Latest News

• Webinar this week!        

  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.  

  
  
• Ultra-hypofractionated versus conventional chemoradiation for newly diagnosed glioblastoma: Survival and toxicity results of a multicenter randomized trial        

  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.

  
  
• Butterfly gliomas: to biopsy or to ablate - a longitudinal cohort study        

  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.

  
  
• Distinguishing true progression from treatment effects in glioblastoma: a practical, evidence-graded imaging framework for the multidisciplinary team        

  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. 

  
  
• An Unexpected Metabolite Reveals a New Weakness in Ependymomas        

  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!