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Neoadjuvant strategies in resectable carcinoma esophagus: a meta-analysis of randomized trials.

ABSTRACT: BACKGROUND:The survival benefit of neoadjuvant therapy in resectable carcinoma esophagus has been elucidated. We performed a meta-analysis in light of new studies and long-term results of past trials. The search strategy was refined to include only "neoadjuvant" so that any bias by adjuvant treatment is eliminated. METHODS:A detailed search of MEDLINE, Embase, and Cochrane Library was done. Only published randomized English language trials were included. Data were categorized as neoadjuvant concurrent chemoradiation (NACRT), neoadjuvant chemotherapy (NACT), neoadjuvant radiotherapy (NART), and neoadjuvant sequential chemoradiotherapy (SCRT). Meta-analysis was done using odds ratio (OR) and 95% CI using fixed/random effects model. Heterogeneity was tested by chi-square and I2 test. Z probability calculated significant difference across subgroups. Outcomes assessed were overall survival (OS) and disease-free survival (DFS) at 3 and 5?years, respectively, mortality (30/90?day) and failures (local/systemic). RESULTS:Twenty-five randomized trials involving 5272 patients were included for quantitative analysis. NACRT was evaluated in 12 studies (2676 patients). Superior 3-year OS (OR = 0.68 CI 0.52-0.90, p = 0.007), 3-year DFS (OR = 0.55 CI 0.45-0.68, p = 0.00001), and 5-year DFS (OR = 0.59 CI 0.47-0.74, p = 0.00001), with lower failures (OR = 0.52 CI 0.37-0.73, p = 0.0001), were seen in favor of NACRT at the cost of increased perioperative mortality (OR = 1.79 CI 1.15-2.80, p = .01). However, 5-year OS (OR = 0.78 CI 0.60-0.1.01, p = 0.06) was not found to be significantly superior. NACT, NART, and SCRT were not found to have any benefit over surgery alone. CONCLUSION:This meta-analysis presents strong evidence favoring NACRT over upfront surgery. It also shows no survival advantage of neoadjuvant chemotherapy.

SUBMITTER: Kumar T

PROVIDER: S-EPMC7085863 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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Neoadjuvant strategies in resectable carcinoma esophagus: a meta-analysis of randomized trials.

Kumar Tarun T Pai Esha E Singh Rajesh R Francis Neville J NJ Pandey Manoj M

World journal of surgical oncology 20200321 1

<h4>Background</h4>The survival benefit of neoadjuvant therapy in resectable carcinoma esophagus has been elucidated. We performed a meta-analysis in light of new studies and long-term results of past trials. The search strategy was refined to include only "neoadjuvant" so that any bias by adjuvant treatment is eliminated.<h4>Methods</h4>A detailed search of MEDLINE, Embase, and Cochrane Library was done. Only published randomized English language trials were included. Data were categorized as n ...[more]

PMID: 32199464

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Project description:BackgroundThere is uncertainty in the treatment options for resectable hypopharyngeal squamous cell carcinoma.MethodsA systematic review of randomised controlled trials (RCTs) was performed. Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library), MEDLINE, EMBASE, Science Citation Index, and Conference Proceedings databases and trial registries were searched until November 2020 for randomized controlled trials performed on resectable hypopharyngeal squamous cell carcinoma. Two systematic review authors independently identified studies and extracted data. The primary outcomes evaluated were overall survival, disease-free survival, any recurrence, local recurrence, loco-regional recurrence, distal recurrence and laryngectomy-free survival. The secondary outcomes were response rates following neoadjuvant treatment and comparison of treatment-related toxicity. Assessment of risk of bias was performed for the selected studies using Cochrane's tool for assessing risk of bias. The studies were evaluated for the quality of evidence using GRADE (Grading of Recommendations, Assessment, Development and Evaluations). Risk ratios (RR), rate ratios, and hazard ratios (HR) were calculated along with 95% confidence intervals (95% CI). The Meta-analysis was performed using a random-effects model.ResultsFive RCTs met the inclusion criteria for this review. The risk of bias was unclear or high for the trials. Non-organ preservation(n = 140) versus organ preservation (n = 144) (two trials): no statistically significant difference could be identified for any of the primary outcomes. Concurrent chemoradiotherapy (n = 37) versus sequential chemotherapy followed by radiotherapy (n = 34) (one trial): no statistically significant difference was noted between the two treatment arms for overall survival, disease-free survival and loco-regional recurrence. Laryngectomy-free survival was found to be superior in concurrent chemoradiotherapy arm (HR:0.28, 95% CI 0.13, 0.57). Induction chemotherapy followed by concurrent chemoradiotherapy (n = 53) versus induction chemotherapy followed by radiotherapy (n = 60) (one trial): no statistically significant difference was noted between the treatment arms for overall survival, disease-free survival and laryngectomy-free survival. Preoperative radiotherapy (n = 24) versus postoperative radiotherapy (n = 23) (one trial): overall survival was found to be better in the postoperative radiotherapy arm (HR:2.44, 95% CI1.18, 5.03). No statistically significant difference was noted in terms of treatment-related toxicity.ConclusionsThere are considerable uncertainties in the management of resectable hypopharyngeal cancer.Trail registrationPROSPERO registration: CRD42019155613.

Dataset Information

Neoadjuvant strategies in resectable carcinoma esophagus: a meta-analysis of randomized trials.

Publications

Neoadjuvant strategies in resectable carcinoma esophagus: a meta-analysis of randomized trials.

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