TY - JOUR
T1 - Serial ctDNA monitoring to predict response to systemic therapy in metastatic gastrointestinal cancers
AU - Parikh, Aparna R.
AU - Mojtahed, Amikasra
AU - Schneider, Jaime L.
AU - Kanter, Katie
AU - Van Seventer, Emily E.
AU - Fetter, Isobel J.
AU - Thabet, Ashraf
AU - Fish, Madeleine G.
AU - Teshome, Bezaye
AU - Fosbenner, Kathryn
AU - Nadres, Brandon
AU - Shahzade, Heather A.
AU - Allen, Jill N.
AU - Blaszkowsky, Lawrence S.
AU - Ryan, David P.
AU - Giantonio, Bruce
AU - Goyal, Lipika
AU - Nipp, Ryan D.
AU - Roeland, Eric
AU - Weekes, Colin D.
AU - Wo, Jennifer Y.
AU - Zhu, Andrew X.
AU - Dias-Santagata, Dora
AU - Iafrate, A. John
AU - Lennerz, Jochen K.
AU - Hong, Theodore S.
AU - Siravegna, Giulia
AU - Horick, Nora
AU - Clark, Jeffrey W.
AU - Corcoran, Ryan B.
N1 - Publisher Copyright:
© 2020 American Association for Cancer Research.
PY - 2020/4/15
Y1 - 2020/4/15
N2 - Purpose: ctDNA offers a promising, noninvasive approach to monitor therapeutic efficacy in real-time. We explored whether the quantitative percent change in ctDNA early after therapy initiation can predict treatment response and progression-free survival (PFS) in patients with metastatic gastrointestinal cancer. Experimental Design: A total of 138 patients with metastatic gastrointestinal cancers and tumor profiling by next-generation sequencing had serial blood draws pretreatment and at scheduled intervals during therapy. ctDNA was assessed using individualized droplet digital PCR measuring the mutant allele fraction in plasma of mutations identified in tumor biopsies. ctDNA changes were correlated with tumor markers and radiographic response. Results: A total of 138 patients enrolled. A total of 101 patients were evaluable for ctDNA and 68 for tumor markers at 4 weeks. Percent change of ctDNA by 4 weeks predicted partial response PR, P < 0.0001) and clinical benefit [CB: PR and stable disease (SD), P < 0.0001]. ctDNA decreased by 98% (median) and >30% for all PR patients. ctDNA change at 8 weeks, but not 2 weeks, also predicted CB (P < 0.0001). Four-week change in tumor markers also predicted response (P = 0.0026) and CB (P = 0.022). However, at a clinically relevant specificity threshold of 90%, 4-week ctDNAchangemore effectively predicted CB versus tumor markers, with a sensitivity of 60% versus 24%, respectively (P = 0.0109). Patients whose 4-week ctDNA decreased beyond this threshold (≥30% decrease) had a median PFS of 175 days versus 59.5 days (HR, 3.29; 95% CI, 1.55-7.00; P < 0.0001). Conclusions: Serial ctDNA monitoring may provide early indication of response to systemic therapy in patients with metastatic gastrointestinal cancer prior to radiographic assessments and may outperform standard tumormarkers, warranting further evaluation.
AB - Purpose: ctDNA offers a promising, noninvasive approach to monitor therapeutic efficacy in real-time. We explored whether the quantitative percent change in ctDNA early after therapy initiation can predict treatment response and progression-free survival (PFS) in patients with metastatic gastrointestinal cancer. Experimental Design: A total of 138 patients with metastatic gastrointestinal cancers and tumor profiling by next-generation sequencing had serial blood draws pretreatment and at scheduled intervals during therapy. ctDNA was assessed using individualized droplet digital PCR measuring the mutant allele fraction in plasma of mutations identified in tumor biopsies. ctDNA changes were correlated with tumor markers and radiographic response. Results: A total of 138 patients enrolled. A total of 101 patients were evaluable for ctDNA and 68 for tumor markers at 4 weeks. Percent change of ctDNA by 4 weeks predicted partial response PR, P < 0.0001) and clinical benefit [CB: PR and stable disease (SD), P < 0.0001]. ctDNA decreased by 98% (median) and >30% for all PR patients. ctDNA change at 8 weeks, but not 2 weeks, also predicted CB (P < 0.0001). Four-week change in tumor markers also predicted response (P = 0.0026) and CB (P = 0.022). However, at a clinically relevant specificity threshold of 90%, 4-week ctDNAchangemore effectively predicted CB versus tumor markers, with a sensitivity of 60% versus 24%, respectively (P = 0.0109). Patients whose 4-week ctDNA decreased beyond this threshold (≥30% decrease) had a median PFS of 175 days versus 59.5 days (HR, 3.29; 95% CI, 1.55-7.00; P < 0.0001). Conclusions: Serial ctDNA monitoring may provide early indication of response to systemic therapy in patients with metastatic gastrointestinal cancer prior to radiographic assessments and may outperform standard tumormarkers, warranting further evaluation.
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U2 - 10.1158/1078-0432.CCR-19-3467
DO - 10.1158/1078-0432.CCR-19-3467
M3 - Article
C2 - 31941831
AN - SCOPUS:85083492640
SN - 1078-0432
VL - 26
SP - 1877
EP - 1885
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 8
ER -