No abstract

UMIN000001396.

The purpose of this study was to quantify circulating tumor cells (CTCs) in advanced gastric cancer (AGC) patients, and to demonstrate the role of CTCs in cancer therapy. This study investigates the hypothesis that CTCs can predict clinical outcomes in patients with AGC. From November 2007 to June 2009, 52 patients with AGC were enrolled into a prospective study. The chemotherapy regimen was an S-1-based regimen (S-1 with or without cisplatin) or paclitaxel. CTCs of whole blood at baseline, 2 weeks, and 4 weeks after initiation of chemotherapy, were isolated and enumerated using immunomagnetics. Patients with ‡4 CTCs at 2-week points and 4-week points had a shorter median progression-free survival (PFS) (1.4, 1.4 months, respectively) than those with the median PFS of <4 CTCs (4.9, 5.0 months, respectively) (log-rank test; P < 0.001, P < 0.001, respectively). Patients with ‡4 CTCs at 2-week points and 4-week points had shorter median overall survival (OS) (3.5, 4.0 months, respectively) than those with the median PFS of <4 CTCs (11.7, 11.4 months, respectively) (log-rank test; P < 0.001, P = 0.001, respectively). In conclusion, this study demonstrates that CTC measurement may be useful as a surrogate marker for determining response to S-1-based or paclitaxel regimens in AGC. (Cancer Sci 2010; 101: 1067-1071 G astric cancer is more prevalent in Asia, Eastern Europe, and Central and South America than in other areas. In Japan, this cancer is one of the most common causes of cancerrelated mortality, despite dramatic advances in diagnosis and treatment. Outcomes are extremely poor in patients with unresectable gastric cancer, with the median survival ranging from 3 to 5 months with the best supportive care.(1-3) The ability to identify patients with the worst prognoses or those destined to progress quickly could have broad clinical applications.Circulating tumor cells (CTCs) or disseminated tumor cells (DTCs) in bone marrow and peripheral blood from patients with cancers have been documented.(4-6) Braun et al. (7,8) reported that 30% of women with primary breast cancer have DTCs in bone marrow, and a 10-year follow-up of these patients revealed a significantly decreased disease-free survival and overall survival (OS) when compared with patients without DTCs. However, aspiration of bone marrow is time consuming and, in many cases, uncomfortable for the patients precluding multiple samplings for therapy monitoring studies. Therefore, recent efforts have concentrated on the detection of CTCs in the peripheral blood of cancer patients. Cristofanilli et al. (9,10) showed in a prospective study that CTC detection provided significant prognostic information for patients with metastatic breast cancer. Cohen et al. (11) showed that the number of CTCs before and during treatment was an independent predictor of PFS and OS in patients with metastatic colorectal cancer. It is not clear whether CTC detection using this system provides prognostic information for patients with advanced gastric cancer. We initiated this study to eva...

Because circulating tumor DNA (ctDNA) studies focusing on only one or a few genes to monitor the disease progress or treatment response are unlikely to find its clinical significance, the development of cell‐free DNA (cfDNA) panel covering hundreds of mutation hot spots is important for the establishment of clinically practical ctDNA detection system. We enrolled 101 patients with metastatic colorectal cancer (mCRC) who received chemotherapy. Amplicon‐based genomic profiling of 14 genes, which are commonly mutated in CRC, in plasma by next‐generation sequencing (NGS) was carried out to evaluate the feasibility of this assay and was compared with their clinical parameters and RAS status in matched tissue samples. Somatic mutations of the 14 genes in plasma cfDNA were detected in 88 patients (87.1%) with mCRC. Mutations in TP53, KRAS, and APC genes were detected in 70 (69.3%), 39 (38.6%), and 24 (23.7%) patients, respectively. Mutant allele frequencies in plasma were significantly associated with metastasis (liver, P = 0.00004, lymph node, P = 0.008, number of metastatic organs, P = 0.0006), tumor markers (CEA, P = 0.000007, CA19‐9, P = 0.006, LDH, P = 0.00001), and tumor diameter (maximum, P = 0.00002, sum of diameter, P = 0.00009). The overall concordance rate of RAS status between ctDNA and matched tissue was 77.2% (78/101). Our data confirmed that mutant allele in cfDNA can be sensitively detected by amplicon‐based NGS system. These results suggest that ctDNA could be a novel diagnostic biomarker to monitor changes in mutational status and tumor burden in patients with mCRC.