Prospective Multicenter Validation of the Detection of ALK Rearrangements of Circulating Tumor Cells for Noninvasive Longitudinal Management of Patients With Advanced NSCLC

Ilié, Marius; Mazières, Julien; Chamorey, Emmanuel; Heeke, Simon; Benzaquen, Jonathan; Thamphya, Brice; Boutros, Jacques; Tiotiu, Angélica; Fayada, Julien; Cadranel, Jacques; Poudenx, M.; Moro-Sibilot, Denis; Barlési, Fabrice; Thariat, Juliette; Clément-Duchêne, Christelle; Tomasini, Pascale; Marquette, Charles‐Hugo; Hofman, Paul; Israël‐Biet, Dominique; Pison, Christophe; Lantuéjoul, Sylvie; Stephanov, Olivier; Juliette, Meyzenc; Mendozat, Christophe; Zaidi, Manel; Coulouvrat, Sandra; Col, Edwige; Chanez, Pascal; Greillier, L.; Mascaux, Céline; Jourdan, Sandrine; Roger, Aurélie; Biemar, Julie; Randriamampionona, Rondro; Chabot, F.; Vignaud, Jean-Michel; Lacomme, Stéphanie; Lomazzi, Sandra; Laurent, Carine; Bulsei, Xavier; Bischoff, Laura L.; Rakotonirina, Raymond; Layouni, Mehdi; Deslée, G.; Mal, Hervé; Kessler, Romain; Vergnon, Jean‐Michel; Pelissier, Isabelle; Cuvelier, A.; Bourdin, Arnaud; Jounieaux, Vincent; Roche, Nicolás; Jouneau, S.; Bonniaud, Philippe; Scherpereel, Arnaud; Mornex, J. F.; Steenhouwer, François; Leroy, Sylvie; Marquette, Charles Hugo; Mazzette, Andrea; Padovani, B.; Long‐Mira, Elodie; Lassalle, Sandra; Pradelli, Johanna; Martinez, Estelle; Habault, Marine; Bonnard, Mélanie; Moutarde, Julie; Yatimi, Rachida; Labsi, Hakima; Gazoppi, Loïc; Lpce, Tumorothèque; Griffonnet, Jennifer; Fontaine, Maureen; Guillemart, A.; Butori, Catherine; Selva, Éric; Otto, Josiane; Hébert, Christophe; Botchiellini, Delphine; Boudouf, Soukaina; Menier, Margaux; Occeli, Estelle; Bellentani, Sophie; Pion, Carine; Fournier, Elodie; Gervais, Radj; Hamond, K.; Marchand-Adam, S.; Plantier, Laurent; Fajolle, Gaelle; Rayez, Mélanie; Fallet, Vincent; Wislez, Marie; Antoine, Martine; Côté, Jean‐François; Chaabane, Nouha; Ruppert, A.-M.; Bertrand, Eliane; Rodenas, Anita; Pontdeme, Gwenaëlle; Mathiot, N.; Ribert, Tamazouzt; Guibert, Nicolas; Rouvière, Damien; Bousquet, Emilie; Bigay-Gamé, L.; Hermant, Christophe; Plat, Gavin; Rouquette, Isabelle; Evrard, Solène; Gouin, Sandrine; Clermont, Estelle; Dormoy, Inge; Coulomb, Christelle; Pradine, Anne; Lambert, Véronique; Laborde, Lilian; Castelnau, Olivier

doi:10.1016/j.jtho.2021.01.1617

Cited by 11 publications

(8 citation statements)

References 31 publications

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“…At diagnosis, the detection of an ALK fusion in plasma is possible, but the sensitivity of detection in comparison with matched tissue samples is variable, often lower than the sensitivity obtained with tissue samples 26,27 . Moreover, different studies demonstrated that the evaluation of the ALK status can be made with circulating tumor cells at baseline, even if this approach seems to be difficult to set up in daily practice 28,29 . ALK translocated lung cancers are a heterogeneous group of tumors and it may become increasingly important to evaluate the genomic background of ALK‐ positive NS‐NSCLC at baseline in order to more clearly predict the behavior of tumors before targeted therapy 30,31 .…”

Section: Alk Ros1 Ntrk and Ret Fusions: The “Big Four” Fusion Targets...mentioning

confidence: 99%

“…26,27 Moreover, different studies demonstrated that the evaluation of the ALK status can be made with circulating tumor cells at baseline, even if this approach seems to be difficult to set up in daily practice. 28,29 ALK translocated lung cancers are a heterogeneous group of tumors and it may become increasingly important to evaluate the genomic background of ALK-positive NS-NSCLC at baseline in order to more clearly predict the behavior of tumors before targeted therapy. 30,31 In addition, tissue or liquid rebiopsies are gaining importance for the profiling of acquired resistance, longitudinal disease monitoring, early detection of tumor progression, and stratification of oligoprogressive disease in ALK+ NSCLC.…”

Section: Alk Rearrangementsmentioning

confidence: 99%

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Fusion‐positive non‐small cell lung carcinoma: Biological principles, clinical practice, and diagnostic implications

Kazdal

Hofman

Christopoulos

et al. 2022

Genes Chromosomes & Cancer

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Based on superior efficacy and tolerability, targeted therapy is currently preferred over chemotherapy and/or immunotherapy for actionable gene fusions that occur in late‐stage non‐small cell lung carcinoma (NSCLC). Consequently, current clinical practice guidelines mandate testing for ALK, ROS1, NTRK, and RET gene fusions in all patients with newly diagnosed advanced non‐squamous NSCLC (NS‐NSCLC). Gene fusions can be detected using different approaches, but today RNA next‐generation sequencing (NGS) or combined DNA/RNA NGS is the method of choice. The discovery of other gene fusions (involving, eg, NRG1, NUT, FGFR1, FGFR2, MET, BRAF, EGFR, SMARC fusions) and their partners has increased progressively in recent years, leading to the development of new and promising therapies and mandating the development and implementation of comprehensive detection methods. The purpose of this review is to focus on recent data concerning the main gene fusions identified in NSCLC, followed by the discussion of major challenges in this domain.

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Section: Alk Ros1 Ntrk and Ret Fusions: The “Big Four” Fusion Targets...mentioning

confidence: 99%

Section: Alk Rearrangementsmentioning

confidence: 99%

Fusion‐positive non‐small cell lung carcinoma: Biological principles, clinical practice, and diagnostic implications

Kazdal

Hofman

Christopoulos

et al. 2022

Genes Chromosomes & Cancer

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“…In most countries, including France, the detection of a genomic alteration in one of these genes leads to treatment with osimertinib (EGFR mutation); alectinib, brigatinib, or lorlatinib (ALK rearrangements); crizotinib (ROS1 rearrangements); the association dabrafenib/trabetinib (BRAFV600 mutation); or larotrectinib or entrectinib (NTRK rearrangements). The tests can be performed with cytological and/or liquid samples but their sensitivity, and even their specificity, are generally more variable than tests with tissue samples [44][45][46][47][48]. The evaluation of PD-L1 can be performed and validated with cytological samples but has not been validated in daily routine with blood samples [41,[49][50][51][52].…”

Section: Biomarkers Assessed At Diagnosis With Cytological Samples And/or Liquid Biopsies Obtained From Advanced Non-squamous Non-small-cmentioning

confidence: 99%

What Is New in Biomarker Testing at Diagnosis of Advanced Non-Squamous Non-Small Cell Lung Carcinoma? Implications for Cytology and Liquid Biopsy

Hofman

2021

JMP

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The discovery and clinical validation of biomarkers predictive of the response of non-squamous non-small-cell lung carcinomas (NS-NSCLC) to therapeutic strategies continue to provide new data. The evaluation of novel treatments is based on molecular analyses aimed at determining their efficacy. These tests are increasing in number, but the tissue specimens are smaller and smaller and/or can have few tumor cells. Indeed, in addition to tissue samples, complementary cytological and/or blood samples can also give access to these biomarkers. To date, it is recommended and necessary to look for the status of five genomic molecular biomarkers (EGFR, ALK, ROS1, BRAFV600, NTRK) and of a protein biomarker (PD-L1). However, the short- and more or less long-term emergence of new targeted treatments of genomic alterations on RET and MET, but also on others’ genomic alteration, notably on KRAS, HER2, NRG1, SMARCA4, and NUT, have made cellular and blood samples essential for molecular testing. The aim of this review is to present the interest in using cytological and/or liquid biopsies as complementary biological material, or as an alternative to tissue specimens, for detection at diagnosis of new predictive biomarkers of NS-NSCLC.

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“…Sixty-six patients with advanced stage lung adenocarcinoma were prospectively included as supplement to the prospective multicentric STALKLUNG trial assessing circulating tumor cells (CTCs) for the use of ALK testing in NSCLC patients (NCT02372448) (4). Formalinfixed, paraffin embedded tissue sections and plasma were collected from each patient.…”

Section: Patient Samplesmentioning

confidence: 99%

Detection of ALK fusion transcripts in plasma of non-small cell lung cancer patients using a novel RT-PCR based assay

et al. 2021

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Background: Detection of genomic rearrangements, like anaplastic lymphoma kinase (ALK) fusions, is a pivotal requirement in non-small cell lung cancer (NSCLC) for the initiation of a targeted treatment. While tissue testing remains the gold standard, detection of these alterations using liquid biopsies is an unmet need.To enable the detection of ALK rearrangements from circulating-free RNA (cfRNA) from NSCLC patients, we have evaluated a novel reverse transcription PCR (RT-PCR) based assay.Methods: Sixty-six patients with advanced stage NSCLC were included in the study. ALK status was determined by immunohistochemistry (IHC) and/or FISH on tissue sections. For the detection of ALK rearrangements from 2ml plasma collected in EDTA or Streck BCT DNA tubes, cfRNA was extracted using a prototype cfRNA sample preparation method and tested by a novel multiplex ALK/RET RT-PCR assay (Roche).Results: Of the forty-two patients with an ALK rearrangement, 30 (71%) were included at baseline. In 10 of the baseline patients, an ALK rearrangement was detected by RT-PCR [baseline sensitivity 33.33% (95% CI: 17.29-52.81%)]. All 24 negative ALK IHC/FISH-negative patients were negative using the RT-PCR based assay (specificity =100%). Conclusions:The prototype Roche ALK/RET RT-PCR assay was able to detect ALK fusion transcripts in the plasma of NSCLC patients at baseline as well as at disease progression with limited sensitivity but high

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Prospective Multicenter Validation of the Detection of ALK Rearrangements of Circulating Tumor Cells for Noninvasive Longitudinal Management of Patients With Advanced NSCLC

Cited by 11 publications

References 31 publications

Fusion‐positive non‐small cell lung carcinoma: Biological principles, clinical practice, and diagnostic implications

Fusion‐positive non‐small cell lung carcinoma: Biological principles, clinical practice, and diagnostic implications

What Is New in Biomarker Testing at Diagnosis of Advanced Non-Squamous Non-Small Cell Lung Carcinoma? Implications for Cytology and Liquid Biopsy

Detection of ALK fusion transcripts in plasma of non-small cell lung cancer patients using a novel RT-PCR based assay

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