Yuming Rong

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.

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.

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.

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.

Comparison of immunological characteristics between paired mismatch repair-proficient and -deficient colorectal cancer patients

BackgroundCurrently, mismatch repair-deficient (dMMR) status is a promising candidate for targeted immune checkpoint inhibition therapy in colorectal cancer (CRC) patients, however, the potential immunological mechanism has not yet been well clarified and some other predictors need to be excavated as well.MethodsWe collected 330 CRC patients by the match of mismatch repair-proficient (167) and dMMR (163), explored the relationship between MMR status and some important immune molecules including MHC class I, CD3, CD4, CD8, CD56, programmed death-1 and programmed death ligand-1, and investigated the risk factors for dMMR status as well as low MHC class I expression. The Pearson Chi square test was used for analyzing the associations between clinicopathological and immune characteristics and MMR status, and two categories logistic regression model was used for univariate and multivariate analysis to predict the odds ratio of risk factors for dMMR status and low MHC class I expression.ResultsMultivariate logistic regression analysis showed that low MHC class I and CD4 expression and high CD8 expression were significant risk factors for dMMR status [odds ratio (OR) = 24.66, 2.94 and 2.97, respectively; all p < 0.05] and dMMR status was the only risk factor for low MHC class I expression (OR = 15.34; p < 0.001).ConclusionsHigh CD8 and low MHC class I expression suggests the contradiction and complexity of immune microenvironment in dMMR CRC patients. Some other immunocytes such as CD56+ cells might also participate in the process of immune checkpoint inhibition, whereas needs further investigations.

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.

Impact of Serum Apolipoprotein A-I on Prognosis and Bevacizumab Efficacy in Patients with Metastatic Colorectal Cancer: a Propensity Score-Matched Analysis

PURPOSE: We aimed to investigate the role of apolipoprotein A-I (ApoA-I) as a predictor of prognosis and treatment efficacy of bevacizumab in patients with metastatic colorectal cancer (mCRC) treated with first-line chemotherapy with or without bevacizumab. METHODS: We conducted a retrospective study on consecutive patients who were diagnosed with mCRC at Sun Yat-sen University Cancer Center. According to their pretreatment ApoA-I level, patients were divided into low– and high–ApoA-I groups. Propensity score-matched method was performed to balance baseline characteristics between two groups. Based on whether they accepted bevacizumab as a first-line therapy, patients were further divided into the chemo + bevacizumab group and the chemo group. Overall survival (OS) and progression-free survival (PFS) were assessed with Kaplan-Meier method, log-rank test, and Cox regression. RESULTS: The optimal cutoff value for the ApoA-I level was determined to be 1.105 g/l. In the propensity-matched cohort of 508 patients, low ApoA-I was significantly associated with inferior OS (P < .001) and PFS (P < .001) than high ApoA-I. Multivariate analysis showed that ApoA-I level was an independent prognostic maker of OS (P < .001) and PFS (P = .001). PFS (P < .001) in either the high– or low–ApoA-I groups could be extended significantly after the administration of bevacizumab, and patients with a high ApoA-I level also had a better OS in the chemo + bevacizumab group than the chemo group (P = .049). CONCLUSIONS: Patients with a low ApoA-I level have poor prognoses, and they did not display an OS benefit from bevacizumab.