Comprehensive profiling of circulating tumor DNA and microbial landscapes in nasopharyngeal cancer across Asia: NCCH1905/A-TRAIN study.

6051 Background: Nasopharyngeal cancer (NPC), a malignancy of the nasopharynx, is strongly associated with Epstein-Barr virus (EBV) infection. Although rare in Western countries, NPC is significantly more prevalent in Southeast Asia, likely due to a combination of environmental and dietary factors, though these remain incompletely understood. Current treatments, primarily radiation and chemotherapy, may not fully address the unique challenges posed by NPC. This study aims to conduct a comprehensive genomic analysis, including circulating tumor DNA (ctDNA), and microbial analysis to clarify NPC pathogenesis by examining patient backgrounds in Asian populations. Methods: This is an Asian multicenter prospective observational study conducted by nine institutions in Japan, Philippines, Malaysia, Thailand, Singapore, Taiwan and Vietnam. Eligible patients had histological diagnosis of NPC with metastatic and/or recurrent disease. ctDNA will be analyzed in blood samples collected at newly initial diagnosis of metastatic disease and/or at disease progression. Genomic profiling will be analyzed using TruSight Oncology 500 ctDNA for plasma (Illumina) and TruSight Oncology 500 (Illumina) for tumor tissue, respectively. Furthermore, we analyzed more than 3,000 viral genes using tumor tissue. Results: Seventy-two samples from 72 NPC patients were analyzed. The median age of the patients was 52 years old (range, 25-78), with 53 (73.6%) males. All the patients were Asian, and the details are as follows: 23 Vietnamese, 15 Chinese, 7 Thai, 6 Taiwanese, 5 Iban, 4 Filipino, 3 Japanese and 3 Malay. The number of patients with a history of surgery and radiotherapy was 10 (13.9%) and 45 (62.5%), respectively. Forty-nine patients (68.1%) had a history of chemotherapy, and all had a history of platinum-based drug administration, while eight (11.1%) had a history of immuno-checkpoint inhibitors administration. Pathogenic variants in ctDNA were detected in 40 out of 72 patients (55.6%). The most frequently deleterious mutations were TP53, NRAS and TGFBR2 . Copy number alteration was observed in 33 patients (45.8%). Comprehensive viral and bacterial analysis was available in 20/72 patients (27.8%), with EBV found in 17 patients and none of the viruses in 3 patients. Actinomyces was dominant in all cases, although the bacterial flora was somewhat different. Conclusions: In this study, we conducted comprehensive genomic and microbial analyses of samples collected from NPC patients in Asia, and detected various genomic features as well as elucidating the characteristics of the microbial flora present in the background. As a result, it was shown that anaerobic bacteria may be involved in the pathogenesis of NPC. These bacterial groups form a tumor microenvironment through inflammation and immune modulation, and it is suggested that they promote tumor formation. Clinical trial information: NCT05099978 .