Pediatric oncology services in the NE region are making progress toward meeting follow-up care goals for childhood cancer survivors. Funding for resource intense programs, transitioning care to adult clinical services, volume of sub-specialty referral, and participation in research are common challenges.

The survival rates of children treated for cancer have dramatically increased after the development of standardized multiple-modality treatment protocols. As a result, there is a rapidly growing population of pediatric cancer survivors in which the long-term genotoxic effects of chemotherapeutic intervention is unknown. To study the genotoxic effects of antineoplastic treatment in children, we performed a comparative analysis of the changes in the frequency of somatic mutations (Mfs) at the hypoxanthine-guanine phosphoribosyltransferase (HPRT)-reporter gene in children treated for acute lymphocytic leukemia (ALL). We measured HPRT Mfs from 130 peripheral blood samples from 45 children with ALL (13, low risk; 22, standard risk; and 10, high risk) from the time of diagnosis, as well as during and after the completion of therapy. We observed a significant increase in mean HPRT Mfs during each phase of therapy (diagnosis, 1.4 ؋ 10 ؊6; consolidation, 52.1 ؋ 10 ؊6 ; maintenance, 93.2 ؋ 10 ؊6; and off-therapy, 271.7 ؋ 10 ؊6) that were independent of the risk group treatment protocol used. This 200-fold increase in mean somatic Mf remained elevated years after the completion of therapy. We did not observe a significant difference in the genotoxicity of each risk group treatment modality despite differences in the compositional and clinical toxicity associated with these treatment protocols. These findings suggest that combination chemotherapy used to treat children with ALL is quite genotoxic, resulting in an increased somatic mutational load that may result in an elevated risk for the development of multi-factorial diseases, in particular second malignancies.

The link between exposure to environmental mutagens and the development of cancer is well established. Yet there is a paucity of data on the relationship between gene-environment interactions and the mechanisms associated with the somatic mutational events involved with malignant transformation, especially in children. To gain insight into somatic mutational mechanisms in children who develop cancer, we determined the background mutant frequency (Mf) in the hypoxanthine phosphoribosyl transferase (HPRT) reporter gene of peripheral blood lymphocytes from pediatric cancer patients at the time of diagnosis and prior to therapeutic intervention. We studied 23 children with hematologic malignancies and 31 children with solid tumors prior to initial therapeutic intervention. Children with solid tumors, specifically sarcomas, and Hodgkin's disease were significantly older and had elevated HPRT Mfs (6.1 x 10(-6) and 3.7 x 10(-6), respectively) at the time of diagnosis, compared to normal controls (2.3 x 10(-6)) and other pediatric tumor groups including children with acute lymphocytic leukemia and non-Hodgkin's lymphoma (ALL/NHL, 1.7 x 10(-6)), central nervous system tumors (CNS, 3.6 x 10(-6)), and neuroblastoma (1.9 x 10(-6)). Of importance is that the significant differences observed in HPRT Mfs between these groups no longer existed after correcting for the effects of age. These data demonstrate that in children who develop cancer there appears to be no significant increase in background HPRT Mf that would indicate significant exposure to genotoxic chemicals or an underlying DNA repair defect resulting in genomic instability. In addition, these data demonstrate the importance of correcting for the effect of age when comparing the frequency of somatic mutations in children and should provide baseline data for future longitudinal biomonitoring studies on the genetic effects of chemotherapy in children treated for cancer.

NEURO-ONCOLOGY • NOVEMBER 2017 were alive at the time of analysis. 2 patients identified as Asian and 7 as White. The MiB labeling index (MiB) ranged from ≤2 to 20%. All underwent surgical resection and GTR was achieved in 5. Of those patients with GTR, 3 (MiB 3-5, 5 and 20%) received adjuvant radiotherapy (RT). A single patient with GTR and elevated MiB of 5% did not receive RT: this patient is progression-free at 38 months and is the only patient with a KPS of 100. There was a single case of recurrence in the patient with highest MiB (20%) treated with GTR, RT, and concurrent temozolomide. This patient is alive >10 years from diagnosis and 5.2 years after recurrence. A majority that received RT (n=6), were referred for neuropsychological evaluation with 4 patients requiring use of methylphenidate. CONCLUSIONS: This tumor has a favorable prognosis even with elevated MiB and in the setting of recurrence. Treatment for recurrence may include GTR and conformal RT with temozolomide. Further research on RT sparing treatments in the adjuvant setting is warranted. Referral for neuropsychological evaluation and symptomatic treatment with methylphenidate should be considered in patients who receive RT. RARE-28. MALIGNANT TRANSFORMATION OF A LOW-GRADE MIDLINE GLIOMA WITH CONCOMITANT BRAFV600E AND H3.3K27 MUTATIONS