Incidence of venous thromboembolism and the role of D-dimer as predictive marker in patients with advanced gastric cancer receiving chemotherapy:A prospective study

AIM To investigated the incidence and risk factors of venous thromboembolism(VTE) in patients with advanced gastric cancer(AGC) receiving chemotherapy.METHODS All consecutive chemotherapy-na?ve patients with AGC who would receive palliative chemotherapy between November 2009 and April 2012 in our hospital were recruited. Their pretreatment clinical and laboratory variables, including D-dimer, were recorded. The frequency of VTE development and survival rates during each chemotherapy cycle and regularly thereafter were assessed.RESULTS A total of 241 patients enrolled between November 2009and April 2012 were analyzed. During a median followup duration of 10.8 mo(95%CI: 9.9-11.7), 27 patients developed VTE and the incidence of VTE was 17.5%(95%CI: 10.5-24.0, 12.0 events/100 person-years). The 6-mo and 1-year cumulative incidences were 7.8%(95%CI: 4.2%-11.4%) and 12.4%(95%CI: 7.3-17.2), respectively. Thirteen(48.1%) patients were symptomatic and the other 14(51.9%) patients were asymptomatic. In multivariate analysis, pretreatment D-dimer level was the only marginally significant risk factor associated with VTE development(hazard ratio = 1.32; 95%CI: 1.00-1.75, P = 0.051).CONCLUSION The incidence of VTE is relatively high in patients with AGC receiving chemotherapy, and pretreatment D-dimer level might be a biomarker for risk stratification of VTE.

Clinical significance of MET gene amplification in metastatic or locally advanced gastric cancer treated with first-line fluoropyrimidine and platinum combination chemotherapy

Objective: To investigate the clinical significance of MET gene amplification in patients with gastric cancer in the palliative setting.Methods: MET amplification was assessed using fluorescence in situ hybridization(FISH) in 50 patients and quantitative polymerase chain reaction(qPCR) in 326 patients;259 patients treated with first-line fluoropyrimidine and platinum were included for survival analysis.Results: The results of FISH and qPCR indicated that the c-MET/CEP7 ratio was correlated with gene copy number. The optimal cutoff value for the copy number using qPCR to detect MET gene amplification with FISH was 5(κ=0.778, P<0.001). Twenty-one out of 326 patients(6.4%) were identified as MET amplification with a copy number of >5 detected by qPCR. MET-amplified gastric cancer was associated with an Eastern Cooperative Oncology Group(ECOG) performance status(PS) score of ≥2(33.3% vs. 10.5% P=0.007), peritoneal metastasis(76.2% vs. 46.2%, P=0.008), and elevated bilirubin levels(28.6% vs. 7.3%, P=0.006). The median overall survival(OS) and progression-free survival(PFS) were 11.9 and 5.6 months, respectively. MET-amplified gastric cancer was not associated with survival outcomes [hazard ratio(HR)=0.68, 95% confidence interval(95% CI): 0.35-1.32,P=0.254 for PFS;HR=0.68, 95% CI: 0.35-1.32, P=0.251 for OS].Conclusions: qPCR can be used to detect MET gene amplification. MET amplification was not a predictor of poor prognosis in patients with metastatic or unresectable gastric cancer.

Clinical implications of neutrophil-to-lymphocyte ratio and MDSC kinetics in gastric cancer patients treated with ramucirumab plus paclitaxel

Objective: We aimed to investigate the prognostic value of neutrophil-to-lymphocyte ratio(NLR) and myeloidderived suppressor cells(MDSCs) in gastric cancer patients treated with second-line ramucirumab plus paclitaxel.Methods: A total of 116 patients with advanced or metastatic gastric cancer who receive ramucirumab plus paclitaxel were prospectively enrolled. Fresh blood samples were collected before and after treatment, and flow cytometry was performed to assess the proportions of monocytic(m MDSCs) and granulocytic MDSCs(g MDSCs).Results: Median age was 58 years and 71(61.2%) patients were male. A baseline NLR≥2.94 was associated with significantly poorer progression-free survival(PFS) and overall survival(OS) vs. an NLR<2.94(P=0.011 and P=0.002, respectively). In multivariate analysis, an NLR≥2.94 was independently associated with poorer PFS[hazard ratio(HR)=1.58;95% confidence interval(95% CI): 1.01-2.49, P=0.046] and OS(HR=1.77;95% CI:1.04-3.04, P=0.036). While m MDSC counts did not significantly change following two cycles of therapy(P=0.530),g MDSC counts decreased significantly after two treatment cycles(P=0.025) but tended to increase in patients with progressive disease after two treatment cycles(P=0.098). A progressive increase in g MDSC counts(≥44%) was associated with a significantly shorter PFS and OS vs. a g MDSC count increase <44%(P=0.001 and P=0.003,respectively).Conclusions: The baseline NLR may help guide clinical decisions during ramucirumab plus paclitaxel therapy for gastric cancer. Our g MDSC kinetics data warrant further clinical validation and mechanistic investigation.

Intra-abdominal desmoid tumors mimicking gastrointestinal stromal tumors——8 cases: A case report

BACKGROUND Intra-abdominal desmoid tumors(DTs) can mimic recurrence or progression of gastrointestinal stromal tumors(GISTs). Differential diagnosis is important to avoid unnecessary or inappropriate treatment.CASE SUMMARY All 8 patients experienced surgical resection of GIST, and median time to diagnosis of DT was 1.8 years after surgical resection. All sites of DT were in the peritoneum around the surgical sites of GIST. The following clinical suspicion coupled with radiological findings contributed to the suspicion of intraabdominal DTs:(1) Occurrence of a new single lesion in the peritoneum around the surgical sites of GIST;(2) uncontrolled lesion with imatinib while other lesions being controlled with imatinib;(3) well-defined ovoid shaped lesion with delayed or mild enhancement and absence of necrosis, hemorrhage, and cystic change on computed tomography; and(4) a lesion showing mild or no hypermetabolic activity on 18 fluorodeoxyglucose-positron emission tomography,contrary to initially hyperactive lesion of GIST. All DTs were surgically removed except for one unresectable DT and only one DT recurred at another site of peritoneum, which was also surgically removed.CONCLUSION Intra-abdominal DT should be a differential diagnosis for a new single lesion in patients with GIST.

New prognostic model for patients with advanced gastric cancer:Fluoropyrimidine/platinum doublet for first-line chemotherapy

BACKGROUND New prognostic factors have been reported in patients with metastatic or recurrent gastric cancer(MRGC),necessitating modifications to the previous prognostic model.AIM To develop a new model,MRGC patients who received fluoropyrimidines/platinum doublet chemotherapy between 2008 and 2015 were analyzed.METHODS A total of 1883 patients was divided into a training set(n=937)and an independent validation set(n=946).RESULTS Multivariate analysis showed that the following six factors were associated with poor overall survival(OS)in the training set:Eastern Cooperative Oncology Group performance score≥2 and bone metastasis(2 points each),peritoneal metastasis,high alkaline phosphatase level,low albumin level,and high neutrophil-lymphocyte ratio(1 point each).A prognostic model was developed by stratifying patients into good(0-1 point),moderate(2-3 points),and poor(≥4 points)risk groups.In the validation set,the median OS of the three risk groups was 15.8,10.1,and 5.7 mo,respectively,and those differences were significant(P<0.001).CONCLUSION We identified six factors readily measured in clinical practice that are predictive of poor prognosis in patients with MRGC.The new model is simpler than the old and more easily predicts OS.