Prospective Upfront Next-Generation Sequencing for Advanced Non-Small Cell Lung Cancer: Real-World Outcomes from the Ion Chiricuță Oncology Institute

Preda, Alexandra Cristina; Todor, Nicolae; Cârlan, Bogdan; Kubelac-Varro, Adelina-Dadiana; Iancu, Dana Ioana; Mocan, Cristina; Vasilica, Mariana Bandi; Kubelac, Milan-Paul; Vlad, Cătălin; Ciuleanu, Tudor Eliade

doi:10.3390/ijms26073403

Open AccessArticle

Prospective Upfront Next-Generation Sequencing for Advanced Non-Small Cell Lung Cancer: Real-World Outcomes from the Ion Chiricuță Oncology Institute

by

Alexandra Cristina Preda

^1,2,

Nicolae Todor

¹

,

Bogdan Cârlan

³,

Adelina-Dadiana Kubelac-Varro

²,

Dana Ioana Iancu

¹,

Cristina Mocan

¹

,

Mariana Bandi Vasilica

¹,

Milan-Paul Kubelac

^1,4,*

,

Cătălin Vlad

^1,2 and

Tudor Eliade Ciuleanu

¹

Oncology Institute “Prof. Dr. Ion Chiricuță” 34–36 Republicii Street, 400015 Cluj-Napoca, Romania

²

Faculty of Medicine, “Iuliu Hațieganu” University of Medicine and Pharmacy, 8 Victor Babeș Street, 400012 Cluj-Napoca, Romania

³

Medlife Oncology Hospital, 65A Carierei Street, 500062 Brașov, Romania

⁴

STAR Institute, Babeș-Bolyai University, 1 Mihail Kogălniceanu Street, 400347 Cluj-Napoca, Romania

^*

Author to whom correspondence should be addressed.

Int. J. Mol. Sci. 2025, 26(7), 3403; https://doi.org/10.3390/ijms26073403

Submission received: 16 March 2025 / Revised: 30 March 2025 / Accepted: 1 April 2025 / Published: 5 April 2025

(This article belongs to the Special Issue Challenges and Future Perspectives in Treatment for Lung Cancer)

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Abstract

Upfront Next-Generation Sequencing (NGS) is increasingly recommended in advanced NSCLC to guide targeted therapy. This prospective single-center study in Romania evaluated routine, upfront NGS in advanced NSCLC at baseline (tissue and/or liquid) and progression (liquid). Baseline FoundationOne NGS (tissue/liquid) was performed in 119 consecutive stage IV NSCLC patients, along with PD-L1 immunohistochemistry (IHC, SP263). Liquid biopsy was repeated at progression. Turnaround time (TAT), the prevalence of actionable targets, and clinical utility were assessed. Patients were predominantly male (68.1%) with a median age of 62 years (range 30–86). Most had ECOG PS 0–1 (79%) and non-squamous histology (67.2%). Never-smokers accounted for 25.2%. The median TAT for the NGS results was 9 days (range 5–21). Overall, 671 genetic alterations were detected in 149 genes. The mean number of distinct mutations per patient dropped from 5.6 at baseline to 4.3 at progression. Tissue samples yielded more alterations (6 per patient) than baseline liquid biopsies (4.6). Squamous tumors had more alterations (7.1 vs. 4.8 in non-squamous), and the number of smokers exceeded that of never-smokers (6 vs. 4.5). TP53 was the most frequent (70.59%). Actionable variants were found in 74.8% of patients, though only 35.3% received personalized therapy, largely due to performance status deterioration, reimbursement, or trial availability barriers. Common targets in non-squamous tumors included EGFR (21%), KRAS G12C (11%), NF1 (11%), and ERBB2 (6%); in squamous tumors, common targets included NF1 (24%), PIK3CA (18%), and ERBB2 (8%). Among smokers, driver mutations were often NF1 (15%), PIK3CA (11%), KRAS G12C (9%), and ERBB2 (8%); never-smokers were dominated by EGFR (45%), NF1 (15%), and KRAS G12C (8%). TMB ≥ 10 mut/Mb was seen in 26.9%; no patients were MSI-H. PD-L1 TPS was <1% in 33% of patients, 1–49% in 20%, ≥50% in 18%, and unknown in 29%. Upfront NGS offers rapid, comprehensive genomic data, guiding tailored therapies and trials in advanced NSCLC. Liquid rebiopsy at progression further refines treatment decisions.

Keywords: next-generation sequencing; FoundationOne; non-small cell lung cancer; personalized treatment

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MDPI and ACS Style

Preda, A.C.; Todor, N.; Cârlan, B.; Kubelac-Varro, A.-D.; Iancu, D.I.; Mocan, C.; Vasilica, M.B.; Kubelac, M.-P.; Vlad, C.; Ciuleanu, T.E. Prospective Upfront Next-Generation Sequencing for Advanced Non-Small Cell Lung Cancer: Real-World Outcomes from the Ion Chiricuță Oncology Institute. Int. J. Mol. Sci. 2025, 26, 3403. https://doi.org/10.3390/ijms26073403

AMA Style

Preda AC, Todor N, Cârlan B, Kubelac-Varro A-D, Iancu DI, Mocan C, Vasilica MB, Kubelac M-P, Vlad C, Ciuleanu TE. Prospective Upfront Next-Generation Sequencing for Advanced Non-Small Cell Lung Cancer: Real-World Outcomes from the Ion Chiricuță Oncology Institute. International Journal of Molecular Sciences. 2025; 26(7):3403. https://doi.org/10.3390/ijms26073403

Chicago/Turabian Style

Preda, Alexandra Cristina, Nicolae Todor, Bogdan Cârlan, Adelina-Dadiana Kubelac-Varro, Dana Ioana Iancu, Cristina Mocan, Mariana Bandi Vasilica, Milan-Paul Kubelac, Cătălin Vlad, and Tudor Eliade Ciuleanu. 2025. "Prospective Upfront Next-Generation Sequencing for Advanced Non-Small Cell Lung Cancer: Real-World Outcomes from the Ion Chiricuță Oncology Institute" International Journal of Molecular Sciences 26, no. 7: 3403. https://doi.org/10.3390/ijms26073403

APA Style

Preda, A. C., Todor, N., Cârlan, B., Kubelac-Varro, A.-D., Iancu, D. I., Mocan, C., Vasilica, M. B., Kubelac, M.-P., Vlad, C., & Ciuleanu, T. E. (2025). Prospective Upfront Next-Generation Sequencing for Advanced Non-Small Cell Lung Cancer: Real-World Outcomes from the Ion Chiricuță Oncology Institute. International Journal of Molecular Sciences, 26(7), 3403. https://doi.org/10.3390/ijms26073403

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Prospective Upfront Next-Generation Sequencing for Advanced Non-Small Cell Lung Cancer: Real-World Outcomes from the Ion Chiricuță Oncology Institute

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