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...

Background. No standard chemotherapy regimen has been established for unresectable or recurrent small bowel adenocarcinoma (SBA).Methods. Clinical courses of 132 patients with unresectable or recurrent SBA who received chemotherapy at 41 institutions in Japan were reviewed retrospectively. Patients were classified into five groups according to first-line chemotherapy regimens: fluoropyrimidine monotherapy (group A), fluoropyrimidine-cisplatin (group B), fluoropyrimidine-oxaliplatin (group C), fluoropyrimidine-irinotecan (group D), and other regimens (group E).Results. The number of patients in each group was as follows: groups A, 60 patients; group B, 17 patients; group C, 22 patients; group D, 11 patients; and group E, 22 patients. Median progression-free survival (PFS) times were as fol-

Background There is growing interest in the clinical significance of intratumoral HER2 heterogeneity. Its prognostic and predictive impacts on trastuzumab efficacy were demonstrated in breast cancer. However, its clinical significance in gastric cancer is still unclear.MethodsTwenty-eight HER2-positive gastric cancer patients who had gastrectomy prior to trastuzumab-based chemotherapy were consecutively enrolled. Intratumoral HER heterogeneity was evaluated using whole-tissue sections by immunohistochemistry. When all tumor cells overexpressed HER2 protein, the tumor was defined as homogeneously HER2 (Homo-HER2)-positive group. The others were defined as heterogeneously HER2 (Hetero-HER2)-positive group.ResultsThere was no significant difference in clinicopathological features between the two groups. The median progression-free survival (PFS) and overall survival (OS) in the Homo-HER2-positive group were significantly longer than those in the Hetero-HER2-positive group (PFS; 20.0 months [95% CI 17.8–22.2] vs. 6.0 months [95% CI 2.3–9.7]; HR 0.11; 95% CI 0.03–0.41; p < 0.001, OS; not reached vs. 14.0 months [95% CI 11.9–16.1]; HR 0.18; 95% CI 0.06–0.61; p = 0.003). In the multivariate analysis, these associations remained significant both in PFS (HR 0.12; 95% CI 0.03–0.46, p = 0.002) and OS (HR 0.21; 95% CI 0.06–0.72, p = 0.013). With respect to response rate, no statistical difference was found between two groups. However, deeper tumor shrinkage was obtained in the Homo-HER2-positive group compared with the Hetero-HER2-positive group (p = 0.046).ConclusionsIntratumoral HER2 heterogeneity may have robust clinical impact on trastuzumab efficacy in patients with HER2-positive gastric cancer. These findings should be validated by larger independent cohorts and further molecular correlative analyses are warranted.Electronic supplementary materialThe online version of this article (10.1007/s00535-018-1464-0) contains supplementary material, which is available to authorized users.

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