Serially Testing Brain Tumor Samples Reveals Treatment Response in Glioblastoma Patients

Glioblastoma (GBM) is the most aggressive form of brain cancer, known for rapid growth, recurrence, and resistance to treatment. Understanding how tumors respond to therapy remains challenging since imaging often fails to distinguish true progression from immune-related inflammation. Now, a new study shows that repeatedly sampling brain tumor tissue during treatment can uncover immune responses and microenvironmental changes that conventional scans may miss.

The research, led by Mass General Brigham (Boston, MA, USA) through the multi-institutional Accelerating GBM Therapies Through Serial Biopsies TeamLab, involved more than 100 scientists and clinicians across the United States. Conducted with funding from Break Through Cancer, the study tested an oncolytic virus immunotherapy called CAN-3110, designed to selectively infect and kill tumor cells while stimulating the immune system. Researchers collected 96 tumor samples over four months from two patients with recurrent GBM enrolled in the clinical trial.

Image: This image shows how immune cells behave in glioblastoma after treatment with intracranial CAN3110 (Photo courtesy of Mass General Brigham)

The findings, published in Science Translational Medicine, revealed that repeated tumor biopsies captured significant immune activation and biochemical shifts within the tumor environment, even when MRI scans suggested disease worsening. This phenomenon, known as pseudoprogression, occurs when immune activity causes inflammation that mimics tumor growth on imaging. Of the two patients treated, one showed a positive immune response while the other maintained stable disease, confirming the potential of longitudinal tissue analysis to detect subtle therapeutic effects.

Using multi-omic analysis, the team integrated genetic, proteomic, metabolic, and AI-enabled pathology data to map tumor evolution over time. The results highlight the value of incorporating serial biopsies into clinical trials to provide real-time insight into treatment efficacy and immune response. The researchers are now expanding the platform to 12 patients and adapting it for additional vaccine-based immunotherapies, aiming to redefine GBM trial design and improve future drug development.

“Standard practice is to not serially sample a patient’s brain tumor as they undergo treatment but instead to take a sample only once before a treatment and then follow a patient’s response using MRI,” said E. Antonio Chiocca, lead investigator of the study. “But this study’s findings suggest that this thinking and practice may need to change to revolutionize how patients can monitor their disease.”

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