Genomic temporal heterogeneity of circulating tumour DNA in unresectable metastatic colorectal cancer under first-line treatment
| Autor: | Qi Zhao, Yi-Chen Yao, Yan-Xing Chen, Ying Jin, Fenghua Wang, Hao-Xiang Wu, Huiyan Luo, Shifu Chen, De Shen Wang, You-Sheng Huang, Mingyan Xu, Yu Hong Li, Feng Wang, Miao Zhen Qiu, Rui-Hua Xu, Ming-Ming He, Zi-Xian Wang |
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| Rok vydání: | 2021 |
| Předmět: |
Proto-Oncogene Proteins B-raf
Oncology medicine.medical_specialty Colorectal cancer Concordance Circulating Tumor DNA chemistry.chemical_compound Temporal heterogeneity Internal medicine Antineoplastic Combined Chemotherapy Protocols Biomarkers Tumor Overall survival Humans Medicine Prospective Studies Liquid biopsy Prospective cohort study Rectal Neoplasms business.industry Gastroenterology Genomics medicine.disease First line treatment chemistry Colonic Neoplasms Mutation Colorectal Neoplasms business DNA |
| Zdroj: | Gut. 71:1340-1349 |
| ISSN: | 1468-3288 0017-5749 |
| Popis: | ObjectiveCirculating tumour DNA (ctDNA) sequencing is increasingly used in the clinical management of patients with colorectal cancer. However, the genomic heterogeneity in ctDNA during treatments and its impact on clinical outcomes remain largely unknown.DesignWe conducted a prospective cohort study (NCT04228614) of 171 patients with unresectable metastatic colorectal cancer (mCRC) who underwent first-line treatment and prospectively collected blood samples with or without tumour samples from patients at baseline and sequentially until disease progression or last follow-up.ResultsThe RAS/BRAF alterations in paired baseline tissue and plasma samples from 63 patients displayed a favourable concordance (81.0%, 51/63). After a period of first-line treatment (median time between baseline and last liquid biopsy, 4.67 months), 42.6% (26/61) of RAS-mutant patients showed RAS clearance and 50.0% (5/10) of BRAF-mutant patients showed BRAF clearance, while 3.6% (3/84) and 0.7% (1/135) of patients showed new RAS or BRAF mutations in ctDNA. Patients with plasma RAS/BRAF clearance showed similar progression-free survival (PFS) and overall survival (OS) with patients who remained RAS/BRAF wild-type, while much better outcomes than those who remained RAS/BRAF mutant. Patients who gained new RAS/BRAF mutations showed similar prognosis as those who maintained RAS/BRAF mutations, and shorter PFS and OS than those who remained RAS/BRAF wild-type.ConclusionThis prospective, serial and large-scale ctDNA profiling study reveals the temporal heterogeneity of mCRC-related somatic variants, which should be given special attention in clinical practice, as evidenced by the finding that the shift in plasma RAS/BRAF mutational status can yield a drastic change in survival outcomes. |
| Databáze: | OpenAIRE |
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