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

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avisTidsskriftartikelForskningpeer review

  • Tenna Vesterman Henriksen
  • Noelia Tarazona, University of Valencia
  • ,
  • Amanda Frydendahl
  • Thomas Reinert
  • Francisco Gimeno-Valiente, Biomedical Research Institute INCLIVA. University of Valencia
  • ,
  • Juan Antonio Carbonell-Asins, INCLIVA Biomedical Research Institute
  • ,
  • Shruti Sharma
  • ,
  • Derrick Renner, Natera Inc, San Carlos, California.
  • ,
  • Dina Hafez, Natera Inc, San Carlos, California.
  • ,
  • Desamparados Roda, University of Valencia
  • ,
  • Marisol Huerta, University of Valencia
  • ,
  • Susana Roselló, University of Valencia
  • ,
  • Anders Husted Madsen
  • Uffe S Løve
  • Per Vadgaard Andersen, Syddansk Universitet
  • ,
  • Ole Thorlacius-Ussing, Aalborg Universitet
  • ,
  • Lene Hjerrild Iversen
  • Kåre Andersson Gotschalck
  • Himanshu Sethi, Natera, Inc
  • ,
  • Alexey Aleshin, Natera Inc, San Carlos, California.
  • ,
  • Andres Cervantes, University of Valencia
  • ,
  • Claus Lindbjerg Andersen

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 stage III colorectal cancer patients treated with curative intent at Danish and Spanish hospitals between 2014-2019. To quantify ctDNA in plasma samples (n=1204), 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%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 (27% ctDNA-increase/month) and fast (137% 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 three months detected recurrence with a median lead-time of 9.8 months compared to 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.

Bidragets oversatte titelCirkulerende tumor DNA i stadie III colorectal cancer, videre end opsporing af minimal residual sygdom, mod evaluering af terapeutisk effekt af adjuverende behandling og klinisk præsentation af tilbagefald: Seriel postoperativ ctDNA monitorering af tilbagefald af tarmkræft
OriginalsprogEngelsk
TidsskriftClinical Cancer Research
Vol/bind28
Nummer3
Sider (fra-til)507-517
Antal sider11
ISSN1078-0432
DOI
StatusUdgivet - feb. 2022

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