The Impact of CDA A79C Gene Polymorphisms on the Response and Hematologic Toxicity in Gemcitabine-Treated Patients: A Meta-Analysis

2014 ◽  
Vol 29 (3) ◽  
pp. 224-232 ◽  
Author(s):  
Hui Li ◽  
Xiangling Wang ◽  
Xiuwen Wang
Keyword(s):  
Response Rate ◽  
Cytidine Deaminase ◽  
Meta Analysis ◽  
Severe Neutropenia ◽  
Hematologic Toxicity ◽  
Severe Anemia ◽  
Wild Type ◽  
Mutant Type ◽  
Nsclc Patients ◽  
The Impact

Purpose To investigate the impact of the cytidine deaminase (CDA) A79C polymorphism on both the response to gemcitabine in non-small cell lung cancer (NSCLC) patients and the risk of hematologic toxicities in patients bearing any kind of cancer taking gemcitabine. Methods The PubMed and Embase databases were searched from the first available article to January 2013. Eligible studies included clinical trials that contained the keywords “gemcitabine” or “cytidine deaminase” and information about response rate of NSCLC patients or hematologic toxicities in patients with any kind of cancer. Relative risk (RR) of different genotypes and 95% confidence intervals (CI) were calculated. Results A total of 7 articles (623 patients from 6 studies) were included. The results showed that patients with wild type CDA (AA and AC) had a significantly lower rate of severe anemia than the homozygote mutant type CC (RR=0.308; 95%CI, 0.113-0.021, p=0.021). However, the rate of severe neutropenia, thrombocytopenia, and the response rate were identical between different CDA genotypes. Conclusion The A79C CDA polymorphism did not show a significant impact on the response rate to gemcitabine in NSCLC patients, while the wild type CDA genotype was indeed correlated to a lower rate of incidence of severe anemia in patients taking gemcitabine.

scholarly journals A meta-analysis reveals the environmental and host factors shaping the structure and function of the shrimp microbiota

PeerJ ◽  
2018 ◽  
Vol 6 ◽  
pp. e5382 ◽  
Author(s):  
Fernanda Cornejo-Granados ◽  
Luigui Gallardo-Becerra ◽  
Miriam Leonardo-Reza ◽  
Juan Pablo Ochoa-Romo ◽  
Adrian Ochoa-Leyva
Keyword(s):  
Developmental Stage ◽  
High Throughput Sequencing ◽  
Meta Analysis ◽  
Biological Factor ◽  
Rrna Gene ◽  
Wild Type ◽  
Biological Factors ◽  
Sequencing Data ◽  
Freshwater Environment ◽  
The Impact

The shrimp or prawn is the most valuable traded marine product in the world market today and its microbiota plays an essential role in its development, physiology, and health. The technological advances and dropping costs of high-throughput sequencing have increased the number of studies characterizing the shrimp microbiota. However, the application of different experimental and bioinformatics protocols makes it difficult to compare different studies to reach general conclusions about shrimp microbiota. To meet this necessity, we report the first meta-analysis of the microbiota from freshwater and marine shrimps using all publically available sequences of the 16S ribosomal gene (16S rRNA gene). We obtained data for 199 samples, in which 63.3% were from marine (Alvinocaris longirostris, Litopenaeus vannamei and Penaeus monodon), and 36.7% were from freshwater (Macrobrachium asperulum, Macrobrachium nipponense, Macrobranchium rosenbergii, Neocaridina denticulata) shrimps. Technical variations among studies, such as selected primers, hypervariable region, and sequencing platform showed a significant impact on the microbiota structure. Additionally, the ANOSIM and PERMANOVA analyses revealed that the most important biological factor in structuring the shrimp microbiota was the marine and freshwater environment (ANOSIM R = 0.54, P = 0.001; PERMANOVA pseudo-F = 21.8, P = 0.001), where freshwater showed higher bacterial diversity than marine shrimps. Then, for marine shrimps, the most relevant biological factors impacting the microbiota composition were lifestyle (ANOSIM R = 0.341, P = 0.001; PERMANOVA pseudo-F = 8.50, P = 0.0001), organ (ANOSIM R = 0.279, P = 0.001; PERMANOVA pseudo-F = 6.68, P = 0.001) and developmental stage (ANOSIM R = 0.240, P = 0.001; PERMANOVA pseudo-F = 5.05, P = 0.001). According to the lifestyle, organ, developmental stage, diet, and health status, the highest diversity were for wild-type, intestine, adult, wild-type diet, and healthy samples, respectively. Additionally, we used PICRUSt to predict the potential functions of the microbiota, and we found that the organ had more differentially enriched functions (93), followed by developmental stage (12) and lifestyle (9). Our analysis demonstrated that despite the impact of technical and bioinformatics factors, the biological factors were also statistically significant in shaping the microbiota. These results show that cross-study comparisons are a valuable resource for the improvement of the shrimp microbiota and microbiome fields. Thus, it is important that future studies make public their sequencing data, allowing other researchers to reach more powerful conclusions about the microbiota in this non-model organism. To our knowledge, this is the first meta-analysis that aims to define the shrimp microbiota.

scholarly journals CTNI-22. RETROSPECTIVE ANALYSIS OF THE COMBINED TREATMENT OF VINCRISTINE, ACNU, CARBOPLATIN AND INTERFERON-β PLUS RADIOTHERAPY (VAC-FERON-R)IN PATIENTS WITH DIFFUSE ASTROCYTOMA

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii47-ii47
Author(s):  
Yoshiki Arakawa ◽  
Yasuhide Makino ◽  
Takeshi Kawauchi ◽  
Masaharu Tanji ◽  
Yohei Mineharu ◽  
...  
Keyword(s):  
Combined Treatment ◽  
Diffuse Astrocytoma ◽  
Wild Type ◽  
Interferon Β ◽  
Mutant Type ◽  
Who Grade ◽  
Integrated Diagnosis ◽  
Significant Difference ◽  
Favorable Clinical Outcome ◽  
The Impact

Abstract OBJECTIVE Diffuse astrocytomas are classified as WHO grade II and its median overall survival (mOS) is 10 to 11 years. The efficacy of chemoradiation in the high-risk feature has been reported. The prognosis is associated with IDH and TERT promoter (TERTp) mutations. Here, we retrospectively analyzed the patients with diffuse astrocytoma treated with vincristine, ACNU, carboplatin and interferon-β plus radiotherapy (VAC-feron-R)in our institute. PATIENTS AND METHODS Between December 2003 to January 2016, 44 patients were diagnosed as diffuse astrocytoma with integrated diagnosis of histological and molecular analysis. The average age was 43.1 years (22–71 years). They received VAC-feron-R as initial treatment in our institute. We analyzed the IDH1/2 and the TERTp mutation using Sangar sequencing and determined the 1p/19q codeletion by the fluorescence in situ hybridization or the multiplex ligation-dependent probe amplification. RESULTS Median follow-up period was 76.5 months, mPFS was 126 months, mOS did not reach, and 10-year survival rate was 60%.IDH status was determined in 29 patients, 9 mutant and 20 wild types. There was no significant difference in PFS and OS between the two groups. TERTp status was determined in 18 patients with IDH wild type, 6 mutant and 12 wild types. mPFS of patients with TERTp wild type did not reach, but that with TERTp mutant type was 34.5 months (p = 0.0356). CONCLUSION Compared with previous clinical studies, VAC-feron-R showed a favorable clinical outcome in diffuse astrocytoma. The impact of TERTp status on prognosis was identified but not IDH status in this cohort.

PIK3CA Mutations and Their Impact on Survival Outcomes of Patients with Cervical Cancer: A Systematic Review

2020 ◽  
Vol 64 (6) ◽  
pp. 547-555
Author(s):  
Vasilios Pergialiotis ◽  
Christina Nikolaou ◽  
Dimitrios Haidopoulos ◽  
Maximos Frountzas ◽  
Nikolaos Thomakos ◽  
...  
Keyword(s):  
Systematic Review ◽  
Cervical Cancer ◽  
Cancer Progression ◽  
Meta Analysis ◽  
Current Evidence ◽  
Survival Outcomes ◽  
Cochrane Central Register ◽  
Wild Type ◽  
Pik3ca Mutations ◽  
The Impact

<b><i>Introduction:</i></b> Several studies have implicated the PIK3/AKT pathway in the pathophysiology of cancer progression as its activation seems to be aberrant in several forms of cancer. The purpose of the present systematic review is to evaluate the impact of PIK3CA mutations on survival outcomes of patients with cervical cancer. <b><i>Methods:</i></b> We used the Medline (1966–2020), Scopus (2004–2020), ClinicalTrials.gov (2008–2020), EMBASE (1980–2020), Cochrane Central Register of Controlled Trials (CENTRAL) (1999–2020), and Google Scholar (2004–2020) databases in our primary search along with the reference lists of electronically retrieved full-text papers. Statistical meta-analysis was performed with the RevMan 5.3 software. <b><i>Results:</i></b> Overall, 12 articles were included in the present study that comprised 2,196 women with cervical cancer. Of those, 3 studies did not report significant differences in survival outcomes among patients with mutated versus wild-type PIK3CA tumors, 5 studies reported decreased survival outcomes, and 3 studies revealed increased survival rates. The meta-analysis revealed that patients with the mutated PIK3CA genotypes had worse overall survival compared to patients with wild-type PIK3CA (HR 2.31; 95% CI: 1.51, 3.55; 95% PI: 0.54, 9.96; data from 3 studies) and the same was observed in the case of DFS rates (HR 1.82; 95% CI: 1.47, 2.25; 95% PI: 1.29, 2.56; data from 4 studies). <b><i>Conclusion:</i></b> Current evidence concerning the impact of PIK3CA mutations on survival outcomes of patients with cervical cancer is inconclusive, although the majority of included studies support a potential negative effect, primarily among those with squamous cell carcinoma tumors.

scholarly journals 3363 Prognostic Value of Immune-Related Biomarkers in Resected Non-Small Cell Lung Cancer

2019 ◽  
Vol 3 (s1) ◽  
pp. 153-153
Author(s):  
Rajwanth R Veluswamy ◽  
Stephanie Tuminello ◽  
Francesca Petralia ◽  
Wil Lieberman-Cribbin ◽  
Pei Wang ◽  
...  
Keyword(s):  
Nk Cells ◽  
Immune Cells ◽  
Immune Cell ◽  
Meta Analysis ◽  
Stage I ◽  
Resected Stage ◽  
Iiia Nsclc ◽  
Nsclc Patients ◽  
Lung Adenocarcinomas ◽  
The Impact

OBJECTIVES/SPECIFIC AIMS: Immune cells within the tumor microenvironment (TME) play an important role in the development and progression of non-small cell lung cancer (NSCLC). However, data evaluating the impact of individual immune cell types on NSCLC outcomes is limited and often conflicting. We performed a meta-analysis of existing data and used The Cancer Genome Atlas (TCGA) to evaluate the effect of several immune cells on surgical outcomes of stage I-IIIA NSCLC. METHODS/STUDY POPULATION: PubMed was searched to identify eligible studies evaluating survival of surgically resected stage I-IIIA NSCLC patients according to immune cell infiltration. Meta-analysis was performed using a linear mixed-effects model to determine overall, disease specific and progression free survival. We then used a similar patient subset found in the TCGA to validate the meta-analysis findings. For the TCGA analysis, sample-specific scores for different immune cells were computed via xCell using level three RNAseq data. After stratifying the cohort by histologic subtype, the association between each cell type and survival was assessed via Cox Regression, while adjusting for stage, gender and smoking status. RESULTS/ANTICIPATED RESULTS: From the meta-analysis (37 articles eligible; N = 8,162 patients), high levels of CD20+ B cells (hazard ratio [HR]: 0.36, 95% confidence interval [CI]: 0.15-0.85), natural killer (NK) cells (HR: 0.64, 95% CI: 0.41-1.0), and dendritic cells (0.34, 95% CI: 0.13-0.84) were significantly associated with better overall survival (OS); T regulatory cells (HR: 1.85, 95% CI: 1.35-2.54) were associated with worst OS. High CD8+ T cell infiltrates were associated with improved disease-free survival (DFS; HR: 0.85, 95% CI 0.73-0.99), while CD68+ macrophages (HR> 2.83, 95% CI: 1.28-6.24) were associated with worst DFS. In the TCGA cohort, lung adenocarcinomas rich in CD4 T cells, CD8 T cells, B cells, and NK cells were associated with improved OS in unadjusted analysis. In adjusted analysis, only NK cells were associated with improved OS (HR: 0.82, 95% CI: 0.69-0.98). There was no significant association of any immune cell type for DFS in lung adenocarcinomas and with both OS and DFS in Squamous Cell Lung Cancers (p>0.05 for all comparisons). DISCUSSION/SIGNIFICANCE OF IMPACT: The presence of tumor infiltration by specific immune cell subsets may potentially predict survival outcomes in resected stage I-III NSCLC patients. However, the impact of immune cells may not be similar in all histologic types and after adjusting for important clinical confounders.

Impact of gemcitabine (G) on the activity of first-line chemotherapy in non-small cell lung cancer (NSCLC): A meta-analysis

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 7138-7138
Author(s):  
G. L. Pappagallo ◽  
O. Belvedere ◽  
O. Vinante ◽  
F. Grossi
Keyword(s):  
Meta Analysis ◽  
Performance Status ◽  
Objective Response ◽  
Response To Treatment ◽  
Third Generation ◽  
First Line ◽  
Significant Difference ◽  
Nsclc Patients ◽  
The Impact ◽  
Line Chemotherapy

7138 Background: A two-drug platinum-based regimen in which cisplatin or carboplatin is combined with a third-generation agent (i.e. paclitaxel, vinorelbine, docetaxel, or G) is the standard first-line treatment for NSCLC patients with good performance status. Encouraging results have recently been reported for nonplatinum regimens composed of two third-generation drugs. Methods: To assess the impact of G on the activity of first-line chemotherapy in NSCLC, we carried out a meta-analysis on data from 4,362 NSCLC patients who were enrolled in 11 randomized trials comparing a G-containing vs. G-free new generation regimens. We constructed 2x2 tables using response to treatment data. For trials with more than one eligible G-free comparator arm, individual comparisons between the G-based treatment arms and each of the comparator arms were analyzed. A general variance-based method was used to estimate the pooled odds ratio (OR) and 95% confidence interval (CI). We assessed for heterogeneity among the trials based on standard methods. Results: Sixteen comparisons contributed to this analysis. G-containing regimens included: G+cisplatin (894), G+docetaxel (565), G+paclitaxel (200 patients), G+vinorelbine (157), G+carboplatin (49). G-free regimens included: vinorelbine+cisplatin (866), carboplatin+paclitaxel (539), docetaxel+cisplatin (494), cisplatin+paclitaxel (439), vinorelbine+carboplatin (159). Comparing G-containing vs. G-free regimens, the OR for progression was 0.867 (CI 95% 0.770–0.977; p = 0.019), with heterogeneity chi-square 11.639 (p = 0.71). No significant difference was observed for complete (OR 0.909, CI 95% 0.556–1.487; P = 0.707) and overall (complete + partial) response (OR 0.987, CI 95% 0.881–1.106; P = 0.819). Conclusions: These data demonstrate that the progression of disease is more likely in patients treated with G-free doublets. Further analyses are required to address whether disease control (objective response + stable disease) is associated with a survival benefit and may therefore be used as a surrogate end point for survival in chemotherapy trials of NSCLC. No significant financial relationships to disclose.

scholarly journals The Prognostic Influence of Venous Thromboembolism in Non-Small Cell Lung Cancer: A Meta-Analysis and Systematic Review

2020 ◽  
Author(s):  
Yu Bai ◽  
Xu Ma ◽  
Sen Han ◽  
Jian Fang
Keyword(s):  
Lung Cancer ◽  
Venous Thromboembolism ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Meta Analysis ◽  
Small Cell ◽  
Cochrane Library ◽  
Small Cell Lung ◽  
Nsclc Patients ◽  
The Impact

Abstract Background: Patients with non-small cell lung cancer (NSCLC) have a significantly higher risk of developing venous thromboembolism (VTE), a condition that significantly influences the prognosis of these patients. However, the impact of VTE on the survival of NSCLC patients remains unclear. We aim to evaluate the impact of VTE on the mortality of patients with NSCLC. Methods: We systematically reviewed all indexed studies examining the prognosis of NSCLC patients with VTE. Web of Science, EMBASE, PubMed, and the Cochrane Library were searched through December 31, 2019 to identify relevant studies. Fixed- or random-effects models were chosen based on heterogeneity. Results: Twelve articles with 6480 patients were included in this analysis. The heterogeneity of these studies was significant (I2=81%, P<0.01). The overall survival (OS) of NSCLC patients with VTE was shorter compared to patients without VTE (HR=1.71, 95% CI [1.39–2.10], P<0.01). Two small groups of SCLC patients were excluded and the remaining patients were divided into the Asian and non-Asian groups. The Asian group showed low heterogeneity (I2=35%, P=0.20), in which NSCLC patients with VTE also had shorter OS (HR=1.49, 95% CI [1.19–1.88], P<0.01). Conclusions: VTE is significantly associated with a shorter OS of NSCLC patients, especially in Asian patients. Proper prevention and management of VTE is the key to improving the survival of patients with NSCLC.

scholarly journals Impact of Smoking History on Response to Immunotherapy in Non-Small-Cell Lung Cancer: A Systematic Review and Meta-Analysis

2021 ◽  
Vol 11 ◽  
Author(s):  
Wenhua Zhao ◽  
Wei Jiang ◽  
Huilin Wang ◽  
Jianbo He ◽  
Cuiyun Su ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Real World ◽  
Response Rate ◽  
Meta Analysis ◽  
Small Cell ◽  
Smoking History ◽  
Small Cell Lung ◽  
Nsclc Patients

ObjectivesTo evaluate the impact of smoking history on the clinical benefit of immunotherapy in patients with non-small cell lung cancer (NSCLC).MethodsTwenty-three randomized clinical trials and seven real-world studies were included in this meta-analysis. Hazard ratios (HRs) and 95% confidence intervals (CIs) for overall survival (OS) and progression-free survival (PFS) and odds ratios for the overall response rate (ORR) were extracted. A fixed-effects or random-effects model was applied to obtain pooled estimates.ResultsData from 16 high-quality trials involving 10,643 NSCLC patients receiving either immunotherapy or chemotherapy/placebo enabled direct comparison of the survival impact of smoking. Anti-PD-1/PD-L1/CTLA-4 immunotherapy was found to significantly prolong OS and PFS as compared to chemotherapy/placebo in smokers (HR for OS, 0.76 [0.69–0.83], P&lt;0.00001; HR for PFS, 0.65 [0.56–0.75], P&lt;0.00001), and these trends were less or not significant in non-smokers (HR for OS, 0.91 [0.78–1.06], P=0.25; HR for PFS, 0.68 [0.45–1.03], P=0.07). Consistent results were obtained for the first-line or second/third-line use of immunotherapy and for non-squamous NSCLC patients only. Furthermore, the data from 7 trials and 7 real-world studies involving 4,777 patients receiving immunotherapy allowed direct comparison of therapeutic outcomes between smokers and non-smokers. Prolonged OS (HR 0.86 [0.75–0.99], P=0.04) and PFS (HR 0.69 [0.60–0.81], P&lt;0.0001) and a higher response rate (ORR 1.20 [0.94–1.53], P=0.15) were observed in smokers compared to non-smokers receiving immunotherapy.ConclusionsImmunotherapy was found to have a greater benefit in NSCLC patients with a smoking history than in those who had never smoked.

Cetuximab Plus Various Chemotherapy Regimens for Patients with KRAS Wild-Type Metastatic Colorectal Cancer

Chemotherapy ◽  
2015 ◽  
Vol 61 (1) ◽  
pp. 51-56 ◽  
Author(s):  
Payam Azadeh ◽  
Nafiseh Mortazavi ◽  
Arezoo Tahmasebi ◽  
Farnaz Hosseini Kamal ◽  
Kambiz Novin
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Overall Response Rate ◽  
Response Rate ◽  
Progression Free Survival ◽  
The Other ◽  
Hematologic Toxicity ◽  
Wild Type ◽  
Standard Chemotherapy ◽  
Free Survival

Background: The aim of this study was to compare the efficacy and hematologic toxicity of cetuximab combined with various types of chemotherapy regimens in patients with KRAS wild-type metastatic colorectal cancer (mCRC). Methods: The response rate, progression-free survival (PFS) and overall survival of the patients were analyzed. Results: In total, 45 patients were included in the study. The overall response rate for the combination of cetuximab and FOLFOX, FOLFIRI and CAPOX was 20, 46 and 30%, respectively, but the differences were not statistically significant. The median PFS for the three groups were 8, 6 and 3.5 months, respectively, but again these differences were not significant. All-grade leukopenia and anemia for the cetuximab plus FOLFOX group were significantly higher than for the other chemotherapy regimens. Conclusion: Our findings suggest that the combination of cetuximab and the three standard chemotherapy regimens resulted in the same outcomes in our patient population of mCRC, with higher hematologic toxicities among the FOLFOX subgroup.

scholarly journals The Predictive Role of PIK3CA Mutation Status on PI3K Inhibitors in HR+ Breast Cancer Therapy: A Systematic Review and Meta-Analysis

2020 ◽  
Vol 2020 ◽  
pp. 1-8 ◽  
Author(s):  
Mingming Wang ◽  
Jin Li ◽  
Jiangsheng Huang ◽  
Mei Luo
Keyword(s):  
Breast Cancer ◽  
Clinical Outcomes ◽  
Fixed Effects ◽  
Meta Analysis ◽  
Pik3ca Mutation ◽  
Breast Cancer Patients ◽  
Wild Type ◽  
Mutation Status ◽  
Type Group ◽  
The Impact

Aim. To evaluate the impact of PIK3CA mutation status on clinical outcomes of HR+ breast cancer treated with PI3K inhibitors. Methods. A comprehensive literature search was conducted in online databases from inception to December 31, 2019. The main characteristics and prognostic data of each eligible study were extracted. The odds ratio (OR) for the overall response rate (ORR) and hazard ratio (HR) for progression-free survival (PFS) were estimated using the fixed-effects Mantel-Haenszel model. Results. A total of 8 studies involving 2670 patients were included for analysis. Overall, the clinical outcomes of PI3K inhibitors were significantly influenced by PIK3CA mutation status in HR+ breast cancer. After the treatment of PI3K inhibitors, HR+ breast cancer patients with PIK3CA mutations presented better ORR (PIK3CA-mutated group: OR=1.98 [95% CI, 1.46 to 2.70]; PIK3CA wild-type group: OR=1.09 [95% CI, 0.78 to 1.53]) and better PFS (PIK3CA-mutated group: HR=0.65 [95% CI, 0.55 to 0.76]; PIK3CA wild-type group: HR=0.87 [95% CI, 0.70 to 1.09]). No publication bias was detected for ORR and PFS in our analysis. Conclusion. In this meta-analysis, it suggests that the association between clinical outcomes of PI3K inhibitors and PIK3CA mutation status is dramatic. PIK3CA mutations were a favorable factor in the clinical outcomes of HR+ breast cancer treated with PI3K inhibitors.

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