Chinese Advanced Gastric Cancer Patients Research Articles

Early results of the randomized, multicenter, controlled evaluation of S-1 and oxaliplatin as neoadjuvant chemotherapy for Chinese advanced gastric cancer patients (RESONANCE Trial).

280 Background: Perioperative chemotherapy brings potential benefits to growing patients with gastric cancer based on several clinical trials including MAGIC, ACTS-GC, CLASSIC and INT-0116. However, the effect of neoadjuvant therapy before D2 gastrectomy remains pending. According to phase II clinical trials, SOX regimen as neoadjuvant chemotherapy is associated with increased rate of D2 lymph nodes dissection and R0 resection. We hypothesize that SOX regimen can improve survival of patients with gastric cancer. Methods: Through CT, EUS and laparoscopic exploration, patients with gastric cancer on the stage IIA-IIIC were included in the study and divided into 2 groups randomly. Patients in neoadjuvant group received 2-4 cycles of SOX before surgery and 4-6 cycles after surgery, while patients in no neoadjuvant group received 8 cycles after surgery. The primary endpoint was 3-y DFS and the secondary endpoint were 5-y OS, ORR, D2/R0 resection rate and side effect. Results: A total of 772 patients were enrolled in the study between September 2012 and July 2019. After neoadjuvant therapy, the downstaging was found in neoadjuvant group (261/386, 67.6%). The pathological efficiency rate and pCR rate of neoadjuvant group were 67.8% and 23.6% respectively. The R0 resection rate in neoadjuvant group was significantly higher than that in adjuvant group(73.1% vs 58.1%, p < 0.05). There was no difference in terms of surgical time, blood loss, postoperative complications and hospital stay. Conclusions: SOX makes increased rate of R0 resection, acceptable adverse effect and no impression on surgeries, which suggest that perioperative chemotherapy using SOX can prolong median survival time, DFS and OS. Clinical trial information: NCT01583361.

Influence of TS (rs34743033) and RUNX1 (rs2014300) gene polymorphisms on survival outcomes of fluorouracil-based chemotherapy in Chinese advanced gastric cancer patients

BackgroundThis study aimed to explore the clinical correlation of single-nucleotide polymorphisms of thymidylate synthase (TS) and runt-related transcription factor 1 (RUNX1) in patients with postoperative stage II and III gastric cancer (GC).Patients and methodsSamples were obtained from 661 patients with postoperative stage II and III GC. TS (rs34743033) and RUNX1 (rs2014300) were genotyped in 261 patients who received postoperative basic platinum and fluorouracil chemotherapy regimens and 400 patients who did not accept chemotherapy.ResultsTS (rs34743033) variant genotypes significantly prolonged the median overall survival (OS) time compared to the patients who only received adjuvant chemotherapy (HR 1.604, 95% CI 1.068–2.410, p=0.021). Moreover, 3R/3R variant genotypes were demonstrated to have a positive effect on the OS of patients who received chemotherapy based on cisplatin (HR 1.754, 95% CI 1.041–2.954, p=0.031) compared to oxaliplatin. A stratification analysis indicated that 2R/3R and 2R/2R variant genotypes were associated with inferior survival in GC patients with intestinal-type tumors, tumor less than 5 cm in size, and poorly differentiated tumors (p<0.05). However, RUNX1 (rs2014300) AA genotypes markedly increased the risk of death in GC patients compared with the GG/GA genotypes (p=0.007), but no significant difference was observed between chemotherapy based on platinum. The stratification analysis showed that the GA/AA genotype was significantly associated with inferior survival in well to moderately differentiated tumors (HR 2.001, 95% CI 1.082–3.703, p=0.023).ConclusionThese preliminary results indicated that the two polymorphisms had a significant effect on postoperative adjuvant chemotherapy. TS (rs34743033) and RUNX1 (rs2014300) may be used as biomarkers to predict prognosis and select chemotherapy regimens in GC patients.

Yield of Staging Laparoscopy for Incurable Factors in Chinese Patients with Advanced Gastric Cancer.

Although the role of staging laparoscopy (SL) in detecting radiologically occult M1 disease has been widely recognized, it is seldom used in China and its clinical value based on Chinese population has been rarely reported. The aim of this study is to identify the yield of SL for Chinese patients with advanced gastric cancer (AGC) and determine the proportions of patients in whom treatment plan is altered. The clinical data were retrospectively collected from 879 AGC patients who underwent SL without any definite signs of disseminated disease on imaging examination. The primary outcomes were the proportions of patients whose laparoscopy identified incurable factors (including M1 diseases and unresectable T4b diseases), and who had their treatment plan altered. SL revealed incurable factors in 130 (14.8%) patients, including macroscopic peritoneal metastasis (n = 92), positive peritoneal cytology (n = 10), liver metastasis (n = 12), para-aortic lymph node metastasis (n = 1), and unresectable T4b tumor (n = 18). After SL, treatment plans were altered in 123 (14.0%) patients, among which 82 (63.1%) patients were not offered any further procedure and referred for chemotherapy. Among 749 M0 patients who immediately proceeded to radical gastrectomy after SL, new incurable factors were found at subsequent operations in 21 (2.8%) patients. Multivariate analysis showed that tumor size ≥8 cm, Borrmann type III and IV, and tumor invasion of T4a and T4b in preoperative imaging examination were the predictive factors for peritoneal metastasis. SL detects additional incurable factors in Chinese AGC patients with potentially resectable disease and optimizes their treatments. A systematic and painstaking inspection of the whole abdominal cavity, including routine entry into the bursa omentalis, is necessary for improving the yield of SL.

Evaluation of MET and HER2 expression in primary and metastatic tumor in Chinese advanced gastric cancer patients.

e15538Background: Gastric cancer is a heterogeneous disease. Whether the expression and amplification of c-Met/HER2 differ between the primary and metastatic lesion and their impacts on prognosis r...

Prognostic value of carbohydrate tumor markers and inflammation-based markers in Chinese advanced gastric cancer patients.

e15053 Background: Gastric cancer is the fourth most common cancer worldwide. In China, most cases are diagnosed as metastatic or recurrent gastric cancer (MRGC) with the 5-year survival rate being...

Polymorphism of TS 3′-UTR predicts survival of Chinese advanced gastric cancer patients receiving first-line capecitabine plus paclitaxel

Capecitabine-containing chemotherapy was widely used in clinic medication. We investigated the association of the thymidylate synthase (TS), methylenetetrahydrofolate reductase (MTHFR), and dihydropyrimidine dehydrogenase (DPD) polymorphisms with the clinical outcome of Chinese advanced gastric cancer patients receiving first-line capecitabine plus paclitaxel. Blood samples were collected prior to treatment from 125 patients with advanced gastric cancer and the TS (two or three repeats of a 28bp sequence in 5'-untranslated region and 6bp insertion or deletion in 3'-untranslated region), MTHFR (C677T) and DPD (IVS14+1G>A) polymorphisms were determined using PCR amplification and Sanger sequencing. The median age of 125 patients was 58years (range, 23-76) with female 42 and male 83, and the response rate, median progression-free survival and overall survival (OS) were 43.2%, 5.2 and 11.0months. The median OS in patients with TS ins6/ins6 genotype (6.8months) was significantly shorter than those in patients with ins6/del6 (11.0months, P=0.016) and del6/del6 (11.5months, P=0.039) genotypes. Cox multivariate analysis also showed that TS ins6/ins6 genotype was the independent poor OS predictor (P=0.001, HR=3.182). No significant associations were found between the polymorphisms of TS 5'-UTR/MTHFR and clinical outcome, and no IVS14+1G>A polymorphism of DPD was found in this study. We first reported that TS 3'-UTR ins6/ins6 genotype could predict the poor survival of advanced gastric cancer patients treated with capecitabine plus paclitaxel, which would be further verified in a large multicenter study.

690P - A Randomized, Controlled Phase III Trial of Docetaxel, Cisplatin and Fluorouracil (DCF) versus Cisplatin Plus Fluorouracil (CF) as First-Line Therapy in Chinese advanced Gastric Cancer

ABSTRACT Background Gastric cancer is the second prevalent cancer in China accounting for more than 200,000 deaths per year. Effective regimens are needed to improve the outcome for gastric cancer patients. TAX 325 study has demonstrated OS benefit and high toxicity of DCF regimen compared with CF in western population. Thus we investigated the effect of modified DCF (mDCF) regimen in Chinese patients with advanced gastric cancer in this prospective, multicenter, open-label, randomized and parallel-controlled phase III study. Methods Eligible no prior palliative chemotherapy, advanced gastric cancer patients were randomized to either mDCF (Docetaxel 60mg/m2 1-hour intravenous infusion (IV) and cisplatin 60mg/m2 1-3-hour IV on day 1, followed by fluorouracil 600mg/m2/d continuous IV for 5 days, every 3 weeks) or modified CF (mCF) (cisplatin 75mg/m2 1-3-hour IV on day 1, followed by fluorouracil 600mg/m2/d continuous IV for 5 days, every 3 weeks). Treatment continued until disease progression, unacceptable toxicity, death, or consent withdrawal. The primary end point was progression-free survival (PFS). Results Between Nov 2008 and Dec 2010, a total of 241 patients were randomized, 234 patients were treated and analyzed (mDCF = 119, mCF = 115) PFS was prolonged with mDCF vs mCF significantly (HR, 0.63; 95% CI, 0.48 to 0.85; P = 0.0018; median PFS, 7.2 months vs.4.9 months), the trend of OS improvement was seen (HR, 0.78; 95% CI, 0.58 to 1.05; P = 0.099; median OS 10.2 months vs. 8.5 months), Overall best response rate (ORR) was improved significantly with mDCF vs mCF (58% vs 39%, P = 0.0244). Treatment related grade 3/4 AEs occurred in 75.6% (DCF) vs 33.0% (CF), P Conclusion mDCF regimen significantly improved PFS and ORR. The safety profile was consistent with previous report. mDCF should be considered as an option for untreated Chinese advanced gastric cancer patients. This study was funded by Sanofi, ClinicalTrials.gov identifier: NCT00811447. Disclosure All authors have declared no conflicts of interest.

HER-2 expression in advanced gastric cancer and its correlation with clinical features, outcome and prognosis

To assess the HER-2 status in Chinese advanced gastric cancer patients and explore its correlation with clinical features, treatment response and prognosis. A total of 107 patients with advanced gastric cancer treated in our hospital from December 2005 to November 2008 were included in this retrospective analysis. HER-2 status was determined by immunohistochemisty (IHC) and/or fluorescence in situ hybridization (FISH). The correlations of HER-2 status with tumor location, pathology, treatment response and prognosis were analyzed and the efficacy of different chemottherapy regimens was compared. The overall positive rate of HER-2 expression was 14.7% (15/102). The HER-2 status was detected by both methods in 102 patients, and the concordance of the two methods was 66.5%. The tumor site distribution was gastroesophageal junction (GEJ) 28.0%, proximal stomach 19.4%, gastric corpus 16.1%, antrum 26.9% and whole stomach 9.7%, respectively. There was no significant difference of HER-2 status among different tumor sites (P = 0.726), and no significant correlation between HER-2 expression and differentiation (P = 0.110). Among the evaluable 51 patients treated by first-line chemotherapy, the total objective effective rate was 23.5%. The median time-to-progression was 7.47 months, and median overall survival time was 11.07 months. The effective rate was 43.8% in patients who received XP regimen chemotherapy (cisplatin + capecitabine), significantly higher than the 14.3% in patients treated with other regimens (P = 0.033). Their overall survival was 14.17 months and 9.53 months, respectively (P = 0.059). The TTP was 6.63 months in HER-2 positive patients and 7.47 months in HER-2 negative patients, with a non-significant difference (P = 0.510). However, there was a improving tendency in the efficacy and OS, showing a effective rate of 45.5% and 17.5% (P = 0.102) and OS of 14.17 months and 10.63 months, respectively (P = 0.205). HER-2-positivity rate in Chinese patients with advanced gastric cancer is similar to those reported in the literature. Along with the increasing use of targeted therapy and targeted agents, the efficacy and survival of gastric cancer patients is improving. HER-2-positive patients may benefit from it.

Thymidine Phosphorylase/β-tubulin III expressions predict the response in Chinese advanced gastric cancer patients receiving first-line capecitabine plus paclitaxel.

BackgroundTo assess the role of Thymidine Phosphorylase and β-tubulin III in clinical outcome of Chinese advanced gastric cancer patients receiving first-line capecitabine plus paclitaxel.MethodsThe clinical data and tumor biopsies prior treatment from 33 advanced gastric cancer patients receiving capecitabine plus paclitaxel (cohort 1, experimental group) and 18 patients receiving capecitabine plus cisplatin (cohort 2, control group) in Beijing Cancer Hospital from July 2003 to December 2008 were retrospectively collected and analyzed for Thymidine Phosphorylase and β-tubulin III expressions by immunohistochemistry. The relationships between expressions of biomarkers and response or survival were determined by statistical analysis.ResultsThe median age of 51 patients was 57 years (range, 27-75) with male 34 and female 17, and the response rate, median progression-free survival and overall survival were 43.1%, 120d and 265d. Among cohort 1, the response rate, median progression-free survival and overall survival in β-tubulin III positive (n = 22) and negative patients (n = 11) were 36.4%/72.7% (positive vs negative, P = 0.049), 86d/237d (P = 0.046) and 201d/388d (P = 0.029), respectively; the response rate (87.5% vs 14.3%, P = 0.01) and median progression-free survival (251d vs 84d, P = 0.003) in Thymidine Phosphorylase positive & β-tubulin III negative patients (n = 8) were also significantly higher than those in Thymidine Phosphorylase negative & β-tubulin III positive patients (n = 7). There was no correlation between β-tubulin III expression and response or survival among cohort 2 (n = 18).ConclusionsIn Chinese advanced gastric cancer, Thymidine Phosphorylase positive & β-tubulin III negative might predict response and prognosis to capecitabine plus paclitaxel chemotherapy. Further prospective evaluation in large samples should be performed to confirm these preliminary findings.