Circulating Tumor DNA in Stage III Colorectal Cancer, beyond Minimal Residual Disease Detection, toward Assessment of Adjuvant Therapy Efficacy and Clinical Behavior of Recurrences.

Fecha de publicación: 01/02/2022 Fecha Ahead of Print: 08/10/2021

Autores de INCLIVA

• Noelia Tarazona Llavero

  Autor

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  Francisco Gimeno Valiente

  Autor

• Juan Antonio Carbonell Asins

  Autor

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  Desamparados Roda Perez

  Autor

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  María Del Sol Huerta Álvaro

  Autor

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  Susana Roselló Keränen

  Autor

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  Andrés Cervantes Ruiperez

  Autor

Participantes ajenos a INCLIVA

• Henriksen, Tenna Vesterman
• Frydendahl, Amanda
• Reinert, Thomas
• Sharma, Shruti
• Renner, Derrick
• Hafez, Dina
• Madsen, Anders Husted
• Love, Uffe S
• Andersen, Per Vadgaard
• Thorlacius-Ussing, Ole
• Iversen, Lene Hjerrild
• Gotschalck, Kare Andersson
• Sethi, Himanshu
• Aleshin, Alexey
• Andersen, Claus Lindbjerg

Grupos y Plataformas de I+D+i

• Grupo de Investigación en Cáncer Colorrectal y Nuevos Desarrollos Terapéuticos en Tumores Sólidos

  

  Leading Researcher

  Andrés Cervantes Ruiperez

• Unidad de Bioinformática

• Unidad de Medicina de Precisión

Abstract

PURPOSE: Sensitive methods for risk stratification, monitoring therapeutic efficacy, and early relapse detection may have a major impact on treatment decisions and patient management for stage III colorectal cancer patients. Beyond assessing the predictive power of postoperative ctDNA detection, we explored the added benefits of serial analysis: assessing adjuvant chemotherapy (ACT) efficacy, early relapse detection, and ctDNA growth rates. EXPERIMENTAL DESIGN: We recruited 168 patients with stage III colorectal cancer treated with curative intent at Danish and Spanish hospitals between 2014 and 2019. To quantify ctDNA in plasma samples (n = 1,204), 16 patient-specific somatic single-nucleotide variants were profiled using multiplex-PCR, next-generation sequencing. RESULTS: Detection of ctDNA was a strong recurrence predictor postoperatively [HR = 7.0; 95% confidence interval (CI), 3.7-13.5; P < 0.001] and directly after ACT (HR = 50.76; 95% CI, 15.4-167; P < 0.001). The recurrence rate of postoperative ctDNA-positive patients treated with ACT was 80% (16/20). Only patients who cleared ctDNA permanently during ACT did not relapse. Serial ctDNA assessment after the end of treatment was similarly predictive of recurrence (HR = 50.80; 95% CI, 14.9-172; P < 0.001), and revealed two distinct rates of exponential ctDNA growth, slow (25% ctDNA-increase/month) and fast (143% ctDNA-increase/month; P < 0.001). The ctDNA growth rate was prognostic of survival (HR = 2.7; 95% CI, 1.1-6.7; P = 0.039). Serial ctDNA analysis every 3 months detected recurrence with a median lead-time of 9.8 months compared with standard-of-care computed tomography. CONCLUSIONS: Serial postoperative ctDNA analysis has a strong prognostic value and enables tumor growth rate assessment. The novel combination of ctDNA detection and growth rate assessment provides unique opportunities for guiding decision-making.See related commentary by Morris and George, p. 438.

©2021 The Authors; Published by the American Association for Cancer Research.