Liquid biopsy comprehensive genomic profiling of lung cancer in the Italian population: A real-world experience

Camilla Porta; Lorenzo Pradelli; Emilia Sicari; Silvia Castellani; Smruthy Sivakumar; Ethan Sokol; Meagan Montesion; Thomas Wieland; Johanna Rambichler; Roberta Minari; Marcello Tiseo

doi:10.1016/j.lungcan.2023.107359

Liquid biopsy comprehensive genomic profiling of lung cancer in the Italian population: A real-world experience

Lung Cancer. 2023 Nov:185:107359. doi: 10.1016/j.lungcan.2023.107359. Epub 2023 Sep 4.

Authors

Affiliations

¹ AdRes HE&OR, Turin, Italy. Electronic address: c.porta@adreshe.com.
² AdRes HE&OR, Turin, Italy.
³ Roche S.p.A., Monza, Italy.
⁴ Foundation Medicine, Inc., Cambridge, MA, USA.
⁵ Foundation Medicine, Munich, Germany, USA.
⁶ Medical Oncology Unit, University Hospital of Parma, Parma, Italy.
⁷ Medical Oncology Unit, University Hospital of Parma, Parma, Italy; Department of Medicine and Surgery, University of Parma, Parma, Italy.

PMID: 37703610
DOI: 10.1016/j.lungcan.2023.107359

Abstract

Objectives: Liquid biopsy with next-generation sequencing (NGS) has emerged as a promising tool for tumor mutation profiling. In this study, we describe the genomic profile of Italian lung cancer patients tested with blood-based comprehensive genomic profiling (CGP) to assess the genomic landscape complexity and its impact on enhancing treatment options for patients.

Materials and methods: Between January 2021 and December 2021, a total of 229 lung cancer patients were profiled by FoundationOne®Liquid CDx (F1LCDx®) assay on circulating tumor DNA (ctDNA). F1LCDx® reports alterations across 324 cancer-related genes and genomic signatures, including tumor fraction (TF) and blood-based tumor mutational burden (bTMB). Detected variants were classified according to the ESMO Scale of Clinical Actionability for molecular Targets (ESCAT).

Results: 90.4% of patients had at least one detectable alteration in plasma. The most frequently mutated genes were TP53 (47.6%), DNMT3A (33.2%), EGFR (20.1%), and KRAS (15.7%). Elevated TF was detected in 18.3% of patients, suggesting high reliability of test results. According to the ESCAT classification, potentially actionable alterations (Tier I-II) were identified in 27.1% of samples. An additional 5.2% harbored an alteration for which an approved drug is available in other cancer types (Tier III). Furthermore, 13.1% of tumors exhibited high bTMB, which may predict response to immunotherapy. Overall, 156 (68.1%) patients were eligible for enrolment in clinical trials.

Conclusion: Liquid biopsy NGS is a viable and valuable approach to guide personalized therapy. The use of blood-based CGP may help identify a larger number of actionable mutations and increase chances of enrolment in clinical trials.

Keywords: Comprehensive genomic profiling; Italy; Liquid biopsy; Lung cancer; Next-generation sequencing; Precision medicine.