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. 2022 May 7:14:17588359221096878.
doi: 10.1177/17588359221096878. eCollection 2022.

Comprehensive genome profiling by next generation sequencing of circulating tumor DNA in solid tumors: a single academic institution experience

Vincenza Caputo  1 , Vincenzo De Falco  1 , Anna Ventriglia  1 , Vincenzo Famiglietti  1 , Erika Martinelli  1 , Floriana Morgillo  1 , Giulia Martini  1 , Carminia Maria Della Corte  1 , Davide Ciardiello  1 , Luca Poliero  1 , Ferdinando De Vita  1 , Michele Orditura  1 , Morena Fasano  1 , Renato Franco  2 , Michele Caraglia  3 , Arianna Avitabile  4 , Roberto Scalamogna  4 , Beatrice Marchi  4 , Fortunato Ciardiello  1 , Teresa Troiani  5 , Stefania Napolitano  6
Affiliations

Comprehensive genome profiling by next generation sequencing of circulating tumor DNA in solid tumors: a single academic institution experience

Vincenza Caputo et al. Ther Adv Med Oncol. .

Abstract

Background: Recently, new evidence of the next-generation sequencing (NGS) liquid biopsy utility in clinical practice has been developed. This assay is emerging as a new promising tool to use as a noninvasive biomarker for cancer mutation profiling. Additional data supporting the clinical validity of cell free DNA (cfDNA) based testing is necessary to inform optimal use of these assays in the clinic.

Materials and methods: A total of 398 cancer patients were analyzed by FoundationOne Liquid Analysis (F1LA), a genomic profiling assay and by standard NGS diagnostic ThermoFisher platform. The association between diagnostic technique was evaluated using a Poisson regression model. FoundationOne Liquid (F1L) and FoundationOne Liquid CDx (F1LCDx) detect 70 and 324 cancer-related genes alterations, respectively, including genomic signatures tumor fraction, blood tumor mutational burden (only for the 324 genes version), and microsatellite instability high status. Both assays used a single DNA extraction method to obtain cfDNA. The real-life clinical impact and feasibility of F1L and F1LCDx were evaluated across different solid tumors in our department.

Results: Between 1 January 2019 and 28 February 2021, 398 samples of different tumor types from 398 patients were analyzed (overall success rate: 92%, in FoundationOne Liquid CDx Analysis success rate: 97%). Most frequent molecular alterations were TP53 (74), APC (40), DNMT3A (39), KRAS (23). The comprehensive clinical impact of F1LA compared with standard diagnostic was 64.7% versus 22.1% [risk ratio (RR) = 2.94; p < 0.001] and the potential clinical impact was 58.6% versus 11.0% (RR = 5.32; p < 0.001), respectively. Furthermore, some clinical cases were selected, in which F1LA detected actionable alterations offering an unexpected therapeutic choice.

Conclusions: Although additional studies are needed to better select patients and setting, NGS F1LA is a useful, noninvasive, and repeatable assay to guide therapeutic choice in oncology. It provides a snapshot of cancer heterogeneity profile that could be incorporated in routinely clinical practice.

Keywords: cfDNA; clinical trials; liquid biopsy; mCRC; precision medicine.

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Conflict of interest statement

Conflict of interest statement: The authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: EM: advisory board for Amgen, Bayer, Merck, Roche, Sanofi, Servier, Biocartis and expert opinion for ESMO (European Society of Medical Oncology). FM: advisory board for MSD, Lilly, and AstraZeneca. FDV: advisory board for Amgen, Lilly, Roche, and Celgene. MO: Honoraria from Epionpharma, Italfarmaco and research funding from Eisai, travel and accommodation expenses for meetings from Roche. AA: Roche employed. RS: Roche employed. BM: Roche employed. FC: Advisory Boards: Roche, Amgen, Merck, Pfizer, Sanofi, Bayer, Servier, BMS, Celgene, Lilly; Institutional Research Grants: Bayer, Roche, Merck, Amgen, AstraZeneca, and Ipsen. TT: advisory board for Amgen, Bayer, Merck, Novartis, Roche, and Sanofi. The remaining authors have no conflicts of interest to declare.

Figures

Figure 1.
Figure 1.
Tumor samples types. (a) Total tumor samples types: 398 liquid samples, both for Foundation Liquid analysis (70) and for Foundation Liquid CDx analysis (324): number of samples for type of tumors and percentage of samples for type of tumor. (b) Tumor samples types – liquid analysis (70): 255 liquid samples for Foundation Liquid analysis (70): number of samples for type of tumors and percentage of samples for type of tumor. (c) Tumor samples types – liquid CDx analysis (324): 143 liquid samples for Foundation Liquid CDx analysis (324): number of samples for type of tumors and percentage of samples for type of tumor. CRC, colorectal cancer.
Figure 2.
Figure 2.
Genetic alterations in the population of Liquid CDx samples. Cutoff VAF ⩾ 0.5. 133 mutations not counted (VAF < 0.5). (a) Summary of gene alterations in 139 samples. (b) Percentage of gene alterations subtypes. (c) The most frequent gene alterations.
Figure 3.
Figure 3.
Selected cases in which Foundation Analysis changes the patient’s clinical history. (a) Schematic representation of selected clinical case: the identification of KIF5B-RET fusion allowed target therapy. (b) Schematic representation of selected clinical case: the identification of EGFR T790M mutation allowed target therapy.
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