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

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 43-43
Author(s):  
S. Matsusaka ◽  
K. Chin ◽  
N. Mizunuma ◽  
M. Ogura ◽  
M. Suenaga ◽  
...  

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.

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 427-427
Author(s):  
S. Matsusaka ◽  
N. Mizunuma ◽  
M. Suenaga ◽  
K. Chin ◽  
E. Shinozaki ◽  
...  

427 Background: The purpose of this study was to identify CEC threshold proposal for determining response to FOLFOX4 plus bevacizumab in metastatic colorectal cancer (mCRC). Methods: All patients were enrolled using institutional review board-approved protocols at the Cancer Institute Hospital and provided informed consent. From July 2007 to June 2008, 33 patients treated with FOLFOX4 plus bevacizumab were enrolled in a prospective study. From January 2007 to June 2007, before bevacizumab was approved by the government in Japan, 31 patients treated with FOLFOX4 as a control were enrolled. The study population consisted of patients aged 18 years or older with histologically proven mCRC. Other inclusion criteria were Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, adequate organ function. CECs of whole blood at the baseline, day 4, 2 weeks after initiation of chemotherapy were isolated and counted using immunomagnetics. Results: There was no correlation between CEC levels and the outcome in the FOLFOX4. In the FOLFOX4 plus bevacizumab, CEC levels at the baseline were significantly associated with the outcome. Patients with 65 or more CECs at the baseline had shorter median PFS (9.2 months), than the median PFS of fewer than 65 CECs at the baseline (18.9 months) in the FOLFOX4 plus bevacizumab (p = 0.003). Patients with 65 or more CECs at the baseline had shorter median OS (23.3 months), than the median OS of fewer than 65 CEC s at the baseline in the FOLFOX4 plus bevacizumab (p = 0.027). In the univariate analysis, lung metastasis, lymph node metastasis, and CEC levels at the baseline predicted PFS. In the univariate Cox regression analyses, peritoneal metastasis, CEC levels at the baseline were associated with OS. In order to evaluate the independent predictive effect of FOLFOX4 plus bevacizumab, multivariate Cox regression analysis was carried out. CEC levels at the baseline were the strongest predictor. Conclusions: A threshold of lower than 65 CEC/4mL at the baseline was a significant predictor of the outcome for colorectal cancer patients treated with FOLFOX4 plus bevacizumab. No significant financial relationships to disclose.


2010 ◽  
Vol 101 (4) ◽  
pp. 1067-1071 ◽  
Author(s):  
Satoshi Matsusaka ◽  
Keisho Chìn ◽  
Mariko Ogura ◽  
Mitsukuni Suenaga ◽  
Eiji Shinozaki ◽  
...  

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 4600-4600
Author(s):  
S. Matsusaka ◽  
K. Chin ◽  
N. Mizunuma ◽  
M. Ogura ◽  
M. Suenaga ◽  
...  

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.


2021 ◽  
Vol 11 ◽  
Author(s):  
Chengcheng Qian ◽  
Renjie Cai ◽  
Wenying Zhang ◽  
Jiongyi Wang ◽  
Xiaohua Hu ◽  
...  

PurposeThe purpose of this study is to explore the prognostic value of associating pre-treatment neutrophil–lymphocyte ratio (NLR) with circulating tumor cells counts (CTCs) in patients with gastrointestinal cancer.Materials and MethodsWe collected the related data of 72 patients with gastric cancer (GC) and colorectal cancer (CRC) who received different therapies from August 2016 to October 2020, including age, gender, primary tumor location, TNM stage, tumor-differentiation, NLR, CTCs, disease-free survival (DFS) and overall survival (OS). We chose the optimal cut-off value of NLR &gt;3.21 or NLR ≤3.21 and CTC &gt;1 or CTC ≤1 by obtaining receiver operating characteristic (ROC) curve. The Kaplan–Meier survival analysis and Cox regression analysis were used to analyze DFS and OS. To clarify the role of the combination of NLR and CTCs counts in predicting the prognosis, we analyzed the DFS and OS when associated NLR and CTCs counts.ResultsA high NLR (&gt;3.21) was associated with shorter DFS (P &lt;0.0001) and OS (P &lt;0.0001). Patients with high CTCs level (&gt;1) had shorter DFS (P = 0.001) and OS (P = 0.0007) than patients with low CTCs level. Furthermore, patients who had both higher NLR and higher CTCs counts had obvious shorter DFS (P &lt;0.0001) and OS (P &lt;0.0001).ConclusionsPatients with higher NLR and more CTCs respectively tended to have poor prognosis with shorter DFS and OS, which might be regarded as predictors of gastrointestinal cancer. In particular, associating NLR and CTCs counts might be a reliable predictor in patients with gastrointestinal cancer.


Oncotarget ◽  
2014 ◽  
Vol 5 (16) ◽  
pp. 6594-6602 ◽  
Author(s):  
Yilin Li ◽  
Xiaotian Zhang ◽  
Sai Ge ◽  
Jing Gao ◽  
Jifang Gong ◽  
...  

2012 ◽  
Vol 23 ◽  
pp. xi118
Author(s):  
S. Matsusaka ◽  
K. Chin ◽  
M. Ogur ◽  
E. Shinozaki ◽  
M. Suenaga ◽  
...  

2022 ◽  
Vol 2022 ◽  
pp. 1-9
Author(s):  
Pengjie Yu ◽  
Shengmao Zhu ◽  
Yushuang Luo ◽  
Ganggang Li ◽  
Yongqiang Pu ◽  
...  

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.


2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 3051-3051 ◽  
Author(s):  
Yukiya Narita ◽  
Keiji Sugiyama ◽  
Seiichiro Mitani ◽  
Kazunori Honda ◽  
Toshiki Masuishi ◽  
...  

3051 Background: Anti-PD-1 monotherapy has proven effective for the patients (pts) with MGC. However, the identification of biomarkers for predicting clinical outcomes remain as critical needs. We aimed to identify baseline characteristics associated with time to treatment failure (TTF) or overall survival (OS) for anti-PD-1/PD-L1 monotherapy as second- or later-line therapy in MGC. Methods: Routine blood count parameters and clinical characteristics at baseline were retrospectively investigated in 31 pts with MGC in Aichi Cancer Center Hospital. Endpoints were TTF and OS following anti-PD-1/PD-L1 monotherapy. Kaplan-Meiyer and Cox regression analysis were applied for survival analyses. Results: Patient characteristics were as follows: median age (range), 68 (47–83); ECOG performance status (PS) 0/1, 21/10; PM +ve/-ve, 12/19; No. of metastatic sites 1–2/≥3, 18/13; No. of prior chemotherapy regimens 1–2/≥3, 11/20; and absolute eosinophil count (AEC) <150/≥150 /μl, 14/17. Objective response rate and disease control rate (RECIST ver. 1.1) were 26% vs. 0% (odds ratio [OR], 3.76; P = 0.12) and 79% vs. 50% (OR, 3.58; P = 0.12) in the PM -ve group (Cohort A) and the PM +ve group (Cohort B), respectively. On univariate analysis, the pts with poor PS, PM +ve, and high AEC were significantly poor TTF; and poor PS and PM +ve were significantly identified as prognostic factors of poor OS. On multivariate analysis, only PM +ve was independent negative impact not only for TTF but also for OS. Median TTF and OS were 5.4 vs. 1.3 months (M) (adjusted hazard ratio [HR], 4.29; 95%CI, 1.60–11.5; P < 0.01) and 28.2 vs. 7.5 M (adjusted HR, 3.68; 95%CI, 1.25–10.8; P = 0.02) in Cohort A and Cohort B. Six-months TTF probabilities of 42% vs. 0% ( P = 0.03) and one-year OS probabilities of 58% vs. 8% ( P< 0.01) were observed in Cohort A compared to in Cohort B. Conclusions: PM -ve in the pts treated with anti-PD-1/PD-L1 monotherapy was associated with better efficacy. In the pts with PM -ve, anti-PD-1/PD-L1 monotherapy could be adapted in first-line therapy. [Table: see text]


2004 ◽  
Vol 22 (4) ◽  
pp. 658-663 ◽  
Author(s):  
Salah-Eddin Al-Batran ◽  
Akin Atmaca ◽  
Susanna Hegewisch-Becker ◽  
Dirk Jaeger ◽  
Sabine Hahnfeld ◽  
...  

Purpose To evaluate the toxicity and activity of infusional fluorouracil (FU), folinic acid (FA), and oxaliplatin, administered every 2 weeks in patients with metastatic gastric cancer. Patients and Methods Forty-one previously untreated patients with measurable adenocarcinoma of the stomach were eligible for the study. Patients received FU 2.6 g/m2 (24-hour continuous infusion), FA 500 mg/m2 (2-hour intravenous infusion), and oxaliplatin 85 mg/m2 (2-hour intravenous infusion) every 2 weeks for 6 weeks. Treatment was continued until progression of disease was observed. Results All patients were assessable for toxicity and 37 of 41 patients were assessable for response. Patient characteristics were: sex (male, 28; female,13), median age 60 years (range, 20 to 77 years), and median Eastern Cooperative Oncology Group performance status of 1. Response was evaluated every 6 weeks. Of 37 assessable patients, one complete and 15 partial remissions were observed (overall response rate, 43%). Stable disease was observed in 12 patients (32%) and progressive disease in nine patients (24%). The median overall survival was 9.6 months. WHO grade 3 or 4 hematologic toxicities included neutropenia in two patients (4.9%) and thrombocytopenia in one patient (2.4%). Other WHO grade 3 or 4 toxicities included diarrhea in three patients (7.3%) and vomiting in two patients (4.9%). There were no cases of grade 3 peripheral neuropathy and no treatment-related deaths. Conclusion Biweekly fluorouracil, folinic acid, and oxaliplatin is active and well-tolerated in patients with advanced gastric cancer. Response rates, time to progression, and overall survival were comparable to those achieved with other combination chemotherapy regimens, including FOLFOX6, with significantly less toxicity.


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