Prospective Multicenter Validation of the Detection of ALK Rearrangements of Circulating Tumor Cells for Noninvasive Longitudinal Management of Patients With Advanced NSCLC
(2021) Journal of Thoracic Oncology — Vol. 16, n° 5, p. 807-816 (2021)
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- Abstract 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.
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Ilié, M., Mazières, J., Chamorey, E., Heeke, S., Benzaquen, J., Thamphya, B., Boutros, J., Tiotiu-Cepuc, I., Fayada, J., Cadranel, J., Poudenx, M., Moro-Sibilot, D., Barlesi, F., Thariat, J., Clément-Duchêne, C., Tomasini, P., Hofman, V., Marquette, C.-H., Hofman, P., et al. (2021). Prospective Multicenter Validation of the Detection of ALK Rearrangements of Circulating Tumor Cells for Noninvasive Longitudinal Management of Patients With Advanced NSCLC. Journal of Thoracic Oncology, 16(5), 807-816. https://doi.org/10.1016/j.jtho.2021.01.1617 (Original work published 2021)