Efficacy and safety of perioperative therapy for locally resectable gastric cancer: A network meta-analysis of randomized clinical trials

Abstract

Background: Gastric cancer (GC) is the fifth most commonly diagnosed malignancy worldwide, with over 1 million new cases per year, and the third leading cause of cancer-related death.

Aim: To determine the optimal perioperative treatment regimen for patients with locally resectable GC.

Methods: A comprehensive literature search was conducted, focusing on phase II/III randomized controlled trials (RCTs) assessing perioperative chemotherapy and chemoradiotherapy in treating locally resectable GC. The R0 resection rate, overall survival (OS), disease-free survival (DFS), and incidence of grade 3 or higher nonsurgical severe adverse events (SAEs) associated with various perioperative regimens were analyzed. A Bayesian network meta-analysis was performed to compare treatment regimens and rank their efficacy.

Results: Thirty RCTs involving 8346 patients were included in this study. Neoadjuvant XELOX plus neoadjuvant radiotherapy and neoadjuvant CF were found to significantly improve the R0 resection rate compared with surgery alone, and the former had the highest probability of being the most effective option in this context. Neoadjuvant plus adjuvant FLOT was associated with the highest probability of being the best regimen for improving OS. Owing to limited data, no definitive ranking could be determined for DFS. Considering nonsurgical SAEs, FLO has emerged as the safest treatment regimen.

Conclusion: This study provides valuable insights for clinicians when selecting perioperative treatment regimens for patients with locally resectable GC. Further studies are required to validate these findings.

Keywords: Efficacy and safety; Gastric cancer; Network meta-analysis; Perioperative treatment.

Figure 1

Flow diagram of article search and study selection.

Figure 2

Network meta-analysis of R0 resection rate. A: Network diagram of R0 resection rate; B: The published biased funnel plot of R0 resection rate; C: Comparisons between each treatment; D: Surface under the cumulative ranking value of R0 resection rate of each intervention. Bold and underlined indicate statistically significant pairwise comparisons. A: Neoadjuvant ECF; B: Neoadjuvant FLOT; C: Neoadjuvant DCS; D: Neoadjuvant CS; E: Neoadjuvant DCF; F: Neoadjuvant DOS; G: Neoadjuvant ECF plus Neoadjuvant Radiotherapy; H: Neoadjuvant FLO; I: Neoadjuvant SOX; J: Neoadjuvant XELOX; K: Neoadjuvant DOX; L: Neoadjuvant XELOX plus Neoadjuvant Radiotherapy; M: Neoadjuvant SOX plus Neoadjuvant Radiotherapy; N: Neoadjuvant CF; O: Neoadjuvant PC; P: Neoadjuvant FOLFOX; Q: Surgery alone.

Figure 3

Network meta-analysis of overall survival. A: Network diagram of overall survival; B: The published biased funnel plot of overall survival; C: Comparisons between each treatment. Bold and underlined indicate statistically significant pairwise comparisons. A: Neoadjuvant plus adjuvant FLOT; B: Neoadjuvant plus adjuvant ECF; C: Neoadjuvant plus adjuvant DCF; D: Adjuvant CapeOX; E: Neoadjuvant ECF plus adjuvant ECF and radiotherapy; F: Neoadjuvant DCS plus adjuvant S-1; G: Neoadjuvant CS plus adjuvant S-1; H: Neoadjuvant plus adjuvant XELOX; I: Neoadjuvant SOX and radiotherapy plus adjuvant SOX; J: Neoadjuvant plus adjuvant SOX; K: Neoadjuvant plus adjuvant CF; L: Neoadjuvant plus adjuvant FOLFOX; M: Adjuvant SOX; N: Surgery alone.

Figure 4

Network meta-analysis of non-surgical severe adverse events. A: Network diagram of higher nonsurgical severe adverse events (SAEs); B: The published biased funnel plot of non-surgical SAEs; C: Comparisons between each treatment. old and underlined indicate statistically significant pairwise comparisons; D: Surface under the cumulative ranking value of non-surgical SAEs of each intervention. A: Neoadjuvant plus adjuvant ECF, B: Neoadjuvant plus adjuvant FLOT, C: Neoadjuvant ECF plus adjuvant ECF and radiotherapy, D: Neoadjuvant plus adjuvant FLO, E: Neoadjuvant plus adjuvant SOX, F: Neoadjuvant DOX plus adjuvant SOX, G: Neoadjuvant plus adjuvant XELOX, H: Adjuvant XELOX, I: Neoadjuvant and radiotherapy plus adjuvant XELOX, J: Neoadjuvant SOX and radiotherapy plus adjuvant SOX, K: Adjuvant SOX, L: Neoadjuvant plus adjuvant FOLFOX.