Prospective Multicenter Validation of the Detection of ALK Rearrangements of Circulating Tumor Cells for Noninvasive Longitudinal Management of Patients With Advanced NSCLC
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Ilié, Marius | Mazières, Julien | Chamorey, Emmanuel | Heeke, Simon | Benzaquen, Jonathan | Thamphya, Brice | Boutros, Jacques | Tiotiu, Angélica | Fayada, Julien | Cadranel, Jacques | Poudenx, Michel | Moro-Sibilot, Denis | Barlesi, Fabrice | Thariat, Juliette | Clément-Duchêne, Christelle | Tomasini, Pascale | Hofman, Véronique | Marquette, Charles-Hugo | Hofman, Paul | Israel-Biet, Dominique | Pison, Christophe | Lantuejoul, Sylvie | Stephanov, Olivier | Juliette, Meyzenc | Mendozat, Christophe | Zaidi, Manel | Coulouvrat, Sandra | Col, Edwige | Chanez, Pascal | Greillier, Laurent | Mascaux, Céline | Jourdan, Sandrine | Roger, Aurélie | Biemar, Julie | Randriamampionona, Rondro | Chabot, François | Vignaud, Jean-Michel | Lacomme, Stéphanie | Lomazzi, Sandra | Laurent, Carine | Bulsei, Xavier | Bischoff, Laura | Rakotonirina, Raymond | Layouni, Mehdi | Deslee, Gaëtan | Mal, Hervé | Kessler, Romain | Vergnon, Jean-Michel | Pelissier, Isabelle | Cuvelier, Antoine | Bourdin, Arnaud | Jounieaux, Vincent | Roche, Nicolas | Jouneau, Stéphane | Bonniaud, Philippe | Scherpereel, Arnaud | Mornex, Jean François | Steenhouwer, François | Leroy, Sylvie | Marquette, Charles Hugo | Mazzette, Andrea | Padovani, Bernard | 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, Ariane | Butori, Catherine | Selva, Eric | Otto, Josiane | Hebert, Christophe | Botchiellini, Delphine | Boudouf, Soukaina | Menier, Margaux | Occeli, Estelle | Bellentani, Sophie | Pion, Carine | Fournier, Elodie | Gervais, Radj | Hamond, Karim | Marchand-Adam, Sylvain | Plantier, Laurent | Fajolle, Gaelle | Rayez, Mélanie | Fallet, Vincent | Wislez, Marie | Antoine, Martine | Cote, Jean-François | Chaabane, Nouha | Ruppert, Anne Marie | Bertrand, Eliane | Rodenas, Anita | Pontdeme, Gwenaëlle | Mathiot, Nathalie | Ribert, Tamazouzt | Guibert, Nicolas | Rouviere, Damien | Bousquet, Emilie | Bigay-Game, Laurence | Hermant, Christophe | Plat, Gavin | Rouquette, Isabelle | Evrard, Solène | Gouin, Sandrine | Clermont, Estelle Taranchon | Dormoy, Inge | Coulomb, Christelle | Pradine, Anne | Lambert, Véronique | Laborde, Lilian | Castelnau, Olivier
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CCSD ; Lippincott, Williams & Wilkins -
International audience.
Introduction: Patients with advanced-stage NSCLC whose tumors harbor an ALK gene rearrangement benefit from treatment with multiple ALK inhibitors (ALKi). Approximately 30% of tumor biopsy samples contain insufficient tissue for successful ALK molecular characterization. This study evaluated the added value of analyzing circulating tumor cells (CTCs) as a surrogate to ALK tissue analysis and as a function of the response to ALKi.Methods: We conducted a multicenter, prospective observational study (NCT02372448) of 203 patients with stage IIIB/IV NSCLC across nine French centers, of whom 81 were ALK positive (immunohistochemistry or fluorescence in situ hybridization [FISH]) and 122 ALK negative on paraffin-embedded tissue specimens. Blood samples were collected at baseline and at 6 and 12 weeks after ALKi initiation or at disease progression. ALK gene rearrangement was evaluated with CTCs using immunocytochemistry and FISH analysis after enrichment using a filtration method.Results: At baseline, there was a high concordance between the detection of an ALK rearrangement in the tumor tissue and in CTCs as determined by immunocytochemistry (sensitivity, 94.4%; specificity 89.4%). The performance was lower for the FISH analysis (sensitivity, 35.6%; specificity, 56.9%). No significant association between the baseline levels or the dynamic change of CTCs and overall survival (hazard ratio = 0.59, 95% confidence interval: 0.24-1.5, p = 0.244) or progression-free survival (hazard ratio = 0.84, 95% confidence interval: 0.44-1.6, p = 0.591) was observed in the patients with ALK-positive NSCLC.Conclusions: CTCs can be used as a complementary tool to a tissue biopsy for the detection of ALK rearrangements. Longitudinal analyses of CTCs revealed promise for real-time patient monitoring and improved delivery of molecularly guided therapy in this population.
