Detection of additional occult malignancy through profiling of ctDNA in late-stage cancer patients

Aldea, Mihaela; Cerbone, Luigi; Bayle, Arnaud; Parisi, Cristiano; Sarkozy, Clémentine; Vasseur, Damien; Verlingue, Loïc; Blanc‐Durand, Félix; Mosele, F.; Sakkal, Madona; Ponce, Santiago; Lavaud, Pernelle; Loriot, Yohann; Hollebecque, Antoine; Massard, C.; Soria, Jean Charles; Lacroix, Ludovic; Rouleau, Etienne; Italiano, Antoîne

doi:10.1016/j.annonc.2021.09.002

Cited by 9 publications

(10 citation statements)

References 8 publications

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“…41,[44][45][46][47][48] In addition, it must be noted the utility of liquid biopsy to detect an occult malignancy in patients with another cancer. 49 Here, our data support the utility of F1LA in the oncological daily patient's approach. The test may be useful for diagnosis (as a complementary assay of tissue analysis), treatment choice in first and subsequent lines, therapy monitoring, residual disease assessing after surgery, for evaluating of therapy response or disease relapse and for evaluating prognosis (Supplementary Table 4).…”

Section: Discussionsupporting

confidence: 72%

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

et al. 2022

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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.

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Section: Discussionsupporting

confidence: 72%

“… 41 , 44 – 48 In addition, it must be noted the utility of liquid biopsy to detect an occult malignancy in patients with another cancer. 49 …”

Section: Discussionmentioning

confidence: 99%

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

et al. 2022

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“…A unique characteristic of the liquid biopsy is the possibility to perform the blood draw necessary for the analysis at the patient's home [186]. It usually is technically faster than the tissue biopsy analysis and it can help to detect and genetically profile an occult malignancy in patients without tissue cancer available [187]. In addition, the ctDNA is more sensitive than the serum protein biomarkers [carcinoembryonic antigen (CEA), for example] [72].…”

Section: Strengths and Weaknesses Of Ctdna Liquid Biopsymentioning

confidence: 99%

Diagnostic value of liquid biopsy in the era of precision medicine: 10 years of clinical evidence in cancer

Caputo

Ciardiello

Corte

et al. 2023

Exploration of Targeted Anti-Tumor Therapy

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Liquid biopsy is a diagnostic repeatable test, which in last years has emerged as a powerful tool for profiling cancer genomes in real-time with minimal invasiveness and tailoring oncological decision-making. It analyzes different blood-circulating biomarkers and circulating tumor DNA (ctDNA) is the preferred one. Nevertheless, tissue biopsy remains the gold standard for molecular evaluation of solid tumors whereas liquid biopsy is a complementary tool in many different clinical settings, such as treatment selection, monitoring treatment response, cancer clonal evolution, prognostic evaluation, as well as the detection of early disease and minimal residual disease (MRD). A wide number of technologies have been developed with the aim of increasing their sensitivity and specificity with acceptable costs. Moreover, several preclinical and clinical studies have been conducted to better understand liquid biopsy clinical utility. Anyway, several issues are still a limitation of its use such as false positive and negative results, results interpretation, and standardization of the panel tests. Although there has been rapid development of the research in these fields and recent advances in the clinical setting, many clinical trials and studies are still needed to make liquid biopsy an instrument of clinical routine. This review provides an overview of the current and future clinical applications and opening questions of liquid biopsy in different oncological settings, with particular attention to ctDNA liquid biopsy.

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“…If in most cases the multiple malignancies are diagnosed based on clinical symptoms or as incidental findings on imaging, a small part of them can be discovered based on the analysis of cfDNA sequencing. Our team recently reported such cases [ 53 ]. The first case concerned a patient followed for lung cancer, for whom a TMPRSS2 - ERG fusion was identified on cfDNA (a pathognomonic alteration for prostatic cancer).…”

Section: Occult Malignancy Identificationmentioning

confidence: 99%

“…On the NGS performed on liquid biopsy, a MYD88 p.(Leu265Pro) mutation was identified, which is a mutation present in 90% of Waldenström macroglonulinemia [ 54 ]. The hematologic diagnostic was confirmed on bone-marrow aspiration with the identification of mature B clones [ 53 ]. If in our experience, these two occult malignancies have been identified based on a fusion, and an SNV, targeted methylation of cfDNA will help us in the near future to know the localization of the tissue of origin [ 55 ].…”

Section: Occult Malignancy Identificationmentioning

confidence: 99%

Next-Generation Sequencing on Circulating Tumor DNA in Advanced Solid Cancer: Swiss Army Knife for the Molecular Tumor Board? A Review of the Literature Focused on FDA Approved Test

Vasseur

Sahli

Bayle

et al. 2022

Cells

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FDA-approved next-generation sequencing assays based on cell-free DNA offers new opportunities in a molecular-tumor-board context thanks to the noninvasiveness of liquid biopsy, the diversity of analyzed parameters and the short turnaround time. It gives the opportunity to study the heterogeneity of the tumor, to elucidate complex resistance mechanisms and to adapt treatment strategies. However, lowering the limit of detection and increasing the panels’ size raise new questions in terms of detection of incidental germline alterations, occult malignancies and clonal hematopoiesis of indeterminate potential mutations. In this review, after a technological discussion and description of the common problematics encountered, we establish recommendations in properly using these FDA-approved tests in a molecular-tumor-board context.

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Detection of additional occult malignancy through profiling of ctDNA in late-stage cancer patients

Cited by 9 publications

References 8 publications

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

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

Diagnostic value of liquid biopsy in the era of precision medicine: 10 years of clinical evidence in cancer

Next-Generation Sequencing on Circulating Tumor DNA in Advanced Solid Cancer: Swiss Army Knife for the Molecular Tumor Board? A Review of the Literature Focused on FDA Approved Test

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