scholarly journals Clinical Trials Targeting the Stroma in Pancreatic Cancer: A Systematic Review and Meta-Analysis

Cancers ◽  
2019 ◽  
Vol 11 (5) ◽  
pp. 588 ◽  
Author(s):  
van Mackelenbergh ◽  
Stroes ◽  
Spijker ◽  
van Eijck ◽  
Wilmink ◽  
...  
Keyword(s):  
Systematic Review ◽  
Pancreatic Cancer ◽  
Clinical Trials ◽  
Hyaluronic Acid ◽  
Meta Analysis ◽  
Tumor Biology ◽  
Progression Free Survival ◽  
Hazard Ratios ◽  
Vegf Pathway ◽  
Endothelial Growth Factor

The tumor microenvironment plays an important role in the initiation and progression of pancreatic adenocarcinoma (PDAC). In this systematic review, we provide an overview of clinical trials with stroma-targeting agents. We systematically searched MEDLINE/PubMed and the EMBASE database, using the PRISMA guidelines, for eligible clinical trials. In total, 2330 records were screened, from which we have included 106 articles. A meta-analysis could be performed on 51 articles which describe the targeting of the vascular endothelial growth factor (VEGF) pathway, and three articles which describe the targeting of hyaluronic acid. Anti-VEGF therapies did not show an increase in median overall survival (OS) with combined hazard ratios (HRs) of 1.01 (95% confidence interval (CI) 0.90–1.13). Treatment with hyaluronidase PEGPH20 showed promising results, but, thus far, only in combination with gemcitabine and nab-paclitaxel in selected patients with hyaluronic acid (HA)high tumors: An increase in median progression free survival (PFS) of 2.9 months, as well as a HR of 0.51 (95% CI 0.26–1.00). In conclusion, we found that anti-angiogenic therapies did not show an increased benefit in median OS or PFS in contrast to promising results with anti-hyaluronic acid treatment in combination with gemcitabine and nab-paclitaxel. The PEGPH20 clinical trials used patient selection to determine eligibility based on tumor biology, which underlines the importance to personalize treatment for pancreatic cancer patients.

671 Update of a systematic review and meta-analysis studying the association between antibiotic use and clinical outcomes of non-small-cell lung cancer patients treated with immune checkpoint inhibitors

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A708-A708
Author(s):  
Pierre-Alain Bandinelli ◽  
Julie Cervesi ◽  
Clément Le Bescop ◽  
Renaud Buffet ◽  
Jean De Gunzburg ◽  
...  
Keyword(s):  
Systematic Review ◽  
Clinical Outcomes ◽  
Time Window ◽  
Checkpoint Inhibitors ◽  
Meta Analysis ◽  
Progression Free Survival ◽  
Antibiotic Use ◽  
Forest Plot ◽  
Antibiotic Exposure ◽  
Hazard Ratios

BackgroundImmune checkpoint inhibitors (ICIs) have been shown to improve patients‘ clinical outcomes in a variety of cancers, but with variable efficacy. Prior research has also suggested that systemic antibiotic (ABX) exposure may impact the intestinal microbiota and result in suboptimal ICI treatment outcomes. Our team published a systematic review and meta-analysis showing that ABX use could indeed decrease the survival of patients diagnosed with non-small-cell lung cancer (NSCLC) and treated with ICIs.1 The present abstract aims at updating this meta-analysis by incorporating new studies that have been published in the period ranging from September 2019 to August 2020.MethodsMedline (through PubMed), the Cochrane Library and major oncology conferences proceedings were systematically searched to identify studies assessing the impact of ABX use on the clinical outcomes of NSCLC patients treated with ICIs. Studies were found eligible for inclusion when they mentioned a hazard ratio (HR) or Kaplan–Meier curves for overall survival (OS) or progression-free survival (PFS) based on antibiotic exposure. Pooled HRs for OS and PFS and HRs for OS and PFS according to different time windows for ABX exposure were calculated.Results6 eligible new studies were identified between September 2019 and August 2020 while 3 other studies were updated with new information. Altogether, 27 studies reported data for OS (6,436 patients, 826 of whom coming from new studies) and 24 for PFS (3,751 patients, 786 of whom coming from new studies). The pooled HR was 1.75 (95% confidence interval [CI]: 1.38–2.23) for OS and 1.57 (95% CI: 1.28–1.92) for PFS, confirming a significantly reduced survival in patients with NSCLC exposed to ABX. The detailed analysis in subgroups based on the time window of exposure (figure 1, figure 2) suggests that the deleterious effect of ABX is stronger when the exposition happens shortly before and after the initiation of the ICI treatment.Abstract 671 Figure 1Forest plot of hazard ratios for overall survival of patients diagnosed with NSCLC and exposed to antibiotics versus not exposed to antibiotics, according to the time window of antibiotic exposureAbstract 671 Figure 2Forest plot of hazard ratios for progression-free survival of patients diagnosed with NSCLC and exposed to antibiotics versus not exposed to antibiotics, according to the time window of antibiotic exposureConclusionsThe update of the meta-analysis confirms the previously reported deleterious effect of ABX on ICI treatment outcomes, taking into account the latest publications in the field. The topic deserves further research to uncover if the effect will stand with 1st line use of ICI together with chemotherapies and/or other approved combinations, elucidate the mechanisms at stake and improve care of patients.ReferencesLurienne L, Cervesi J, Duhalde L, de Gunzburg J, Andremont A, Zalcman G, et al. NSCLC immunotherapy efficacy and antibiotic use: a systematic review and meta-analysis. J Thorac Oncol 2020;15:1147–1159.

Preoperative Platelet to Lymphocyte Ratio as a Prognostic Factor for Resectable Pancreatic Cancer: A Systematic Review and Meta-Analysis

2020 ◽  
Vol 37 (6) ◽  
pp. 447-455
Author(s):  
Romualdas Riauka ◽  
Povilas Ignatavicius ◽  
Giedrius Barauskas
Keyword(s):  
Systematic Review ◽  
Pancreatic Cancer ◽  
Prognostic Factor ◽  
Meta Analysis ◽  
Disease Free Survival ◽  
Platelet To Lymphocyte Ratio ◽  
Resectable Pancreatic Cancer ◽  
Lymphocyte Ratio ◽  
Asian Patients ◽  
Hazard Ratios

<b><i>Introduction:</i></b> Various inflammatory markers have been investigated for a prognostic role in patients with resectable pancreatic cancer. However, the value of preoperative platelet to lymphocyte ratio (PLR) remains controversial. We performed a systematic review and meta-analysis of PLR as a preoperative prognostic factor for resectable pancreatic cancer. <b><i>Material and Methods:</i></b> Systematic literature search was conducted for studies assessing PLR influence as a preoperative prognostic factor in resectable pancreatic cancer patients. Random-effects model was applied for pooling hazard ratios and 95% confidence intervals related to overall survival (OS) and disease-free survival (DFS). <b><i>Results:</i></b> Fourteen articles with 2,743 patients were included in the study. According to the analysis, high PLR had no correlation with decreased OS. Due to high heterogeneity among studies, subgroup analysis was performed. Better OS was associated with low PLR in Asian patients, patients with mixed type of operation performed, and patients with preoperative PLR ≤150. Low PLR was associated with significantly better DFS. <b><i>Conclusions:</i></b> PLR is a predictive factor of better DFS in patients with resectable pancreatic cancer. However, available evidence does not support PLR as a reliable prognostic factor for OS.

Therapeutic efficacy of specific immunotherapy for glioma: a systematic review and meta-analysis

2018 ◽  
Vol 29 (4) ◽  
pp. 443-461 ◽  
Author(s):  
Sara Hanaei ◽  
Khashayar Afshari ◽  
Armin Hirbod-Mobarakeh ◽  
Bahram Mohajer ◽  
Delara Amir Dastmalchi ◽  
...  
Keyword(s):  
Systematic Review ◽  
Overall Survival ◽  
Clinical Trials ◽  
Specific Immunotherapy ◽  
Data Extraction ◽  
Meta Analysis ◽  
Progression Free Survival ◽  
Control Group ◽  
Free Survival ◽  
Median Difference

Abstract Although different immunotherapeutic approaches have been developed for the treatment of glioma, there is a discrepancy between clinical trials limiting their approval as common treatment. So, the current systematic review and meta-analysis were conducted to assess survival and clinical response of specific immunotherapy in patients with glioma. Generally, seven databases were searched to find eligible studies. Controlled clinical trials investigating the efficacy of specific immunotherapy in glioma were found eligible. After data extraction and risk of bias assessment, the data were analyzed based on the level of heterogeneity. Overall, 25 articles with 2964 patients were included. Generally, mean overall survival did not statistically improve in immunotherapy [median difference=1.51; 95% confidence interval (CI)=−0.16–3.17; p=0.08]; however, it was 11.16 months higher in passive immunotherapy (95% CI=5.69–16.64; p<0.0001). One-year overall survival was significantly higher in immunotherapy groups [hazard ratio (HR)=0.69; 95% CI=0.52–0.92; p=0.01]. As the hazard rate in the immunotherapy approach was 0.83 of the control group, 2-year overall survival was significantly higher in immunotherapy (HR=0.83; 95% CI=0.69–0.99; p=0.04). Three-year overall survival was significantly higher in immunotherapy as well (HR=0.67; 95% CI=0.48–0.92; p=0.01). Overall, median progression-free survival was significantly higher in immunotherapy (standard median difference=0.323; 95% CI=0.110–0.536; p=0.003). However, 1-year progression-free survival was not remarkably different between immunotherapy and control groups (HR=0.94; 95% CI=0.74–1.18; p=0.59). Specific immunotherapy demonstrated remarkable improvement in survival of patients with glioma and could be a considerable choice of treatment in the future. Despite the current promising results, further high-quality randomized controlled trials are required to approve immunotherapeutic approaches as the standard of care and the front-line treatment for glioma.

Role of gemcitabine-based combination therapy in the management of advanced pancreatic cancer: A systematic review and meta-analysis of randomized trials.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e14577-e14577
Author(s):  
Domenico Ciliberto ◽  
Cirino Botta ◽  
Pierpaolo Correale ◽  
Roberto Mazzanti ◽  
Giovanni Mantovani ◽  
...  
Keyword(s):  
Systematic Review ◽  
Pancreatic Cancer ◽  
Clinical Trials ◽  
Combination Therapy ◽  
Randomized Clinical Trials ◽  
Meta Analysis ◽  
Single Agent ◽  
Advanced Pancreatic Cancer ◽  
Final Analysis ◽  
Combination Regimens

e14577 Background: Pancreatic cancer is the 4th leading cause of cancer-related death worldwide. Single-agent chemotherapy with gemcitabine represents a cornerstone for advanced disease treatment. To date, almost all trials, designed to evaluate the benefit of the addition of a second agent to gemcitabine, failed to demonstrate an improvement in overall survival (OS). We performed a systematic review and a meta-analysis of randomized clinical trials to assess the efficacy and safety of gemcitabine-based combination regimens versus gemcitabine alone in the management of pancreatic cancer. Methods: Clinical trials were selected by searching Medline database and abstracts from major cancer meetings. We considered the Jan 1997 - Jan 2012 time frame. Primary end-point was OS, secondary end-points were response rate (RR), disease control rate (DCR) and safety. Hazard ratios (HRs) of OS, odds-ratios (ORs) of RR, DCR and risk ratios of grade 3-4 toxicity rates, were extracted as presented in retrieved studies and used for statistical analysis. Meta-analytic estimates were derived using random-effects model. Results: Thirty-three trials for a total of 10371 patients were selected and included in the final analysis. The analysis showed for combination chemotherapy a benefit in terms of OS (HR: 0.92; 95%CI: 0.88-0.96; p < 0.001). OR of both RR and DCR demonstrated a significant advantage for combination therapy (OR for RR: 0.63, 95%CI: 0.50-0.80, p=0.006; OR for DCR: 0.78; 95%CI: 0.64-0.94; p=0.002). Toxicities were more frequent in the combination treatment group and a significant value in term of risk ratio was reached for diarrhea (0.53, 95%CI: 0.36-0.79), nausea (0.74, 95%CI: 0.56-0.96), neutropenia (0.74, 95%CI: 0.62-0.89) and thrombocytopenia (0.59, 95%CI: 0.44-0.79). Conclusions: Combinationchemotherapy compared to gemcitabine alone significantly improves OS. However, this advantage seems to be marginal and at the cost of increased toxicity, suggesting the use of gemcitabine-based combination regimens only in selected patients. New approaches based on preclinical findings, in the era of targeted therapy, are eagerly awaited on this specific topic.

scholarly journals Prognostic role of pretreatment blood lymphocyte count in patients with solid tumors: a systematic review and meta-analysis

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Jiawen Zhao ◽  
Weijia Huang ◽  
Yongxian Wu ◽  
Yihuan Luo ◽  
Bo Wu ◽  
...  
Keyword(s):  
Systematic Review ◽  
Solid Tumors ◽  
Clinical Outcomes ◽  
Lymphocyte Count ◽  
Meta Analysis ◽  
Progression Free Survival ◽  
Prognostic Impact ◽  
Cancer Type ◽  
Hazard Ratios

Abstract Background To evaluate the prognostic value of pretreatment lymphocyte counts with respect to clinical outcomes in patients with solid tumors. Methods Systematic literature search of electronic databases (Pubmed, Embase and Web of Science) up to May 1, 2018 was carried out by two independent reviewers. We included Eligible studies assessed the prognostic impact of pretreatment lymphocytes and had reported hazard ratios (HR) with 95% confidence intervals (CIs) for endpoints including overall survival (OS) and progression-free survival (PFS). Only English publications were included. Results A total of 42 studies comprising 13,272 patients were included in this systematic review and meta-analysis. Low pretreatment lymphocyte count was associated with poor OS (HR = 1.27, 95% CI 1.16–1.39, P < 0.001, I2 = 58.5%) and PFS (HR = 1.27, 95% CI 1.15–1.40, P < 0.001, I2 = 25.7%). Subgroup analysis disaggregated by cancer type indicated that low pretreatment lymphocytes were most closely associated with poor OS in colorectal cancer followed by breast cancer and renal cancer. Conclusions Low pretreatment lymphocyte count may represent an unfavorable prognostic factor for clinical outcomes in patients with solid tumors.

scholarly journals Impact of intraoperative margin clearance on survival following pancreatoduodenectomy for pancreatic cancer: a systematic review and meta-analysis

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Emrullah Birgin ◽  
Erik Rasbach ◽  
Patrick Téoule ◽  
Felix Rückert ◽  
Christoph Reissfelder ◽  
...  
Keyword(s):  
Systematic Review ◽  
Pancreatic Cancer ◽  
Frozen Section ◽  
Meta Analysis ◽  
Tumor Biology ◽  
Surgical Techniques ◽  
Positive Margin ◽  
Residual Tumor ◽  
Permanent Section ◽  
Pancreatic Neck

AbstractThe use of intraoperative margin revision to achieve margin clearance in patients undergoing pancreatoduodenectomy for pancreatic cancer is controversial. We performed a systematic review and meta-analysis to summarize the evidence of intraoperative margin revisions of the pancreatic neck and its impact on overall survival (OS). Nine studies with 4501 patients were included. Patient cohort was stratified in an R0R0-group (negative margin on frozen and permanent section), R1R0-group (revised positive margin on frozen section which turned negative on permanent section), and R1R1-group (positive margin on frozen and permanent section despite margin revision). OS was higher in the R1R0-group (HR 0.83, 95% CI 0.72–0.96, P = 0.01) compared to the R1R1-group but lower compared to the R0R0-group (HR 1.20; 95% CI 1.05–1.37, P = 0.008), respectively. Subgroup analyses on the use of different margin clearance definitions confirmed an OS benefit in the R1R0-group compared to the R1R1-group (HR 0.81; 95% CI 0.65–0.99, P = 0.04). In conclusion, intraoperative margin clearance of the pancreatic neck margin is associated with improved OS while residual tumor indicates aggressive tumor biology. Consensus definitions on margin terminologies, clearance, and surgical techniques are required.

scholarly journals Systematic Review and Meta-Analysis of the Use of Hyaluronic Acid Injections to Restore Interproximal Papillae

2021 ◽  
Author(s):  
Arturo Sanchez-Perez ◽  
Tania Rosa-Vela ◽  
Bibiana Mateos-Moreno ◽  
Alfonso Jornet-Garcia ◽  
Carlos Navarro-Cuellar
Keyword(s):  
Systematic Review ◽  
Clinical Trials ◽  
Hyaluronic Acid ◽  
Randomised Controlled Trial ◽  
Social Relationships ◽  
Controlled Trial ◽  
Meta Analysis ◽  
Black Triangle ◽  
Interdental Papilla ◽  
Randomised Controlled

The absence of interdental papillae leads to the appearance of black triangle. For most patients, the appearance of these triangles is an important reason for concern and affects their social relationships. Multiple reconstruction techniques have been developed with different degrees of success and predictability. The main aim of this study was to evaluate the efficiency of hyaluronic acid (HA) injected into interproximal papillae six months after injection and to perform a systematic review and meta-analysis. After a systematic review, five articles were selected: a clinical randomised controlled trial and four clinical trials. In total, eighty-five patients with a deficiency in upper papillae in the front of the maxilla and jaw were included in the study. The height variable was evaluated (mm) six months after HA injection. In total, one hundred and four interproximal papillae were studied. Three articles showed an important difference in favour of intervention. The total result regarding in the injection of AH was favourable with an approximate average filling of 0.7 mm in the height of the interdental papilla. The injection of HA for the reconstruction of deficient papillae in the region of the upper and lower maxilla was a possible option treatment strategy.

scholarly journals Systematic Review and Meta-Analysis of the Use of Hyaluronic Acid Injections to Restore Interproximal Papillae

2021 ◽  
Vol 11 (22) ◽  
pp. 10572
Author(s):  
Arturo Sanchez-Perez ◽  
Tania Rosa Vela-García ◽  
Bibiana Mateos-Moreno ◽  
Alfonso Jornet-García ◽  
Carlos Navarro-Cuellar
Keyword(s):  
Systematic Review ◽  
Clinical Trials ◽  
Hyaluronic Acid ◽  
Social Relationships ◽  
Treatment Strategy ◽  
Randomised Controlled Trials ◽  
Meta Analysis ◽  
Controlled Trials ◽  
Interdental Papilla ◽  
Randomised Controlled

The absence of interdental papillae leads to the appearance of black triangles. For most patients, the appearance of these triangles is an important reason for concern and affects their social relationships. Multiple reconstruction techniques have been developed with different degrees of success and predictability. The main aim of this study was to evaluate the efficiency of hyaluronic acid (HA) injected into interproximal papillae 6 months after injection and to perform a systematic review and meta-analysis. After a systematic review, seven articles were selected: two clinical randomised controlled trials and five clinical trials. In total, 127 patients with a deficiency in upper papillae in the front of the maxilla and jaw were included in the study. The height variable was evaluated (mm) 6 months after HA injection. In total, 166 interproximal papillae were studied. Four articles showed an important difference in favour of intervention. The total result regarding in the injection of HA was favourable with an approximate average filling of 0.47 mm in the height of the interdental papilla. The injection of HA for the reconstruction of deficient papillae in the region of the upper and lower maxilla was a possible option treatment strategy in mild black triangles.

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