Liquid versus tissue biopsy for detecting actionable alterations according to the ESMO Scale for Clinical Actionability of molecular Targets in patients with advanced cancer: a study from the French National Center for Precision Medicine (PRISM)

Bayle, Arnaud; Peyraud, F.; Belcaid, Laïla; Brunet, M.; Aldea, Mihaela; Clodion, R.; Dubos, P.; Vasseur, Damien; Nicotra, Claudio; Géraud, Arthur; Sakkal, Madona; Cerbone, Luigi; Blanc‐Durand, Félix; Mosele, F.; Romano, Paola; Camus, Maud Ngo; Soubeyran, Isabelle; Khalifa, Emmanuel; Alame, M.; Blouin, Laura; Dinart, D.; Bellera, C.; Hollebecque, Antoine; Ponce, Santiago; Loriot, Yohann; Besse, Benjamin; Lacroix, Ludovic; Rouleau, Etienne; André, Fabrice; Italiano, Antoîne

doi:10.1016/j.annonc.2022.08.089

Cited by 18 publications

(9 citation statements)

References 13 publications

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“…A recent French study that compared the results of FMI analysis between matched FFPE and liquid samples showed that the number of actionable alterations was identical in 42% of cases; in the remaining cases, the number of actionable alterations detected was higher in tissue (35%) than in ctDNA (23%) samples (9). Our rates of detection of actionable alterations using liquid biopsy and tissue samples was comparable with that reported in the literature (9).…”

Section: Discussionsupporting

confidence: 88%

“…PROFILER-02, a multicenter randomized, prospective study, evaluated the proportion of metastatic cancer patients who received targeted agent recommendations based on two large NGS panels (8). According to the test used, the detection of abnormality genomic alterations varied between 5% and 31.9%, and only 15% of the patients initiated targeted treatment (8)(9)(10).…”

Section: Introductionmentioning

confidence: 99%

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Clinical management of molecular alterations identified by high throughput sequencing in patients with advanced solid tumors in treatment failure: Real-world data from a French hospital

et al. 2023

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BackgroundIn the context of personalized medicine, screening patients to identify targetable molecular alterations is essential for therapeutic decisions such as inclusion in clinical trials, early access to therapies, or compassionate treatment. The objective of this study was to determine the real-world impact of routine incorporation of FoundationOne analysis in cancers with a poor prognosis and limited treatment options, or in those progressing after at least one course of standard therapy.MethodsA FoundationOneCDx panel for solid tumor or liquid biopsy samples was offered to 204 eligible patients.ResultsSamples from 150 patients were processed for genomic testing, with a data acquisition success rate of 93%. The analysis identified 2419 gene alterations, with a median of 11 alterations per tumor (range, 0–86). The most common or likely pathogenic variants were on TP53, TERT, PI3KCA, CDKN2A/B, KRAS, CCDN1, FGF19, FGF3, and SMAD4. The median tumor mutation burden was three mutations/Mb (range, 0–117) in 143 patients with available data. Of 150 patients with known or likely pathogenic actionable alterations, 13 (8.6%) received matched targeted therapy. Sixty-nine patients underwent Molecular Tumor Board, which resulted in recommendations in 60 cases. Treatment with genotype-directed therapy had no impact on overall survival (13 months vs. 14 months; p = 0.95; hazard ratio = 1.04 (95% confidence interval, 0.48–2.26)].ConclusionsThis study highlights that an organized center with a Multidisciplinary Molecular Tumor Board and an NGS screening system can obtain satisfactory results comparable with those of large centers for including patients in clinical trials.

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Section: Discussionsupporting

confidence: 88%

Section: Introductionmentioning

confidence: 99%

Clinical management of molecular alterations identified by high throughput sequencing in patients with advanced solid tumors in treatment failure: Real-world data from a French hospital

et al. 2023

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“…In addition, although a tissue biopsy allows one to learn about the genomic landscape of a specific tumor site, ctDNA may provide more information about tumor heterogeneity, especially if the tumor is metastatic [ 100 ]. When a large panel is utilized, this new technology has clinical potential to routinely monitor or detect cancer, identify biomarkers of ICI efficacy, including TMB, and subsequently match cancer patients with targeted therapies [ 101 ].…”

Section: Limitations Of Tmb As a Clinical Biomarkermentioning

confidence: 99%

The Efficacy of Tumor Mutation Burden as a Biomarker of Response to Immune Checkpoint Inhibitors

Moeckel

Bakhl

Georgakopoulos-Soares

et al. 2023

IJMS

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Cancer is one of the leading causes of death in the world; therefore, extensive research has been dedicated to exploring potential therapeutics, including immune checkpoint inhibitors (ICIs). Initially, programmed-death ligand-1 was the biomarker utilized to predict the efficacy of ICIs. However, its heterogeneous expression in the tumor microenvironment, which is critical to cancer progression, promoted the exploration of the tumor mutation burden (TMB). Research in various cancers, such as melanoma and lung cancer, has shown an association between high TMB and response to ICIs, increasing its predictive value. However, the TMB has failed to predict ICI response in numerous other cancers. Therefore, future research is needed to analyze the variations between cancer types and establish TMB cutoffs in order to create a more standardized methodology for using the TMB clinically. In this review, we aim to explore current research on the efficacy of the TMB as a biomarker, discuss current approaches to overcoming immunoresistance to ICIs, and highlight new trends in the field such as liquid biopsies, next generation sequencing, chimeric antigen receptor T-cell therapy, and personalized tumor vaccines.

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“…25 Second, a substantial fraction of tissue-based testing orders do not provide results due to insufficient or low-quality material. 26,27 Third, tissue-based sequencing may not capture molecular heterogeneity that is present within tumors or across multiple lesions; this heterogeneity is particularly important with regard to the detection of subclonal resistance mutations. 24,28,29 Used alone, ctDNA-based testing may produce false-negative results for low-shedding tumors as well as false-positive results from clonal hematopoiesis of indeterminate potential (CHIP).…”

Section: Introductionmentioning

confidence: 99%

“…14,33 Concurrent genomic sequencing of both ctDNA and tissue-hereafter, concurrent testing-may provide advantages in timely clinical treatment decision-making for patients with advanced cancer compared with the use of single-modality testing. 15,25,27,[34][35][36][37][38] At present, there is evolving evidence that concurrent testing may provide benefit to patients as acknowledged by NCCN non-small cell lung cancer (NSCLC) guidelines that support complementary (concurrent) testing. 2 In addition, the importance of monitoring ESR1 (OMIM 133430) resistance variants in response to aromatase inhibitor therapy among patients with breast cancer has been recently established and highlights the possible benefits of ctDNA testing for this population.…”

Section: Introductionmentioning

confidence: 99%

Concurrent Tissue and Circulating Tumor DNA Molecular Profiling to Detect Guideline-Based Targeted Mutations in a Multicancer Cohort

Iams,

Mackay,

Ben-Shachar

et al. 2024

JAMA Netw Open

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ImportanceTissue-based next-generation sequencing (NGS) of solid tumors is the criterion standard for identifying somatic mutations that can be treated with National Comprehensive Cancer Network guideline–recommended targeted therapies. Sequencing of circulating tumor DNA (ctDNA) can also identify tumor-derived mutations, and there is increasing clinical evidence supporting ctDNA testing as a diagnostic tool. The clinical value of concurrent tissue and ctDNA profiling has not been formally assessed in a large, multicancer cohort from heterogeneous clinical settings.ObjectiveTo evaluate whether patients concurrently tested with both tissue and ctDNA NGS testing have a higher rate of detection of guideline-based targeted mutations compared with tissue testing alone.Design, Setting, and ParticipantsThis cohort study comprised 3209 patients who underwent sequencing between May 2020, and December 2022, within the deidentified, Tempus multimodal database, consisting of linked molecular and clinical data. Included patients had stage IV disease (non–small cell lung cancer, breast cancer, prostate cancer, or colorectal cancer) with sufficient tissue and blood sample quantities for analysis.ExposuresReceived results from tissue and plasma ctDNA genomic profiling, with biopsies and blood draws occurring within 30 days of one another.Main Outcomes and MeasuresDetection rates of guideline-based variants found uniquely by ctDNA and tissue profiling.ResultsThe cohort of 3209 patients (median age at diagnosis of stage IV disease, 65.3 years [2.5%-97.5% range, 43.3-83.3 years]) who underwent concurrent tissue and ctDNA testing included 1693 women (52.8%). Overall, 1448 patients (45.1%) had a guideline-based variant detected. Of these patients, 9.3% (135 of 1448) had variants uniquely detected by ctDNA profiling, and 24.2% (351 of 1448) had variants uniquely detected by solid-tissue testing. Although largely concordant with one another, differences in the identification of actionable variants by either assay varied according to cancer type, gene, variant, and ctDNA burden. Of 352 patients with breast cancer, 20.2% (71 of 352) with actionable variants had unique findings in ctDNA profiling results. Most of these unique, actionable variants (55.0% [55 of 100]) were found in ESR1, resulting in a 24.7% increase (23 of 93) in the identification of patients harboring an ESR1 mutation relative to tissue testing alone.Conclusions and RelevanceThis study suggests that unique actionable biomarkers are detected by both concurrent tissue and ctDNA testing, with higher ctDNA identification among patients with breast cancer. Integration of concurrent NGS testing into the routine management of advanced solid cancers may expand the delivery of molecularly guided therapy and improve patient outcomes.

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Liquid versus tissue biopsy for detecting actionable alterations according to the ESMO Scale for Clinical Actionability of molecular Targets in patients with advanced cancer: a study from the French National Center for Precision Medicine (PRISM)

Cited by 18 publications

References 13 publications

Clinical management of molecular alterations identified by high throughput sequencing in patients with advanced solid tumors in treatment failure: Real-world data from a French hospital

Clinical management of molecular alterations identified by high throughput sequencing in patients with advanced solid tumors in treatment failure: Real-world data from a French hospital

The Efficacy of Tumor Mutation Burden as a Biomarker of Response to Immune Checkpoint Inhibitors

Concurrent Tissue and Circulating Tumor DNA Molecular Profiling to Detect Guideline-Based Targeted Mutations in a Multicancer Cohort

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