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

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.

Actionable mutational profiling in solid tumors using hybrid‐capture‐based next‐generation sequencing in a real‐world setting in Spain

“…reported the integration of NGS studies (350 patients) into a Spanish reference public healthcare hospital, founding that TP53 (51.0%), KRAS (26.6%), and EGFR (12.9%) were the most frequently mutated genes. Moreover, they found that actionable genetic alterations were significantly more frequent in never‐smokers (87.7%, p < 0.001), 22 as we have found in our study. Also, in study of Sorin et al 24 .…”

“…To our knowledge, this is the largest cohort‐level study in Spain to profile the analyses of cancer biopsy samples using NGS in routine clinical practice. The recent study published by Simarro et al 22 . evaluated the implementation of NGS for lung cancer biopsy samples in routine clinical practice, 22 in contrast to our study which analyzed biopsy samples of another cancer in addition to lung cancer, using NGS routinely.…”

“…The recent study published by Simarro et al 22 . evaluated the implementation of NGS for lung cancer biopsy samples in routine clinical practice, 22 in contrast to our study which analyzed biopsy samples of another cancer in addition to lung cancer, using NGS routinely.…”

“…23 There are also other observational studies with some parallels to ours, considering the difference in the number and characteristics of the patients. The aforementioned study by Simarro et al 22 reported the integration of NGS studies (350 patients) into a Spanish reference public healthcare hospital, founding that TP53 (51.0%), KRAS (26.6%), and EGFR (12.9%) were the most frequently mutated genes. Moreover, they found that actionable genetic alterations were significantly more frequent in neversmokers (87.7%, p < 0.001), 22 as we have found in our study.…”

“…The aforementioned study by Simarro et al 22 reported the integration of NGS studies (350 patients) into a Spanish reference public healthcare hospital, founding that TP53 (51.0%), KRAS (26.6%), and EGFR (12.9%) were the most frequently mutated genes. Moreover, they found that actionable genetic alterations were significantly more frequent in neversmokers (87.7%, p < 0.001), 22 as we have found in our study. Also, in study of Sorin et al 24 it was described the genomic landscape of patients with lung cancer (n = 997) with NGS in a Canadian hospital, founding a higher prevalence of KRAS mutations (39.2%) compared with most geographical locations, which proved the important to assess institutional rates of actionable driver mutations to help guide governing bodies.…”