Chenxi Yin

Initial LDH level can predict the survival benefit from bevacizumab in the first-line setting in Chinese patients with metastatic colorectal cancer

Background Markers to predict the efficacy of bevacizumab treatment have been not fully validated in most cancers, including metastatic colorectal cancer (mCRC). The aim of this study was to investigate the potential role of lactate dehydrogenase (LDH) in predicting the survival benefit from first-line bevacizumab treatment, in Chinese patients with mCRC. Methods All the patients were diagnosed with mCRC at the Sun Yat-sen University Cancer Center from 2003 to 2013. The study group and the control group were classified by receiving bevacizumab or not. The serum LDH value of all the patients had been detected before the first-line treatment. The primary end point was progression-free survival (PFS). Results The median PFS of the study and the control group (patients who received bevacizumab or not) was 11.3 and 9.1 months, respectively (P=0.004). In the control group, the median PFS of the high LDH level and the low LDH level groups was 6.9 and 10.2 months, respectively (P<0.001). However, in the study group, the corresponding median PFS was 9.9 and 11.9 months, respectively (P=0.145). In addition, for the low LDH level group, the median PFS was 11.9 and 10.2 months for patients who received bevacizumab or not, respectively (P=0.066); however, the median PFS of patients receiving bevacizumab or not was significantly different in the high LDH level group (9.9 and 6.9 months, respectively) (P=0.012). Conclusion The addition of bevacizumab in the first-line treatment setting could improve the PFS of mCRC patients notably. However, the benefit could only be potentially reflected on patients with high serum LDH level.

Gamma-glutamyl transpeptidase level is a novel adverse prognostic indicator in human metastatic colorectal cancer

Biomarkers have been utilized for prognosis in colorectal cancer; however, relatively few have been identified. We compared the prognostic value of serum alkaline phosphatase (ALP), lactate dehydrogenase (LDH) and gamma‐glutamyl transpeptidase (GGT) with carcinoembryonic antigen (CEA) and carbohydrate antigen 19‐9 (CA19‐9) in patients with metastatic colorectal cancer (mCRC).

Lymph Node Ratio and pN Staging Show Different Superiority As Prognostic Predictors Depending on the Number of Lymph Nodes Dissected in Chinese Patients With Luminal A Breast Cancer

BACKGROUND The lymph node ratio (LNR) classification has shown superiority to pN staging (the number of positive lymph nodes) in breast cancers, but it has not been examined according to whether sufficient lymph nodes have been dissected. METHODS All Chinese patients with luminal A breast cancer with positive lymph nodes seen at Sun Yat-sen University Cancer Center between 1995 and 2009 were enrolled. Disease-free survival (DFS) and overall survival (OS) were the endpoints, and the patients were further classified into 2 groups according to whether ≤ 10 or > 10 lymph nodes were dissected. RESULTS For the whole group, the OS curves of the pN stages overlapped, whereas they were separated in the LNR survival curves. LNR was an independent prognostic factor for OS and DFS, whereas the pN stage was not. In the ≤ 10 lymph nodes dissected group, both OS and DFS curves were clearly separated in the pN staging but overlapped in the LNR classification. In the > 10 lymph nodes dissected group, LNR showed no overlap in the OS curves and was an independent prognostic factor of OS and DFS when compared with pN staging. CONCLUSION In Chinese patients with luminal A breast cancer, LNR classification and the pN stage show different superiority as prognostic predictors according to whether > 10 or < 10 lymph nodes are dissected.

Prognostic Model Built on Blood-based Biomarkers in Patients with Metastatic Colorectal Cancer

BACKGROUND We had previously showed that the neutrophil lymphocyte ratio (NLR), γ-glutamyl transpeptidase (GGT) and carcinoembryonic antigen (CEA) are prognostic factors for metastatic colorectal cancer (mCRC) patients. In this study we developed a prognostic model based on these three indices. MATERIALS AND METHODS A total of 243 patients who were initially diagnosed as mCRC between 2005 and 2010 in the Sun Yat-sen University Cancer Center were studied. The endpoint was overall survival (OS). RESULTS NLR>3, elevated GGT and elevated CEA were confirmed as independent risk factors which could predict poor prognosis. Patients could be divided into three groups according to the number of risk factors they had. Those with two or three were defined as the high risk group, individuals with one risk factor as the modest risk group and patients without risk factor as the low risk group. The OS values for these three groups were 16.2 months (2.80~68.8), 24.2 months (4.07~79.0), and 37.2 months (12.6~87.8), respectively (p<0.001). CONCLUSIONS We developed a simple but useful model based on NLR, GGT and CEA to provide prognostic information to clinical practice in highly selected mCRC patients. Further prospective and multi-center studies are warranted to test our model.

A high LDL-C to HDL-C ratio predicts poor prognosis for initially metastatic colorectal cancer patients with elevations in LDL-C.

Although lipid disequilibrium has been documented for several types of cancer including colorectal cancer (CRC), it remains unknown whether lipid parameters are associated with the outcome of metastatic CRC (mCRC) patients. Here, we retrospectively examined the lipid profiles of 453 mCRC patients and investigated whether any of the lipid parameters correlated with the outcome of mCRC patients. Pretreatment serum lipids, including triglyceride, cholesterol, high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C), were collected in 453 initially mCRC patients. The LDL-C to HDL-C ratio (LHR) was calculated and divided into the first, second, and third tertiles. Univariate and multivariate analyses were performed to evaluate the impact of lipids on overall survival (OS) and progression-free survival (PFS). Nearly two-fifths of the patients (41.3%) exhibited elevations in LDL-C while most patients (88.3%) showed normal HDL-C levels. Decreased HDL-C (P=0.542) and increased LDL-C (P=0.023) were prognostic factors for poor OS, while triglyceride (P=0.542) and cholesterol (P=0.215) were not. Multivariate analysis revealed that LDL-C (P=0.031) was an independent prognostic factor. Triglyceride, cholesterol, HDL-C, and LDL-C did not correlate with PFS. Among patients with elevations in LDL-C levels, patients in the third tertile of the LHR had a markedly shorter median OS compared to those in the first or second tertile (P=0.012). Thus, increased LDL-C level is an independent prognostic factor for poor prognosis in mCRC patients, and a high LHR predicts poor prognosis for initially mCRC patients with elevations in LDL-C.

Elevated preoperative neutrophil-to-lymphocyte ratio is associated with poor prognosis in gastrointestinal stromal tumor patients

Purpose To investigate the prognostic relevance of preoperative peripheral neutrophil- to-lymphocyte ratio (NLR) in gastrointestinal stromal tumor (GIST) patients. Materials and methods We enrolled 129 consecutive GIST patients who underwent initial curative surgical resection with or without adjuvant/palliative imatinib treatment in our study. Blood NLR was calculated as neutrophil count (number of neutrophils ×109/L) divided by lymphocyte count (number of lymphocytes ×109/L). Survival curves were constructed by using the Kaplan–Meier method. Univariate and multivariate Cox proportional hazard regression models were performed to identify associations with outcome variable. All tests were two-sided, and P<0.05 was considered statistically significant. Results The optimal cut-off value of NLR was 2.07 in the receiver operating characteristic curve analysis. The median overall survival (OS) of high NLR group was 113.0 months, whereas that of the low NLR group had not reached the median OS both in the general (P<0.001) and subgroup analyses. The elevated NLR suggested shorter OS in the high malignant potential groups (P=0.01) and the combined low and moderate groups (P=0.02). Increased NLR indicated poor OS in patients regardless of whether if received imatinib treatment or not (P=0.005, and P=0.032, respectively). High NLR indicated poor OS of patients in stage I and II disease (P=0.005) and a clear tendency that increased level of NLR is inimical to OS. Conclusion Elevated NLR was detected as an independent adverse prognostic factor. Elevated preoperative NLR predicts poor clinical outcome in GIST patients and may serve as a cost-effective and broadly available independent prognostic biomarker.

The Effects of Anti-inflammatory Drug Treatment in Gastric Cancer Prevention: an Update of a Meta-analysis.

Gastric cancer has high incidence and fatality rates, making chemoprevention agents necessary. There is an ongoing debate about aspirin/nonsteroidal anti-inflammatory drugs (NSAIDs) use can significant reduce the risk of GC. We conducted a meta-analysis of existing studies evaluating the association of anti-inflammatory drug and GC. We performed a systematic literature search of PubMed, Web of Science, Embase, OVID, Cochrane Library and Clincialtrials.gov up to August 31, 2015. Either a fixed-effects or a random-effects model using was based on the result of homogeneity analysis. Subgroup, sensitivity, meta-regression, and publication bias analyses were evaluated. Forty-seven studies were finally included in this meta-analysis. The overall GC risk reduction benefit associated with anti-inflammatory drug use represented an RR of 0.78 (95% CI 0.71 to 0.85) and an adjusted RR of 0.74 (95% CI 0.71 to 0.77). Besides, the prevention benefit of aspirin/NSAIDs ingestion appeared to be confined to those patients with regiment of short or middle-term (≤5 years), high-frequency (>30 times per month) and low dose (<200 mg per day). Further, our data also suggest that COX-2 inhibitors use is a more effective approach in GC prevention (RR, 0.45; 95% CI, 0.29-0.70). In this meta-analysis, our finding support short or middle-term (≤5 years), high-frequency (>30 times per month) and low dose (<200 mg per day) aspirin/NSAIDs intake is a well method for GC prevention and also confirm the inverse association between aspirin/NSAIDs use and GC risk. Additionally, selective COX-2 inhibitors use probably a more effective approach to reduce GC risk.

A Potential Administration-time Dependent Effect of Bevacizumab inImproving Overall Survival and Increasing Metastasis in MetastaticColorectal Cancer

Background: The effectiveness of Bevacizumab has been demonstrated for the treatment of metastatic colorectal cancer. However, the minimum number of bevacizumab cycles needed to improve overall survival is unknown. In addition, anti-angiogenic treatment has been shown in preclinical studies to accelerate metastasis. To investigate these two issues, we performed a retrospective case-control study in Chinese patients with metastatic colorectal cancer. Methods: Patients initially diagnosed as metastatic colorectal cancer at the Sun Yat-sen University Cancer Center from 2004 to 2010 were recruited. All patients treated with bevacizumab served as experimental group; patients not treated with bevacizumab were control group. The primary endpoints were overall survival and the incidence of new metastatic lesions in the liver and other organs. Results: Patients received more than 4 cycles of bevacizumab showed a significantly prolonged overall survival than patients in the control group. The median overall survival was 31.53 months (95% CI, 23.22-39.85 months) and 19.70 months (95% CI, 16.61-22.79 months; P=0.031) for the experimental and control groups, respectively. The patients receiving bevacizumab more than 3 times showed an increased risk compared to the patients in control group of developing new metastatic lesions in the liver (17/23 versus 25/55, respectively, P=0.022) and other organs (14/23 versus 19/55, respectively, P=0.032). Conclusion: More than 4 doses of bevacizumab were required to improve overall survival in metastatic colorectal cancer; a potentially accelerated metastasis rate was observed after more than 3 doses of bevacizumab. However, studies with larger patient sample sizes are urgently needed to validate our findings.

Efficacy of Taxane-Based Regimens in a First-line Setting for Recurrent and/or Metastatic Chinese Patients with Esophageal Cancer

OBJECTIVE To compare the efficacy of taxane-based regimens in the first line setting retrospectively in Chinese patients with recurrent and/or metastatic esophageal cancer. METHODS We analyzed 102 recurrent and/or metastatic esophageal cancer patients who received taxanes-based regimens in a first-line setting from January 2009 to December 2013. Sixteen (15.7%) patients were administered Nab-PTX based chemotherapy and 86 patients (84.3%) received paclitaxel (PTX) or docetaxel (DTX) based chemotherapy. Patients in the PTX/DTX group could be further divided into TP (71 patients) and TPF (15 patients) groups. RESULTS The objective response rate (ORR) of all patients was 20.6%, and the disease control rate (DCR) was 67.6%. The median overall survival (OS) was 10.5 months (95% CI 10.1-16.4) and the median progression-free survival (PFS) was 6.04 months (95% CI 5.09-7.91). The DCR was higher in the TPF group than the TP group (93.3% vs. 59.1%; p = 0.015 ). There were no significant differences in ORR, OS, and PFS among Nab-PTX, TPF and TP groups. CONCLUSIONS The three regimens of Nab-PTX based, TP and TPF proved active in a first line setting of Chinese patients with recurrent and/or metastatic esophageal cancer, and should thus be regarded as alternative treatments.

The Efficacy of Bevacizumab in Different Line Chemotherapy for Chinese Patients with Metastatic Colorectal Cancer.

Objective: To evaluate the effect of bevacizumab in different lines for Chinese patients with metastatic colorectal cancer (mCRC). Methods: Patients of mCRC treated with bevacizumab or not at Sun Yat-sen University Cancer Center from 2007 to 2013 were recruited as study and control group. Endpoints were overall survival (OS), progression free survival (PFS), objective response rate (ORR) and disease control rate (DCR). Corresponding survival rates of first- and second-line in study and control group were compared. Results: 1. Median OS of study and control group were 44.8 (95% CI: 37.1~52.4) months, 36.1 (95% CI: 32.8~39.5) months respectively, which were significantly different (P=0.004). 2. In the first line treatment, median OS of study and control group were 49.9(95% CI: 40.1~59.8) months and 36.1 (95% CI: 32.7~39.4) months (P=0.002), respectively. And median PFS were 10.1(95% CI: 8.7~11.5) months and 6.2 (95% CI: 5.5~6.8) months (P<0.001), respectively. 3. In the second line treatment, median OS of study and control group were 34.8 (95% CI: 26.3~43.3) months and 24.6 (95% CI: 22.2~27.0) months (P=0.022), respectively. And the mPFS were 6.3 (95% CI: 4.7~7.8) months and 3.1 (95% CI: 2.5~3.6) months (P<0.001), respectively. 4. Median OS of first- and second-line treatment of the study groups were 49.9(95% CI: 40.1~59.8) months and 34.8 (95% CI: 26.3~43.3) months (P=0.189), respectively. Conclusion: The combination of bevacizumab and chemotherapy had a promising efficacy in Chinese mCRC patients. However, their OS were statistically insignificant between first- and second-line of bevacizumab groups.