Session Item

The optimal selection of patients who are suited for oligometastasis-directed ablative therapy remains a challenge. In recent years, liquid biopsy approaches analyzing cell-free DNA (cfDNA) from the blood samples of patients with cancer are increasingly utilized in clinical practice to predict metastatic potential of disease or prognosis. The purpose of this study was to determine the profile of cfDNA using next-generation sequencing of plasma cfDNA in patients with oligometastatic colorectal cancer (CRC) and investigate its association with progression-free survival (PFS) after ablative therapy. 

We analyzed oligometastatic CRC patients who underwent definitive irradiation using stereotactic body radiotherapy or proton beam therapy for metastatic lesion at National Cancer Center Hospital East in Japan between December 2011 and December 2017. In this study, cfDNA was purified from 4ml patient plasma and fragmented DNA was ligated with adapters to make libraries. Library construction and sequencing were performed using the Illumina Novaseq 6000 sequencing platform (Illumina, San Diego, CA) with SureSelect NCC oncopanel v.2 which can investigate 114 genes exon. We aligned FASTQs to the human genome (hg19), and identified point mutations using Sure call 4.1.1.5. Clinical data was extracted from medical records. PFS was statistically compared according to sequence data.

A total of 20 patients with oligometastatic CRC (median age 72 [range, 54-85] years; 12 [60%] male) were included in this study. The median amount of cfDNA was 42.1 (range, 25.3-100.8) ng. The mutation of cfDNA were detected as follows; TP53 (9/20: 45%), APC (8/20: 40%), KRAS (3/20: 15%), PIK3CA (3/20: 15%), NF1 (1/20: 5%), BRCA1 (1/20: 5%), ERBB2 (1/20: 5%), FBXW7 (1/20: 5%), and KIT (2/20: 10%), respectively. Allele frequency was 0.6-7.8% (median 1.5%). Clonal mutations were confirmed in 11 cases and multiclonal mutations in 5 cases. The median follow-up period was 18 months for surviving patients (range, 3-71 months). The median PFS duration was 10 months (95%CI: 5- NA). The amount of cfDNA, number of mutations, and types of mutated genes were not associated with PFS. Multi clonality of the gene mutation showed tendency of poor PFS (14 vs 4 months, HR 3.1 [95%CI: 0.8-11.3], p=0.07).

This is the first study regarding genomic profiling of cfDNA from patients with oligometastatic colorectal cancer. Pre-irradiation cfDNA analysis would be predictive tool for early recurrence of oligometastatic CRC, although further accumulation of data are needed.