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Circulating tumor DNA is a sensitive marker for routine monitoring of treatment response in advanced colorectal cancer
- Source :
- Carcinogenesis. 41:1507-1517
- Publication Year :
- 2020
- Publisher :
- Oxford University Press (OUP), 2020.
-
Abstract
- Accurate assessment of chemotherapy response provides the means to terminate ineffective treatment, trial alternative drug regimens or schedules and reduce dose to minimize toxicity. Here, we have compared circulating tumor DNA (ctDNA) with carcinoembryonic antigen (CEA) for the cycle by cycle assessment of chemotherapy response in 30 patients with metastatic colorectal cancer. CtDNA (quantified using individualized digital droplet PCR (ddPCR) assays) and CEA levels were determined immediately prior to each chemotherapy cycle over time periods ranging from 42–548 days (average of 10 time points/patient). Twenty-nine/thirty (97%) patients had detectable ctDNA compared with 83% whose tumors were CEA-positive (>5 ng/ml) during the monitoring course. Over the course of treatment, 20 disease progression events were detected by computed tomography; ctDNA predicted significantly more of these events than CEA (16 (80%) versus 6 (30%), respectively; P-value = 0.004). When progression was detected by both ctDNA and CEA, the rise in ctDNA occurred significantly earlier than CEA (P-value = 0.046). Partial responses to chemotherapy were also detected more frequently by ctDNA, although this was not significant (P-value = 0.07). In addition, another 28 colorectal cancer patients who underwent potentially curative surgery and showed no evidence of residual disease were monitored with ctDNA for up to 2 years. Clinical relapse was observed in 6/28 (21%) patients. Four out of 6 of these patients showed a significant increase in ctDNA at or prior to relapse. Overall, ctDNA analyses were able to be performed in a clinically relevant timeline and were a more sensitive and responsive measure of tumor burden than CEA.
- Subjects :
- 0301 basic medicine
Oncology
Cancer Research
medicine.medical_specialty
Treatment response
Colorectal cancer
medicine.medical_treatment
Tumor burden
Circulating Tumor DNA
03 medical and health sciences
0302 clinical medicine
Carcinoembryonic antigen
Internal medicine
Antineoplastic Combined Chemotherapy Protocols
Biomarkers, Tumor
medicine
Humans
Prospective Studies
Prospective cohort study
Chemotherapy
biology
business.industry
DNA, Neoplasm
General Medicine
Prognosis
medicine.disease
Tumor Burden
030104 developmental biology
Circulating tumor DNA
030220 oncology & carcinogenesis
Toxicity
biology.protein
Colorectal Neoplasms
business
Follow-Up Studies
Subjects
Details
- ISSN :
- 14602180 and 01433334
- Volume :
- 41
- Database :
- OpenAIRE
- Journal :
- Carcinogenesis
- Accession number :
- edsair.doi.dedup.....d5d2a279beabf7db5263bcdf36450365