Diagnostic work-up and systemic treatment for advanced non-squamous non-small-cell lung cancer in four Southeast Asian countries.

BACKGROUND: Lung cancer is the second most common cancer and leading cause of cancer mortality worldwide. Recent advances in molecular testing and targeted therapy have improved survival among patients with metastatic non-small-cell lung cancer (NSCLC). We sought to quantify and describe molecular testing among metastatic non-squamous NSCLC cases in selected Southeast Asian countries and describe first-line therapy chosen. PATIENTS AND METHODS: A retrospective study was conducted based on incident lung cancer cases diagnosed between 2017 and 2019 in Lampang (Thailand), Penang (Malaysia), Singapore and Yogyakarta (Indonesia). Cases (n = 3413) were defined using the International Classification of Diseases for Oncology third edition. In Singapore, a clinical series obtained from the National Cancer Centre was used to identify patients, while corresponding population-based cancer registries were used elsewhere. Tumor and clinical information were abstracted by chart review according to a predefined study protocol. Molecular testing of epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK) gene rearrangement, ROS1 gene rearrangement and BRAF V600 mutation was recorded. RESULTS: Among 2962 cases with a specified pathological diagnosis (86.8%), most patients had non-squamous NSCLC (75.8%). For cases with staging information (92.1%), the majority presented with metastatic disease (71.3%). Overall, molecular testing rates in the 1528 patients with stage IV non-squamous NSCLC were 67.0% for EGFR, 42.3% for ALK, 39.1% for ROS1, 7.8% for BRAF and 36.1% for PD-L1. Among these patients, first-line systemic treatment included chemotherapy (25.9%), targeted therapy (35.6%) and immunotherapy (5.9%), with 31% of patients having no record of antitumor treatment. Molecular testing and the proportion of patients receiving treatment were highly heterogenous between the regions. CONCLUSIONS: This first analysis of data from a clinically annotated registry for lung cancer from four settings in Southeast Asia has demonstrated the feasibility of integrating clinical data within population-based cancer registries. Our study results identify areas where further development could improve patient access to optimal treatment.

Purified hexameric Epstein-Barr virus-encoded BARF1 protein for measuring anti-BARF1 antibody responses in nasopharyngeal carcinoma patients.

WHO type III nasopharyngeal carcinoma (NPC) is highly prevalent in Indonesia and 100% associated with Epstein-Barr virus (EBV). NPC tumor cells express viral proteins, including BARF1, which is secreted and is considered to have oncogenic and immune-modulating properties. Recently, we found conserved mutations in the BARF1 gene in NPC isolates. This study describes the expression and purification of NPC-derived BARF1 and analyzes humoral immune responses against prototype BARF1 (B95-8) and purified native hexameric BARF1 in sera of Indonesian NPC patients (n = 155) compared to healthy EBV-positive (n = 56) and EBV-negative (n = 16) individuals. BARF1 (B95-8) expressed in Escherichia coli and baculovirus, as well as BARF1-derived peptides, did not react with IgG or IgA antibodies in NPC. Purified native hexameric BARF1 protein isolated from culture medium was used in enzyme-linked immunosorbent assay (ELISA) and revealed relatively weak IgG and IgA responses in human sera, although it had strong antibody responses to other EBV proteins. Higher IgG reactivity was found in NPC patients (P = 0.015) than in regional Indonesian controls or EBV-negative individuals (P < 0.001). IgA responses to native BARF1 were marginal. NPC sera with the highest IgG responses to hexameric BARF1 in ELISA showed detectable reactivity with denatured BARF1 by immunoblotting. In conclusion, BARF1 has low immunogenicity for humoral responses and requires native conformation for antibody binding. The presence of antibodies against native BARF1 in the blood of NPC patients provides evidence that the protein is expressed and secreted as a hexameric protein in NPC patients.