Dataset Information

Neoadjuvant treatment of pancreatic adenocarcinoma: a systematic review and meta-analysis of 5520 patients.

ABSTRACT: Recent years have seen standardization of the anatomic definitions of pancreatic adenocarcinoma, and increasing utilization of neoadjuvant therapy (NAT). The aim of the current review was to summarize the evidence for NAT in pancreatic adenocarcinoma since 2009, when consensus criteria for resectable (R), borderline resectable (BR), and locally advanced (LA) disease were endorsed.PubMed search was undertaken along with extensive backward search of the references of published articles to identify studies utilizing NAT for pancreatic adenocarcinoma. Abstracts from ASCO-GI 2014 and 2015 were also searched.A total of 96 studies including 5520 patients were included in the final quantitative synthesis. Pooled estimates revealed 36% grade ??3 toxicities, 5% biliary complications, 21% hospitalization rate and low mortality (0%, range 0-16%) during NAT. The majority of patients (59%) had stable disease. On an intention-to-treat basis, R0-resection rates varied from 63% among R patients to 23% among LA patients. R0 rates were >?80% among all patients who were resected after NAT. Among R and BR patients who underwent resection after NAT, median OS was 30 and 27.4 months, respectively.The current study summarizes the recent literature for NAT in pancreatic adenocarcinoma and demonstrates improving outcomes after NAT compared to those historically associated with a surgery-first approach for pancreatic adenocarcinoma.

SUBMITTER: Dhir M

PROVIDER: S-EPMC5634869 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Neoadjuvant treatment of pancreatic adenocarcinoma: a systematic review and meta-analysis of 5520 patients.

Dhir Mashaal M Malhotra Gautam K GK Sohal Davendra P S DPS Hein Nicholas A NA Smith Lynette M LM O'Reilly Eileen M EM Bahary Nathan N Are Chandrakanth C

World journal of surgical oncology 20171010 1

<h4>Background</h4>Recent years have seen standardization of the anatomic definitions of pancreatic adenocarcinoma, and increasing utilization of neoadjuvant therapy (NAT). The aim of the current review was to summarize the evidence for NAT in pancreatic adenocarcinoma since 2009, when consensus criteria for resectable (R), borderline resectable (BR), and locally advanced (LA) disease were endorsed.<h4>Methods</h4>PubMed search was undertaken along with extensive backward search of the reference ...[more]

PMID: 29017581

Similar Datasets

Project description:INTRODUCTION:Although the only curative strategy for pancreatic cancer is surgical resection, up to 85% of patients relapse after surgery. The efficacy of neoadjuvant treatment in resectable pancreatic cancer (RPC) remains unclear and there is no systematic review focusing fully on this issue. Recently, two prospective trials of neoadjuvant treatment in RPC were terminated early because of slow recruiting and existing randomised controlled trials (RCTs) have too small sample sizes. Therefore, to overcome probable biases, it would be more reasonable to include both RCTs and non-randomised studies (NRSs) with selected criteria. This review aims to investigate the effect of neoadjuvant chemotherapy (CTx) and chemoradiation therapy (CRT) in RPC using RCTs and specific NRSs. METHOD AND ANALYSIS:This systematic review will include conventional RCTs as group I, and quasi-randomised controlled trials, non-randomised controlled trials and prospective cohort studies as group II. Two groups will be assessed and analysed separately. Comprehensive literature search will use Medline, Embase, Cochrane library and Scopus databases. Additionally, we will search references from relevant studies and abstracts from major conferences. Two authors will independently identify, screen, include studies, extract data and assess the risk of bias. Discrepancies will be resolved by consensus with another author. An independent methodologist will categorise and assess NRSs to minimise heterogeneity. In each study group, meta-analysis will be conducted using a random-effect model and statistical heterogeneity will be evaluated using I(2)-statistics. Publication bias will be visualised with contour-enhanced funnel plots and analysed with Egger's test. In group I, cumulative meta-analysis will be considered because the CTx regimen and CRT protocol have changed. The quality of evidence will be summarised using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach. ETHICS AND DISSEMINATION:This review does not use primary data, and formal ethical approval is not required. Findings will be disseminated through peer-reviewed journals and committee conferences. TRIAL REGISTRATION NUMBER:CRD42015023820.

Project description:BackgroundFOLFIRINOX is a standard treatment for metastatic pancreatic cancer patients. The effectiveness of neoadjuvant FOLFIRINOX in patients with borderline resectable pancreatic cancer (BRPC) remains debated.MethodsWe performed a systematic review and patient-level meta-analysis on neoadjuvant FOLFIRINOX in patients with BRPC. Studies with BRPC patients who received FOLFIRINOX as first-line neoadjuvant treatment were included. The primary endpoint was overall survival (OS), and secondary endpoints were progression-free survival, resection rate, R0 resection rate, and grade III-IV adverse events. Patient-level survival outcomes were obtained from authors of the included studies and analyzed using the Kaplan-Meier method.ResultsWe included 24 studies (8 prospective, 16 retrospective), comprising 313 (38.1%) BRPC patients treated with FOLFIRINOX. Most studies (n = 20) presented intention-to-treat results. The median number of administered neoadjuvant FOLFIRINOX cycles ranged from 4 to 9. The resection rate was 67.8% (95% confidence interval [CI] = 60.1% to 74.6%), and the R0-resection rate was 83.9% (95% CI = 76.8% to 89.1%). The median OS varied from 11.0 to 34.2 months across studies. Patient-level survival data were obtained for 20 studies representing 283 BRPC patients. The patient-level median OS was 22.2 months (95% CI = 18.8 to 25.6 months), and patient-level median progression-free survival was 18.0 months (95% CI = 14.5 to 21.5 months). Pooled event rates for grade III-IV adverse events were highest for neutropenia (17.5 per 100 patients, 95% CI = 10.3% to 28.3%), diarrhea (11.1 per 100 patients, 95% CI = 8.6 to 14.3), and fatigue (10.8 per 100 patients, 95% CI = 8.1 to 14.2). No deaths were attributed to FOLFIRINOX.ConclusionsThis patient-level meta-analysis of BRPC patients treated with neoadjuvant FOLFIRINOX showed a favorable median OS, resection rate, and R0-resection rate. These results need to be assessed in a randomized trial.

Project description:IntroductionThe optimal dose and treatment modality of neoadjuvant radiotherapy applied for treating borderline resectable and locally advanced pancreatic ductal adenocarcinoma (PDAC) have been debated topics in oncology. The objective of the present network meta-analysis (NMA) is to study and compare the efficacy and safety of neoadjuvant radiotherapy comprehensively using different doses in patients with borderline resectable pancreatic cancer (BRPC) and locally advanced pancreatic cancer (LAPC).Methods and analysisFour electronic databases, including PubMed, EMBASE, Cochrane library and Web of science, will be searched thoroughly to identify relevant studies published from 2006 to October 2020. Electronic searching by titles using neoadjuvant treatments for PDAC will be performed in the annual meetings of European Society of Medical Oncology and American Society of Clinical Oncology (2018-2020).Clinicaltrialsgov will also be searched for grey literature. Two reviewers will perform search strategies and extract data independently. R0 resection rate and local control rate are defined as primary outcomes. Secondary outcomes include overall survival, disease-free survival and acute and late grade 3 and grade 4 toxicities. For randomised control trials, the risk of bias will be assessed using the Cochrane Risk of Bias Tool, while the risk of bias for non-randomised, observational studies will be evaluated using the Risk Of Bias In Non-randomised Studies-of Interventions. The quality of evidence will be evaluated using the version of Cochrane tool and Grades of Recommendation, Assessment, Development and Evaluation. Subgroup analysis and sensitivity analysis will be conducted in the present NMA.Ethics and disseminationThis study will synthesise the evidence regarding dose schedule of neoadjuvant radiotherapy in patients with BRPC and LAPC. We hope the findings from this NMA will help clinicians and patients select the optimal modality and dose schedule of neoadjuvant radiotherapy with respect to patient-reported outcomes. As no primary data collection will be undertaken, no ethics approval is required. The results will be disseminated through peer-reviewed journal.Prospero registration numberCRD42020222408.

Project description:Background: Non-randomized studies have investigated multi-agent gemcitabine-based neo-adjuvant therapies (GEM-NAT) in borderline resectable pancreatic ductal adenocarcinoma (BR-PDAC). Treatment sequencing and specific elements of neoadjuvant treatment are still under investigation. The present meta-analysis aims to assess the effectiveness of GEM-NAT on overall survival (OS) in BR-PDAC. Patients and Methods: A meta-analysis of individual participant data (IPD) on GEM-NAT for BR-PDAC were performed. The primary outcome was OS after treatment with GEM-based chemotherapy. In the Individual Patient Data analysis data were reappraised and confirmed as BR-PDAC on provided radiological data. Results: Six studies investigating GEM-NAT were included in the IPD metanalysis. The IPD metanalysis was conducted on 271 patients who received GEM-NAT. Pooled median patient-level OS was 22.2 months (95%CI 19.1-25.2). R0 rates ranged between 81 and 95% (I 2 = 0%, p = 0.64), respectively. Median OS was 27.8 months (95%CI 23.9-31.6) in the patients who received NAT-GEM followed by resection compared to 15.4 months (95%CI 12.3-18.4) for NAT-GEM without resection and 13.0 months (95%CI 7.4-18.5) in the group of patients who received upfront surgery (p < 0.0001). R0 rates ranged between 81 and 95% (I 2 = 0%, p = 0.64), respectively. Overall survival in the R0 group was 29.3 months (95% CI 24.3-34.2) vs. 16.2 months (95% CI 7·9-24.5) in the R1 group (p = 0·001). Conclusions: The present study is the first meta-analysis combining IPD from a number of international centers with BR-PDAC in a cohort that underwent multi-agent gemcitabine neoadjuvant therapy (GEM-NAT) before surgery. GEM-NAT followed by surgical resection improve survival and R0 resection in BR-PDAC. Also, GEM-NAT may result in a good palliative option in non-resected patients because of progressive disease after neoadjuvant treatment. Results from randomized controlled trials (RCTs) are awaited to validate these findings.

Project description:BackgroundSurgery is the main treatment option for patients with local gastric cancer. However, surgery alone is usually not sufficient for stomach cancer patients, and combined therapies are recommended for these patients. In recent studies, some preoperative treatments have shown benefits. However, the treatment selection is still uncertain because previous studies failed to obtain a statistically significant difference between preoperative chemotherapy and preoperative chemoradiotherapy. Therefore, we plan to perform a systematic review and meta-analysis to compare the benefits among these preoperative treatments.Methods/designThis review includes randomized controlled trials with or without blinding as well as published studies, high-quality unpublished studies, full articles and meeting abstracts with an English context if sufficient results were provided for analysis. Data sources include the Cochrane Central Register of Controlled Trials, Embase, MEDLINE, major relevant international conferences and manual screening of references. Patients with a diagnosis of resectable primary gastric or EGJ adenocarcinoma (stage II or higher) who underwent surgery alone or preoperative treatment followed by surgery and who were pathologically confirmed as proposed by the AJCC 2017 guidelines without age, sex, race, subtypes of adenocarcinoma and molecular pathology limitations will be included. The following three interventions will be included: surgery alone, neoadjuvant chemistry followed by surgery and neoadjuvant chemoradiotherapy followed by surgery. All-cause mortality, overall survival (OS, the time interval from diagnosis to death) and/or progression-free survival (PFS, the time interval from diagnosis to disease progression or death from any cause) will be defined as major results of concern. The clinical and pathological response rate (according to RECIST and tumour regression score), R0 resection rate, quality of life and grade 3 or above adverse events (according to the National Cancer Institute Common Terminology Criteria for Adverse Events, NCI-CTCAE) will be defined as the secondary outcomes.DiscussionThe aim of this systematic review is to compare the benefits of different preoperative treatments for patients with locoregional stomach cancer. This systematic review will improve the understanding of the relative efficacy of these treatment options by providing the latest evidence on the efficacy of various treatment options in the management of gastric cancer patients and may guide clinical practice.Systematic review registrationPROSPERO CRD4202123718.

Dataset Information

Neoadjuvant treatment of pancreatic adenocarcinoma: a systematic review and meta-analysis of 5520 patients.

Publications

Neoadjuvant treatment of pancreatic adenocarcinoma: a systematic review and meta-analysis of 5520 patients.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets