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

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Circulating Tumor DNA in Stage III Colorectal Cancer, beyond Minimal Residual Disease Detection, toward Assessment of Adjuvant Therapy Efficacy and Clinical Behavior of Recurrences. / Henriksen, Tenna Vesterman; Tarazona, Noelia; Frydendahl, Amanda et al.

I: Clinical Cancer Research, Bind 28, Nr. 3, 02.2022, s. 507-517.

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

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Henriksen, TV, Tarazona, N, Frydendahl, A, Reinert, T, Gimeno-Valiente, F, Carbonell-Asins, JA, Sharma, S, Renner, D, Hafez, D, Roda, D, Huerta, M, Roselló, S, Madsen, AH, Løve, US, Andersen, PV, Thorlacius-Ussing, O, Iversen, LH, Gotschalck, KA, Sethi, H, Aleshin, A, Cervantes, A & Andersen, CL 2022, 'Circulating Tumor DNA in Stage III Colorectal Cancer, beyond Minimal Residual Disease Detection, toward Assessment of Adjuvant Therapy Efficacy and Clinical Behavior of Recurrences', Clinical Cancer Research, bind 28, nr. 3, s. 507-517. https://doi.org/10.1158/1078-0432.CCR-21-2404

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Henriksen TV, Tarazona N, Frydendahl A, Reinert T, Gimeno-Valiente F, Carbonell-Asins JA et al. Circulating Tumor DNA in Stage III Colorectal Cancer, beyond Minimal Residual Disease Detection, toward Assessment of Adjuvant Therapy Efficacy and Clinical Behavior of Recurrences. Clinical Cancer Research. 2022 feb.;28(3):507-517. Epub 2021 okt. 8. doi: 10.1158/1078-0432.CCR-21-2404

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@article{7a3412fcc1144f93839d8aaf0d0f61c7,
title = "Circulating Tumor DNA in Stage III Colorectal Cancer, beyond Minimal Residual Disease Detection, toward Assessment of Adjuvant Therapy Efficacy and Clinical Behavior of Recurrences",
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 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.",
keywords = "CHEMOTHERAPY, COLON-CANCER, FLUOROURACIL, SURGERY",
author = "Henriksen, {Tenna Vesterman} and Noelia Tarazona and Amanda Frydendahl and Thomas Reinert and Francisco Gimeno-Valiente and Carbonell-Asins, {Juan Antonio} and Shruti Sharma and Derrick Renner and Dina Hafez and Desamparados Roda and Marisol Huerta and Susana Rosell{\'o} and Madsen, {Anders Husted} and L{\o}ve, {Uffe S} and Andersen, {Per Vadgaard} and Ole Thorlacius-Ussing and Iversen, {Lene Hjerrild} and Gotschalck, {K{\aa}re Andersson} and Himanshu Sethi and Alexey Aleshin and Andres Cervantes and Andersen, {Claus Lindbjerg}",
year = "2022",
month = feb,
doi = "10.1158/1078-0432.CCR-21-2404",
language = "English",
volume = "28",
pages = "507--517",
journal = "Clinical Cancer Research",
issn = "1078-0432",
publisher = "AMER ASSOC CANCER RESEARCH",
number = "3",

}

RIS

TY - JOUR

T1 - Circulating Tumor DNA in Stage III Colorectal Cancer, beyond Minimal Residual Disease Detection, toward Assessment of Adjuvant Therapy Efficacy and Clinical Behavior of Recurrences

AU - Henriksen, Tenna Vesterman

AU - Tarazona, Noelia

AU - Frydendahl, Amanda

AU - Reinert, Thomas

AU - Gimeno-Valiente, Francisco

AU - Carbonell-Asins, Juan Antonio

AU - Sharma, Shruti

AU - Renner, Derrick

AU - Hafez, Dina

AU - Roda, Desamparados

AU - Huerta, Marisol

AU - Roselló, Susana

AU - Madsen, Anders Husted

AU - Løve, Uffe S

AU - Andersen, Per Vadgaard

AU - Thorlacius-Ussing, Ole

AU - Iversen, Lene Hjerrild

AU - Gotschalck, Kåre Andersson

AU - Sethi, Himanshu

AU - Aleshin, Alexey

AU - Cervantes, Andres

AU - Andersen, Claus Lindbjerg

PY - 2022/2

Y1 - 2022/2

N2 - 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.

AB - 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.

KW - CHEMOTHERAPY

KW - COLON-CANCER

KW - FLUOROURACIL

KW - SURGERY

UR - http://www.scopus.com/inward/record.url?scp=85123834862&partnerID=8YFLogxK

U2 - 10.1158/1078-0432.CCR-21-2404

DO - 10.1158/1078-0432.CCR-21-2404

M3 - Journal article

C2 - 34625408

VL - 28

SP - 507

EP - 517

JO - Clinical Cancer Research

JF - Clinical Cancer Research

SN - 1078-0432

IS - 3

ER -