INNV-23. Precision medicine in diffuse intrinsic pontine glioma: a case report

Abstract Diffuse intrinsic pontine glioma (DIPG) is an aggressive pediatric brain tumor with no curative therapies. Standard of care is focal radiation therapy (RT), with a 2-year survival rate <10%. Patients who receive re-irradiation have post-progression median overall survival of 6 months. These tumors were historically not biopsied due to their eloquent location and poor prognosis. However, in the past few years, with advanced neurosurgical techniques, tissue diagnosis has been pursued when feasible which led to greater understanding in tumor biology. Unfortunately, outcomes have not yet reflected these advances. Here, we describe the case of a long-term survivor of DIPG following targeted therapy. The patient presented at 5 years of age with headaches and left cranial nerve VI palsy and had neuro-radiological findings consistent with “typical DIPG”. A biopsy was not obtained, and the patient was treated with focal RT 60 Gy. He had a good response to RT with reduction in symptoms and tumor size. Thirty months following initial diagnosis, he developed an asymptomatic solid nodule at the anterior fornix with stable appearance of the original pontine mass. A biopsy of the lesion was performed, with histopathology confirming metastatic relapse diffuse midline glioma, H3 K27M-mutant. Next-generation sequencing of the tumor was positive for the following alterations: H3F3A K28M, EP300 L415P (subclonal), and ATM R3008H.The patient was treated with further RT to the metastatic lesion. Subsequently, he was started on Olaparib (PARP inhibitor) based on somatic ATM mutation, via the compassionate use program of AstraZeneca. The patient remains alive with a Lansky performance score of 100% on continuing Olaparib, six years from relapse. This case highlights the importance of molecular testing and utility of precision therapy in brain tumors. Ongoing research effort is needed to understand the mechanism of response, and patient cohorts that may benefit from specific targeted therapies.