NVTG-08 PERSONALIZED TREATMENT OF MELANOMA BRAIN METASTASES THROUGH HIGH THROUGHPUT DRUG SCREENING

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Abstract Melanoma is an increasing clinical concern, with an expected increase in incidence over the next 20 years. Compounding this problem, as many as 70% of all metastatic patients will develop brain metastases as a manifestation of their disease. Current strategies including immunotherapy, targeted therapy, and local therapies (surgery, SRS, and LITT) have greatly improved patient outcomes yet fail to cure the majority of patients, with intracranial progression a major driver of mortality. Novel treatment strategies are needed to provide immediate options for our patients. To combat this issue, we have developed a pipeline of high throughput drug screening of patient derived tumor microspheres, capable of screening over 100,000 compounds rapidly for potential therapeutic options for patient at time of progression following standard of care. These high throughput results are further paired with tumor derived genomic sequencing to identify potential biomarkers of drug responsiveness. Through this work we will identify potential patient specific therapy options for use in compassionate care trials and through utilization of blood brain barrier permeabilization strategies (LITT or low frequency ultrasound) we plan to expand the pool of available therapies to include those therapies traditionally not capable of reaching drug concentration intracranially. If successful, this strategy has the potential for reshaping both individual patient outcomes, but identifying novel candidate therapies for future clinical trial design.

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