GBM patients who had exceptional responses to immunotherapy. The researchers found that MAPK/ERK activation increases inflammatory signals, promotes T-cell infiltration into tumors, and may help immune cells recognize and attack cancer cells.

The team cautions that MAPK activation is necessary but not sufficient for immunotherapy response; in other words, some patients with this pathway activation still do not respond. If validated in human studies, MAPK/ERK activity could become a biomarker to help identify which GBM patients are most likely to benefit from immunotherapies.

Results from the Phase 1 INB-200 study of gamma-delta T cells for newly diagnosed glioblastoma have now been published in the Journal of Clinical Oncology. While the publication provides additional details on the novel cell therapy, the most up-to-date clinical results can be found in an abstract presented at the ASCO 2026 conference.

A Phase 1 trial enrolled 46 patients with first recurrence glioblastoma (GBM) who had previously received standard surgery, radiation, and temozolomide. The study was designed prior to 2016, so 6 of the 46 patients included had IDH mutations. The researchers tested relatlimab, an antibody that blocks LAG-3, an immune checkpoint that acts as another "brake" on exhausted T cells. Half the patients received relatlimab alone, while the other half received it with nivolumab (Opdivo), a PD-1 checkpoint inhibitor. Although Opdivo has previously failed as a monotherapy to improve survival in GBM trials, combining it with LAG-3 blockade may help overcome some of the immune suppression seen in GBM. The study's primary goal was safety, which was achieved. While the trial was not designed to prove efficacy, the one-year survival was 52.2% with the combination versus 34.8% with relatlimab alone, and researchers found evidence of increased immune-cell infiltration into tumors. It is also worth noting that the five patients who survived longer than two years were in the combination therapy group. A randomized Phase 2 trial is now underway to determine whether the combination improves outcomes.

A new study published in Neuro-Oncology Advances adds to growing evidence that gabapentinoids (ie, medications such as gabapentin and pregabalin commonly used for nerve pain and seizures) may have anti-tumor effects in glioblastoma (GBM). Researchers analyzed data from 11,924 adults with newly diagnosed GBM from a nationwide Turkish registry. After adjusting for clinical factors, postoperative gabapentinoid use was associated with improved overall survival (hazard ratio 0.75). The survival association was strongest in patients age 55 and older (HR 0.70), while no significant benefit was observed in patients younger than 55. Both gabapentin and pregabalin were associated with improved survival in the older subgroup.

The findings follow a 2025 study from researchers at UCSF, Mass General Brigham, and collaborating institutions, published in Nature Communications, which reported that gabapentin use was associated with longer survival in GBM patients. Both studies are retrospective and cannot prove that gabapentin or pregabalin directly improve outcomes, but they support further investigation of gabapentinoids as potential repurposed therapies targeting the interaction between neurons and glioblastoma cells.

Researchers from the Hebrew University of Jerusalem and Harvard Medical School have identified a potential new strategy for overcoming temozolomide (TMZ) resistance in glioblastoma (GBM). In a study published in Cancer Medicine, investigators showed that an experimental compound called BA-101, a selective inhibitor of neuronal nitric oxide synthase (nNOS), reduced growth and invasion of resistant GBM cells and improved the effectiveness of TMZ in laboratory and mouse models.

The researchers found that resistant GBM cells rely on increased production of nitric oxide through the nNOS pathway to survive chemotherapy. By blocking this pathway, BA-101 appeared to weaken the tumor’s defenses and restore sensitivity to TMZ. However, the approach remains experimental and will require additional preclinical testing and clinical trials before it can be evaluated in patients.

Our Copayment Assistance program is running low on funding and will close to new and renewal applications soon. If you have been thinking of applying, go to braintumorcopays.org and follow the directions to send in an application!

The Phase 3 trial results for DCVax-L showing extended survival for both newly diagnosed and recurrent glioblastoma (GBM) were published previously in JAMA, but new additional statistical analyses of the results using propensity score matching were presented by Dr. Marnix Bosch at the British Neuro-Oncology Society (BNOS) Annual Meeting last week. The more rigorous analyses (available here) show the trial results are even better than previously reported, and that the vaccine more than doubled the 5 year survival rate for newly diagnosed GBM.

One of the biggest challenges with CAR-T therapy for high-grade gliomas has been the tumor's ability to suppress the immune system. A new study published in Nature proposes a solution by designing CAR-T cells that attack not only the tumor itself, but also the immunosuppressive cells protecting it. Rather than targeting one of the more familiar glioblastoma (GBM) markers, such as EGFRvIII or IL13Rα2, the researchers identified GPNMB as an ideal dual-purpose target because it is found on both GBM cells and tumor-associated macrophages (the immune cells that help shield the tumor from attack). By simultaneously eliminating both the cancer cells and their protective microenvironment, the treatment produced dramatic results in mouse models, including what appeared to be long-term cures in many animals. While these findings are still preclinical, the study introduces a promising new strategy for CAR-T therapy.