Circulating tumor cells (CTCs) as a surrogate marker for determining response to chemotherapy in advanced gastric cancer (AGC)

4600 Background: The purpose of this study was to quantitate 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 CTC levels can predict clinical outcomes in patients with AGC. Methods: Eligibility criteria: PS (ECOG) of 0 to 2; histopathology of adenocarcinoma; adequate major organ functions. Chemotherapy regimen was S-1 based regimen (S-1 with or without cisplatin) or paclitaxel. Treatment was continued unless disease progression was observed. CTCs of whole blood in baseline, 2 week and 4 week after initiation of chemotherapy were isolated and enumerated using immunomagnetics. Results: From November 2007 to September 2008, thirty patients with unresectable or recurrent gastric cancer were enrolled onto a prospective study. Pts characteristics were as follows: median age: 60 years (range 24–78), PS 0/1/2: 21/8/1, primary tumor ±: 21/9 and regimen S-1/S-1with cisplatin/paclitaxel: 3/15/12. Among 30 pts, best response rates were 36.7% (CR/PR/SD/PD: 0/11/8/11). Patients with ≥4 CTCs at 2 week points and 4 week points had the shorter median progression-free survival (PFS) (1.4, 1.4 months, respectively), than the median PFS of <4 CTCs (6.3, 6.3 months, respectively) (logrank test; p=0.0008, p=8.78E-07, respectively). A finding of <4, CTCs of 2 week and 4 week after initiation of chemotherapy was associated with significantly longer overall survival (OS) as compared with these patients with ≥4 CTCs (p=0.016702, p=0.027788 respectively). Conclusions: These data demonstrate that CTC measurement may be useful as a surrogate marker for determining response to S1 based regimen or paclitaxel regimen in AGC. No significant financial relationships to disclose.

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Circulating tumor cells as a surrogate marker for determining response to chemotherapy in patients with advanced gastric cancer

Cancer Science ◽

10.1111/j.1349-7006.2010.01492.x ◽

2010 ◽

Vol 101 (4) ◽

pp. 1067-1071 ◽

Cited By ~ 64

Author(s):

Satoshi Matsusaka ◽

Keisho Chìn ◽

Mariko Ogura ◽

Mitsukuni Suenaga ◽

Eiji Shinozaki ◽

...

Keyword(s):

Gastric Cancer ◽

Advanced Gastric Cancer ◽

Tumor Cells ◽

Circulating Tumor Cells ◽

Surrogate Marker ◽

Response To Chemotherapy

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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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Circulating tumor cells as a surrogate marker for determining response to chemotherapy in Japanese patients with metastatic colorectal cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.4_suppl.486 ◽

2012 ◽

Vol 30 (4_suppl) ◽

pp. 486-486 ◽

Cited By ~ 2

Author(s):

Satoshi Matsusaka ◽

Mitsukuni Suenaga ◽

Yuji Mishima ◽

Yasuhito Terui ◽

Eiji Shinozaki ◽

...

Keyword(s):

Colorectal Cancer ◽

Metastatic Colorectal Cancer ◽

Tumor Cells ◽

Circulating Tumor Cells ◽

Surrogate Marker ◽

Progression Free Survival ◽

Japanese Patients ◽

Rank Test ◽

Treatment Benefit ◽

Response To Chemotherapy

486 Background: The purpose of this study was to investigate the potential of circulating tumor cells (CTCs) as a surrogate marker of clinical outcome in metastatic colorectal cancer (mCRC) patients in order to identify Japanese patients responsive to oxaliplatin-based chemotherapy. Methods: The treatment regimen was oxaliplatin-based chemotherapy. Collection of CTCs from whole blood was performed at baseline and at 2 and 8-12 weeks after initiation of chemotherapy. Isolation and enumeration of CTCs was performed using immunomagnetics. Results: Between January 2007 and April 2008, 64 patients with mCRC were enrolled in this prospective study.Patients with ≥3 CTCs at baseline and at 2 and 8-12 weeks had a shorter median progression-free survival (8.5, 7.3, and 1.9 months, respectively) than those with <3 CTCs (9.7, 10.4 and 9.1 months, respectively) (log-rank test: p=0.047, p<0.001, and p<0.001, respectively). Patients with ≥3 CTCs at 2 and 8-12 weeks had a shorter median overall survival (10.2 and 4.1 months, respectively) than those with <3 CTCs (29.1 and 29.1 months, respectively) (p<0.001 and p=0.001, respectively). A spurious early rise in CEA level was observed in 11 patients showing a partial response. On the other hand, no rise in early CTC level was observed among responders. Conclusions: The clinical utility of CTC enumeration in improving our ability to accurately assess treatment benefit and in expediting the identification of effective treatment regimens for individual Japanese patients.

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Clinical significance of phenotyping and karyotyping of circulating tumor cells in patients with advanced gastric cancer

Oncotarget ◽

10.18632/oncotarget.2175 ◽

2014 ◽

Vol 5 (16) ◽

pp. 6594-6602 ◽

Cited By ~ 43

Author(s):

Yilin Li ◽

Xiaotian Zhang ◽

Sai Ge ◽

Jing Gao ◽

Jifang Gong ◽

...

Keyword(s):

Gastric Cancer ◽

Advanced Gastric Cancer ◽

Tumor Cells ◽

Circulating Tumor Cells ◽

Clinical Significance

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Detection and HER2 Expression of Circulating Tumor Cells in Advanced Gastric Cancer Patients

Annals of Oncology ◽

10.1016/s0923-7534(20)32326-7 ◽

2012 ◽

Vol 23 ◽

pp. xi118

Author(s):

S. Matsusaka ◽

K. Chin ◽

M. Ogur ◽

E. Shinozaki ◽

M. Suenaga ◽

...

Keyword(s):

Gastric Cancer ◽

Advanced Gastric Cancer ◽

Cancer Patients ◽

Tumor Cells ◽

Circulating Tumor Cells ◽

Her2 Expression ◽

Gastric Cancer Patients

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Circulating tumor cells as a surrogate marker for determining response to chemotherapy in Japanese patients with metastatic colorectal cancer

Cancer Science ◽

10.1111/j.1349-7006.2011.01926.x ◽

2011 ◽

Vol 102 (6) ◽

pp. 1188-1192 ◽

Cited By ~ 46

Author(s):

Satoshi Matsusaka ◽

Mitsukuni Suenaga ◽

Yuji Mishima ◽

Ryoko Kuniyoshi ◽

Koichi Takagi ◽

...

Keyword(s):

Colorectal Cancer ◽

Metastatic Colorectal Cancer ◽

Tumor Cells ◽

Circulating Tumor Cells ◽

Surrogate Marker ◽

Japanese Patients ◽

Response To Chemotherapy

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Application of Circulating Tumor Cells and Circulating Free DNA from Peripheral Blood in the Prognosis of Advanced Gastric Cancer

Journal of Oncology ◽

10.1155/2022/9635218 ◽

2022 ◽

Vol 2022 ◽

pp. 1-9

Author(s):

Pengjie Yu ◽

Shengmao Zhu ◽

Yushuang Luo ◽

Ganggang Li ◽

Yongqiang Pu ◽

...

Keyword(s):

Gastric Cancer ◽

Neoadjuvant Chemotherapy ◽

Neoadjuvant Therapy ◽

Advanced Gastric Cancer ◽

Tumor Cells ◽

Circulating Tumor Cells ◽

Peripheral Blood ◽

Circulating Free Dna ◽

Free Dna ◽

N Stage

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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Initial dose of apatinib in Chinese patients with chemotherapy-refractory advanced or metastatic adenocarcinoma of stomach or gastroesophageal junction in third- or later-line setting: 500 mg or 850 mg?

Journal of Clinical Oncology ◽

10.1200/jco.2018.36.4_suppl.35 ◽

2018 ◽

Vol 36 (4_suppl) ◽

pp. 35-35 ◽

Cited By ~ 3

Author(s):

Wenying Deng ◽

Shukui Qin ◽

Jin Li ◽

Lu Wen ◽

Junsheng Wang ◽

...

Keyword(s):

Gastric Cancer ◽

Clinical Trial ◽

Advanced Gastric Cancer ◽

Initial Dose ◽

Gastroesophageal Junction ◽

Objective Response ◽

Progression Free Survival ◽

Chinese Patients ◽

Best Response ◽

Line Setting

35 Background: A fine balance between maintaining efficacy and reducing toxicity is necessary for drug therapies in many cancers. This study seeks to review the data from phase IV clinical trial of Ahead-G201 to help elucidate the optimal initial dose of apatinib in advanced gastric cancer. Methods: Pts data from the Ahead-G201 study at cut-off date of Jul 10, 2017 were extracted to explore the correlation of apatinib initial dose (500 mg vs 850 mg) with safety and clinical efficacy. Results: 864 of eligible pts received apatinib at an initial dose of 500 mg, and 58 pts received at 850 mg. Dose interruption occurred in 258 pts (33.1%) at 500 mg and in 27 pts (46.5%) at 850 mg. For safety, the most common adverse events (AEs) were proteinuria, hypertension and leukocyte decrease in both groups. Moreover, the incidence of all AEs and grade 3-4 AEs in pts at 500 mg was significantly lower than pts at 850 mg (Table). For efficacy, pts at 500 mg achieved an objective response rate (ORR) of 10.8% and a disease control rate (DCR) of 70.6%, at best response, which were 10.3% and 55.2% in pts at 850 mg. Pts at 500 mg got a significantly longer median progression-free survival (mPFS) and median overall survival (mOS) than pts at 850 mg (PFS, 4.6 mos vs 2.2 mos; OS, 6.8 mos vs 4.0 mos). Multivariate analysis indicated that apatinib treatment at an initial dose of 500 mg was significantly associated with longer mOS in advanced gastric cancer pts (6.8 mos vs 4.0 mos: hazard ratio, 0.5; 95%CI, 0.3 to 0.8), compared to initial dose of 850 mg. Conclusions: Compared to receiving apatinib at initial dose of 850mg, oral administration of apatinib starting from 500 mg seemed to bring more clinical benefit for patients with advanced gastric cancer, whilst with lower toxicities. Clinical trial information: NCT02426034. [Table: see text]

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