Abstract 1103
Background
Liquid biopsy system using the detection of circulating tumor DNA (ctDNA) is expected to provide the utility as a novel diagnostic tool for cancers.
Methods
We prospectively enrolled a total of 101 metastatic colorectal cancer(mCRC) patients with liver metastasis. We investigated frequency of detectable mutations in cell-free DNA (cfDNA), concordance rate of RAS mutation between tissue and cfDNA, and relationship between the mutant allele frequencies (MAFs) and clinicopathological factors. We further investigated the relationship between time course of ctDNA and chemoresponse. Amplicon-based deep sequencing with molecular barcode (including hotspots of 14 genes) was performed to detect the ctDNA.
Results
Mutation(s) in plasma cfDNA were detected in 87.1% (88/101) of patients. The frequencies of plasma cfDNA mutation at TP53, KRAS, APC, and PIK3CA were 68.3%, 38.6%, 23.7%, and 14.8%, respectively. RAS mutational concordance rate between tissues and cfDNA was 76.2% (77/101). MAFs were significantly associated with CEA (P < 0.0001), CA19-9 (P = 0.006), LDH (P < 0.0001) levels and the number of metastatic organs (P < 0.0001). Patients with liver or lymph node metastasis had significantly higher MAF compared with those without metastases (P < 0.0001, P = 0.008, respectively). The patients with lower MAF at 8 weeks after initiation of chemotherapy showed significantly longer survival than those with higher MAF (>median vs ≤ median, PFS, P = 0.001, OS, P = 0.049). Increase of MAF had been observed earlier than tumor markers before disease progression were confirmed by computed tomography (P = 0.01).
Conclusions
Our results suggested that this cfDNA assay could detect mutations at a high rate of mCRC patients, and could be a useful tool for early detection of chemoresistance as well as a prognostic marker in the clinic.
Clinical trial identification
Legal entity responsible for the study
The Cancer Institute Hospital of the Japanese Foundation for Cancer Research, Institutional Review Board.
Funding
Has not received any funding.
Editorial Acknowledgement
Cancer Precision Medicine Center, JFCR: Ms.Aya Imai, Dr. Hiroshi Ohnishi, Mr. Yuki Sano Clinical Examination Center, JFCR: Ms. Kazumi Kaihara and Dr. Konosuke Nakayama University of Chicago: Dr. Yusuke Nakamura.
Disclosure
All authors have declared no conflicts of interest.
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