<p>Enumeration And Characterization Of Circulating Tumor Cells And Its Application In Advanced Gastric Cancer</p>

Objective. To explore the application value of circulating tumor cells (CTCs) and circulating free DNA (cfDNA) from peripheral blood in the prognosis of advanced gastric cancer (AGC). Here, we measured CTCs and cfDNA quantity for predicting the outcome of patients. Patients and Methods. Forty-five patients with advanced gastric cancer who underwent neoadjuvant chemotherapy and surgical treatment were enrolled in this study. All patients received neoadjuvant chemotherapy with paclitaxel + S-1 + oxaliplatin (PSOX) regimen, and CTCs and cfDNA of the peripheral blood were detected before and after neoadjuvant therapy. Relationships between the number/type of CTC or cfDNA and the efficacy of neoadjuvant chemotherapy were analyzed. Results. Among 45 patients, 43 (95.6%) were positive, and the positive rate of mesenchymal CTC was increased with the increase in the T stage. The proportion of mesenchymal CTC was positively correlated with the N stage ( P < 0.05 ), and the larger N stage will have the higher proportion of mesenchymal CTC. Patients with a small number of mesenchymal CTC before neoadjuvant chemotherapy were more likely to achieve partial response (PR) with neoadjuvant therapy. Patients with positive CA-199 were more likely to achieve PR with neoadjuvant therapy ( P < 0.05 ). Patients in the PR group were more likely to have decreased/unchanged cfDNA concentration after neoadjuvant therapy ( P = 0.119 ). After neoadjuvant therapy (before surgery), the cfDNA concentration was higher and the efficacy of neoadjuvant therapy (SD or PD) was lower ( P = 0.045 ). Conclusions. Peripheral blood CTC, especially interstitial CTC and cfDNA, has a certain value in predicting the efficacy and prognosis of neoadjuvant chemotherapy in advanced gastric cancer.

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Use of circulating tumor cells to predict response to chemotherapy in patients with advanced gastric cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2011.29.4_suppl.43 ◽

2011 ◽

Vol 29 (4_suppl) ◽

pp. 43-43

Author(s):

S. Matsusaka ◽

K. Chin ◽

N. Mizunuma ◽

M. Ogura ◽

M. Suenaga ◽

...

Keyword(s):

Gastric Cancer ◽

Advanced Gastric Cancer ◽

Tumor Cells ◽

Circulating Tumor Cells ◽

Cox Regression ◽

Performance Status ◽

Univariate Analysis ◽

Eastern Cooperative Oncology Group ◽

Cox Regression Analysis ◽

Response To Chemotherapy

43 Background: 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. The purpose of this study was to identify CTC threshold proposal for determining response to chemotherapy in AGC. Methods: From November 2007 to June 2009, fifty-two patients with AGC were enrolled into a prospective study. All patients were enrolled using institutional review board-approved protocols at the Cancer Institute Hospital and provided informed consent. The study population consisted of patients of aged 18 years or older with histologically proven AGC. Other inclusion criteria were Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 2; adequate organ function. The subjects were five patients treated with S-1 (40 mg/m2, twice daily, days 1-28, repeated every 6 weeks), twenty-six patients treated with S-1 plus CDDP (S-1 40 mg/m2, twice daily, days 1-21, CDDP 60 mg/m2, day 8, repeated every 5 weeks), and twenty-one patients treated with paclitaxel (80 mg/m2, weekly). CTCs of whole blood at baseline, two weeks and four weeks after initiation of chemotherapy, were isolated and enumerated using immunomagnetics. Results: Patients with ≥4 CTCs at two-week points and four-week points had a shorter median PFS (1.4, 1.4 months, respectively), than those with the median PFS of <4 CTCs (4.9, 5.0 months, respectively) (p<0.001, p<0.001, respectively). Patients with ≥4 CTCs at two-week points and four-week points had shorter median OS (3.5, 4.0 months, respectively) than those with the median PFS of <4 CTCs (11.7, 11.4 months, respectively) (p<0.001, p=0.001, respectively). In univariate analysis, PS, treatment regimen, Line of chemotherapy, and CTC levels at 2 weeks and 4 weeks predicted PFS and OS. In order to evaluate the independent predictive effect of chemotherapy, multivariate Cox regression analysis was carried out. CTC levels at 2 weeks and 4 weeks were the strongest predictors. Conclusions: A threshold of lower than 4 CTC/7.5 ml at 2 weeks and 4 weeks was a significant predictor of the outcome for AGC patients treated with S-1 based regimen or paclitaxel regimen. No significant financial relationships to disclose.

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