Join us tomorrow for an educational webinar on "Phase 2 Study of frontline BPM31510 with Standard of Care in Newly Diagnosed Glioblastoma" with Dr. David Reardon. To join, visit virtualtrials.org/webinar.

The FDA just approved the first FET-PET imaging drug in the U.S. (Pixclara®) for patients with glioma, including adults and children 1 month and older. FET-PET has been studied extensively in Europe and is recommended as an additional diagnostic tool in clinical practice guidelines, including the NCCN Guidelines. It provides information about tumor biology that is different from conventional MRI and may be particularly helpful when a brain MRI is difficult to interpret. Studies of FET-PET have reported sensitivity of approximately 80% or higher for helping distinguish tumor progression from treatment-related changes.

From our friends at the End Brain Cancer Initiative, registration is now open for the Caregivers Self-Care and Tools online educational event on November 6, 2026 at 11am PT. The Keynote Speaker for the event is Dr. Jennifer Nosker, a clinical neuropsychologist and scientist at Brigham and Women's Hospital and Instructor at Harvard Medical School. Dr. Nosker will provide education to caregivers about the different types of cognitive changes that can occur in brain tumor patients, while simultaneously giving practical tools to help navigate these challenges. To register, click here!

A new study of 176 patients with IDH-wildtype glioblastoma (GBM) found evidence of intratumoral hemorrhage on MRI in 105 patients (59.6%). Previous studies have reported much lower rates of 2.3%-29.2%, and the authors caution that differences in MRI techniques and definitions may explain the discrepancy. The authors note their study did not use susceptibility-weighted MRI or confirm hemorrhage pathologically; therefore, 59.6% should not be interpreted as the true percentage of GBMs that hemorrhage.

The researchers found that hemorrhagic tumors had more SETD2 alterations and fewer alterations in PDGFRA, KIT, KDR and PIK3R1, genes involved in tumor growth and blood-vessel signaling. However, none of these differences remained statistically significant after correction for multiple comparisons, making the findings preliminary. Importantly, hemorrhage in GBM was not associated with shorter progression-free or overall survival. The findings suggest that the tendency of some GBMs to bleed may be linked to tumor biology, but larger studies are needed to confirm the molecular associations and determine their clinical significance.

Researchers at MIT have developed an experimental technology called HITMAN (highly-localized electric-field-induced tumor therapy using magnetically actuated nanoantennas), which uses tiny injectable devices to generate localized electric fields that kill cancer cells. The approximately 150-nanometer devices can be activated wirelessly from outside the body using a low-frequency magnetic field. In early preclinical experiments using patient-derived, chemotherapy-resistant glioblastoma cells, HITMAN killed 52.2% of cancer cells, while sparing healthy neurons and astrocytes.   

The researchers then implanted the patient-derived tumors into the brains of mice. HITMAN substantially slowed tumor growth and extended median survival, with no detectable toxicity to surrounding healthy tissue or major organs. The treatment also reduced the ability of tumor cells to form new colonies, suggesting potential to reduce recurrence. The researchers believe the localized electric fields disrupt cancer cells' bioelectric activity and cause protein-folding stress and membrane damage, ultimately leading to cell death. The technology has not yet been tested in humans, but it is an interesting new approach for electrical field therapy. 

Dichloroacetate (DCA) inhibits pyruvate dehydrogenase kinase (PDK), helping shift cancer cells away from the “Warburg effect” (their tendency to rely heavily on glycolysis and produce excess lactate). Earlier preclinical studies provided evidence that DCA may alter GBM metabolism and potentially make tumor cells more vulnerable to cell death.

A new study has now provided additional evidence that DCA reaches recurrent GBMs and produces the intended metabolic changes. In 37 patients undergoing surgery for recurrent GBM, patients received either one week of DCA or no DCA prior to surgery. The resected enhancing and non-enhancing tumor tissue, and serial plasma DNA and lactate levels were analyzed. Patients who received the DCA had reduced markers of PDK activity and tumor-cell proliferation and significantly lowered blood lactate levels. DCA was well tolerated, but the study did not show that DCA improved progression-free survival. The researchers conclude that, although the study did not show a clinical benefit, the metabolic effects warrant further investigation, particularly in combination with other treatments. 

 We recently reported on NEO100, an unusual treatment that delivers highly purified perillyl alcohol directly through the nose, allowing patients to self-administer the drug at home. Earlier results were intriguing, particularly because some of the longest survivors had IDH1-mutant tumors.

 Can a Gut-Derived Compound Make Immunotherapy Work Better?

 This is an interesting example of how advances against glioblastoma may come from **combining treatments rather than continually searching for a single “magic bullet.”** Researchers are studying whether extracellular vesicles – tiny particles that can cross the blood-brain barrier – can make glioblastoma cells more vulnerable to CAR T-cell therapy. They are using mathematical modeling and sophisticated image analysis to understand exactly how the two interact.

  This is an interesting approach that makes a lot of sense. After glioblastoma surgery, we usually wait several weeks for the surgical wound to heal before starting radiation and chemotherapy. Unfortunately, glioblastoma does not wait.

Disclaimer: GT Medical is a proud sponsor of the Musella Foundation!

This is an interesting new approach that is now making the important jump from laboratory studies into its **first human trial**.

 This is an interesting new approach, but it is important to understand that it is still at the **preclinical research stage**—there is not yet a drug being tested in glioblastoma patients.

The investigational treatment NEO100, a highly purified form of perillyl alcohol, showed encouraging preliminary results in a Phase IIa trial for patients with recurrent or progressive IDH1-mutant grade 3 or 4 gliomas. The NEO100 treatment is self-administered by patients through the nose four times a day, using a nasal mask and nebulizer, with the intranasal delivery intended to help overcome the blood-brain barrier. In the single-arm study, 24 patients received treatment in 28-day cycles; researchers compared the results with historical results for patients receiving treatment for recurrent high-grade glioma.

The study met its primary endpoint, with 49% of patients progression-free at six months (compared with an expected 20% based on the study's historical benchmark). Median overall survival was reported as 26 months, with 87% of patients alive at six months, 61% at one year, and 54% at two years. Five patients were still receiving treatment when the preliminary results were reported, including one who had remained progression-free for 19 months, and the company reported several radiographic responses, including one patient whose enhancing tumor largely resolved after prolonged treatment. NEO100 was reportedly well tolerated, with the company describing no significant toxicity even with prolonged treatment, although the full safety and efficacy data have not yet been published in a peer-reviewed journal.

It is important to note that this was a small, non-randomized trial, and our understanding of the prognosis of recurrent IDH1-mutant tumors continues to evolve (for example, recent research suggests that acquired RAS-MAPK mutations may be associated with shorter survival). Despite these caveats, the results are encouraging for a disease with no approved targeted therapies and very few salvage options in the recurrent setting. The company plans to meet with the FDA to discuss the next steps and a potential registrational trial. 

The ETERNITY study looked at 185 people who had survived at least 5 years after a diagnosis of glioblastoma, IDH-wildtype, or grade 4 IDH-mutant astrocytoma, with patients surviving an average of about nine years. The researchers found that 78% had some measurable impairment in at least one area of thinking or memory. The most common difficulties involved processing speed, mental flexibility, and finding words, while recognition memory was less often affected. Importantly, however, cognitive function was mostly stable over time; the only consistent decline seen across the group was a small worsening in the ability to recall verbal information after a delay. Tumor location mattered; tumors involving the left side of the brain were associated with poorer verbal memory and word fluency, while temporal lobe involvement was particularly associated with memory difficulties. Patients who had experienced multiple tumor recurrences also tended to have worse cognitive flexibility. For patients and families, the findings are encouraging in that surviving many years does not necessarily mean that cognitive abilities will continue to decline, although some lasting difficulties may remain after the tumor and its treatment have affected the brain. The study did not evaluate potential treatments for the cognitive deficits observed, but the authors emphasized that regular neurocognitive monitoring and greater attention to preserving cognitive function should be an important focus of long-term care.

A new preclinical study from Stanford has added to the growing understanding of how gliomas leverage normal brain activity for growth. Researchers found that NLGN3, a protein made by normal neurons, interacts with the CSPG4 protein found on glioma cells, activating a mechanosensing pathway involving PIEZO1 that ultimately promotes tumor growth. This discovery broadens potential treatment targets beyond NLGN3 itself, possibly to CSPG4; however, the major challenge is that this pathway also appears to help maintain normal oligodendrocyte precursor cells, so blocking it could potentially interfere with healthy brain function. Nevertheless, this work provides important new insights into how gliomas exploit neuronal activity and could help researchers find ways to disrupt this process without harming normal neuron-glial signaling the brain needs.  

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.