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. 2023 Mar 10;15(6):1705.
doi: 10.3390/cancers15061705.

Impact of Molecular Testing Using Next-Generation Sequencing in the Clinical Management of Patients with Non-Small Cell Lung Cancer in a Public Healthcare Hospital

Javier Simarro  1   2 , Gema Pérez-Simó  1   2 , Nuria Mancheño  3 , Emilio Ansotegui  4 , Carlos Francisco Muñoz-Núñez  5 , José Gómez-Codina  2   6 , Óscar Juan  6 , Sarai Palanca  1   2   7
Affiliations

Impact of Molecular Testing Using Next-Generation Sequencing in the Clinical Management of Patients with Non-Small Cell Lung Cancer in a Public Healthcare Hospital

Javier Simarro et al. Cancers (Basel). .

Abstract

Next-generation sequencing (NGS) is a molecular approach able to provide a comprehensive molecular profile of non-small cell lung cancer (NSCLC). The broad spectrum of biomarker-guided therapies has positioned molecular diagnostic laboratories as a central component of patient clinical management. Here, we show the results of an UNE-EN ISO 15189:2022 NGS-accredited assay in a cohort of 350 patients. TP53 (51.0%), KRAS (26.6%) and EGFR (12.9%) were the most frequently mutated genes. Furthermore, we detected co-occurring and mutually exclusive alterations, as well as distinct molecular profiles according to sex and smoking habits. Actionable genetic alterations were significantly more frequent in female patients (80.5%, p < 0.001) and in never-smoker patients (87.7%, p < 0.001). When NGS was established as the main molecular testing strategy, 36.4% of patients received at least one line of targeted treatment. Among 200 patients with stage IV NSCLC, first-line treatment with targeted therapies was associated with a longer progression-free survival (PFS) (13.4 months (95% CI, 10.2-16.6) (p = 0.001)). Similarly, the overall survival (OS) of patients receiving at least one targeted drug was significantly longer (26.2 months (95% CI, 11.8-40.5) (p < 0.001)). Our results show that the implementation of NGS in the public healthcare system has provided a broader application of precision medicine.

Keywords: molecular diagnosis; next-generation sequencing; non-small cell lung cancer; quality management system; translational research.

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Conflict of interest statement

The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of the data; in the writing of the manuscript; or in the decision to publish the results.

Figures

Figure 1
Figure 1
Molecular alterations detected in NGS studies. (A) Patient distribution according to the number of genetic alterations detected. (B,C) Percentage of samples with molecular alterations in the genes included in the study. Variants detected at frequencies of >3% (A) and <3% (B). Amp: amplification. F: fusion.
Figure 2
Figure 2
Association of sex and smoking status with specific molecular alterations. Frequency of gene alterations in the global cohort and in the evaluated subgroups is depicted. ns: not statistically significant. * Comparison using Fisher’s exact test.
Figure 3
Figure 3
Mosaic plot showing relationships of co-occurrence and mutual exclusivity between the molecular alterations detected in our cohort. For each comparison, the most frequently altered gene is depicted on the X-axis. Frequency of patients included in each of the four subgroups defined by the presence/absence of both genetic alterations is depicted in the graph. * Comparison using Fisher’s exact test.
Figure 4
Figure 4
Actionable molecular alterations detected using NGS in our cohort. Percentage of patients with actionable genetic variants (green) in the global cohort (A), according to sex (B) and according to smoking status (C). Patient distribution according to the level of evidence of the detected variants in the global cohort (D), according to sex (E) and according to smoking status (F). Purple: patients who are candidates for treatment with approved drugs, blue: patients eligible for phase I–II clinical trials. ns: not statistically significant.
Figure 5
Figure 5
First-line progression-free survival of patients with stage IV NSCLC stratified by therapeutic approach.
Figure 6
Figure 6
Overall survival of patients with stage IV NSCLC stratified by the treatment strategies administered during the course of the disease.
See this image and copyright information in PMC

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