DIPG-54. A NON-INVASIVE PROGNOSTIC CIRCULATING miRNAs SIGNATURE IN DIFFUSE INTRINSIC PONTINE GLIOMAS

Abstract Diffuse intrinsic pontine gliomas (DIPG) are the most common brainstem tumors of childhood and represent one of the most challenging paediatric tumours to treat. A non-randomized, open label phase II pilot study was conducted at Fondazione IRCCS Istituto Nazionale Tumori (Milan) to assess the efficacy in terms of objective response rate according to the RECIST criteria of combining nimotuzumab and vinorelbine with radiation in newly-diagnosed DIPG. Serum specimens were collected at baseline. microRNA expression profiling was performed using Agilent platform and Human miRNA SureSelect 8x60K containing 2006 miRNAs annotated on miRBase19.0. Primary data analysis yielded a matrix containing 330 detectable miRNA. Association with PFS allowed us to disclose a signature of 10 miRNAs able to stratify high and low risk patients (HR=4.33, 95%CI 1.49–12.54; p=4.27E-05). To test the 10 ct-miRNA model performance, we collected an independent cohort of the same sample size (n=24) and we derived the index values and risk stratification. The distribution of index values covers a range similar to the discovery cohort. Imposing the signature threshold patients were divided in high/low risk and Kaplan-Meier curves confirmed the different PFS time for the two groups with HR=3.5 (95%CI: 1.8–8.01, p-value=0.0002) for the high-risk patients, reaching AUC=0.833. Our signature is a biomarker based on non-invasive procedures for prognosis able to enter into clinical practice. Further validation on multicenter case series is warranted.