Liquid Biopsies for Circulating Tumor DNA Detection May Reveal Occult Hematologic Malignancies in Patients With Solid Tumors.
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Aldea Mihaela, Tagliamento Marco, Bayle Arnaud, Vasseur Damien, Vergé Véronique, Marinello Arianna, Danlos François-Xavier, Blanc-Durand Felix, Bernard Elsa, Cerbone Luigi, Mosele Maria Fernanda, Renneville Aline, Hadoux Julien, Loriot Yohann, Sakkal Madona, Vozy Aurore, Sarkozy Clementine, Smolenschi Cristina, Nicotra Claudio, Martin-Romano Patricia, Boccon-Gibod Clementine, Habza Wafikaamira, Lazarovici Julien, Ponce Santiago, Hollebecque Antoine, Marzac Christophe, Lacroix Ludovic, Barlesi Fabrice, André Fabrice, Besse Benjamin, Rouleau Etienne, Italiano Antoine, Micol Jean-Baptiste
Аннотация
MATERIALS AND METHODS: Adult patients with advanced solid cancers enrolled in the Gustave Roussy Cancer Profiling study (ClinicalTrials.gov identifier: NCT04932525) underwent at least one liquid biopsy (FoundationOne Liquid CDx). Molecular reports were discussed within the Gustave Roussy Molecular Tumor Board (MTB). Potential CH alterations were observed, and patients referred to hematology consultation in the case of pathogenic mutations in JAK2, MPL, or MYD88, irrespective of the variant allele frequency (VAF), or in DNMT3A, TET2, ASXL1, IDH1, IDH2, SF3B1, or U2AF1 with VAF ≥ 10%, while also considering patient cancer-related prognosis. TP53 mutations were discussed case-by-case.
RESULTS: Between March and October 2021, 1,416 patients were included. One hundred ten patients (7.7%) carried at least one high-risk CH mutation: DNMT3A (n = 32), JAK2 (n = 28), TET2 (n = 19), ASXL1 (n = 18), SF3B1 (n = 5), IDH1 (n = 4), IDH2 (n = 3), MPL (n = 3), and U2AF1 (n = 2). The MTB advised for hematologic consultation in 45 patients. Overall, 9 patients of 18 actually addressed had confirmed hematologic malignancies that were occult in six patients: two patients had myelodysplastic syndrome, two essential thrombocythemia, one a marginal lymphoma, and one a Waldenström macroglobulinemia. The other three patients were already followed up in hematology.
CONCLUSION: The incidental findings of high-risk CH through liquid biopsy may trigger diagnostic hematologic tests and reveal an occult hematologic malignancy. Patients should have a multidisciplinary case-by-case evaluation.