Clinical Impact of Presurgery Circulating Tumor DNA after Total Neoadjuvant Treatment in Locally Advanced Rectal Cancer: A Biomarker Study from the GEMCAD1402 Trial
Por:
Vidal, J, Casadevall, D, Bellosillo, B, Pericay, C, Garcia-Carbonero, R, Losa, F, Layos, L, Alonso, V, Capdevila, J, Gallego, J, Vera, R, Salud, A, Martin-Richard, M, Nogue, M, Cillan, E, Maurel, J, Faull, I, Raymond, V, Fernandez-Martos, C and Montagut, C
Publicada:
15 may 2021
Ahead of Print:
16 mar 2021
Resumen:
Purpose: Total neoadjuvant treatment (TNT) is a valid strategy for patients with high-risk locally advanced rectal cancer (LARC). Biomarkers of response to TNT are an unmet clinical need. We aimed to determine the value of circulating tumor DNA(ctDNA) to predict tumor response, recurrence, and survival in patients with LARC treated with TNT.
Experimental Design: The GEMCAD 1402 was a phase II randomized, multicentric clinical trial that randomized 180 patients with LARC to modified schedule of fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) +/- aflibercept, followed by chemoradiation and surgery. Plasma samples were collected at baseline and after TNT within 48 hours before surgery (presurgery). An ultra-sensitive assay that integrates genomic and epigenomic cancer signatures was used to assess ctDNA status. ctDNA results were correlated with variables of local tumor response in the surgery sample, local/systemic recurrence, and survival.
Results: A total of 144 paired plasma samples from 72 patients were included. ctDNA was detectable in 83% of patients at baseline and in 15% following TNT (presurgery). No association was found between ctDNA status and pathologic response. Detectable presurgery ctDNA was significantly associated with systemic recurrence, shorter disease-free survival (HR, 4; P = 0.033), and shorter overall survival (HR, 23; P < 0.0001).
Conclusions: In patients with LARC treated with TNT, presurgery ctDNA detected minimal metastatic disease identifying patients at high risk of distant recurrence and death. This study sets the basis for prospective clinical trials that use liquid biopsy to personalize the therapeutic approach following TNT.
Filiaciones:
Vidal, J:
Hosp Mar IMIM, Dept Med Oncol, CIBERONC, Barcelona, Spain
Casadevall, D:
Hosp Mar IMIM, Dept Med Oncol, CIBERONC, Barcelona, Spain
Bellosillo, B:
Hosp Mar, Dept Pathol, Barcelona, Spain
Pericay, C:
Complex Sanitari Parc Tauli, Dept Med Oncol, Sabadell, Spain
Garcia-Carbonero, R:
Hosp Univ Doce Octubre, Dept Med Oncol, Imas12, UCM,CNIO,CIBERONC, Madrid, Spain
Losa, F:
Hosp St Joan Despi Moises Broggi, Dept Med Oncol, St Joan Despi, Spain
Layos, L:
Hosp Badalona Germans Trias & Pujol, Inst Catala Oncol, Dept Med Oncol, Badalona, Spain
Alonso, V:
Hosp Univ Miguel Servet, Dept Med Oncol, CIBERONC, IISA, Zaragoza, Spain
Capdevila, J:
Hosp Univ Vall dHebron, Dept Med Oncol, Barcelona, Spain
:
Hosp Gen Univ Elche, Dept Med Oncol, Elche, Spain
Vera, R:
Complejo Hosp Navarra, Inst Invest Sanitarias Navarra IdISNA, Dept Med Oncol, Navarra, Spain
Salud, A:
Hosp Arnau de Vilanova Lleida, Dept Med Oncol, Lleida, Spain
Martin-Richard, M:
Hosp Santa Creu & Sant Pau, Dept Med Oncol, Barcelona, Spain
Nogue, M:
Hosp Granollers, Dept Med Oncol, Granollers, Spain
Cillan, E:
Hosp St Joan de Deu Fundacio Althaia, Dept Med Oncol, Manresa, Spain
Maurel, J:
Hosp Clin Barcelona, Dept Med Oncol, Barcelona, Spain
Faull, I:
Guardant Hlth, Redwood City, CA USA
Raymond, V:
Guardant Hlth, Redwood City, CA USA
Fernandez-Martos, C:
Hosp Quiron Salud, Dept Med Oncol, Av Blasco Ibanez 14, Valencia 46010, Spain
Montagut, C:
Hosp Mar IMIM, Dept Med Oncol, CIBERONC, Barcelona, Spain
Green Submitted, Bronze
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