Pooled Hazard Ratios For Overall Survival Research Articles

Baseline functioning scales of EORTC QLQ-C30 predict overall survival in patients with gastrointestinal cancer: a meta-analysis.

A consensus has not been reached on the value of quality of life (QoL) as a prognostic factor for survival in gastrointestinal cancer. This meta-analysis aimed to investigate the association between functioning scales of the EORTC QoL Questionnaire Core 30 (QLQ-C30) and the overall survival (OS) in patients with gastrointestinal cancer. A systematic literature search was conducted in PubMed, Web of Science, and Embase databases, until February 7, 2023. The studies included were those that investigated the association between baseline QoL measured by the functioning scales of EORTC QLQ-C30 and OS in patients with gastrointestinal cancer. The prognostic capacity of QoL was calculated by pooling the adjusted hazard ratios (HR) with 95% confidence intervals (CI). Twenty-four studies' analyses reported by 22 eligible articles involving 11,609 patients were included. When compared with good parameters of QoL, poor global QoL (HR 1.81; 95% CI 1.53-2.13), physical functioning (HR 1.51; 95% CI 1.31-1.74), social functioning (HR 1.67; 95% CI 1.30-2.15), and role functioning scale (HR 1.42; 95% CI 1.20-1.29) were significantly associated with decreased OS. For each 10-point increase in QLQ-C30 parameters, the pooled HR of OS was 0.87 (95% CI 0.83-0.92) for global QoL, 0.87 (95% CI 0.83-0.92) for physical functioning, and 0.93 (95% CI 0.88-0.97) for role functioning. However, each 10-point increase in social, emotional, or cognitive functioning scale did not significantly predict OS. Baseline health-related QoL defined by the physical functioning or global QoL scale of EORTC QLQ-C30 significantly predicts OS in patients with gastrointestinal cancer.

Antibiotic use reduces the efficacy of immune checkpoint inhibitors in patients with urothelial carcinoma: A systematic review and meta-analysis

ContextAntibiotics have been suggested to diminish the efficacy of immune checkpoint inhibitors (ICIs) by alterations of the gut microbiota. ObjectiveTo perform a meta-analysis summarizing the effect of antibiotics on the overall survival (OS) and progression-free survival (PFS) of urothelial cancer (UC) patients receiving ICI. Evidence acquisitionPubMed, EMBASE (Ovid), and the Cochrane Library were searched to identify studies published up to July 14, 2023. Studies reporting the associations between antibiotics use and OS and PFS in UC patients treated with ICI were included in this systematic review and meta-analysis. The random-effect model was used to pool the Hazard Ratios (HRs) for OS and PFS with 95% confidence interval (95%CI). The ROBINS-I was used to assess the risk of bias in the included studies, while the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) framework was used to inform the quality of evidence. Evidence synthesisThirteen nonrandomized studies involving a total of 5,095 ICI-treated UC patients were included in this review, of which 1434 (28%) received antibiotics. Overall, compared to patients who did not receive antibiotics, the pooled HRs for OS and PFS in those who received antibiotics were 1.45 [95% CI 1.25–1.68] and 1.40 [95% CI 1.05–1.87], respectively. Subgroup analysis revealed that the types of ICI and timing of antibiotic initiation did not influence the effect of antibiotics on OS and PFS in UC patients (P > 0.05). ConclusionsAntibiotic use significantly reduced OS and PFS in UC patients receiving ICI. While antibiotics remain crucial for the treatment of infections in UC patients, antibiotics should be prescribed cautiously in UC patients receiving ICI. Patient summaryAntibiotic use is associated with worsened survival in UC patients receiving immune checkpoint inhibitors.

Prognostic role of the prognostic nutritional index in patients with pancreatic cancer who underwent curative resection without preoperative neoadjuvant treatment: Asystematic review and meta-analysis.

BackgroundThe prognostic nutrition index (PNI), which has been evaluated in various kinds of cancers, offered a simple yet effective approach to predict the prognosis. The aim of this meta-analysis is to reveal the correlation between preoperative PNI and the prognosis of patients with pancreatic ductal adenocarcinoma (PDAC) who underwent curative resection.MethodsWe searched the PubMed, Embase, Web of Science and Cochrane Library databases, and extracted the hazard ratio (HR) with 95% confidential interval (CI) from eligible studies. The pooled HR with 95% CI was applied to evaluate the association between PNI and overall survival (OS), recurrence-free survival (RFS).ResultsA total of fourteen studies with 3,385 patients were included for meta-analysis. The results (the pooled HR: 1.664, 95% CI: 1.424–1.994, I² = 42.6%, p value = 0.046) indicated that low preoperative PNI was closely related to poor OS. In addition, the results suggested that PNI was negatively correlated with RFS (the pooled HR: 1.369, 95%CI: 1.080–1.734). The robustness of these pooled results was verified by our subgroup analysis and sensitivity analysis. Moreover, different cutoff values among studies are responsible for the heterogeneity of pooled HR of OS through meta-regression analysis (p value = 0.042). Funnel plots, Begg's test (p value = 0.228) and Egger’s test (p value = 0.702) indicated no significant publication bias in OS.ConclusionPreoperative PNI might be a promising marker to predict the prognosis of PDAC patients who underwent curative resection.

Viral infection and glioma: a meta-analysis of prognosis

BackgroundGlioma is the most common primary brain tumor, occurring due to the carcinogenesis of glial cells in the brain and spinal cord. Many aspects of the mechanism of its tumorigenesis remain unknown. The relationship between viral infection and glioma is one of the most important research aspects in this field. Currently, there is a lack of systematic reviews and meta-analyses to evaluate the effect of viral infection on the prognosis of glioma patients. The purpose of this study was to evaluate the relationship between viral infection and the prognosis of glioma patients, aimed at evaluating the prognostic value of the detection of viral infection.MethodsThrough careful and comprehensive retrieval of results from the PubMed, Embase, and Cochrane databases, eligible articles were selected strictly according to the inclusion and exclusion criteria. The regional sources, detection methods, detection indicators, patient survival, and other data from the samples in the papers were extracted, and the integrated analysis was conducted using Stata 15.1. We conducted a subgroup analysis of the relationship between the degree of infection and prognosis in cytomegalovirus (CMV) patients.ResultsA total of 11 studies were included in the analysis. Among them, 7 studies involved the relationship between CMV infection and the prognosis of patients with glioma, 2 studies involved human papillomavirus (HPV), 2 studies involved human herpesvirus-6 (HHV-6), and one study involved simian virus 40 (SV40), woolly monkey sarcoma virus (WMSV) and human endogenous retrovirus K113 (HERV-K113). In the CMV study, the pooled Hazard ratio (HR) of Overall survival (OS) was 1.024 (CI: 0.698–1.501), with a P value of 0.905. The pooled HR of Progression free survival (PFS) was 1.067 (CI: 0.770–1.478), with a P value of 0.697. The pooled HR value of low-degree infection versus high-degree infection was 1.476 (CI: 0.799–2.727), with a P value of 0.213. In the HPV study, the pooled HR of OS was 1.467 (CI: 0.552–3.901), with a P value of 0.443.ConclusionCMV infection has no significant effect on the prognosis of glioma patients. Using the IEA as the detection index, the degree of CMV infection was found to have a significant impact on the prognosis of glioma patients; it was not found to possess a significant prognostic value after the integration of different indicators. Neither HPV nor HHV-6 infection has a significant effect on the prognosis of glioma patients. SV40 and WMSV infection are associated with poor prognosis in patients with low-grade glioma.Trial RegistrationThis meta-analysis registered in https://www.crd.york.ac.uk/PROSPERO/, PROSPERO ID: CRD42019127648.

The impact of iron chelation therapy on patients with lower/intermediate IPSS MDS and the prognostic role of elevated serum ferritin in patients with MDS and AML: A meta-analysis.

Serum ferritin (SF) has been identified as a potential prognostic factor for patients undergoing stem cell transplantation, but the prognostic value of SF in acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) patients and the impact of iron chelation therapy (ICT) on MDS patients are controversial. The present meta-analysis aimed to better elucidate these relationships.Three electronic databases were searched systematically to identify reports on the prognostic role of SF in MDS and AML patients, and those investigating the impact of ICT on prognosis of MDS patients. The hazard ratios (HRs) and its 95% confidence interval (95%CI) were extracted from the identified studies using Cox proportional hazard regression model for overall survival (OS) and progression of MDS to AML.Twenty reports including 1066 AML patients and 4054 MDS patients were included in present study. The overall pooled HRs for OS of AML and MDS patients with elevated SF prior to transplantation was 1.73 (1.40-2.14), subgroup analyses stratified by the cut-off value of SF ≥1400/1000 ng/mL showed that the pooled HRs were 1.45 (0.98-2.15) and 1.65 (1.30-2.10), respectively. The pooled HRs for ICT in MDS patients was 0.30 (0.23-0.40). For ICT, the pooled HRs for the progression of MDS to AML was 0.84 (0.61-1.61).SF has a negative impact on the OS of AML and MDS patients when it is higher than 1000 ng/mL. ICT can improve the OS of MDS patients with iron overload but it is not associated with the progression of MDS to AML.

Prognostic value of ZEB-1 in solid tumors: a meta-analysis

BackgroundZinc-finger E-box binding homeobox 1 (ZEB-1) plays crucial roles in epithelial-to-mesenchymal transition during tumor carcinogenesis. Published studies have examined the potential value of ZEB-1 as a biomarker for the prognosis of cancer. Nevertheless, the prognostic significance of ZEB-1 in human solid tumor remains inconclusive. Therefore, we performed the present meta-analysis to evaluate the prognostic value of ZEB-1 in patients with solid tumors.MethodsThe 13 included studies (1616 patients) were exact electronic searched from Web of Science, PubMed and EBSCO until September 2018. Pooled hazard ratios (HR) and the corresponding 95% confidence intervals (CI) for overall survival (OS) were analyzed through random or fixed effects models. Univariate and multivariate analyses were independently performed. Subgroup analyses, heterogeneity and publication bias were investigated to further enhance reliability.ResultsThis research indicated that elevated expression of ZEB-1 significantly predicted worse OS in patients with solid tumors. In the univariate analysis, the pooled HR for OS was 1.66 (95% CI: 1.45–1.90; P < 0.01). Meanwhile, in multivariate analysis, the pooled HR for OS was 2.28 (95% CI: 1.58–3.30; P < 0.01). Begg’s funnel plot and Begg’s test did not show evidence of significant publication bias, both in univariate analysis and multivariate analysis.ConclusionsHigh expression of ZEB-1 was associated with poorer OS, suggesting that ZEB-1 may be a potential biomarker for the prediction of prognosis, and a novel therapeutic target in human solid tumors.

Checkpoint inhibitors in combination with chemotherapy for first-line treatment of advanced non-small cell lung cancer: A systematic review and meta-analysis of randomized controlled trials (RCTs).

e20558 Background: Non-small cell lung cancer (NSCLC) accounts for ~85% of lung cancers among which the metastatic disease represents ~ 57%, and long-term prognosis remains poor. Combined chemoimmunotherapy can have synergistic anticancer activities through the immunomodulatory impact of checkpoint inhibitors and the immunogenic effect of chemotherapy. Methods: We systematically conducted a comprehensive literature search using PUBMED, EMBASE and SCOPUS databases through January 31, 2019. RCTs of first-line chemotherapy +/- immunotherapy in patients with advanced NSCLC were incorporated in the analysis. A generic inverse variance method was used to calculate the estimated pooled Hazard ratio (HR) for overall survival (OS) and progression-free survival (PFS). The mantel-haenszel method was used to calculate the estimated pooled risk ratio (RR) with 95% confidence interval (CI) for pooled overall response rate (ORR), all-grade adverse events (AEs), and high-grade AEs (grade 3). Heterogeneity was assessed with Cochrane Q -statistic. Random effects were used due to significant heterogeneity among studies. Results: Nine phase 2 &amp; 3 RCTs (Keynote – 021,189, 407, IMpower – 130, 131, 132, 150, checkmate-227, and Govindan et al) including 5042 patients with advanced NSCLC patients were included in the meta-analysis. The study arm used standard chemotherapy regimens in combination with ipilimumab, pembrolizumab, atezolizumab, or nivolumab while control arm used only standard chemotherapy regimens. The pooled HR for PFS was 0.65 (95% CI: 0.57-0.73; P = 0.00001), the pooled HR for OS was 0.72 (95% CI: 0.61-0.86; P = 0.0003), and the pooled RR for ORR was 1.45 (95 CI: 1.23-1.72; P = 0.0001). The pooled RRs for all-grade AEs and high-grade AEs were 1.03 (95% CI: 0.99-1.07; P = 0.13) and 1.21 (95% CI: 1.1-1.34; P = 0.0001), respectively. Conclusions: The combined chemoimmunotherapy can significantly improve PFS, OS, and ORR compared to standard chemotherapy for the first-line treatment of advanced NSCLC. The combined regimen results in a slightly higher risk of high-grade AEs without a significant increase in the risk of all-grade AEs.

Prognostic value of 18F-FDG PET/CT functional parameters in patients with head and neck cancer: a meta-analysis.

We performed this meta-analysis to evaluate the prognostic value of maximum of standardized uptake value (SUVmax), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) in patients with head and neck cancer. Articles including prognostic value of PET/CT were searched in PubMed and subsequently analyzed. The primary outcome of interest was event-free survival, and the secondary outcome of interest was overall survival. Statistical analysis was performed using hazard ratio (HR) and odds ratio. Review manager 5.3 was used to generate the eligible data. A total of 28 studies with 1871 patients were included in this meta-analysis. The pooled HR for event-free survival was 1.84 [95% confidence interval (CI): 1.43-2.37, P<0.00001] with SUVmax, 3.38 (95% CI: 2.68-4.27, P<0.00001) with MTV, and 3.55 (95% CI: 2.69-4.70, P<0.00001) with TLG. Meanwhile, the pooled HR for overall survival was 1.07 (95% CI: 1.01-1.13, P=0.02) with SUVmax, 3.41 (95% CI: 2.33-4.97, P<0.00001) with MTV, and 2.75 (95% CI: 1.84-4.12, P<0.00001) with TLG. The results of analysis suggested that tumors with high volumetric parameters were associated with worse survival outcome. Prognostic value of MTV and TLG is superior to SUVmax, and MTV and TLG can be used as prognostic biomarkers to predict outcome in patients with head and neck cancer.

Checkpoint inhibitors in combination with chemotherapy for first-line treatment of advanced squamous non-small cell lung cancer: A systematic review and meta-analysis of randomized controlled trials (RCTs).

121 Background: Squamous Non-small cell lung cancer (NSCLC) accounts for ~30% of lung cancers, and long-term survival remains poor for advanced disease. Combined chemo-immunotherapy can have synergistic anticancer activities through the immunomodulatory impact of checkpoint inhibitors and the immunogenic effect of chemotherapy. Methods: We systematically conducted a comprehensive literature search using PUBMED, EMBASE and SCOPUS databases through October 1, 2018. RCTs of first-line chemotherapy +/- immunotherapy in patients with advanced squamous NSCLC were incorporated in the analysis. A generic inverse variance method was used to calculate the estimated pooled Hazard ratio (HR) for overall survival (OS) and progression-free survival (PFS). The mantel-haenszel method was used to calculate the estimated pooled risk ratio (RR) with 95% confidence interval (CI) for pooled overall response rate (ORR), all-grade adverse events (AEs), and high-grade AEs (≥grade 3). Heterogeneity was assessed with Cochrane Q -statistic. Random effects were used due to significant heterogeneity among studies. Results: Three phase 3 RCTs (Keynote – 407, IMpower – 131, and Govindan et al) including 1991 patients with advanced squamous NSCLC patients were included in the meta-analysis. The study arm used standard chemotherapy regimens in combination with ipilimumab, pembrolizumab, or atezolizumab, while control arm used only standard chemotherapy regimens. The pooled HR for PFS was 0.71 (95% CI: 0.56-0.9; P = 0.005), the pooled HR for OS was 0.84 (95% CI: 0.68-1.04; P = 0.11), and the pooled RR for ORR was 1.19 (95 CI: 0.9-1.56; P = 0.22). The pooled RRs for all-grade AEs and high-grade AEs were 1.17 (95% CI: 0.99-1.39; P = 0.07) and 1.36 (95% CI: 1.19-1.56; P = 0.0001), respectively. Conclusions: The combined chemo-immunotherapy improves PFS without significant improvement in OS &amp; ORR compared to standard chemotherapy for the first-line treatment of advanced squamous NSCLC. The combined regimen results in a slightly higher risk of high-grade AEs without a significant increase in the risk of all-grade AEs.

Checkpoint inhibitors in combination with chemotherapy for first-line treatment of advanced non-small cell lung cancer: A systematic review and meta-analysis of randomized controlled trials (RCTs).

117 Background: Non-small cell lung cancer (NSCLC) accounts for ~85% of lung cancers among which the metastatic disease represents ~ 57%, and long-term prognosis remains poor. Combined chemo-immunotherapy can have synergistic anticancer activities through the immunomodulatory impact of checkpoint inhibitors and the immunogenic effect of chemotherapy. Methods: We systematically conducted a comprehensive literature search using PUBMED, EMBASE and SCOPUS databases through October 1, 2018. RCTs of first-line chemotherapy +/- immunotherapy in patients with advanced NSCLC were incorporated in the analysis. A generic inverse variance method was used to calculate the estimated pooled Hazard ratio (HR) for overall survival (OS) and progression-free survival (PFS). The mantel-haenszel method was used to calculate the estimated pooled risk ratio (RR) with 95% confidence interval (CI) for pooled overall response rate (ORR), all-grade adverse events (AEs), and high-grade AEs (≥ grade 3). Heterogeneity was assessed with Cochrane Q-statistic. Random effects were used due to significant heterogeneity among studies. Results: Seven phase 2 &amp; 3 RCTs (Keynote-021,189, 407, IMpower-131, 150, checkmate-227, and Govindan et al) including 3785 patients with advanced NSCLC were included in the analysis. IMpower 150 trial allowed EGFR or ALK mutated patients. The study arm used standard treatment regimens in combination with ipilimumab, pembrolizumab, atezolizumab, or nivolumab, while control arm used only standard treatment regimens. The pooled HR for PFS was 0.65 (95% CI: 0.56-0.77; P=0.00001), the pooled HR for OS was 0.73 (95% CI: 0.59-0.90; P=0.003), and the pooled RR for ORR was 1.45 (95 CI: 1.17-1.8; P=0.0007). The pooled RRs for all-grade AEs and high-grade AEs were 1.1 (95% CI: 1-1.21; P=0.05) and 1.28 (95% CI: 1.13-1.46; P=0.0001), respectively. Conclusions: Adding immunotherapy to standard regimen significantly improves PFS, OS, and ORR for the first-line treatment of advanced NSCLC. The combined regimen results in a slightly higher risk of high-grade AEs without a significant increase in the risk of all-grade AEs.

Checkpoint inhibitors in combination with chemotherapy for first-line treatment of advanced nonsquamous non-small cell lung cancer: A systematic review and meta-analysis of randomized controlled trials (RCTs).

125 Background: RCTs have tested the role of adding immunotherapy to standard therapy in patients with advanced non-squamous non-small cell lung cancer (NSCLC) in the first-line setting. We conducted a systematic review and meta-analysis of RCTs to assess the efficacy and toxicity of adding immunotherapy in this patient population. Methods: We systematically conducted a comprehensive literature search using PUBMED, EMBASE and SCOPUS databases through October 1, 2018. RCTs of first-line standard therapy +/- immunotherapy in patients with advanced non-squamous NSCLC were incorporated in the analysis. A generic inverse variance method was used to calculate the estimated pooled Hazard ratio (HR) for overall survival (OS) and progression-free survival (PFS). The mantel-haenszel method was used to calculate the estimated pooled risk ratio (RR) with 95% confidence interval (CI) for pooled overall response rate (ORR), all-grade adverse events (AEs), and high-grade AEs (≥grade 3). Heterogeneity was assessed with Cochrane Q-statistic. Random effects were used due to significant heterogeneity among studies. Results: Three phase 2 &amp; 3 RCTs (Keynote – 021,189 and IMpower – 150) including 1431 patients with advanced non-squamous NSCLC patients were included in the analysis. Keynote 021 &amp; 189 trials did not allow patients with EGFR or ALK mutations, while IMpower 150 trial allowed EGFR or ALK mutations. The study arm used standard regimens in combination with pembrolizumab or atezolizumab while control arm used only standard regimens. The pooled HR for PFS was 0.57 (95% CI: 0.5-0.65; P=0.00001), the pooled HR for OS was 0.61 (95% CI: 0.43-0.87; P=0.006), and the pooled RR for ORR was 1.83 (95 CI: 1.13-2.95; P=0.01). The pooled RRs for all-grade AEs and high-grade AEs were 1 (95% CI: 0.99-1.02; P=0.48) and 1.11 (95% CI: 0.97-1.28; P=0.14), respectively. Conclusions: Pooled data showed significant improvement in PFS, OS &amp; ORR with chemo-immunotherapy compared to the standard treatment regimen for the first-line treatment of advanced non-squamous NSCLC. There was no increase in the risk of all-grade and high-grade AEs.

Clinicopathologic Features and Prognostic Implications of Golgi Phosphoprotein 3 in Non-small Cell Lung Cancer: A Meta-analysis.

Background: A number of studies have investigated the role of Golgi phosphoprotein-3 (GOLPH3) in the pathogenesis and progression of non-small cell lung cancer (NSCLC). However, the results of previous studies are heterogeneous and controversial. The aim of this meta-analysis was to clarify its association with the clinicopathological characteristics of patients and evaluate the prognostic significance of GOLPH3 in NSCLC.Methods: A systematic search was conducted through PMC, PubMed, Medline, Web of Science, Chinese National Knowledge Infrastructure and Wanfang database. The odds ratio (OR) and hazard ratio (HR) with 95 % CI were calculated by STATA 12.0.Results: 8 qualified studies with a total of 1001 patients with NSCLC were included. Pooled results showed that GOLPH3 was highly expressed in tumor tissues compared with adjacent lung tissues (OR, 7.55), and overexpression of GOLPH3 was significantly correlated with advanced clinical stage (OR, 3.42), poor differentiation of tumor (OR, 1.97) and positive lymph node metastasis (OR, 2.58), but no association with histological type, gender, age or tumor size was found in NSCLC patients. In addition, the pooled HR for overall survival was 1.79 by univariate analysis and 1.91 by multivariate analysis. The pooled HR for progression-free survival was 2.50.Conclusions: GOLPH3 could be a risk factor for progression of NSCLC and might act as a potential prognostic biomarker for NSCLC patients.

The effect of surgery on the survival status of patients with locally advanced cervical cancer after radiotherapy/chemoradiotherapy: a meta-analysis

BackgroundTo determine the effect of surgery on the survival status of patients with locally advanced cervical cancer after radiotherapy/chemoradiotherapy.MethodsPubMed, Web of Science, ProQuest and Medline were searched using the key words “cervical cancer”, “locally advanced disease”, “radiotherapy” and “surgery or hysterectomy”. Eight articles were selected and analysed using the STATA 12.0 software package. The log hazard ratio (HR) and its standard error for overall survival were calculated to assess the effect of surgery on patients with locally advanced cervical cancer after radiotherapy/chemoradiotherapy.ResultsIn total, 2176 patients with locally advanced cervical cancer were identified. The pooled HR for overall survival was 1.13 (95% confidence interval (CI) 0.906–1.409), and there were no differences among the eight manuscripts (z = 1.08, p = 0.278). In the subgroup analysis, the pooled HR for overall survival was 1.169 (95% CI 0.924–1.480), and no differences among patients with stage IB-IIB disease were found in six articles (z = 1.30, p = 0.193). There was no publication bias regarding overall survival or stage IB-IIB disease.ConclusionsThis meta-analysis suggested that surgery had no effect on overall survival after radiotherapy/chemoradiotherapy; therefore, it is not recommended for patients with locally advanced cervical cancer.

Meta-analysis for the efficacy of S-1-based regimens as the first-line treatment in Asian chemotherapy-naive patients with advanced non-small-cell lung cancer.

We performed a meta-analysis to evaluate the efficacy and safety for S-1-based regimens as the first-line treatment in Asian chemotherapy-naive patients with advanced non-small-cell lung cancer. Eligible randomized clinical trials (RCTs) were included, of which data were extracted by inclusion criteria and exclusion one. Odds ratio and hazard ratio (HR) of outcomes including objective response rate (ORR), progression-free survival (PFS), overall survival (OS) and adverse effects (AEs) were explored for the final analysis. Twenty-one RCTs including 3263 patients were fit into the analysis. Pooled HR for PFS was 1.01 (95% CI: 0.92-1.10; p=0.88), the pooled HR for OS was 0.95 (95% CI: 0.85-1.06; p=0.33) and the pooled odds ratio for ORR was 0.74 (95% CI: 0.61-0.90; p=0.003). S-1-based regimens showed milder AEs in high-grade nausea/vomit, anorexia, leukopenia, neutropenia and febrile neutropenia (all p<0.05). The present study has revealed that S-1-based regimens are accompanied by the similar efficacy and slighter AEs compared with standard regimens as the first-line treatment in Asian chemotherapy-naive patients with advanced non-small-cell lung cancer.

MTOR PATHWAY PROTEIN IMMUNOEXPRESSION AS A PROGNOSTIC FACTOR FOR SURVIVAL IN HNC: A SYSTEMATIC REVIEW AND META-ANALYSIS

Activated proteins in the mTOR pathway are deregulated in multiple types of cancer. These proteins may be important targets for anticancer therapy. The aim of this study was to summarize existing cohort studies to determine whether immunoexpression of mTOR pathway proteins are important prognostic factors for survival in head and neck cancer (HNC) patients. A systematic review was performed using the Cochrane, Lilacs, PubMed, ScienceDirect, Scopus and Web of Science databases (up to 23 January 2015). A meta-analysis was conducted to measure the frequency of protein expression in HNC patient samples and the prognostic value of mTOR pathway proteins for overall survival (OS) and disease-free survival (DFS). 12 studies were included in the final analysis. The meta-analysis revealed that the frequency of overall expression of mTOR pathway proteins was 74.42% (CI: 63.3 to 84.0, P < 0,001, n=2,016 samples). The survival meta-analysis showed a pooled hazard ratio for OS and DFS of 1.44 (95% confidence interval [95% CI] 1.14-1.73) and 1.18 (95% CI 0.71-1.64), respectively. This systematic review and meta-analysis support evidence that mTOR pathway proteins can be used as predictive markers for survival in HNC patients because their expression was significantly associated with poor OS and short DFS.

Circulating Vitamin D and Overall Survival in Breast Cancer Patients: A Dose-Response Meta-Analysis of Cohort Studies.

Studies have shown that vitamin D could have a role in breast cancer survival; however, the evidence of the relationship between patients’ vitamin D levels and their survival has been inconsistent. This meta-analysis explores possible dose-response relationships between vitamin D levels and overall survival by allowing for differences in vitamin D levels among populations of the various studies. Studies relating vitamin D (25-OH-D [25-hydroxyvitamin D]) levels in breast cancer patients with their survival were identified by searching PubMed and Embase. A pooled HR (hazard ratio) comparing the highest with the lowest category of circulating 25-OH-D levels were synthesized using the Mantel-Haenszel method under a fixed-effects model. A two-stage fixed-effects dose-response model including both linear (a log-linear dose-response regression) and nonlinear (a restricted cubic spline regression) models were used to further explore possible dose-response relationships. Six studies with a total number of 5984 patients were identified. A pooled HR comparing the highest with the lowest category of circulating 25-OH-D levels under a fixed-effects model was 0.67 (95% confidence interval = 0.56-0.79, P < .001). Utilizing a dose-response meta-analysis, the pooled HR for overall survival in breast cancer patients was 0.994 (per 1 nmol/L), Pfor linear trend < .001. At or above a 23.3 nmol/L threshold, for a 10 nmol/L, 20 nmol/L, or 25 nmol/L increment in circulating 25-OH-D levels, the risk of breast cancer overall mortality decreased by 6%, 12%, and 14%, respectively. There was no significant nonlinearity in the relationship between overall survival and circulating 25-OH-D levels. Our findings suggest that there is a highly significant linear dose-response relationship between circulating 25-OH-D levels and overall survival in patients with breast cancer. However, better designed prospective cohort studies and clinical trials are needed to further confirm these findings.

Prognostic role of telomere length in malignancies: A meta-analysis and meta-regression

Telomere length (TL) has been associated with several health conditions including cancer. To quantify the effect of TL on outcomes in malignancies and explore the role of type of TL measurement we conducted a librarian-led systematic search of electronic databases identified publications exploring the prognostic role of TL on cancer outcomes. Overall survival (OS) was the primary outcome measure while other time-to-event endpoints were secondary outcomes. Data from studies reporting a hazard ratio (HR) with 95% confidence interval (CI) and/or p-value were pooled in a meta-analysis. HRs were weighted by generic inverse variance and computed by random effects modeling. All statistical tests were two-sided. Sixty-one studies comprising a total of 14,720 patients were included of which 41 (67%) reported OS outcomes. Overall, the pooled HR for OS was 0.88 (95%CI=0.69–1.11, p=0.28). Long (versus short) telomeres were associated with improved outcomes in chronic lymphatic leukemia (CLL) and urothelial cancer (HR=0.45, 95%CI=0.29–0.71 and HR=0.68, 95%CI=0.46–1.00, respectively), conversely worse OS was seen with hepatocellular carcinoma (HR=1.90, 95%CI=1.51–2.38). Pooled HRs (95% CI) for progression-free survival, relapse/disease-free survival, cancer-specific survival, and treatment-free survival were 0.56 (0.41–0.76), 0.76 (0.53–1.10), 0.72 (0.48–1.10), and 0.48 (0.39–0.60), respectively. There was substantial heterogeneity of tissues and methods used for TL measurement and no clear association between TL and outcome was identified in subgroups. In conclusion, there is inconsistent effect of TL on cancer outcomes possibly due to variable methods of measurement. Standardization of measurement and reporting of TL is warranted before the prognostic value of TL can be accurately assessed.

Prognostic role of TET2 deficiency in myelodysplastic syndromes: A meta-analysis.

Tet methylcytosine dioxygenase2 gene (TET2) is one of the most frequently mutated gene in myeloid neoplasm, but the prognostic role of TET2 aberrations in myelodysplastic syndromes (MDS) remains unclear. Therefore, we performed a meta-analysis. Fourteen eligible studies with 1983 patients were included in this meta-analysis. Among these, 2 studies evaluated the impact that the TET2 expression level had on the prognosis. The combined hazard ratios (HR) estimated for overall survival (OS) was 1.00 (95%CI: 0.74 to 1.37; p=0.989) when comparing those with TET2 mutations with those without. Among the patients treated with hypomethylating agents (HMAs) or hematopoietic stem cell transplantation (HSCT), the pooled HR for OS was 1.02 (95% CI: 0.77-1.35, p=0.89) and 1.54 (95%CI: 0.69 to 3.44; p=0.29), respectively. We also conducted an analysis of the response rate to HMAs, and the OR was 1.73 (95%CI: 1.11 to 2.70; p=0.016). Additionally, subgroup analyses showed the pooled HR for OS was 0.93(95%CI: 0.44 to 1.98; P=0.849) in WHO-classified CMML patients and 1.02(95%CI: 1.02 to 3.46; p=0.042) in studies evaluated TET2 expression level. The analysis suggested TET2 mutations had no significant prognostic value on MDS. However, the response rates to HMAs were significantly different between those with and without TET2 mutations, and the low expression level of TET2 gene was significantly associated with a poor OS in MDS patients.

The efficacy and potential predictive factors of PD-1/PD-L1 blockades in epithelial carcinoma patients: a systematic review and meta analysis.

BackgroundThis systematic analysis aims to assess the efficacy of PD-1/PD-L1 blockades compared with non-PD-1/PD-L1 therapy and investigate the potential predictive factors in epithelial carcinoma patients.ResultsA total of 11 trials with 6716 patients of melanoma, non-small cell lung cancer (NSCLC) and renal cell carcinoma (RCC) were included. The pooled HRs (95%CI) were 0.67 (0.62, 0.73), p < 0.001 for OS and 0.66 (0.57, 0.76), p < 0.001 for PFS. In subgroup analyses, HRs were 0.58 (0.50, 0.66), p < 0.001 in PD-L1 ≥ 1% group, 0.75 (0.63, 0.89), p = 0.001 in PD-L1 < 1% group for OS and 0.59 (0.48, 0.72), p < 0.001 in PD-L1 ≥ 1% group, 0.80 (0.59, 1.07), p = 0.136 in PD-L1 < 1% group for PFS. The p values of pooled HRs for OS in different age, sex and ECOG score groups were less than 0.001. In NSCLC patients, aggregated HRs for OS were 1.40 (0.92, 2.12), p = 0.114 in EGFR mutant group and 0.88 (0.59, 1.32), p = 0.536 in never smokers.MethodsA systematic search from January 2010 to April 2016 was conducted for eligible clinical trials. Based on the data of hazard ratios (HRs) and 95% confidence intervals (CIs) for overall survival (OS) and progression-free survival (PFS), we assessed the pooled HRs and proposed the subgroup analyses.ConclusionsPD-1/PD-L1 blockades prolonged OS and PFS in epithelial carcinoma patients. PD-L1 expression was a predictive factor for PFS but not predictive for OS. Age, sex and ECOG score were excluded to predict any of the efficacy endpoints. Smoking history and EGFR wild type were associated with extended OS in NSCLC patients.

Prognostic significance of pretreated serum lactate dehydrogenase level in nasopharyngeal carcinoma among Chinese population: A meta-analysis.

Background:A large number of studies have investigated the prognostic value of pretreated lactate dehydrogenase (LDH) level in nasopharyngeal carcinoma (NPC) patients while the role of it was inconsistent and inconclusive. Hence, the aim of the current study was to conduct a meta-analysis of all published studies to quantify the prognostic impact of pretreated serum LDH in NPC for Chinese population.Objectives:The aim of the current study was to conduct a meta-analysis of all published studies to quantify the prognostic impact of pretreated serum lactate dehydrogenase (LDH) in nasopharyngeal carcinoma (NPC) for Chinese population.Methods:The PubMed, Medline, Embase, and Web of Science databases were searched for studies that assessed survival outcome and LDH in NPC. Overall survival (OS) was the primary survival outcome. Distant metastasis-free survival (DMFS) and disease-free survival (DFS) were secondary outcomes. The pooled hazard ratios (HRs), associated with 95% confidence intervals (95% CIs), were combined to calculate overall effects. The Cochran Q and I2 statistics were used to assess heterogeneity. When apparent heterogeneity was observed, sensitivity and meta-regression analyses were performed to explore its origin.Results:Sixteen studies, which included 14,803 patients, were enrolled in the current meta-analysis to yield statistics. Overall, the pooled HR for OS in 11 eligible studies with high LDH level was 1.79 (95% CI = 1.47–2.12), and the pooled HR for DMFS in 9 eligible studies with high LDH level was 1.85 (95% CI = 1.48–2.22). Meanwhile, the pooled HR for DFS in 5 eligible studies with high LDH level was 1.63 (95% CI = 1.34–1.91). Egger test and funnel plots revealed that the publication bias in the current meta-analysis was insignificant.Conclusions:The present meta-analysis demonstrated that high pretreated LDH level is significantly associated with poorer OS, DMFS, and DFS, suggesting that pretreated LDH could sever as a prognostic factor in NPC among Chinese population.