Abstract
Background: Alternatives in treatment-strategies exist for resectable gastric cancer. Our aims were: (1) to assess the benefit of perioperative, neoadjuvant and adjuvant treatment-strategies and (2) to determine the optimal adjuvant regimen for gastric cancer treated with curative intent. Methods: PubMed, EMBASE, CENTRAL, and ASCO/ESMO conferences were searched up to August 2017 for randomized-controlled-trials on the curative treatment of resectable gastric cancer. We performed two network-meta-analyses (NMA). NMA-1 compared perioperative, neoadjuvant and adjuvant strategies only if there was a direct comparison. NMA-2 compared different adjuvant chemo(radio)therapy regimens, after curative resection. Overall-survival (OS) and disease-free-survival (DFS) were analyzed using random-effects NMA on the hazard ratio (HR)-scale and calculated as combined HRs and 95% credible intervals (95% CrIs). Results: NMA-1 consisted of 9 direct comparisons between strategies for OS (14 studies, n = 4187 patients). NMA-2 consisted of 16 direct comparisons between adjuvant chemotherapy/chemoradiotherapy regimens for OS (37 studies, n = 10,761) and 14 for DFS (30 studies, n = 9714 patients). Compared to taxane-based-perioperative-chemotherapy, surgery-alone (HR = 0.58, 95% CrI = 0.38–0.91) and perioperative-chemotherapy regimens without a taxane (HR = 0.79, 95% CrI = 0.58–1.15) were inferior in OS. After curative-resection, the doublet oxaliplatin-fluoropyrimidine (for one-year) was the most efficacious adjuvant regimen in OS (HR = 0.47, 95% CrI = 0.28–0.80). Conclusions: For resectable gastric cancer, (1) taxane-based perioperative-chemotherapy was the most promising treatment strategy; and (2) adjuvant oxaliplatin-fluoropyrimidine was the most promising regimen after curative resection. More research is warranted to confirm or reproach these findings.
Highlights
Gastric adenocarcinoma is one of the leading causes of cancer related mortality on a global scale [1]
From a total of 5461 unique references, identified by searching PubMed, Embase and Central, 73 references remained after title and abstract screening. 20 references were excluded after full text assessment including the SAMIT trial for the primary analysis as it included R1 resected patients [10]
When taxane-based neoadjuvant and taxane-based adjuvant chemotherapy were separated from non-taxane containing neoadjuvant/adjuvant chemotherapy the network lost the ability to detect any significant difference between comparisons (Figures S1 and S2)
Summary
Gastric adenocarcinoma is one of the leading causes of cancer related mortality on a global scale [1]. There is no global consensus on the optimum treatment strategy Perioperative chemotherapy is the preferred treatment strategy in many countries in Europe, as there is evidence this will reduce the number of relapses [2]. In Asian countries, after a curative resection, adjuvant chemotherapy, usually without any neoadjuvant therapy, is the standard of care [5]. In the United States adjuvant chemotherapy with radiotherapy after curative resection is a frequently applied treatment strategy, based on the intergroup 0116 trial [6]. Our aims were: (1) to assess the benefit of perioperative, neoadjuvant and adjuvant treatment-strategies and (2) to determine the optimal adjuvant regimen for gastric cancer treated with curative intent. NMA-2 compared different adjuvant chemo(radio)therapy regimens, after curative resection.
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