Treatment Sequencing and Response Assessment in High-Grade Glioma

In this episode, Dr. Shonka asks Dr. Chong how he sequences therapy across the disease course. For newly diagnosed DMG, both rely on radiation followed by temozolomide — acknowledging that benefit is limited — and then move to dordaviprone at first recurrence for H3 K27M-mutant disease. The unsolved question, both agree, has moved to third line and beyond. Dr. Shonka details what remains in her toolbox: re-irradiation, bevacizumab (Avastin) alone or with radiation, lomustine, and, for supratentorial tumors, tumor-treating fields (TTFields, Optune) when the patient has the willingness and a caregiver to support that regimen. She mentions an ongoing pediatric DMG TTFields trial that she hopes will inform adult practice. Dr. Chong agrees the third-line approach is largely a “kitchen sink” one and leans on clinical-trial enrollment and rational combinations based on molecular profiling at progression. Both also discuss combining TTFields with immunotherapy in glioblastoma as a forward-looking direction. The conversation turns to response assessment. Dr. Chong outlines the RANO (Response Assessment in Neuro-Oncology) framework and RANO 2.0 updates. In glioblastoma, perfusion imaging, time since radiation (at least 12 weeks), and changes in contrast enhancement are useful tools. These are harder to apply in DMG, where baseline lesions often lack enhancement, show minimal edema, and have low cerebral blood volume (rCBV). For DMG, he relies on subtle T2/FLAIR changes and clinical signs of progression, especially brainstem or spinal cord symptoms that may not appear on MRI. Both note that MR spectroscopy and amino acid PET have played a limited role in their DMG practice so far.

In the next episode, “Patient Communication and Closing Thoughts,” Dr. Shonka and Dr. Chong discuss how they frame prognosis and treatment goals in the initial visit.