LAUSR

Abstract INTRODUCTION Infantile glioblastoma is rare with poor prognosis. Recent molecular study for infantile hemispheric high grade glioma found its association with ALK/ROS1/NTRK/MET pathway. This suggested the potential use of targeted therapy for refractory / relapse patients. CASE: A newborn presented with apnea, CT brain showed intracranial haemorrhage. MRI then showed a left parietal tumour with bleeding and mass effect. Craniotomy achieved subtotal resection. Chemotherapy VCR/CPM alternating with CDDP/VP-16 was given for one year. Patient was stable with static residual tumour during chemotherapy. However patient developed status epilepticus two weeks after off treatment. MRI showed significant tumour progression which required 2nd & 3rd debulking surgery. Molecular assay by nanostring panel showed BRAF-KIAA1549 fusion. MEK inhibitor Trametinib was tried for 3 months and stopped as disease progression. Further molecular assay by RNASeq showed presence of ROS1 fusion (ZCCHC8-ROS1) while absent of BRAF fusion. Patient underwent 4th debulking surgery as impending herniation while waiting for the targeted therapy. It was complicated with right hemiplegia and facial nerve palsy postoperatively. Finally, ROS1 inhibitor Entrectinib was started 2 weeks later. It was well tolerated without significant adverse reaction. Patient made dramatic neurological recovery including improved facial nerve palsy, able to walk unaided and self feed. MRI brain 1 and 3 months after Entrectinib showed interval reduction in residual tumour. Patient is currently progression-free for 6 months. CONCLUSION Early molecular study for infantile glioblastoma is useful to guide novel therapy. Molecular result may varies between different panels or change over time, to be interpreted with caution.