From Next-Generation Sequencing to Clinical Decisions in Lung Cancer: Five-Patient Case Series
Alibek S. Abdrashov, Akerke M. Akter, Sardor B. Almetov, Dinara M. Musirali, Yerassyl Y. Yeltay, Khojahmet E. Baimyrza, Nursultan S. Nurdinov
Amina Medical Center, Khoja Akhmet Yassawi International Kazakh-Turkish University
Precision oncology increasingly relies on next-generation sequencing (NGS) to support treatment decisions, yet clinically meaningful findings do not always translate into timely care. This retrospective descriptive molecular case series reviewed five de-identified lung cancer NGS reports generated between July 2024 and February 2026 together with available clinicopathological records. Formalin-fixed paraffin-embedded tumour tissue was analysed using the Oncomine Comprehensive Assay on the Ion GeneStudio™ S5 Plus System, with bioinformatic processing in Ion Reporter™ Software. Each case was evaluated for clinicopathological concordance, need for orthogonal verification or complementary biomarker testing, clinical actionability, treatment-access implications, and the next organisational step. The five profiles included EML4::ALK and TPM3::ROS1 fusions and complex profiles involving BRCA2/PIK3CA, ATR/POLE/MSH2/SETD2, and NF1/MSH2/TSC2. The ALK-rearranged case showed the most pronounced morphology–molecular discordance: earlier records included squamous-cell classification, EGFR-negative and ALK-negative results, and PD-L1 expression of 0%, whereas later surgical pathology documented poorly differentiated adenocarcinoma and comprehensive NGS detected EML4::ALK. After reassessment and confirmation, ALK-inhibitor therapy was introduced. Recurrent barriers included pathology reassessment, verification of unexpected findings, distinction between biological significance and validated lung-cancer actionability, molecular tumour board review, and early evaluation of treatment access. These findings support treating NGS as the beginning of a clinical implementation pathway rather than as a stand-alone therapeutic recommendation. A structured pathway integrating quality review, clinicopathological interpretation, parallel confirmation and access assessment, molecular tumour board review, defined responsibilities, target timelines, and outcome tracking may improve regional precision-oncology practice but requires prospective validation.
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