scholarly journals Pharmacoethnicity of FOLFIRINOX versus gemcitabine plus nab-paclitaxel in metastatic pancreatic cancer: a systematic review and meta-analysis

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yoon Suk Lee ◽  
Jong-chan Lee ◽  
Jae-Hyeong Kim ◽  
Jaihwan Kim ◽  
Jin-Hyeok Hwang
Keyword(s):  
Pancreatic Cancer ◽  
Overall Survival ◽  
Survival Benefit ◽  
Meta Analysis ◽  
Progression Free Survival ◽  
Metastatic Pancreatic Cancer ◽  
Cochrane Library ◽  
Chemotherapeutic Regimen ◽  
Free Survival ◽  
Ethnic Subgroups

AbstractTreatment outcomes between FOLFIRINOX (5-fluorouracil, leucovorin, irinotecan, and oxaliplatin) and GNP (gemcitabine with albumin-bound paclitaxel) as first-line chemotherapy regimens for metastatic pancreatic cancer (PC) were assessed according to ethnic groups categorized as Western or Asian subgroups. PubMed, EMBASE, and Cochrane library were searched. Thirteen studies were eligible in this meta-analysis. Overall survival was not significantly different between FOLFIRINOX and GNP (HR 1.00, 95% CI 0.83–1.20, P = 0.990). However, the Western subgroup showed a higher survival benefit for FOLFIRINOX over GNP (HR 0.84, 95% CI 0.74–0.95, P = 0.006) whereas the Asian subgroup showed the survival benefit for GNP over FOLFIRINOX (HR 1.29, 95% CI 1.03–1.60, P = 0.030). Progression free survival was not significantly different between the two regimens in the Western subgroup (HR 1.01, 95% CI 0.84–1.20, P = 0.950) and the Asian subgroup (HR 1.13, 95% CI 0.97–1.33, P = 0.110). Occurrence of febrile neutropenia was significantly higher in FOLFIRINOX at both ethnic subgroups; however, that of peripheral neuropathy was significantly higher only in GNP of the Asian subgroup. Therefore, pharmacoethnicity might be a factor worth considering when deciding on a frontline chemotherapeutic regimen although the overall survival was not significantly different between FOLFIRINOX and GNP for metastatic PCs.

scholarly journals Comparison of the survival outcomes of laparoscopy versus laparotomy in treatment of early-stage ovarian cancer: a systematic review and meta-analysis

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Qingduo Kong ◽  
Hongyi Wei ◽  
Jing Zhang ◽  
Yilin Li ◽  
Yongjun Wang
Keyword(s):  
Ovarian Cancer ◽  
Overall Survival ◽  
Early Stage ◽  
Meta Analysis ◽  
Progression Free Survival ◽  
Cochrane Library ◽  
Survival Outcomes ◽  
Free Survival ◽  
Review Manager ◽  
Early Stage Ovarian Cancer

Abstract Background Laparoscopy has been widely used for patients with early-stage epithelial ovarian cancer (eEOC). However, there is limited evidence regarding whether survival outcomes of laparoscopy are equivalent to those of laparotomy among patients with eEOC. The result of survival outcomes of laparoscopy is still controversial. The aim of this meta-analysis is to analyze the survival outcomes of laparoscopy versus laparotomy in the treatment of eEOC. Methods According to the keywords, Pubmed, Embase, Cochrane Library and Clinicaltrials.gov were searched for studies from January 1994 to January 2021. Studies comparing the efficacy and safety of laparoscopy versus laparotomy for patients with eEOC were assessed for eligibility. Only studies including outcomes of overall survival (OS) were enrolled. The meta-analysis was performed using Stata software (Version 12.0) and Review Manager (Version 5.2). Results A total of 6 retrospective non-random studies were included in this meta-analysis. The pooled results indicated that there was no difference between two approaches for patients with eEOC in OS (HR = 0.6, P = 0.446), progression-free survival (PFS) (HR = 0.6, P = 0.137) and upstaging rate (OR = 1.18, P = 0.54). But the recurrence rate of laparoscopic surgery was lower than that of laparotomic surgery (OR = 0.48, P = 0.008). Conclusions Laparoscopy and laparotomy appear to provide comparable overall survival and progression-free survival outcomes for patients with eEOC. Further high-quality studies are needed to enhance this statement.

scholarly journals Association between neutropenia and survival to nab-paclitaxel and gemcitabine in patients with metastatic pancreatic cancer

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Giandomenico Roviello ◽  
Monica Ramello ◽  
Martina Catalano ◽  
Alberto D’Angelo ◽  
Raffaele Conca ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Overall Survival ◽  
Response Rate ◽  
Progression Free Survival ◽  
Metastatic Pancreatic Cancer ◽  
Common Side Effect ◽  
First Line ◽  
Free Survival ◽  
Grade 3 ◽  
Toxicity Criteria

Abstract Neutropenia is a common side effect associated with nab-paclitaxel gemcitabine (Nab-Gem) therapy. We retrospectively investigated the association between neutropenia induced by first-line Nab-Gem and survival in metastatic pancreatic carcinoma patients. Metastatic pancreatic patients treated with first-line Nab-Gem were included in this retrospective analysis. Neutropenia was categorized using the National Cancer Institute Common Toxicity Criteria scale. Outcome measures were overall survival (OS), progression-free survival (PFS) and response rate. 115 patients were analyzed. Median PFS was 7 months (95% CI 5–8) for patients with grade ≥ 3 neutropenia and 6 months (95% CI 5–6) for patients with grade < 3 neutropenia [p = 0.08; hazard ratio (HR 0.68)]. Median OS was 13 months (95% CI 10–18) for patients with grade ≥ 3 neutropenia and 10 months (95% CI 8–13) for patients with grade < 3 neutropenia (p = 0.04; HR 0.44). In multivariate analysis, the occurrence of grade ≥ 3 neutropenia showed a statistically significant association with OS (HR 0.62; 95% CI 0.09–0.86; p = 0.05). Nab-Gem-induced neutropenia is associated with longer survival in metastatic pancreatic cancer patients.

scholarly journals Prognostic and Clinicopathological Significance of C-Reactive Protein to Albumin Ratio in Patients With Pancreatic Cancer: A Meta-Analysis

Dose-Response ◽  
2020 ◽  
Vol 18 (2) ◽  
pp. 155932582093129
Author(s):  
Qinfen Xie ◽  
Lidong Wang ◽  
Shusen Zheng
Keyword(s):  
Pancreatic Cancer ◽  
Meta Analysis ◽  
Disease Free Survival ◽  
Progression Free Survival ◽  
Cochrane Library ◽  
Survival Outcomes ◽  
C Reactive Protein ◽  
Free Survival ◽  
Albumin Ratio ◽  
Reactive Protein

Background: This meta-analysis explored the correlation between the C-reactive protein to albumin ratio (CAR) and survival outcomes and clinicopathological characteristics in patients with pancreatic cancer. Methods: PubMed, Embase, Web of Science, and Cochrane Library databases were comprehensively searched through October 17, 2019. Pooled hazard ratios (HRs) and 95% confidence intervals (CIs) were used to evaluate the association between CAR and overall survival (OS), progression-free survival (PFS), and disease-free survival (DFS) in pancreatic cancer. Results: The meta-analysis included 11 studies comprising 2271 patients. The pooled results showed that a high CAR was predictive of worse OS (HR = 1.84, 95% CI = 1.65-2.06, P < .001), PFS (HR = 1.53, 95% CI = 1.27-1.85, P < .001), and DFS (HR = 1.77, 95% CI = 1.30-2.41, P < .001). An elevated CAR was also associated with male sex (OR = 1.38, 95% CI = 1.10-1.74, P = .006). Conclusion: Elevated pretreatment CAR effectively predicts inferior survival outcomes in patients with pancreatic cancer and may be a powerful prognostic indicator for these patients.

scholarly journals Network Meta-Analysis of Efficacy and Safety of Chemotherapy and Target Therapy in the First-Line Setting of Advanced Pancreatic Cancer

Cancers ◽  
2019 ◽  
Vol 11 (11) ◽  
pp. 1746 ◽  
Author(s):  
Kun-I Lin ◽  
Jia-Lian Yang ◽  
Yu-Chao Lin ◽  
Che-Yi Chou ◽  
Jin-Hua Chen ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Overall Survival ◽  
Meta Analysis ◽  
Advanced Pancreatic Cancer ◽  
Progression Free Survival ◽  
Current Evidence ◽  
P Value ◽  
Efficacy And Safety ◽  
First Line ◽  
Free Survival

Both gemcitabine and fluoropyrimidine are recommended backbones in the first-line treatment of pancreatic ductal adenocarcinoma (PDAC). To compare the efficacy and safety of these two therapeutic backbones, and to investigate the optimal therapies, we conducted a network meta-analysis. By retrospective analysis of randomized controlled trials (RCT), the most preferred therapeutic regimen may be predicted. The eligible RCTs of the gemcitabine-based therapies and fluoropyrimidine-based therapies were searched up to 31 August 2019. In a frequentist network meta-analysis, treatments were compared and ranked according to overall survival (OS) and progression-free survival (PFS). Thirty-two trials with 10,729 patients were included. The network meta-analyses results for overall survival and progression-free survival showed that fluoropyrimidine-based therapy seems to be the most effective treatment choice. Compared to gemcitabine combined with taxanes or immunotherapy, fluoropyrimidine-based therapy had comparable treatment effects (PFS: 0.67, p-Value = 0.11; 0.76, p-Value = 0.32; OS: 0.80, p-Value = 0.16; 0.77, p-Value = 0.21). Moreover, the combination of immunotherapy and gemcitabine had tolerable toxicities. Based on current evidence, fluoropyrimidine-based therapies and the combination of gemcitabine and taxanes were the most effective therapies in the advanced pancreatic cancer, and the combination of immunotherapy and gemcitabine can be developed into a new form of therapy.

scholarly journals The impact of LncRNA dysregulation on clinicopathology and survival of pancreatic cancer: a systematic review and meta-analysis (PRISMA compliant)

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Elahe Seyed Hosseini ◽  
Ali Nikkhah ◽  
Amir Sotudeh ◽  
Marziyeh Alizadeh Zarei ◽  
Fatemeh Izadpanah ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Overall Survival ◽  
Random Effects ◽  
Meta Analysis ◽  
Disease Free Survival ◽  
Progression Free Survival ◽  
Free Survival ◽  
Diagnosis And Prognosis ◽  
The Impact ◽  
Disease Free

Abstract Purpose An increasing number of studies have reported a significant association between long non-coding RNAs (lncRNAs) dysregulation and pancreatic cancers. In the present study, we aimed to gather articles to evaluate the prognostic value of long non coding RNA in pancreatic cancer. Experimental design We systematically searched all eligible articles from databases of PubMed, Web of Science, and Scopus to meta-analysis of published articles and screen association of multiple lncRNAs expression with clinicopathology and/or survival of pancreatic cancer. The pooled hazard ratios (HRs) and their 95% confidence intervals (95% CIs) were used to analysis of overall survival, disease-free survival and progression-free survival were measured with a fixed or random effects model. Results A total of 39 articles were included in the present meta-analysis. Our results showed that dysregulation of lncRNAs were linked to overall survival (39 studies, 4736 patients HR = 0.41, 95% CI 0.25 ± 0.58, random-effects in pancreatic cancer. Moreover, altered lncRNAs were also contributed to progression-free survival (8 studies, 1180 patients HR: 1.88, 95% CI (1.35–2.62) and disease-free survival (2 studies, 285 patients, HR: 6.07, 95% CI 1.28–28.78). In addition, our findings revealed the association between dysregulated RNAs and clinicopathological features in this type of cancer. Conclusions In conclusion, dysregulated lncRNAs could be served as promising biomarkers for diagnosis and prognosis of pancreatic cancer.

Randomized Phase II Trial Evaluating Two Sequential Treatments in First Line of Metastatic Pancreatic Cancer: Results of the PANOPTIMOX-PRODIGE 35 Trial

2021 ◽  
pp. JCO.20.03329
Author(s):  
Laetitia Dahan ◽  
Nicolas Williet ◽  
Karine Le Malicot ◽  
Jean-Marc Phelip ◽  
Jérôme Desrame ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Overall Survival ◽  
Phase Ii ◽  
Progression Free Survival ◽  
Metastatic Pancreatic Cancer ◽  
Free Survival ◽  
Dismal Prognosis ◽  
Stop And Go ◽  
Sequential Treatments ◽  
Grade 3

PURPOSE Metastatic pancreatic cancer (mPC) still harbors a dismal prognosis. Our previous trial (PRODIGE 4—ACCORD 11) demonstrated the superiority of 6-month chemotherapy with fluorouracil, leucovorin, irinotecan, and oxaliplatin (FOLFIRINOX) over gemcitabine for overall survival. The high limiting oxaliplatin-related neurotoxicity supports the evaluation of an oxaliplatin stop-and-go strategy and a sequential strategy in mPC. METHODS In this phase II study, patients were randomly assigned to receive either 6 months of FOLFIRINOX (arm A), 4 months of FOLFIRINOX followed by leucovorin plus fluorouracil maintenance treatment for controlled patients (arm B), or a sequential treatment alternating gemcitabine and fluorouracil, leucovorin, and irinotecan every 2 months (arm C). The primary end point was progression-free survival at 6 months. RESULTS Between January 2015 and November 2016, 276 patients (mean age: 63 years; range: 40-76 years) were enrolled (A: 91, B: 92, and C: 90). Grade 3 or 4 neurotoxicity occurred in 10.2% of patients in arm A and 19.8% in arm B. The median ratio of received dose/targeted dose of oxaliplatin was 83% in arm A and 92% in arm B. The 6-month progression-free survival was 47.1% in A, 42.9% in B, and 34.1% in C. The median overall survival was 10.1 months in arm A, 11.2 in arm B, and 7.3 in arm C. Median survival without deterioration in quality-of-life scores was higher in the maintenance arm (11.4 months) than in arms A and C (7.2 and 7.5 months, respectively). CONCLUSION Maintenance with leucovorin plus fluorouracil appears to be feasible and effective in patients with mPC controlled after 4 months of induction chemotherapy with FOLFIRINOX. Severe neurotoxicity was higher in the maintenance therapy arm, probably because of the higher cumulative dose of oxaliplatin.

Retrospective analysis of institutional outcomes with FOLFIRINOX versus nab-paclitaxel plus gemcitabine in metastatic pancreatic cancer.

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 776-776
Author(s):  
Amisha Singh ◽  
Rachna T. Shroff ◽  
Ali McBride
Keyword(s):  
Pancreatic Cancer ◽  
Overall Survival ◽  
Adverse Effects ◽  
Progression Free Survival ◽  
Treatment Discontinuation ◽  
Metastatic Pancreatic Cancer ◽  
Line Treatment ◽  
Second Line ◽  
Office Visits ◽  
Free Survival

776 Background: With an estimated six percent five-year survival, metastatic pancreatic adenocarcinoma is one of the most lethal cancers in the United States. Previously, treatments with FOLFIRINOX (FFX) or gemcitabine plus nab-paclitaxel (G+A) have demonstrated improved overall survival versus gemcitabine alone. The purpose of this study is to compare institutional outcomes for the two regimens, FFX vs. G+A in metastatic pancreatic cancer. Methods: We conducted a retrospective review of medical records of all metastatic pancreatic cancer patients from 2010 to 2018 who received first line treatment with FFX or G+A at University of Arizona Cancer Center. Results: Thirty-five patients received combination treatment with G+A and 29 patients received FFX. Patient demographics: median age was 66 years in FFX vs 70 years in the G+A group; baseline CA-19-9 was 791 in FFX vs 738 in the G+A group. Median ECOG score was 1 for both groups. Median overall survival was 11.5 months in the FFX group (range 0-39 mos) vs 5 months in the G+A group (range 0-37 mos). Overall survival at 6 months was 75.9% vs 51.4% in FFX vs G+A groups respectively. Median progression-free survival was 6 months with FFX (range 0-25 mos) and 3 months with G+A (range 0-24 mos). Twenty-one of 29 patients in the FFX group pursued second line treatment, compared to 12 of 35 patients in the G+A group. Time to next treatment was 6 months in the FFX group vs 5 months in the G+A group. More adverse effects were noted with FFX, the most common being neuropathy and neutropenia, leading to treatment discontinuation due to adverse effects in 31% of patients, compared to 3% of patients in the G+A group. FFX patients required a higher median no. of office visits (35 visits vs 18 visits in the G+A group). Conclusions: FFX showed improved progression-free survival vs G+A; however, this could be due to more patients pursuing second line treatment in the FFX group. Compared to G+A, FFX patients had higher rates of treatment discontinuation due to adverse effects. FFX patients also required more office visits and further analysis is necessary to assess whether this resulted in poorer quality of life and increased total cost of care for patients treated with FFX.

Thalidomide As Maintenance Therapy in Multiple Myeloma (MM) Improves Progression Free Survival (PFS) and Overall Survival (OS): A Meta-Analysis

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 1855-1855 ◽  
Author(s):  
Ajay K. Nooka ◽  
Madhusmita Behera ◽  
Lawrence H. Boise ◽  
Melanie Watson ◽  
Jonathan L. Kaufman ◽  
...  
Keyword(s):  
Overall Survival ◽  
Maintenance Therapy ◽  
Meta Analysis ◽  
Single Agent ◽  
Progression Free Survival ◽  
Outcome Data ◽  
Phase Iii ◽  
Cochrane Library ◽  
Free Survival ◽  
Manual Search

Abstract Abstract 1855 Background: Conflicting data regarding the survival benefit of thalidomide maintenance exist in the literature. Recent phase 3 study MMRC.M10 has demonstrated significant toxicity with thalidomide maintenance in combination with steroids. The role of thalidomide maintenance in prolonging PFS and OS is less clear. We conducted a meta-analysis of phase III randomized control trials (RCT) that evaluated thalidomide as maintenance therapy in transplant-eligible patients. Methods: We conducted an electronic literature search of public databases (MEDLINE, EMBASE, Cochrane library) and manual search of conference proceedings of ASH and ASCO. There were seven phase III RCTs that reported the maintenance therapy of thalidomide and survival in MM (Total Therapy 2, IFM 99-02, ALLG trial, HOVON 50, MRC IX trial, NCIC CTG MY.10). One study (Abdelkefi et al., 2008) was retracted and hence not included in the analysis. A formal meta-analysis was conducted using Comprehensive Meta Analysis software (Version 2.0). The outcome data were pooled and reported as hazard ratio (HR). The primary outcome of interest was progression free survival (PFS) and overall survival (OS). Results: A total of 3194 patients (maintenance arm/control arm- 1479/1715, median age 58 years) were evaluated. The 3 year-OS ( HR 0.80, 95% CI 0.70 to 0.917, P=0.001) and 3 year-PFS (HR 0.62, 95% CI 0.55 to 0.69, P=0.000) were superior with maintenance therapy. ‘Steroid and thalidomide’ maintenance therapy was associated with significant OS and PFS improvement (OS HR 0.65, 95% CI 0.47 to 0.89); PFS (HR 0.54, 95% CI 0.44 to 0.67). Overall toxicities with thalidomide maintenance were peripheral neuropathy (PN) 2.184 (95% CI 1.523–3.133) and thromboembolic events (TEE) 1.632 (95% CI 1.076–2.475). Toxicities were increased with thalidomide and steroid maintenance - PN 28.78 (95% CI 1.676–494.13); TEE 2.896 (95% CI 0.76–11.06). Conclusions: Thalidomide as a single agent or in combination with steroids as maintenance therapy improves progression free survival and overall survival. However, high toxicity with steroid combination was observed. Disclosures: Kaufman: Millenium; Onyx; Novartis; Keryx: Consultancy; Merck, Celgene: Research Funding. Lonial:Millennium: Consultancy; Novartis: Consultancy; Celgene: Consultancy; BMS: Consultancy; Onyx: Consultancy; Merck: Consultancy.

scholarly journals Efficacy and Safety of Nilutamide in Patients with Metastatic Prostate Cancer who Underwent Orchiectomy: A Systematic Review and Metaanalysis

2019 ◽  
Vol 14 (2) ◽  
pp. 108-115 ◽  
Author(s):  
Muhammed Rashid ◽  
K. Shamshavali ◽  
Manik Chhabra
Keyword(s):  
Prostate Cancer ◽  
Overall Survival ◽  
Metastatic Prostate Cancer ◽  
Response Rate ◽  
Meta Analysis ◽  
Progression Free Survival ◽  
Cochrane Library ◽  
Control Group ◽  
Efficacy And Safety ◽  
Free Survival

Background: Prostate cancer is the sixth leading cause of death, among all cancer deaths By 2030, this burden is expected to increase with 1.7 million new cases and 499,000 new deaths. We aimed to evaluate the efficacy and safety of Nilutamide in metastatic prostate cancer (mPCa) patients who underwent orchiectomy. Methods: A comprehensive search was conducted in the Medline/PubMed and Cochrane Library. References from included studies and studies from clinicaltrials.gov were explored without language and date restrictions. We included only randomized controlled trials, comparing the safety and efficacy of Nilutamide in Metastatic Prostate Cancer (mPCa) patients who underwent orchiectomy with placebo. The outcomes of concerns were survival and the response of drug and safety.. Quality of the included studies was assessed using the Cochrane Risk of Bias Tool. Two authors were independently involved in the study selection, data extraction and quality assessment. Disagreements between the two reviewers were resolved by consulting a third reviewer. Results: A total of five out of 244 studies were included in meta-analysis involving1637 participants. Nilutamide group showed improved response rate (RR=1.77, 95%CI 1.46-2.14, p<0.00001), disease progression (RR=0.59, 95%CI 0.47-0.73, p<0.00001), complete response (RR=2.13, 95%CI 1.40-3.23, p=0.003) and clinical benefit (RR=1.23, 95%CI 1.13-1.34, p<0.00001) when compared to placebo; however, stable disease favored the control group (RR=0.80, 95%CI 0.68-0.94, p=0.007). In addition, patients on Nilutamide showed prolonged progression-free survival and overall survival. Nausea and vomiting were the most common adverse events reported in Nilutamide group. Conclusion: Evidence suggests that patients with mPCa who underwent orchiectomy receiving Nilutamide showed significant improvement in progression-free survival and overall survival response rate and clinical benefits in comparison with the placebo group.

scholarly journals Safety and Efficacy of Anti-PD-1/PD-L1 Inhibitors Compared With Docetaxel for NSCLC: A Systematic Review and Meta-Analysis

2021 ◽  
Vol 12 ◽  
Author(s):  
Long Ma ◽  
Gang Jin ◽  
Keying Yao ◽  
Yi Yang ◽  
Ruitong Chang ◽  
...  
Keyword(s):  
Overall Survival ◽  
Meta Analysis ◽  
Progression Free Survival ◽  
Cochrane Library ◽  
Efficacy And Safety ◽  
High Quality Research ◽  
Free Survival ◽  
Randomized Controlled ◽  
Grade 3 ◽  
Docetaxel Chemotherapy

Objective: To evaluate the efficacy and safety of anti-PD-1/PD-L1 Inhibitors versus docetaxel for non-small cell lung cancer by meta-analysis.Methods: Randomized controlled trials (RCTs) about anti-PD-1/PD-L1 Inhibitors versus docetaxel on the treatment of NSCLC were searched in CNKI, WF, VIP, PubMed, EMBASE, Cochrane Library, and Web of Science databases. Two reviewers independently screened literature, extracted data and evaluated the risk of bias of eligible studies. Meta-analysis was performed by RevMan5.3 software.Results: Compared with the use of docetaxel chemotherapy for NSCLC, the overall survival and progression-free survival of the anti-PD-1/PD-L1 Inhibitors regimen are better [overall survival: (HR= 0.73, 95%CI:0.69∼0.77, P&lt;0.00001], progression-free survival: (HR= 0.89, 95%CI:0.83∼0.94, P&lt;0.00001]), and lower incidence of treatment-related grade 3 or higher adverse events ([OR=0.20, 95% CI: 0.13∼0.31, P&lt;0.00001]).Conclusion: Compared with the docetaxel chemotherapy regimen, the anti-PD-1/PD-L1 Inhibitors has certain advantages in terms of efficacy and safety. The results still need to be confirmed by a multi-center, large sample, and high-quality research.

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