Abstract Diffuse midline glioma (DMG) is a pediatric brain cancer with limited treatment options and a dismal prognosis. We present the treatment course and outcome of an adolescent male diagnosed with a thalamic DMG carrying a histone H3.3 K27M alteration. Tumor biopsies were taken at diagnosis for histological analysis, molecular profiling, and ex vivo drug sensitivity testing (DST). Standard-of-care radiotherapy led to a partial tumor regression, but two months later the patient had progressive disease after an ineffective molecular-guided therapy based on tumor genomic analysis. At the time of recurrence and seven months after diagnosis, the patient started a novel and personalized functional precision medicine (FPM)-guided combination of disulfiram, a repurposed drug based on the DST results obtained after diagnosis on the patient’s tumor cells, and ONC201, the most advanced investigational drug for H3 K27M DMG. Neuroimaging demonstrated a treatment response, and the patient lived for fifteen more months after starting this FPM therapy. Disulfiram was discontinued after three months due to significant peripheral neuropathy. Our case supports the feasibility of DST of patient-derived tumor cells to identify personalized therapies for DMG and other cancer patients, and points to the need for further evaluation of the efficacy and safety of this treatment strategy. We will discuss the benefits and risks of this approach, particularly considering its use in children, adolescents, and young adults with pediatric brain cancers.
Tan et al. (Fri,) studied this question.