Efficacy and Safety Assessment of the Addition of Bevacizumab to Adjuvant Therapy Agents in Cancer Patients: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Aim

To evaluate the efficacy and safety of bevacizumab in the adjuvant cancer therapy setting within different subset of patients.

Methods & Design/ Results

PubMed, EMBASE, Cochrane and Clinical trials.gov databases were searched for English language studies of randomized controlled trials comparing bevacizumab and adjuvant therapy with adjuvant therapy alone published from January 1966 to 7^th of May 2014. Progression free survival, overall survival, overall response rate, safety and quality of life were analyzed using random- or fixed-effects models according to the PRISMA guidelines. We obtained data from 44 randomized controlled trials (30,828 patients). Combining bevacizumab with different adjuvant therapies resulted in significant improvement of progression free survival (log hazard ratio, 0.87; 95% confidence interval (CI), 0.84–0.89), overall survival (log hazard ratio, 0.96; 95% CI, 0.94–0.98) and overall response rate (relative risk, 1.46; 95% CI: 1.33–1.59) compared to adjuvant therapy alone in all studied tumor types. In subgroup analyses, there were no interactions of bevacizumab with baseline characteristics on progression free survival and overall survival, while overall response rate was influenced by tumor type and bevacizumab dose (p-value: 0.02). Although bevacizumab use resulted in additional expected adverse drug reactions except anemia and fatigue, it was not associated with a significant decline in quality of life. There was a trend towards a higher risk of several side effects in patients treated by high-dose bevacizumab compared to the low-dose e.g. all grade proteinuria (9.24; 95% CI: 6.60–12.94 vs. 2.64; 95% CI: 1.29–5.40).

Conclusions

Combining bevacizumab with different adjuvant therapies provides a survival benefit across all major subsets of patients, including by tumor type, type of adjuvant therapy, and duration and dose of bevacizumab therapy. Though bevacizumab was associated with increased risks of some adverse drug reactions such as hypertension and bleeding, anemia and fatigue were improved by the addition of bevacizumab.     

Practical Role of Mutation Analysis for Imatinib Treatment in Patients With Advanced Gastrointestinal Stromal Tumors: A Meta-Analysis

Background

Imatinib has become the standard first line treatment of gastrointestinal stromal tumors (GIST) in the advanced phase and adjuvant setting. We carried out an up-to-date meta-analysis to determine the practical role of mutation analysis for imatinib treatment in patients with advanced GIST.

Methods

Eligible studies were limited to imatinib treatment for patients with advanced GIST and reported on mutation analysis. Statistical analyses were conducted to calculate the odds ratio (OR), hazard ratio (HR) and 95% confidence interval (CI) using fixed-effects and random-effects models.

Results

A total of 2834 patients from 3 randomized controlled trials and 12 cohort studies were included. The ORs of response rates in KIT exon 11-mutant GISTs were 3.504 (95% CI 2.549-4.816, p<0.001) and 3.521 (95% CI 1.731-7.165, p=0.001) compared with KIT exon 9-mutant and wild type GISTs, respectively. The HRs of progression-free survival in KIT exon 11-mutant GISTs were 0.365 (95% CI 0.301-0.444, p<0.001) and 0.375 (95% CI 0.270-0.519, p<0.001) compared with KIT exon 9-mutant and wild type GISTs. The HRs of overall survival in KIT exon 11-mutant GISTs were 0.388 (95% CI 0.293-0.515, p<0.001) and 0.400 (95% CI 0.297-0.538, p<0.001) compared with KIT exon 9-mutant and wild type GISTs. No statistical significant differences were found between KIT exon 9-mutant and wild type. The overall response rate in KIT-exon 11-mutant GISTs were 70.5% (65%-75.9%) compared with 57.1% (51%-63.2%) in KIT-positive GISTs. No evidence of publication bias was observed.

Conclusion

Patients with advanced GIST harboring a KIT exon 11 mutation have the best response rate and long-term survival with imatinib treatment. Mutation analysis would be more helpful than KIT expression analysis to decide appropriate therapy for a specific patient.     

Overall Survival Benefits for Combining Targeted Therapy as Second-Line Treatment for Advanced Non-Small-Cell-Lung Cancer: A Meta-Analysis of Published Data

Background

Combining targeted therapy has been extensively investigated in previously treated advanced non-small-cell lung cancer (NSCLC), but it is still unclear whether combining targeted therapy might offer any benefits against standard monotherapy with erlotinib. We thus performed a meta-analysis of randomized controlled trials to compare the efficacy and safety of combining targeted therapy versus erlotinib alone as second-line treatment for advanced NSCLC.

Methods

Several databases were searched, including Pubmed, Embase and Cochrane databases. The endpoints were overall survival (OS), progression-free survival (PFS), overall response rate (ORR) and grade 3 or 4 adverse event (AEs). The pooled hazard ratio (HR) or odds ratio (OR), and 95% confidence intervals (CI) were calculated employing fixed- or random-effects models depending on the heterogeneity of the included trials.

Results

Eight eligible trials involved 2417 patients were ultimately identified. The intention to treatment (ITT) analysis demonstrated that combining targeted therapy significantly improved OS (HR 0.90, 95%CI: 0.82–0.99, p = 0.024), PFS (HR 0.83, 95%CI: 0.72–0.97, p = 0.018), and ORR (OR 1.35, 95%CI 1.01–1.80, P = 0.04). Sub-group analysis based on phases of trials, EGFR-status and KRAS status also showed that there was a tendency to improve PFS and OS in combining targeted therapy, except that PFS for patients with EGFR-mutation or wild type KRAS favored erlotinib monotherapy. Additionally, more incidence of grade 3 or 4 rash, fatigue and hypertension were observed in combining targeted therapy.

Conclusions

With the available evidence, combining targeted therapy seems superior over erlotinib monotherapy as second-line treatment for advanced NSCLC. More studies are still needed to identify patients who will most likely benefit from the appropriate combining targeted therapy.     

Optimal timing of combining sorafenib with trans-arterial chemoembolization in patients with hepatocellular carcinoma: A meta-analysis

BackgroundThe combination therapy of trans-arterial chemoembolization (TACE) and sorafenib were proved to be one of the effective methods for intermediate and advanced hepatocellular carcinoma (HCC). Although it has been confirmed that the combination therapy can prolong survival for advanced HCC effectively, the therapeutic efficacy and safety are still controversial and the clinical value has not been determined. This meta-analysis aims to evaluate the efficacy and safety of combination therapy and discuss the optimal timing of combination for better clinical benefits.Data sourcesPubMed, EMBASE, the Cochrane Library, MEDLINE, and Web of Science were systematically reviewed to search for relevant studies published before May 15, 2021. Studies comparing the efficacy and safety of TACE + sorafenib with TACE + placebo / alone were adopted. Two reviewers independently extracted study outcomes. The data were analyzed through fixed/random-effect meta-analysis models with Review Manager (Version 5. 3) software.Results7 randomized controlled trials (RCTs) were included with 1464 patients with unresectable HCC (734 in TACE + sorafenib group and 730 in TACE + placebo or alone group). Meta-analysis showed that objective response rate (ORR) and disease control rate (DCR) were slightly improved in TACE + sorafenib group (ORR: risk ratio = 1.24; 95% confidence interval: 1.08–1.42; P = 0.002; DCR: risk ratio = 1.09; 95% confidence interval: 1.01–1.18; P = 0.02). The combination therapy obviously improved time to progression (TTP) (hazard ratio: 0.73; 95% confidence interval: 0.55–0.96; P = 0.03) and progression-free survival (PFS) (hazard ratio 0.62; 95% confidence interval: 0.52–0.73, P < 0.00001) but not overall survival (OS) (hazard ratio: 0.93; 95% confidence interval: 0.59–1.46; P = 0.75) or time to untreatable progression (TTUP) (hazard ratio: 0.76; 95% confidence interval: 0.31–1.89; P = 0.56). In addition, the incidence of adverse reactions (AEs) in combination group were higher than TACE + placebo / alone group. Furthermore, the subgroup analysis showed that the heterogeneity of TTP was notably decreased (pre-TACE: P = 0.12, I² = 48%; post-TACE: P = 0.58, I² = 0%), and the hazard ratio was 0.59 (95% confidence interval: 0.51–0.68; P < 0.00001) in pre-TACE subgroup which indicated that combination before TACE significantly prolonged TTP but not in combination after TACE (hazard ratio: 0.88; 95% confidence interval: 0.62–1.24; P = 0.46). In term of AEs, sensitivity analysis indicated that the risk ratio for hand-foot skin reaction, diarrhea, rash/desquamation, and hypertension was 7.41, 2.58, 2.14, 1.55 in pre-TACE subgroup respectively and was 11.34, 3.26, 3.61, 4.11 in post-TACE subgroup respectively (All P < 0.05).ConclusionThe combination of TACE and sorafenib significantly can improve TTP and PFS, and reduce the level of risk of adverse reactions of unresectable HCC, especially in the combination before TACE.     

The Pan-Immune-Inflammation Value predicts the survival of patients with anaplastic lymphoma kinase-positive non-small cell lung cancer treated with first-line ALK inhibitor

BackgroundAnaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors (TKIs) have significantly improved the clinical outcomes of patients with ALK-positive non-small cell lung cancer (NSCLC). However, reliable biomarkers to predict the prognostic role of this treatment are lacking. The Pan-Immune-Inflammation Value (PIV) has recently been demonstrated as a novel comprehensive biomarker to predict survival of patients with solid tumors. Our study aimed to evaluate the prognostic power of PIV in this group of patients.Patients and methods94 patients with advanced ALK-positive NSCLC who received first-line ALK inhibitors were enrolled in this study. PIV was calculated as the product of peripheral blood neutrophil, monocyte, and platelet counts divided by lymphocyte count. Kaplan-Meier method and Cox hazard regression models were used for survival analyses.ResultsThe 1-year progression-free survival (PFS) was 63.5%, and the 5-year overall survival (OS) rate was 55.1%. Patients with higher PIV, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and systemic immune inflammation index (SII) had worse PFS in univariate analysis, but only the PIV (hazard ratio [HR] = 2.90, 95% confidence interval [CI]: 1.79–4.70, p < 0.001) was an independent prognostic factor in multivariate analysis. Similarly, patients with higher PIV, NLR, PLR, and SII had a worse OS in the univariate analysis, but only the PIV (HR = 4.70, 95% CI: 2.00–11.02, p < 0.001) was significantly associated with worse OS in multivariate analysis.ConclusionPIV is a comprehensive and convenient predictor of both PFS and OS in patients with ALK-positive advanced NSCLC who received first-line ALK TKIs. Prospective clinical trials are required to validate the value of this new parameter.     

Optimal timing of combining sorafenib with trans-arterial chemoembolization in patients with hepatocellular carcinoma: A meta-analysis

BackgroundThe combination therapy of trans-arterial chemoembolization (TACE) and sorafenib were proved to be one of the effective methods for intermediate and advanced hepatocellular carcinoma (HCC). Although it has been confirmed that the combination therapy can prolong survival for advanced HCC effectively, the therapeutic efficacy and safety are still controversial and the clinical value has not been determined. This meta-analysis aims to evaluate the efficacy and safety of combination therapy and discuss the optimal timing of combination for better clinical benefits.Data sourcesPubMed, EMBASE, the Cochrane Library, MEDLINE, and Web of Science were systematically reviewed to search for relevant studies published before May 15, 2021. Studies comparing the efficacy and safety of TACE + sorafenib with TACE + placebo / alone were adopted. Two reviewers independently extracted study outcomes. The data were analyzed through fixed/random-effect meta-analysis models with Review Manager (Version 5. 3) software.Results7 randomized controlled trials (RCTs) were included with 1464 patients with unresectable HCC (734 in TACE + sorafenib group and 730 in TACE + placebo or alone group). Meta-analysis showed that objective response rate (ORR) and disease control rate (DCR) were slightly improved in TACE + sorafenib group (ORR: risk ratio = 1.24; 95% confidence interval: 1.08–1.42; P = 0.002; DCR: risk ratio = 1.09; 95% confidence interval: 1.01–1.18; P = 0.02). The combination therapy obviously improved time to progression (TTP) (hazard ratio: 0.73; 95% confidence interval: 0.55–0.96; P = 0.03) and progression-free survival (PFS) (hazard ratio 0.62; 95% confidence interval: 0.52–0.73, P < 0.00001) but not overall survival (OS) (hazard ratio: 0.93; 95% confidence interval: 0.59–1.46; P = 0.75) or time to untreatable progression (TTUP) (hazard ratio: 0.76; 95% confidence interval: 0.31–1.89; P = 0.56). In addition, the incidence of adverse reactions (AEs) in combination group were higher than TACE + placebo / alone group. Furthermore, the subgroup analysis showed that the heterogeneity of TTP was notably decreased (pre-TACE: P = 0.12, I² = 48%; post-TACE: P = 0.58, I² = 0%), and the hazard ratio was 0.59 (95% confidence interval: 0.51–0.68; P < 0.00001) in pre-TACE subgroup which indicated that combination before TACE significantly prolonged TTP but not in combination after TACE (hazard ratio: 0.88; 95% confidence interval: 0.62–1.24; P = 0.46). In term of AEs, sensitivity analysis indicated that the risk ratio for hand-foot skin reaction, diarrhea, rash/desquamation, and hypertension was 7.41, 2.58, 2.14, 1.55 in pre-TACE subgroup respectively and was 11.34, 3.26, 3.61, 4.11 in post-TACE subgroup respectively (All P < 0.05).ConclusionThe combination of TACE and sorafenib significantly can improve TTP and PFS, and reduce the level of risk of adverse reactions of unresectable HCC, especially in the combination before TACE.     

Prognostic Value of Ezrin in Solid Tumors: A Meta-Analysis of the Literature

Purpose

Ezrin is a cytoskeletal protein involved in tumor growth and invasion. However its prognostic value for survival in patients with solid tumor remains controversial.

Methods

Several databases were searched, including Pubmed, Embase and Cochrane databases. The endpoints were overall survival (OS), progression-free survival (PFS). The pooled hazard ratio (HR) or odds ratio (OR), and 95% confidence intervals (CI) were calculated employing fixed- or random-effects models depending on the heterogeneity of the included trials.

Results

Twenty-seven eligible trials involving 4693 patients were ultimately identified. A summary hazard ratio (HR) of all studies and sub-group hazard ratios were calculated. The combined HR suggested that a positive Ezrin expression had an impact on overall survival (OS) [1.95, 95% confidence interval (CI) 1.60–2.39; P<0.001] in all eligible studies and progress free survival (PFS): (2.30 95% CI 1.0–3.61; P = 0.001). Similar results were also observed in subgroup analysis, according to tumor types, regions, patients'' number and publication year.

Conclusions

Our findings suggested that Ezrin protein expression might be a factor for a poor prognosis in patients with solid tumor. So large well-designed prospective studies are now needed to confirm the clinical utility of Ezrin as an independent prognostic marker.     

Clinical significance of preoperative neutrophil-lymphocyte versus platelet-lymphocyte ratio in patients with operable colorectal cancer

The objective of this study was to clarify whether the neutrophil-lymphocyte ratio (NLR) and the platelet-lymphocyte ratio (PLR) are significant prognostic markers in patients with resectable colorectal cancer (CRC). A total of 200 patients who underwent curative resection for CRC were enrolled. The NLR and PLR were positively correlated (p?<?0.001). Both the NLR and PLR were shown to be good prognostic biomarkers of overall survival (OS) (p?=?0.002 and p?=?0.001, respectively). The PLR was an independent prognostic factor of OS based on multivariate analysis (hazard ratio, 1.971; 95% confidence interval, 1.102–3.335; p?=?0.021).     

Addition of bevacizumab to chemotherapy in advanced non-small cell lung cancer: a systematic review and meta-analysis

IntroductionRecently, studies have demonstrated that the addition of bevacizumab to chemotherapy could be associated with better outcomes in patients with advanced non-small cell lung cancer (NSCLC). However, the benefit seems to be dependent on the drugs used in the chemotherapy regimens. This systematic review evaluated the strength of data on efficacy of the addition of bevacizumab to chemotherapy in advanced NSCLC.MethodsPubMed, EMBASE, and Cochrane databases were searched. Eligible studies were randomized clinical trials (RCTs) that evaluated chemotherapy with or without bevacizumab in patients with advanced NSCLC. The outcomes included overall survival (OS), progression-free survival (PFS), response rate (RR), toxicities and treatment related mortality. Hazard ratios (HR) and odds ratios (OR) were used for the meta-analysis and were expressed with 95% confidence intervals (CI).ResultsWe included results reported from five RCTs, with a total of 2,252 patients included in the primary analysis, all of them using platinum-based chemotherapy regimens. Compared to chemotherapy alone, the addition of bevacizumab to chemotherapy resulted in a significant longer OS (HR 0.89; 95% CI 0.79 to 0.99; p = 0.04), longer PFS (HR 0.73; 95% CI 0.66 to 0.82; p<0.00001) and higher response rates (OR 2.34; 95% CI 1.89 to 2.89; p<0.00001). We found no heterogeneity between trials, in all comparisons. There was a slight increase in toxicities in bevacizumab group, as well as an increased rate of treatment-related mortality.ConclusionsThe addition of bevacizumab to chemotherapy in patients with advanced NSCLC prolongs OS, PFS and RR. Considering the toxicities added, and the small absolute benefits found, bevacizumab plus platinum-based chemotherapy can be considered an option in selected patients with advanced NSCLC. However, risks and benefits should be discussed with patients before decision making.     

Pooling analysis reveals that galectin-1 is a reliable prognostic biomarker in various cancers

Galectin-1 is reported to be upregulated in various human cancers. However, the relationship between galectin-1 expression and cancer prognosis has not been systematically assessed. In this study, we searched PubMed, Web of Science, and Embase to collect all relevant studies and a meta-analysis was performed. We found that increased galectin-1 expression was associated with tumor size (odds ratio [OR] = 1.75; 95% confidence interval [CI]: 1.06–2.89; p = 0.029), clinical stage (OR = 3.89; 95% CI: 2.40–6.31; p < 0.001), and poorer differentiation (OR = 1.39; 95% CI: 1.14–1.69; p = 0.001), but not with age (OR = 1.07; 95% CI: 0.82–1.39; p = 0.597), sex (OR = 0.89; 95% CI: 0.74–1.07; p = 0.202), or lymph node metastasis (OR = 2.57; 95% CI: 0.98–6.78; p = 0.056). In addition, we found that high galectin-1 expression levels were associated with poor overall survival (HR = 2.12; 95% CI: 1.71–2.64; p < 0.001). The results were further validated using The Cancer Genome Atlas data set. Moreover, high galectin-1 expression was significantly associated with disease-free survival (hazard ratio [HR] = 1.60; 95% CI: 1.17–2.19; p = 0.003), progression-free survival (HR = 1.93; 95% CI: 1.65–2.25; p < 0.001), and cancer-specific survival (HR = 1.82; 95% CI: 1.30–2.55; p < 0.001). Our meta-analysis demonstrated that galectin-1 might be a useful common biomarker for predicting prognosis in patients with cancer.     

Efficacy of adjuvant immunochemotherapy with polysaccharide K for patients with curative resections of gastric cancer

Non-specific immunopotentiators, such as polysaccharide K (PSK), also known as OK-432, induce anti-tumor effects via immunological responses. The efficacy of combination immunochemotherapy using these immunopotentiators has been examined by multiple previous studies. The survival benefits of immunochemotherapy for patients with curative resections of gastric cancers are not widely accepted. To clarify this issue, we performed a meta-analysis to evaluate the effect of immunochemotherapy on survival in patients with curative resections of gastric cancer. For this study, we compared the results of chemotherapy and immunotherapy using the biological response modifier PSK as an immunopotentiator. The meta-analysis included 8,009 patients from eight randomized controlled trials after central randomization. The overall hazard ratio for eligible patients was 0.88 (95% confidence interval, 0.79–0.98; P = 0.018) with no significant heterogeneity [χ ²(8) for heterogeneity = 11.7; P = 0.16]. The results of this meta-analysis suggest that adjuvant immunochemotherapy with PSK improves the survival of patients after curative gastric cancer resection.     

Angiogenesis Inhibitor Bevacizumab Increases the Risk of Ischemic Heart Disease Associated with Chemotherapy: A Meta-Analysis

Concerns have arisen regarding the risk of ischemic heart disease with the novel antiangiogenic agent bevacizumab, a recombinant humanised monoclonal antibody to the vascular endothelial growth factor that is widely used in cancer treatment. Currently, the role of bevacizumab in ischemic heart disease is controversial. This meta-analysis was therefore performed to assess the overall risk of ischemic heart disease associated with the use of bevacizumab. The databases of PubMed, EMBASE and Web of Science were searched for English language studies of randomised controlled trials comparing bevacizumab with control therapy published through October 25, 2012. Summary incidence rates, relative risks (RRs) and 95% confidence intervals (CIs) were calculated using random-effects or fixed-effects models based on the heterogeneity of the included studies. A total of 4,617 patients from 7 randomised controlled trials were identified and included for analysis. Among those patients receiving bevacizumab, the summary incidence of ischemic heart disease was 1.0% (95% CI, 0.6%–1.4%). Patients treated with bevacizumab had a significantly increased risk of ischemic heart disease with an RR of 2.49 (95% CI, 1.37–4.52) compared with controls. In addition, both high doses and low doses of bevacizumab increased the risk of cardiac ischemia (low dose at 2.5 mg/kg per week: RR, 2.14 [95% CI, 1.09–4.19]; high dose at 5 mg/kg per week: RR, 4.81 [95% CI, 1.03–22.42]). Bevacizumab was also found to significantly increase the risk of cardiac ischemia in patients with colorectal cancer (RR, 2.13; 95% CI, 1.11–4.06) compared with controls. This meta-analysis shows the use of bevacizumab was associated with an increased risk of developing ischemic heart disease in colorectal cancer patients receiving this drug. Our conclusions are limited by the available data. Further evaluations of high-quality RCTs are needed.     

Efficacy of adjuvant Immunochemotherapy with polysaccharide K for patients with curatively resected colorectal cancer: a meta-analysis of centrally randomized controlled clinical trials

The benefits of immunochemotherapy employing the biological response modifier polysaccharide K (PSK) for patients with curatively resected colorectal cancer was reassessed by means of a meta-analysis of data with center randomization from 1,094 patients enrolled in three clinical trials. In all three trials, patients were followed up for at least 5 years after surgery and enrollment of the last patient and outcomes for standard chemotherapy were compared with those for chemotherapy plus PSK. The endpoints were overall survival and disease-free survival; and intent-to-treat analysis was performed without patient exclusion. Data were analyzed using the weighted average of the individual log hazard ratios. The overall survival risk ratio for all eligible patients was 0.71 (95% confidence interval (CI) : 0.55–0.90; P=0.006), and the disease-free survival risk ratio was 0.72 (95% CI: 0.58–0.90; P=0.003). The results of this meta-analysis suggest that adjuvant immunochemotherapy with PSK can improve both survival and disease-free survival of patients with curatively resected colorectal cancer.     

A Bayesian Meta-Analysis of Multiple Treatment Comparisons of Systemic Regimens for Advanced Pancreatic Cancer

Background

For advanced pancreatic cancer, many regimens have been compared with gemcitabine (G) as the standard arm in randomized controlled trials. Few regimens have been directly compared with each other in randomized controlled trials and the relative efficacy and safety among them remains unclear.

Methods

A systematic review was performed through MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and ASCO meeting abstracts up to May 2013 to identify randomized controlled trials that included advanced pancreatic cancer comparing the following regimens: G, G+5-fluorouracil, G+ capecitabine, G+S1, G+ cisplatin, G+ oxaliplatin, G+ erlotinib, G+ nab-paclitaxel, and FOLFIRINOX. Overall survival and progression-free survival with 95% credible regions were extracted using the Parmar method. A Bayesian multiple treatment comparisons was performed to compare all regimens simultaneously.

Results

Twenty-two studies were identified and 16 were included in the meta-analysis. Median overall survival, progression free survival, and response rates for G arms from all trials were similar, suggesting no significant clinical heterogeneity. For overall survival, the mixed treatment comparisons found that the probability that FOLFIRINOX was the best regimen was 83%, while it was 11% for G+ nab-paclitaxel and 3% for G+ S1 and G+ erlotinib, respectively. The overall survival hazard ratio for FOLFIRINOX versus G+ nab-paclitaxel was 0.79 [0.50–1.24], with no obvious difference in toxicities. The hazard ratios from direct pairwise comparisons were consistent with the mixed treatment comparisons results.

Conclusions

FOLFIRINOX appeared to be the best regimen for advanced pancreatic cancer probabilistically, with a trend towards improvement in survival when compared with other regimens by indirect comparisons.     

Matrix metalloproteinase 2 overexpression and prognosis in colorectal cancer: a meta-analysis

Many studies investigated the relationship between matrix metalloproteinase 2 (MMP-2) overexpression and survival in patients with colorectal cancer (CRC), but yielded inconsistent results. To derive a more precise estimate of the prognostic significance of MMP-2 overexpression, we reviewed published studies and carried out a meta-analysis. Eligible articles were identified for the period up to March 2012 in electronic databases. To evaluate the correlation between MMP-2 overexpression and the prognosis in CRC, pooled hazard ratio (HR) and its 95?% confidence interval (95?% CI) for poorer overall and progression-free survival were appropriately derived from fixed-effects or random-effects models using standard meta-analysis techniques. Thirteen studies with a total of 1,919 CRC patients stratifying overall survival (OS) and/or progression-free survival in CRC patients by MMP-2 expression status were eligible for analysis. Ten studies investigated the OS in a total of 1,612 cases with CRC, and five studies investigated the progression-free survival in a total of 508 patients CRC. The combined HR estimate for OS and progression-free survival was 1.74 (95?% CI, 1.34?C2.26) and 1.35 (95?% CI, 1.07?C1.80), respectively. Both subgroup analyses and sensitivity analysis further identified the prognostic role of MMP-2 overexpression in patients with CRC. There was no evidence for publication bias. In conclusion, MMP-2 overexpression is associated with poorer overall and progression-free survival in patients with CRC.     

Clinical significance of preoperative neutrophil-lymphocyte versus platelet-lymphocyte ratio in patients with operable colorectal cancer

The objective of this study was to clarify whether the neutrophil-lymphocyte ratio (NLR) and the platelet-lymphocyte ratio (PLR) are significant prognostic markers in patients with resectable colorectal cancer (CRC). A total of 200 patients who underwent curative resection for CRC were enrolled. The NLR and PLR were positively correlated (p?相似文献   

Cisplatin or Not in Advanced Gastric Cancer: A Systematic Review and Meta-Analysis

Background

Cisplatin-based chemotherapy is frequently used to treat advanced gastric cancer (GC). Although it leads to increased overall survival (OS) when added to single agents or chemotherapy doublets, toxicity is also generally increased. The purpose of this meta-analysis study was to compare the efficacy of fchemotherapy with and without cisplatin in patients with advanced GC.

Methods

Randomised trials that compared first-line cisplatin-based chemotherapy with regimens in which cisplatin was replaced by other agents were identified by electronic searches of PubMed, EMBASE, the Web of Science, and the Cochrane Central Register of Controlled Trials. Meta-analysis was performed using a fixed or random effects model. OS, reported as a hazard ratio (HR) and a 95% confidence interval (CI), was the primary outcome measure.

Results

Fourteen trials (5 phase III and 9 phase II), including 2,981 patients, were identified. Overall, chemotherapy regimens without cisplatin significantly improved OS (HR, 0.79; 95% CI, 0.68–0.92; p = 0.003), progression-free survival (PFS) (HR, 0.77; 95% CI, 0.66–0.90; p = 0.001), and response rate (RR) (OR, 1.25; p = 0.004) when compared to cisplatin-containing regimens. A subgroup analysis according to histology, site of the primary tumour and extent of disease was not possible due to lack of data.

Conclusions

Compared with cisplatin-based doublets and triplets, combinations in which cisplatin was replaced by new drugs improved outcome and RRs in randomised trials for advanced GC and therefore should be strongly considered in the metastatic setting. A limitation of this meta-analysis is that we cannot identify a subgroup of patients (according to histology, site of primary tumour or burden of metastatic disease) which could derive greater benefit from cisplatin-free chemotherapy.     

Systematic review and meta-analysis of the association between bridging therapy and outcomes of chimeric antigen receptor T cell therapy in patients with large B cell lymphoma

BackgroundThe existing evidence about the impact of bridging therapy (BT) on chimeric antigen receptor (CAR)-T cell therapy in patients with large B cell lymphoma (LBCL) is conflicting. Therefore, we reviewed all available evidence to examine the association between BT and CAR-T therapy outcomes by systematic review and meta-analysis approach.MethodsTwo reviewers independently searched Embase, PubMed, Web of Science, and Cochrane library to identify all records that described BT for LBCL treated with CAR-T. We then applied a fixed- or random-effects meta-analysis to estimate the pooled hazard ratios (HRs) and rate ratio (RRs) for efficacy and safety endpoints and assessed differences across various BT modalities. The Newcastle-Ottawa Scale was used to evaluate study quality.ResultsTwenty-six reports from 24 studies involving 2014 patients were included in the analysis. Pooled results showed that patients requiring BT had significantly worse 1-year overall survival rate (RR = 0.76, 95% confidence interval [CI] 0.68–0.85, P < 0.001), 1-year progression-free survival rate (RR = 0.71, 95% CI 0.60–0.85, P < 0.001), progression-free survival (HR = 1.35, 95% CI 1.07–1.69, P = 0.01), overall response rate (RR = 0.88, 95% CI 0.81–0.95, P = 0.001), complete response rate (RR = 0.78, 95% CI 0.65–0.93, P = 0.005), and grade ≥3 immune effector cell-associated neurotoxicity syndrome (RR = 1.43, 95% CI 1.10–1.87, P = 0.007), and tended to have poorer overall survival (HR = 1.42, 95% CI 0.99–2.02, P = 0.056) and grade ≥3 cytokine release syndrome (RR = 1.59, 95% CI 0.92–2.75, P = 0.096). Prolonged cytopenias were the common toxicity event associated with BT. Radiotherapy may serve as a promising BT option that can provide safe and effective disease control for patients with LBCL before CAR-T infusion. The inconsistency of patient baselines in the current study hindered further comparisons between different BT modalities. Most of the available evidence was rated as low quality because of concerns over low comparability.ConclusionBT appears to be associated with comparatively poor efficacy and safety outcomes after CAR-T infusion. However, due to the considerable heterogeneity between the BT and non-BT cohorts at disease baseline, no definitive conclusions can be made for the true impact of BT on CAR-T until further randomized studies are conducted.