Clinical Topics & News

Molecular Profiling of Lung Malignancies in Veterans: What We Have Learned About the Impact of Agent Orange Exposure



There are no studies in oncologic literature that report biomarker alterations in Vietnam War veterans with lung cancers. Our study elucidates genetic mutations in veterans with lung cancer exposed to Agent Orange (AO) and compares them to non-Agent Orange exposed (NAO) veterans.


We collected data of veterans with lung cancers from VA Central California Health Care System who had NGS testing via Foundation One CDx from January 2007 to January 2022. We collected data of AO versus NAO veterans including age, race, gender, smoking and exposure history, histologic subtypes, treatment modalities, PDL-1, and molecular mutations. Median PFS and OS were calculated between AO and NAO in all veterans and adenocarcinoma group after first-line therapy in months by Kaplan-Meier R log-rank test.


There were total of 58 lung cancer veterans, 27 AO and 31 NAO. 33 (56.9%) veterans had adenocarcinoma (20 AO vs 13 NAO). Veterans were White (81%), male (93%) and all had tobacco exposure. The median age at diagnosis was 72 years in both groups. 65.5% had stage III-IV disease. Veterans with AO adenocarcinoma had more early stage I-II disease (50%) as compared to NAO (16%). The AO group had more PDL1 expression (TPS > 1%). 15/31 (48.4%) NAO received immunotherapy vs 7/27 (25.9%) AO. 104 molecular mutations were identified. Veterans with AO had more ROS1, MET, and NRAS while NAO had more EGFR, KRAS, and NF1 mutations. In adenocarcinoma group, AO had more MET and less KRAS while NAO has more KRAS, TP53, and EGFR. The median PFS and OS for all veterans with AO vs NAO were 8 mo vs 6 mo and 12 mo vs 10 mo, respectively (non-significant [NS]). In adenocarcinoma group the median PFS and OS for AO vs NAO veterans were 8 mo vs 4 mo and 11.75 mo vs 6 mo, respectively (NS).


Our study is the first to report molecular biomarkers in AO and NAO veterans with lung cancers. We found different markers between the groups. The median PFS and OS of AO and adenocarcinoma AO veterans were longer due to early stage diagnoses while NAO vetera

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