Association of SMAD4 loss with drug resistance in clinical cancer patients: A systematic meta-analysis

Background Drug resistance frequently led to the failure of chemotherapy for malignant cancers, hence causing cancer relapse. Thus, understanding mechanism of drug resistance in cancer is vital to improve the treatment efficacy. Here, we aim to evaluate the association between SMAD4 expression and the drug resistance in cancers by performing a meta-analysis. Method Relevant studies detecting SMAD4 expression in cancer patients treated with chemo-drugs up till December 2020 were systematically searched in four common scientific databases using selected keywords. The pooled hazard ratio (HR) was the ratio of hazard rate between SMAD4neg population vs SMAD4pos population. The HRs and risk ratios (RRs) with 95% confidence intervals (CIs) were used to explore the association between SMAD4 expression losses with drug resistance in cancers. Result After an initial screening according to the inclusion and exclusion criteria, eleven studies were included in the meta-analysis. There were a total of 2092 patients from all the included studies in this analysis. Results obtained indicated that loss of SMAD4 expression was significantly correlated with drug resistance with pooled HRs (95% CI) of 1.23 (1.01–1.45), metastasis with pooled RRs (95% CI) of 1.10 (0.97–1.25) and recurrence with pooled RRs (95% CI) of 1.32 (1.06–1.64). In the subgroup analysis, cancer type, drug type, sample size and antibody brand did not affect the significance of association between loss of SMAD4 expression and drug resistance. In addition, there was no evidence of publication bias as suggested by Begg’s test. Conclusion Findings from our meta-analysis demonstrated that loss of SMAD4 expression was correlated with drug resistance, metastasis and recurrence. Therefore, SMAD4 expression could be potentially used as a molecular marker for cancer resistance.

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The association between immune-related adverse events and the prognosis of solid cancer patients treated with immunotherapy: a systematic review and meta-analysis

Therapeutic Advances in Medical Oncology ◽

10.1177/1758835920980546 ◽

2020 ◽

Vol 12 ◽

pp. 175883592098054

Author(s):

Huilin Xu ◽

Ximing Xu ◽

Wei Ge ◽

Jinju Lei ◽

Dedong Cao

Keyword(s):

Adverse Events ◽

Cancer Patients ◽

Meta Analysis ◽

Progression Free Survival ◽

Cochrane Library ◽

Good Survival ◽

Solid Cancer ◽

Cancer Type ◽

Early Effect ◽

Overall Response

Background: Immune-related adverse events (irAEs) are common during immune checkpoint inhibitor (ICI) treatment and reported to be associated with good survival. This study evaluated the association between onset timing of irAEs and survival of cancer patients treated with ICIs. Methods: Databases including PubMed, Embase, and the Cochrane library were systematically searched to retrieve clinical studies assessing the relationship between irAEs and survival in cancer patients with ICIs. The overall response rate for treatment response and hazard ratio (HR) for overall survival (OS) and progression-free survival (PFS) were calculated using RevMan 5.3. Subgroup analysis in terms of cancer type, ICIs type, region, specific irAEs, accordingly. Results: A total of 34 studies were included. The HRs for OS and PFS in cancer patients with versus without irAEs were 0.57 [95% confidence interval (CI): 0.44, 0.74; p < 0.0001], and 0.50 (95% CI: 0.37, 0.67; p < 0.00001), respectively. The odds ratio for overall response in cancer patients with irAEs was 4.72 (95% CI: 3.48, 6.40; p < 0.00001) compared with those without irAEs. Subgroup analyses suggested that the prognostic role of irAEs was associated with cancer types and region, but not irAEs types. The landmark analysis of OS revealed that there is a non-proportional (early) effect of irAEs on OS in ICI-treated cancer patients (landmark >12 weeks, HROS = 1.08; 95% CI: 0.89, 1.30; p = 0.46). Conclusion: Our findings suggest that the occurrence of irAEs could be a prognostic factor for cancer patients who were treated with ICIs.

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Chemotherapy for Late-Stage Cancer Patients: Meta-Analysis of Complete Response Rates

F1000Research ◽

10.12688/f1000research.6760.1 ◽

2015 ◽

Vol 4 ◽

pp. 232 ◽

Cited By ~ 10

Author(s):

Martin L. Ashdown ◽

Andrew P. Robinson ◽

Steven L. Yatomi-Clarke ◽

M. Luisa Ashdown ◽

Andrew Allison ◽

...

Keyword(s):

Cancer Patients ◽

Late Stage ◽

Meta Analysis ◽

Complete Response ◽

Drug Regimen ◽

Cancer Type ◽

Late Stage Cancer ◽

Pubmed Database ◽

Wide Range ◽

Cancer Types

Complete response (CR) rates reported for cytotoxic chemotherapy for late-stage cancer patients are generally low, with few exceptions, regardless of the solid cancer type or drug regimen. We investigated CR rates reported in the literature for clinical trials using chemotherapy alone, across a wide range of tumour types and chemotherapeutic regimens, to determine an overall CR rate for late-stage cancers. A total of 141 reports were located using the PubMed database. A meta-analysis was performed of reported CR from 68 chemotherapy trials (total 2732 patients) using standard agents across late-stage solid cancers—a binomial model with random effects was adopted. Mean CR rates were compared for different cancer types, and for chemotherapeutic agents with different mechanisms of action, using a logistic regression. Our results showed that the CR rates for chemotherapy treatment of late-stage cancer were generally low at 7.4%, regardless of the cancer type or drug regimen used. We found no evidence that CR rates differed between different chemotherapy drug types, but amongst different cancer types small CR differences were evident, although none exceeded a mean CR rate of 11%. This remarkable concordance of CR rates regardless of cancer or therapy type remains currently unexplained, and motivates further investigation.

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The prognosis of cancer patients undergoing liposomal doxorubicin-based chemotherapy: a systematic review and meta-analysis

10.21203/rs.2.10907/v1 ◽

2019 ◽

Author(s):

Kaiping Zhang ◽

Zhi Sun ◽

Yin Zhang ◽

Chaozhao Liang ◽

Li Zhang ◽

...

Keyword(s):

Cancer Patients ◽

Liposomal Doxorubicin ◽

Chinese Literature ◽

Meta Analysis ◽

Cancer Prognosis ◽

Cochrane Library ◽

Cancer Type ◽

Conventional Chemotherapy ◽

China National Knowledge Infrastructure ◽

Drug Tolerability

Abstract Background It is well known that liposome-based delivery of cytotoxic chemotherapeutics has been proposed as a putative strategy to enhance drug tolerability and efficacy compared to the conventional chemotherapy. However, its potential effects on improving cancer patients prognosis remain largely unknown. The current meta-analysis is to explore the prognosis of cancer patients undergoing liposomal doxorubicin-based chemotherapy. Methods A detailed review of English and Chinese literature was conducted from PubMed, Embase, Cochrane Library, China Biology Medicine disc (CBM), China National Knowledge Infrastructure (CNKI) up to March 21st, 2019. We evaluate its possible correlations using hazard ratios (HRs) with 95% confidence intervals (CIs). The pooled data were calculated by STATA software and Review Manager 5.3 software. Results Consequently, 26 studies including 7943 patients were satisfied in current analysis. We found that there were no significant differences between liposomal and conventional chemotherapy in OS (HR=0.98, 95%CI: 0.93-1.04, P=0.544) and PFS (HR=1.00, 95%CI: 0.92-1.10, P=0.945). Likewise, subgroup-analysis regarding country, cancer type and sample sizes also showed the similar results of the two paired groups. Conclusion Taken together, our findings have demonstrated that there was no association of undergoing liposomal doxorubicin-based chemotherapy with cancer prognosis. However, detailed and further studies are needed to confirm these conclusions.

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Tau: At the Interface Between Neurodegeneration and Cancer?

10.20944/preprints202010.0349.v1 ◽

2020 ◽

Author(s):

Stéphanie Papin ◽

Paolo Paganetti

Keyword(s):

Meta Analysis ◽

Expression Level ◽

Cancer Type ◽

Cancer Resistance ◽

Tumor Cell Death ◽

Microtubule Network ◽

Related Disorder ◽

P53 Signaling ◽

Tau Expression

For its microtubule-binding properties, the expression level of the neurodegeneration-associated protein Tau is pondered as a potential modifier of cancer resistance to chemotherapy since decades. Indeed, Tau binds microtubules at the same site as taxanes, a class of chemotherapeutic drugs designed to stabilize the microtubule network in order to stall cell division and to induce tumor cell death. Whilst independent studies report the association between low Tau expression and superior taxane response, the data were refused by a meta-analysis, suggesting interference of other parameters. Unpredictably, Tau expression level was identified as a prognostic cancer marker, whereby its positive or negative predictive value for survival depended on the cancer type. With recent experimental evidence linking Tau to P53 signaling, DNA stability and protection and to the implication of Tau in cancer is strengthened. The identification of a role of Tau at the interface between two major aging-related disorder families, neurodegeneration and cancer, offers clues for the epidemiological observation inversely correlating these disorders. Elucidating how Tau is mechanistically implicated in cellular pathways common to these devastating illnesses may extend the Tau-targeting therapeutic opportunities to cancer.

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Anticoagulants for the treatment of venous thromboembolism in patients with cancer: An updated pairwise and network meta-analysis of randomized trials.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.e14692 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. e14692-e14692

Author(s):

Shima Sidahmed ◽

Ahmed Abdalla ◽

Babikir Kheiri ◽

Areeg Bala ◽

Mohammed Salih ◽

...

Keyword(s):

Venous Thromboembolism ◽

Cancer Patients ◽

Vitamin K ◽

Major Bleeding ◽

Metastatic Cancer ◽

Meta Analysis ◽

Number Needed To Treat ◽

Cancer Type ◽

Significant Difference ◽

All Cause Mortality

e14692 Background: Cancer-associated venous thromboembolism (VTE) is common. Although low molecular weight heparin (LMWH) is the standard therapy in this setting, little is known with regard to non-vitamin K antagonist oral anticoagulants (NOACs). Therefore, we thought about evaluating the safety and efficacy of various anticoagulants in this vulnerable population. Methods: Electronic database search was conducted to identify randomized clinical trials (RCTs) that compared LMWH, NOACs, and/or vitamin-K-antagonists (VKA) in cancer patients. We performed frequentist direct and Bayesian network meta-analysis using random-effects model to calculate odds ratios (ORs), 95% confidence intervals (CIs), and 95% credible intervals (CrIs). The primary outcome was VTE (pulmonary embolism and deep-vein thrombosis) recurrence. Secondary outcomes were major bleeding and all-cause mortality. Results: We identified 13 RCTs with 6,595 total patients (mean age 62.4 ± 12.2; 50.4% female; 17.7% hematological malignancies; and 6 months median follow-up). The most common cancer type was colorectal and 48% of the population had metastatic cancer at baseline. NOACs were associated with significantly reduced VTE recurrence compared with VKA (OR = 0.58; 95% CI = 0.40-0.83; P < 0.01; number needed to treat [NNT] = 40) and LMWH (OR = 0.46; 95% CI = 0.25-0.85; P = 0.01; NNT = 20). LMHW was associated with significantly reduced VTE recurrence compared with VKA (OR = 0.52; 95% CI = 0.39-0.71; P < 0.01; NNT = 18). NOACs were associated with significantly reduced major bleeding compared with VKA (OR = 0.56; 95% CI = 0.35-0.91; P = 0.02; NNT = 64). There was no significant difference identified between the anticoagulant groups in regard to all-cause mortality. Conclusions: Among cancer patients with VTE, NOACs were associated with significantly reduced VTE recurrence compared to LMWH and VKA, and significantly reduced major bleeding compared with VKA. LMWH was associated with significantly reduced VTE recurrence compared with VKA.

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The Significance of SIX1 as a Prognostic Biomarker for Survival Outcome in Various Cancer Patients: A Systematic Review and Meta-Analysis

Frontiers in Oncology ◽

10.3389/fonc.2021.622331 ◽

2021 ◽

Vol 11 ◽

Author(s):

Guang Zhu ◽

Ying Liu ◽

Lei Zhao ◽

Zhenhua Lin ◽

Yingshi Piao

Keyword(s):

Systematic Review ◽

Overall Survival ◽

Cancer Patients ◽

Human Cancer ◽

Meta Analysis ◽

Disease Free Survival ◽

Cancer Type ◽

Free Survival ◽

Cancer Types ◽

Disease Free

Sine Oculis Homeobox Homolog 1 (SIX1) is reported to promote cancer initiation and progression in many preclinical models and is demonstrated in human cancer tissues. However, the correlation between SIX1 and cancer patients’ prognosis has not yet been systematically evaluated. Therefore, we performed a systematic review and meta-analysis in various human cancer types and extracted some data from TCGA datasets for further verification and perfection. We constructed 27 studies and estimated the association between SIX1 expression in various cancer patients’ overall survival and verified with TCGA datasets. Twenty-seven studies with 4899 patients are include in the analysis of overall, and disease-free survival, most of them were retrospective. The pooled hazard ratios (HRs) for overall and disease-free survival in high SIX1 expression patients were 1.54 (95% CI: 1.32-1.80, P<0.00001) and 1.83 (95% CI: 1.31-2.55, P=0.0004) respectively. On subgroup analysis classified in cancer type, high SIX1 expression was associated with poor overall survival in patients with hepatocellular carcinoma (HR 1.50; 95% CI: 1.17-1.93, P =0.001), breast cancer (HR 1.31; 95% CI: 1.10-1.55, P =0.002) and esophageal squamous cell carcinoma (HR 1.89; 95% CI: 1.42-2.52, P<0.0001). Next, we utilized TCGA online datasets, and the consistent results were verified in various cancer types. SIX1 expression indicated its potential to serve as a cancer biomarker and deliver prognostic information in various cancer patients. More works still need to improve the understandings of SIX1 expression and prognosis in different cancer types.

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Pembrolizumab versus the standard of care for cancer therapy: A meta-analysis of 12 KEYNOTE trials comparing overall survival.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.e14159 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. e14159-e14159 ◽

Cited By ~ 1

Author(s):

Nathaniel Parker ◽

Ammar Al-Obaidi ◽

Quoc Van Truong ◽

Robert Badgett

Keyword(s):

Overall Survival ◽

Cancer Patients ◽

Checkpoint Inhibitors ◽

Meta Analysis ◽

Antineoplastic Agent ◽

Standard Of Care ◽

Phase Iii ◽

Cancer Type ◽

Random Effects Models ◽

Phase Iii Trials

e14159 Background: Pembrolizumab (P) is an antineoplastic agent approved for multiple different tumor origins as well as tumor agnostic based on MSI status. Thus understanding the tumor characteristics most predictive of response is essential. Living meta-analysis provides a method to continuously assimilate emerging trials. In this study, we created a living meta-analysis to compare the effect of P on overall survival (OS). Methods: Meta-analysis was conducted according to the PRISMA guidelines. PubMed and Cochrane databases, and conference abstracts (e.g. ASCO, ESMO), were searched for phase III KEYNOTE RCT’s that reported OS among cancer patients receiving P. Results: 12 phase III trials involving 7,319 patients (3,861 in P arms) treated for 6 different types of cancer were retrieved. Median follow up was 12.9 months [range: 0.1-35.5]. Treatment was P alone, SOC chemo, and P + chemo in 11 (40%), 13 (46%), and 4 (14%) arms, respectively. P significantly improved OS (HR 0.71, 95% CI: 0.59-0.85, p <0.001, I2 = 0%) when used in any cancer type, setting, or therapy for advanced refractory or chemo-naïve cancer patients. The mean median OS was 12.5 vs 11.1 months in the total populations for all P and control arms, respectively (Table). Conclusions: Among all trials, P was associated with improved OS. Additional meta-analysis will be performed with R software (version 3.3.3; R Fdn.). Random-effects models will be used to compare OS. Heterogeneity will be assessed with Cochrane Q -statistic and quantified with I2test via subgroup analyses for cancer type, setting, therapy, and PD-L1%. This meta-analysis is continuously updated at http://openmetaanalysis.github.io/checkpoint-inhibitors. [Table: see text]

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Prevalence and Prognostic Significance of Hyponatremia in Lung Cancer Patients: Systematic Review and Meta-Analysis

10.21203/rs.3.rs-104861/v1 ◽

2020 ◽

Author(s):

Eszter Bartalis ◽

Marin Gergics ◽

Benedek Tinusz ◽

Mária Földi ◽

Szabolcs Kiss ◽

...

Keyword(s):

Lung Cancer ◽

Systematic Review ◽

Cancer Patients ◽

Systematic Reviews ◽

Meta Analysis ◽

Prognostic Significance ◽

Small Cell ◽

Cancer Type ◽

Lung Cancer Patients ◽

Significant Difference

Abstract Background The prevalence of hyponatremia is highly variable among lung cancer patients. It is also an important predictive factor, according to numerous studies. However, its prevalence and prognostic significance in subgroups of lung cancer patients, e.g. in small cell and non-small cell lung cancers (SCLC and NSCLC, respectively), have not yet been evaluated in a meta-analysis.Methods We report this systematic review and meta-analysis according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA 2009) Statement. We have registered our meta-analysis and review’s protocol to the PROSPERO International Prospective Register of Systematic Reviews, with the following registration number: CRD42020167013. A systematic search was done in the following sources: MEDLINE, Embase, CENTRAL, Web of Science, ClinicalTrials.gov, a WHO Global Health Library. We extracted the effect measure for each outcome as the relative risk (RR) with the related 95% confidence interval (CI). Results We identified a total of 8127 potentially eligible studies and we included 25 studies in our evaluation. The prevalence of hyponatremia in lung cancer patients varied between 3% and 56.1% with an average of 23% without any significant differences between the following subgroups: cancer type (p=0.780), gender (p=0.223), age (p=0.773), ECOG state (p=0.317) and the extent of disease (p=0.999). Hyponatremia was more consistently an independent prognostic factor in NSCLC than in SCLC. The overall survival (OS) was significantly lower in hyponatremic compared to normonatremic patients at 10 months (RR: 0.59, 95% CI, 0.47 to 0.74, p<0.001) and at 20 months (RR: 0.44, 95% CI, 0.33 to 0.59, p<0.001), with worse survival rates in NSCLC than in SCLC (27% vs 42%) (p<0.001). If hyponatremia was corrected, OS at 10 months was 1.83 times higher than in the uncorrected hyponatremia group (95% CI, 1.37 to 2.44, p<0.001), but at 20 months no statistically significant difference could be found between these subgroups (p=0.067).Conclusions Low serum sodium levels have a negative impact on mortality at 10 and 20 months, which is more pronounced among NSCLC patients. The correction of hyponatremia has a positive effect on OS rates at 10 months, but this advantage disappears by 20 months.

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Nivolumab versus the standard of care for cancer therapy: A meta-analysis of 6 CHECKMATE trials comparing overall survival.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.e15165 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. e15165-e15165

Author(s):

Ammar Al-Obaidi ◽

Nathaniel Parker ◽

Quoc Van Truong

Keyword(s):

Overall Survival ◽

Cancer Patients ◽

Survival Data ◽

Meta Analysis ◽

Antineoplastic Agent ◽

Standard Of Care ◽

Phase Iii ◽

Cancer Type ◽

Random Effects Models ◽

Line Setting

e15165 Background: Nivolumab (N) is an antineoplastic agent approved for multiple different tumor origins as well as tumor agnostic based on MSI status. Thus, understanding the tumor characteristics most predictive of response is essential. Living meta-analysis provides a method to continuously assimilate emerging trials. In this study, we created a living meta-analysis to compare the effect of N on overall survival (OS). Methods: Meta-analysis was conducted according to the PRISMA guidelines. PubMed and Cochrane databases, and conference abstracts (e.g. ASCO, ESMO), were searched for phase III CHECKMATE RCT’s that reported OS among cancer patients receiving N. Results: Six phase III trials involving 3,342 patients (1,826 in N arms) treated for 4 different types of cancer were retrieved. Median follow up was 12.1 months [range: 5.1-25.2]. Improved efficacy and safety were observed in all N arms compared to control groups (22.8% ORR; 17.4% grade 3-5 AE vs 15.1% ORR; 51% grade 4-5 AE). Treatment was N alone, SOC chemo, and N + chemo in four (33%), six (50%), and two (16%) arms, respectively. Primary endpoints were OS in the first-line setting in 50% of all arms. Excluding one RCT due to insufficient survival data, the mean median OS was 11.1 [95% CI: 7.5-14.4] vs 8.7 [95% CI: 5.1-13.2] months in the total populations for all N and control arms, respectively. N improved OS when used in any cancer type, setting, or therapy for advanced refractory or chemo-naive cancer patients. Also, efficacy of N was improved with PD-L1% (Table). Conclusions: Among all trials, N was associated with improved OS. Additional meta-analysis is ongoing with R software (version 3.3.3; R Fdn.). Random-effects models will be used to compare OS. Heterogeneity will be assessed with Cochrane Q-statistic and quantified with I2test via subgroup analyses for cancer type, setting, therapy, and PD-L1%. [Table: see text]

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Venous Thromboembolism in Pediatric Cancer Patients with Central Venous Catheter—A Systematic Review and Meta-analysis

Seminars in Thrombosis and Hemostasis ◽

10.1055/s-0041-1729886 ◽

2021 ◽

Author(s):

Rasmus Søgaard Hansen ◽

Mads Nybo ◽

Anne-Mette Hvas

Keyword(s):

Venous Thromboembolism ◽

Cancer Patients ◽

Solid Tumors ◽

Pediatric Cancer ◽

Lymphoblastic Leukemia ◽

Meta Analysis ◽

Cancer Type ◽

Central Venous ◽

Increased Risk ◽

Pediatric Cancer Patients

AbstractPediatric cancer patients hold an increased risk of venous thromboembolism (VTE) due to their cancer. Central venous catheters (CVCs) further increase the VTE risk. This systematic literature review elucidates the VTE incidence in pediatric cancer patients with CVC. MEDLINE and EMBASE were searched in August 2020 without time limits. We included studies reporting original data on patients ≤18 years with any CVC type and any cancer type, who were examined for VTE with ≥7 days follow-up. In total, 682 unique records were identified, whereof 189 studies were assessed in full text. Altogether, 25 studies were included, containing 2,318 pediatric cancer patients with CVC, of which 17% suffered VTE. Fifteen studies (n = 1,551) described CVC-related VTE and reported 11% CVC-related VTE. Concerning cancer type, 991 children suffered from acute lymphoblastic leukemia (ALL) and 616 from solid tumors. Meta-analysis revealed VTE incidence (95% confidence interval) of 21% (8–37) for ALL and 7% (0.1–17) for solid tumors. Additionally, 20% of children with tunneled or nontunneled CVC and 12% of children with implantable ports suffered VTE. In conclusion, pediatric cancer patients with CVC have substantial VTE risk. Children with ALL and CVC have higher VTE incidence than children with solid tumors and CVC. Implantable port catheter should be preferred over tunneled or nontunneled CVC to reduce VTE risk. Thrombophilia investigation does not seem relevant in pediatric cancer patients with CVC and VTE. To prevent VTE, intensified catheter care is recommended, especially in children with ALL.

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