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Neoadjuvant Chemoradiation Treatment for Resectable Esophago-Gastric Cancer: A Systematic Review and Meta-Analysis.

ABSTRACT: Background: Neoadjuvant chemoradiation (CRT) remains controversial in the treatment of the oesophagus or gastro-oesophageal junction (GOJ) carcinomas. Methods: We conducted a meta-analysis to assess the efficacy and safety of Neoadjuvant CRT plus surgery comparing with neoadjuvant CT plus surgery or surgery alone. Feasible studies were searched from electronic databases. The outcomes of survival, R0 resection rate and adverse effects were analyzed. The outcomes were measured with relative risk (RR) and odds ratio(OR). Results: Seventeen records including 4095 patients were included. Neoadjuvant CRT improved 1-,2-,3-and 5-year survival. The relative risk (RR) [95% confidence interval (CI),P value] was respectively 1.08(1.03-1.14,0.002), 1.21(1.12-1.32,<0.00001),1.31(1.09-1.58,0.004),1.38(1.17-1.62, <0.001).In subgroup analysis, patients with squamous cell carcinoma benefited more survival advantage from neoadjuvant CRT than those with adenocarcinoma[1.23(1.15-1.33)vs1.11 (1.03-1.19)]. A significant advantage was observed in analysis of neoadjuvant CRT for PFS [1.32 (1.22-1.44),<0.00001]. Tests for DFS between neoadjuvant CRT and neoadjuvant CT or surgery alone were not statistically significant[1.06 (0.97-1.17,0.19)]. Neoadjuvant CRT was associated with higher R0 resection [2.58(1.75-3.82),<0.00001] and pCR rate [4.37(2.68-7.13),<0.00001]. Neoadjuvant CRT lowered the local recurrence rate [0.52(0.39-0.69),<0.00001] and didn't control distant metastasis rate[0.85(0.67-1.08),0.19].There was no evidence that neoadjuvant CRT increased the treatment-related mortality[1.27(0.95-1.71),0.11]. Neoadjuvant CRT plus surgery did not increase the risk of adverse events morbidity[1.14(0.99-1.32),0.08]. Conclusion: Patients with oesophagus or GOJ carcinomas can obtain a survival advantage from neoadjuvant CRT. The addition of radiation was efficacy and safe in range. However, these results need further high-quality prospective RCTs confirmation.

SUBMITTER: Meng X

PROVIDER: S-EPMC6329872 | biostudies-other | 2019

REPOSITORIES: biostudies-other

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Neoadjuvant Chemoradiation Treatment for Resectable Esophago-Gastric Cancer: A Systematic Review and Meta-Analysis.

Meng Xiangyu X Wang Lu L Zhao Yan Y Zhu Bo B Sun Ting T Zhang Tao T Gu Xiaohu X Zheng Zhichao Z

Journal of Cancer 20190101 1

<b>Background:</b> Neoadjuvant chemoradiation (CRT) remains controversial in the treatment of the oesophagus or gastro-oesophageal junction (GOJ) carcinomas. <b>Methods:</b> We conducted a meta-analysis to assess the efficacy and safety of Neoadjuvant CRT plus surgery comparing with neoadjuvant CT plus surgery or surgery alone. Feasible studies were searched from electronic databases. The outcomes of survival, R0 resection rate and adverse effects were analyzed. The outcomes were measured with r ...[more]

PMID: 30662540

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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: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.

Project description:BackgroundCarcinoma of the esophagus is an aggressive malignancy with an increasing incidence. Its virulence, in terms of symptoms and mortality, justifies a continued search for optimal therapy. The large and growing number of patients affected, the high mortality rates, the worldwide geographic variation in practice, and the large body of good quality research warrants a systematic review with meta-analysis.MethodsA systematic review and meta-analysis investigating the impact of neoadjuvant or adjuvant therapy on resectable thoracic esophageal cancer to inform evidence-based practice was produced.MEDLINE, CANCERLIT, Cochrane Library, EMBASE, and abstracts from the American Society of Clinical Oncology and the American Society for Therapeutic Radiology and Oncology were searched for trial reports. Included were randomized trials or meta-analyses of neoadjuvant or adjuvant treatments compared with surgery alone or other treatments in patients with resectable thoracic esophageal cancer. Outcomes of interest were survival, adverse effects, and quality of life. Either one- or three-year mortality data were pooled and reported as relative risk ratios.ResultsThirty-four randomized controlled trials and six meta-analyses were obtained and grouped into 13 basic treatment approaches. Single randomized controlled trials detected no differences in mortality between treatments for the following comparisons:- Preoperative radiotherapy versus postoperative radiotherapy.- Preoperative and postoperative radiotherapy versus postoperative radiotherapy. Preoperative and postoperative radiotherapy was associated with a significantly higher mortality rate.- Postoperative chemotherapy versus postoperative radiotherapy.- Postoperative radiotherapy versus postoperative radiotherapy plus protein-bound polysaccharide versus chemoradiation versus chemoradiation plus protein-bound polysaccharide. Pooling one-year mortality detected no statistically significant differences in mortality between treatments for the following comparisons:- Preoperative radiotherapy compared with surgery alone (five randomized trials).- Postoperative radiotherapy compared with surgery alone (five randomized trials).- Preoperative chemotherapy versus surgery alone (six randomized trials).- Preoperative and postoperative chemotherapy versus surgery alone (two randomized trials).- Preoperative chemoradiation therapy versus surgery alone (six randomized trials). Single randomized controlled trials detected differences in mortality between treatments for the following comparison:- Preoperative hyperthermia and chemoradiotherapy versus preoperative chemoradiotherapy in favour of hyperthermia. Pooling three-year mortality detected no statistically significant difference in mortality between treatments for the following comparison:- Postoperative chemotherapy compared with surgery alone (two randomized trials). Pooling three-year mortality detected statistically significant differences between treatments for the following comparisons:- Preoperative chemoradiation therapy versus surgery alone (six randomized trials) in favour of preoperative chemoradiation with surgery.- Preoperative chemotherapy compared with preoperative radiotherapy (one randomized trial) in favour of preoperative radiotherapy.ConclusionFor adult patients with resectable thoracic esophageal cancer for whom surgery is considered appropriate, surgery alone (i.e., without neoadjuvant or adjuvant therapy) is recommended as the standard practice.

Project description:BackgroundNeoadjuvant combination immunotherapy is changing the treatment landscape for patients with cancer. Exploring the incidence of immune-related adverse events (irAEs) in relation to this novel approach may provide valuable insights for future clinical investigations.MethodsThis review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. PubMed, Embase, Cochrane Library, American Society of Clinical Oncology (ASCO), and European Society of Medical Oncology (ESMO) websites were searched for all relevant literature from their inception to November 24, 2023. We then extracted the required data from the included studies and used the R software to analyze the pooled incidence of irAEs. Subgroup analyses examined the pooled incidence of irAEs according to cancer and combination types using a random-effects model.ResultsSixteen studies involving 501 patients were included in the meta-analysis. Considering the heterogeneity of the study design, we analyzed the randomized controlled studies (RCTs) and the single-arm studies separately. In RCTs, the incidence of any-grade irAEs was 95.0% (95% confidence interval [CI] 87.3-99.3) and that of grade ≥3 irAEs was 24.0% (95% CI 13.7-36.0). In single-arm studies, the incidence of any-grade irAEs was 89.4% (95% CI 75.0-98.0) and grade ≥3 irAEs was 20.3% (95% CI 8.7-35.2). In both RCTs and single arms, the most common any- grade irAEs were rash and fatigue, while the most common grade ≥3 irAEs was abnormal liver function and colitis. Due to irAEs, 9.4% of patients in RCTs and 6.9% of patients in single-arm studies did not complete the prescribed neoadjuvant treatment cycle.ConclusionThis study comprehensively summarized the incidence of irAEs in neoadjuvant combination immunotherapy. The occurrence of irAEs varies depending on the cancer and combination types. Our meta-analysis provides clinicians with essential guidance for the management of patients with cancer.Systematic review registrationhttps://www.crd.york.ac.uk/prospero, identifier CRD42023387969.

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.

Dataset Information

Neoadjuvant Chemoradiation Treatment for Resectable Esophago-Gastric Cancer: A Systematic Review and Meta-Analysis.

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Neoadjuvant Chemoradiation Treatment for Resectable Esophago-Gastric Cancer: A Systematic Review and Meta-Analysis.

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