The Optimal Treatment for Resectable Esophageal Cancer: A Network Meta-Analysis of 6168 Patients.
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ABSTRACT:
SUBMITTER: Yuan M
PROVIDER: S-EPMC7988076 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Background: Controversy continues regarding the optimal strategy of multimodality therapies for resectable gastric cancer. The aim of this network meta-analysis was to determine the efficacy of surgery combined with neoadjuvant or adjuvant chemotherapy (CT), radiotherapy (RT), and chemoradiotherapy (CRT) by integrating the direct and indirect method. Methods: A systematic search for randomized controlled trials (RCTs) was performed through Medline, Embase, CENTRAL, and PMC databases. Overall survival (OS) was the primary outcome of interest. A Bayesian network meta-analysis was conducted and treatments were ranked based on their effectiveness for improving survival. Results: Fifty-six RCTs involving 12,435 patients were included. Overall analysis showed that neoadjuvant CRT resulted in a statistically significantly better OS compared with adjuvant CT, adjuvant RT, adjuvant CRT, neoadjuvant CT, neoadjuvant RT, and surgery alone. Moreover, subgroup analysis of D2 lymphadenectomy revealed that neoadjuvant CRT was not significant superior to neoadjuvant CT (HR = 0.67, 95% CrI 0.41-1.08), adjuvant CRT (HR = 0.67, 95% CrI 0.37-1.21), and adjuvant CT (HR = 0.60, 95% CrI 0.35-1.04). With a tendency to survival benefit, neoadjuvant CRT had an 89% probability of being the best selection. Conclusions: Our study showed no significant survival advantage for neoadjuvant CRT, though the highest probability of being the best treatment was observed. Further clinical trials are essential to determine the value of neoadjuvant CRT, especially in D2 lymphadenectomy subgroup.
| S-EPMC6603377 | biostudies-literature
Project description:BackgroundEsophageal cancer is a highly malignant cancer with a very poor prognosis. For resectable esophageal cancer, neoadjuvant treatment could improve the prognosis of esophageal cancer. However, current clinical neoadjuvant treatment options for esophageal cancer are still limited. The application of immunotherapy is a potentially beneficial new neoadjuvant treatment option for esophageal cancer. The objective of this meta-analysis is to evaluate the efficacy and safety of immunotherapy for the neoadjuvant treatment of esophageal cancer.MethodsWe will search Wanfang Database, SinoMed, China National Knowledge Infrastructure, Embase, Web of Science, Pubmed, and Cochrane Library for relevant articles published before July, 2021. We will also search the unpublished clinical trials of neoadjuvant immunotherapy in esophageal cancer in preprint website (such as bioRXiv and medRxiv) up to July, 2021. We will perform a meta-analysis to evaluate the efficacy and safety of neoadjuvant immunotherapy for resectable esophageal cancer. Randomized controlled trials (RCTs) will be included in this study. The risk of bias will be evaluated for each included study using the Cochrane Handbook for Systematic Reviews of Interventions. We will use RevMan 5.3 software for statistical analysis of the data.ResultsThe results of this study will provide evidence of immunotherapy using as neoadjuvant treatment for esophageal cancer. This meta-analysis will be submitted to a peer-reviewed journal seeking for publication.ConclusionThe results of this study will provide a reliable basis for clinicians and patients to formulate the best pre-surgical treatment plan for resectable esophageal cancer.Systematic review registrationINPLASY202120026.
| S-EPMC8177427 | biostudies-literature
Project description:BACKGROUND:Studies comparing upfront surgery with neoadjuvant treatment in pancreatic cancer may report only patients who underwent resection and so survival will be skewed. The aim of this study was to report survival by intention to treat in a comparison of upfront surgery versus neoadjuvant treatment in resectable or borderline resectable pancreatic cancer. METHODS:MEDLINE, Embase and the Cochrane Library were searched for studies reporting median overall survival by intention to treat in patients with resectable or borderline resectable pancreatic cancer treated with or without neoadjuvant treatment. Secondary outcomes included overall and R0 resection rate, pathological lymph node rate, reasons for unresectability and toxicity of neoadjuvant treatment. RESULTS:In total, 38 studies were included with 3484 patients, of whom 1738 (49·9 per cent) had neoadjuvant treatment. The weighted median overall survival by intention to treat was 18·8?months for neoadjuvant treatment and 14·8?months for upfront surgery; the difference was larger among patients whose tumours were resected (26·1 versus 15·0?months respectively). The overall resection rate was lower with neoadjuvant treatment than with upfront surgery (66·0 versus 81·3 per cent; P?<?0·001), but the R0 rate was higher (86·8 (95 per cent c.i. 84·6 to 88·7) versus 66·9 (64·2 to 69·6) per cent; P?<?0·001). Reported by intention to treat, the R0 rates were 58·0 and 54·9 per cent respectively (P?=?0·088). The pathological lymph node rate was 43·8 per cent after neoadjuvant therapy and 64·8 per cent in the upfront surgery group (P?<?0·001). Toxicity of at least grade III was reported in up to 64 per cent of the patients. CONCLUSION:Neoadjuvant treatment appears to improve overall survival by intention to treat, despite lower overall resection rates for resectable or borderline resectable pancreatic cancer. PROSPERO registration number: CRD42016049374.
| S-EPMC6033157 | biostudies-literature
Project description:Different neoadjuvant therapy regimens are available for rectal cancer, but the relative effects are controversial. The aim of the present network meta-analysis (NMA) was to estimate the relative efficacy and safety of neoadjuvant therapies for resectable rectal cancer. MEDLINE, EMBASE and Cochrane Central Registry of Controlled Trials were searched for publications dated from 1946 up to June 2018. The present study included randomized clinical trials that compared treatments for resected rectal cancer: Surgery alone, surgery preceded by neoadjuvant radiotherapy (RT), neoadjuvant chemotherapy (CT) or neoadjuvant chemoradiotherapy (CRT). Direct pairwise comparisons and NMA were conducted. A total of 23 randomized controlled trials were included in the present study. RT had an overall survival (OS) benefit when compared with surgery alone [HR (hazard ratio), 0.89; 95% confidence interval (CI), 0.82-0.97; quality of evidence, high]. All three neoadjuvant regimens were associated with lower local recurrence (LR) when compared with surgery alone [RT: odds ratio (OR), 0.44; 95% CI, 0.35-0.65; quality of evidence, high; CRT: OR, 0.34; 95% CI, 0.23-0.56; quality of evidence, low and CT: OR, 0.32; 95% CI, 0.11-1.00; quality of evidence, low]. There were no significant differences in OS and LR between CRT and RT (OS: OR, 1.10); 95% CI, 0.93-1.20; LR: OR, 0.81; 95% CI, 0.61-1.10). Ranking probabilities indicated that CRT was the best strategy for local control, with a surface under the cumulative ranking curve (SUCRA) of 78.78%. Patients treated with RT had improved disease-free survival compared with those treated with surgery alone (HR, 0.82; 95% CI, 0.64-1.00; quality of evidence, low). Neoadjuvant RT or CRT did not significantly improve distant metastases compared with surgery alone (RT: OR, 0.87; 95% CI, 0.69-1.10 and CRT: OR, 0.75; 95% CI, 0.47-1.10). CRT had an improved pathological complete response rate compared with RT (OR, 4.90; 95% CI, 21.80-17.00; quality of evidence, low). No significant difference for the risk of anastomotic leak between each treatment was observed in the NMA. In conclusion, RT decreased the LR and improved OS compared with surgery alone for resected rectal cancer. CRT was the best neoadjuvant therapy analyzed and CT was likely the second best for all outcomes based on SUCRA. However, these findings were limited by overall low quality of evidence.
| S-EPMC7086160 | biostudies-literature
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.
| S-EPMC529457 | biostudies-literature
Project description:Objective This systematic review and meta-analysis aimed to investigate the role of neoadjuvant immunochemotherapy with or without radiotherapy [NIC(R)T] compared to traditional neoadjuvant therapies, without immunotherapy [NC(R)T]. Summary background data NCRT followed by surgical resection is recommended for patients with early-stage esophageal cancer. However, it is uncertain whether adding immunotherapy to preoperative neoadjuvant therapy would improve patient outcomes when radical surgery is performed following neoadjuvant therapy. Methods We searched PubMed, Web of Science, Embase, and Cochrane Central databases, as well as international conference abstracts. Outcomes included R0, pathological complete response (pCR), major pathological response (mPR), overall survival (OS) and disease-free survival (DFS) rates. Results We included data from 5,034 patients from 86 studies published between 2019 and 2022. We found no significant differences between NICRT and NCRT in pCR or mPR rates. Both were better than NICT, with NCT showing the lowest response rate. Neoadjuvant immunotherapy has a significant advantage over traditional neoadjuvant therapy in terms of 1-year OS and DFS, with NICT having better outcomes than any of the other three treatments. There were no significant differences among the four neoadjuvant treatments in terms of R0 rates. Conclusions Among the four neoadjuvant treatment modalities, NICRT and NCRT had the highest pCR and mPR rates. There were no significant differences in the R0 rates among the four treatments. Adding immunotherapy to neoadjuvant therapy improved 1-year OS and DFS, with NICT having the highest rates compared to the other three modalities. Systematic Review Registration https://inplasy.com/inplasy-2022-12-0060/, identifier INPLASY2022120060.
| S-EPMC10213267 | biostudies-literature
Project description: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.
| S-EPMC6329872 | biostudies-other
Project description:BackgroundThe National Comprehensive Cancer Network (NCCN) guidelines did not give an explicit comparison of the efficacy between surgery and radiotherapy in treating Stage-III N2 non-small cell lung cancer (NSCLC) patients, leaving a paucity for clinical reference. Through this study, we try to locate the optimum treatment strategy including surgical type for these patients.MethodsA systematic literature search was performed from PubMed, Cochrane Library, Embase, and Google Scholars. The endpoints were overall survival (OS), mean OS, and progression-free survival (PFS). The treatments comprised radiotherapy, lobectomy, and pneumonectomy. Network meta-analysis was carried out for calculating the odds ratio (OR) for binary variants. All the analyses implemented Stata 17.0 MP.ResultsEight clinical trials reporting 1756 patients met the inclusion criteria. Radiotherapy and surgery were equivalent in improving patients' OS (OR = 0.842, 95% confidence interval [CI]: [0.645, 1.099]). The mean OS of patients were similar in terms of radiotherapy, lobectomy, and pneumonectomy. Besides, radiotherapy and surgery had equivalent effects in improving PFS (OR = 0.896, 95% CI: [0.718, 1.117]).ConclusionsSince lobectomy and pneumonectomy following neoadjuvant treatments had equivalent efficacy in prolonging OS for patients with stage-IIIA N2 NSCLC compared with definitive radiotherapy, young patients with favorable performance status (0) should try surgery to pursue better prognosis while elderly patients with unfavorable PS or radiosensitive pathology types should accept definitive radiotherapy. More high-quality clinical trials are needed to support our findings.
| S-EPMC9280794 | biostudies-literature
Project description:The efficacy of surgery alone for patients with locally advanced esophageal cancer (EC) is still unsatisfactory. Presently, induction therapy followed by surgery is the standard treatment. Preoperative chemotherapy (CT) and chemoradiation (CRT) are proven effective induction therapies; however, few sample studies have addressed these treatments, thus, their superiority remains uncertain. We performed a systemic review and meta analysis to test the hypothesis that induction CRT prior to surgery could improve survival compared with induction CT alone.A comprehensive search of PubMed and the Ovid database for relevant studies comparing EC patients undergoing resection after treatment with induction CT alone or induction CRT was conducted. Hazard ratios (HR) and 95% confidence intervals (95% CI) were extracted from these studies to provide pooled estimates of the effect of induction therapy on overall survival.Five studies met the criteria for analysis. Statistical analysis demonstrated a survival benefit of induction CRT compared with induction CT alone (HR0.73, 95% CI 0.61-0.89; P = 0.002). Further analysis showed that induction CRT perioperative mortality and complication rates were higher than for induction CT alone (HR 2.96, 95% CI 1.38-6.37; HR1.6, 95% CI 1.30-1.98; P = 0.01, respectively).Published evidence comparing the different efficacies of induction CT and induction CRT is sparse, with few samples of adenocarcinoma. This analysis supports the view that, compared with induction CT, induction CRT could achieve a long-term survival benefit in EC patients.
| S-EPMC4773296 | biostudies-other
Project description:Background: Several neoadjuvant treatments are available for patients with resectable gastroesophageal cancer. We did a Bayesian network meta-analysis (NMA) to compare available treatments, summarizing the direct and indirect evidence. Method: We searched relevant databases for randomized controlled trials of neoadjuvant treatments for resectable gastroesophageal cancer which compared two or more of the following treatments: surgery alone, perioperative docetaxel, oxaliplatin, leucovorin, and fluorouracil (FLOT), and neoadjuvant treatments listed in National Comprehensive Cancer Network guideline. Then we performed a NMA to summarize the direct and indirect evidence to estimate the relative efficacy for outcomes including overall survival (OS), progression-free survival and R0 resection rate. We calculated odds ratio (OR) and hazard ratio (HR) with 95% credible intervals (CrI) for dichotomous data and time-to-event data, respectively. We also calculated the surface under the cumulative ranking curve (SUCRA) value of each intervention to obtain a hierarchy of treatments. Result: Eight eligible trials (2434 patients) were included in our NMA. The treatment with the highest probability of benefit on OS as compared with surgery alone was perioperative FLOT [HR = 0.58 with 95% CrI: (0.43, 0.78), SUCRA = 93%], followed by preoperative radiotherapy, paclitaxel, and carboplatin (RT/PC) [HR = 0.68 with 95% CrI: (0.53, 0.87), SUCRA = 72%], perioperative cisplatin with fluorouracil (CF) [HR = 0.70 with 95% CrI: (0.51, 0.95), SUCRA = 68%], and perioperative epirubicin, cisplatin, and fluorouracil or capecitabine (ECF/ECX) [HR = 0.75 with 95% CrI: (0.60, 0.94), SUCRA = 56%]. Conclusion: Compared with surgery alone, perioperative CF, perioperative ECF/ECX, perioperative FLOT, and preoperative RT/PC significantly improved survival. Perioperative FLOT is likely to be the most effective neoadjuvant treatment for the disease. Further clinical studies are needed and justified.
| S-EPMC6087755 | biostudies-literature