Glioblastoma zebrafish Avatars guide therapeutic decisions in a patient with gliosarcoma: a case report.

BACKGROUND: Glioblastoma is the most common and lethal brain tumor. Therapeutic options after recurrence are scarce and with no agreement as to which treatment to offer. Also, no functional tests are currently in use to guide clinical decisions. As a result, patients often undergo multiple treatments, being exposed to toxicities and wasting valuable time. METHODS: Here we report a case of a 37-year-old man with a left temporal glioblastoma (gliosarcoma subtype), who underwent several surgeries and treatments. Tumor DNA sequencing revealed no actionable mutations. At the second recurrence, brain MRI showed three new left-hemisphere nodular lesions, leading to a third surgery. However, twenty-days post-surgery the patient relapsed. Therapeutic options available for this patient were no longer well defined and 13 possible off-label options emerged. Fresh tumor samples were used to generate patient-derived zebrafish xenografts (zAvatars) to test the 13 options in combination with radiotherapy. RESULTS: Pemetrexed, and Pemetrexed with Doxorubicin together with Radiotherapy, were both effective in inducing apoptosis. Due to toxicity concerns, the physician opted for the combination of radiotherapy and pemetrexed, with doxorubicin introduced later. The patient recovered and was stable for two months, consistent with the zAvatar prediction. CONCLUSIONS: The rapid establishment of zAvatars from glioblastoma tumor samples allows for the testing of drug combinations and the tailoring of treatment in a personalized and timely manner. A future pipeline of tumor sequencing together with zAvatars testing, since the first surgery, may help manage patients more effectively, potentially improving their Progression free survival (PFS) and overall survival (OS).