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Association of emergence of new mutations in circulating tumuor DNA during chemotherapy with clinical outcome in metastatic colorectal cancer
- Source :
- BMC Cancer, BMC Cancer, Vol 21, Iss 1, Pp 1-10 (2021)
- Publication Year :
- 2021
- Publisher :
- Springer Science and Business Media LLC, 2021.
-
Abstract
- Background The understanding of molecular changes in mCRC during treatment could be used to personalise therapeutic strategies. The aim of our study was to explore the association of circulating tumour DNA (ctDNA) with clinical outcome in metastatic colorectal cancer (mCRC). Methods Sequential patients with mCRC receiving standard first-line chemotherapy were included prospectively. Both plasma ctDNA and serum CEA were assessed in samples obtained before treatment and after 4 cycles of chemotherapy (C4). Computed tomography (CT) scans were carried out at baseline and post-C4 (8–10 weeks) and were assessed using Response Evaluation Criteria In Solid Tumours version 1.1 (RECIST v1.1). Target-capture deep sequencing with a panel covering 1021 genes was performed to detected somatic mutations in ctDNA. Results A total of 20 patients were prospectively included and treated with either leucovorin, fluorouracil, and oxaliplatin (FOLFOX) (15/20) or leucovorin, fluorouracil, and irinotecan (FOLFIRI) (5/20). Median follow-up was 6.9 months (range 1.6–26.6). Somatic mutations for baseline ctDNA analysis were identified in 85% (17/20) of the patients. Mutation variations of ctDNA after chemotherapy were tested in 16/20 (80.0%) of the patients. In multivariate analyses, a high baseline molecular tumour burden index (mTBI) in ctDNA was associated with a higher risk of disease progression, as well as emergence of new mutations in ctDNA during chemotherapy. Patients with newly detected mutations had shorter progression-free survival (PFS) compared to those without (median 3.0 versus 7.3 months; hazard ratio (HR), 5.97; 95% confidence interval (CI), 0.70–50.69; P = 0.0003). Fold changes in mTBI from baseline to post-C4 were obtained in 80.0% (16/20) of the patients, which were also related to PFS. Patients with fold reduction in mTBI above 0.8-fold had longer PFS compared to those below (median 9.3 versus 4.1 months; HR, 4.51; 95% CI, 1.29–15.70; P = 0.0008). Conclusions Newly detected mutations in ctDNA during treatment might potentially be associated with clinical outcome in mCRC and may provide important clinical information.
- Subjects :
- Male
0301 basic medicine
Oncology
Cancer Research
Colorectal cancer
medicine.medical_treatment
Kaplan-Meier Estimate
Circulating Tumor DNA
0302 clinical medicine
FOLFOX
Antineoplastic Combined Chemotherapy Protocols
RC254-282
Metastatic colorectal cancer
New mutation
Hazard ratio
Neoplasms. Tumors. Oncology. Including cancer and carcinogens
High-Throughput Nucleotide Sequencing
Middle Aged
Prognosis
Fluorouracil
030220 oncology & carcinogenesis
FOLFIRI
Female
Colorectal Neoplasms
Circulating tumour DNA
medicine.drug
Adult
Proto-Oncogene Proteins B-raf
medicine.medical_specialty
Proto-Oncogene Proteins p21(ras)
03 medical and health sciences
Next generation sequencing
Internal medicine
Biomarkers, Tumor
Genetics
medicine
Humans
Aged
Neoplasm Staging
Chemotherapy
business.industry
Research
Biomarker
medicine.disease
Oxaliplatin
Irinotecan
030104 developmental biology
Mutation
Tomography, X-Ray Computed
business
Subjects
Details
- ISSN :
- 14712407
- Volume :
- 21
- Database :
- OpenAIRE
- Journal :
- BMC Cancer
- Accession number :
- edsair.doi.dedup.....1bbf1b6459822ab0a90c3b772868f37e