Mutation profile in liquid biopsy tested by next generation sequencing in Mexican patients with non-small cell lung carcinoma and its impact on survival.

Background: Lung cancer represents a significant global health concern, often diagnosed in its advanced stages. The advent of massive DNA sequencing has revolutionized the landscape of cancer treatment by enabling the identification of target mutations and the development of tailored therapeutic approaches. Unfortunately, access to DNA sequencing technology remains limited in many developing countries. In this context, we emphasize the critical importance of integrating this advanced technology into healthcare systems in developing nations to improve treatment outcomes.
Methods: We conducted an analysis of electronic clinical records of patients with confirmed advanced non-small cell lung cancer (NSCLC) and a verified negative status for the epidermal growth factor receptor ( EGFR ) mutation. These patients underwent next-generation sequencing (NGS) for molecular analysis. We performed descriptive statistical analyses for each variable and conducted both univariate and multivariate statistical analyses to assess their impact on progression-free survival (PFS) and overall survival (OS). Additionally, we classified genetic mutations as actionable or non-actionable based on the European Society for Medical Oncology Scale of Clinical Actionability of Molecular Targets (ESCAT) guidelines.
Results: Our study included a total of 127 patients, revealing the presence of twenty-one distinct mutations. The most prevalent mutations were EGFR (18.9%) and Kirsten rat sarcoma viral oncogene homolog ( KRAS ) (15.7%). Notably, anaplastic lymphoma kinase ( ALK ) [hazard ratio (HR): 0.258, P<0.001], tumor mutation burden (TMB) (HR: 2.073, P=0.042) and brain magnetic resonance imaging (MRI) (HR: 0.470, P=0.032) demonstrated statistical significance in both the univariate and multivariate analyses with respect to PFS. In terms of OS, ALK (HR: 0.285, P<0.001) and EGFR (HR: 0.482, P=0.024) exhibited statistical significance in both analyses. Applying the ESCAT classification system, we identified actionable genomic variations (ESCAT level-1), including EGFR , ALK , breast cancer ( BRAF ) gene, c-ros oncogene 1 ( ROS1 ), and rearranged during transfection ( RET ) gene, in 32.3% of the patients.
Conclusions: Our findings from massive DNA sequencing underscore that 32.3% of patients who test negative for the EGFR mutation possess other targetable mutations, enabling them to receive personalized, targeted therapies at an earlier stage of their disease. Implementing massive DNA sequencing in developing countries is crucial to enhance survival rates among NSCLC patients and guide more effective treatment strategies.
Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-23-1029/coif). The authors have no conflicts of interest to declare.
(2024 Journal of Thoracic Disease. All rights reserved.)