RARE-43. FAVORABLE OUTCOME OF A YOUNG GIRL WITH RECURRENT METASTATIC PINEOBLASTOMA ASSOCIATED WITH A DICER1 MUTATION

Pineoblastomas have been thought to portend a poor prognosis, especially in younger children or those with metastases. Long term survivors after relapse, especially for those with metastatic disease are rare. We report a young girl with a DICER1 mutation who survived recurrent metastatic pineoblastoma. She was initially diagnosed at the age of 3 with a localized pineoblastoma, underwent gross total surgical resection, and received high dose chemotherapy with autologous stem cell transplant per COG ACNS0334 without radiation therapy. 16 months after completion of treatment, she relapsed at primary site with widespread spinal metastasis. She then received cranial spinal radiation of 3600Gy with proton beam, with boost to primary to 5580Gy, followed by chemotherapy with Temozolomide, Irinotecan and Avastin per COG ACNS0821. She is now 3 years and 3 months from completion of treatment, is doing well clinically with stable imaging findings. No particular alteration was identified from the tumor molecular testing of her initial pineoblastoma. Of note, she was diagnosed with pleuropulmonary blastoma soon after her initial diagnosis of pineoblastoma, and was found to have a DICER1 mutation (c.2062C>T; pR688*) thought to be a nonsense mutation. While radiation therapy following recurrence is known to improve the outcome, more recent studies suggest that tumors lacking the molecular features of high grade glioma also has a positive impact on prognosis. In addition, we speculate that DICER1 mutations might increase sensitivity of cancer cells to some chemotherapy through modulating gene expression and /or interfering with DNA repair mechanisms, therefore, affecting treatment outcome.