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MP2PRT: Discovering Biomarkers of Outcome: EBV DNA Quantification and the Relationship of EBV and LINE1 Retrotransposon Expression in Pediatric Patients With Nasopharyngeal Carcinoma (NPC) Enrolled on ARAR0331

Nasopharyngeal carcinoma (NPC) is a malignant neoplasm of epithelial cells. Plasma Epstein-Barr Virus (pEBV) DNA levels have been found to correlate with treatment response and survival in both pediatric and adult NPC. A completed Children's Oncology Group (COG) clinical trial, ARAR0331, treated pediatric NPC patients with induction chemotherapy followed by chemoradiotherapy with excellent survival. In this study, >95% of patients had EBV positive tumors. As a secondary objective of ARAR0331, plasma was collected at multiple time points throughout therapy to evaluate pEBV, but the analysis had not been completed as part of ARAR0331. ARAR0331 showed a higher proportion of adolescents and more Black patients, compared to White or Asian, providing a unique opportunity to compare racial subgroups. Unfortunately, patients treated on ARAR0331 had significant morbidity from treatment toxicity. Therefore, the next clinical trial will be aimed at reducing this toxicity. Discovering biomarkers of outcome is critical to correctly assigning patients to treatment groups. With support from the Cancer Moonshot Molecular Profiling to Predict Response to Treatment (MP2PRT) program, our primary analyses evaluated use of pEBV to predict outcomes or response to treatment using specimens from ARAR0331. In secondary analyses, we are evaluating EBV RNA expression using RNA in situ hybridization and LINE1 retrotransposon using immunohistochemistry. We are analyzing tumor mutations and investigation of L1TD1 and EBV insertion via whole genome sequencing (WGS). We also processed tumor specimens using single nuclei sequencing, RNA exome and multiplex immunofluorescence to evaluate immune response and spatial relationships of immune and tumor cells. Understanding NPC tumors and their immune microenvironment will help us improve future clinical trials.