Oncologic Benefit of Adjuvant Chemoradiation after D2 Gastrectomy: A Stepwise Hierarchical Pooled Analysis and Systematic Review

Chai Hong Rim,Won Sup Yoon,In-Soo Shin,Hye Yoon Lee,Sunmin Park

doi:10.3390/cancers12082125

Chai Hong Rim, Won Sup Yoon + Show 3 more

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https://doi.org/10.3390/cancers12082125

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Abstract

Our study aimed to evaluate the benefits of chemoradiotherapy (CRT) after D2 gastrectomy, as compared to adjuvant chemotherapy, alone. PubMed, MEDLINE, Embase, and the Cochrane Library were systematically searched. We applied stepwise analyses that enabled the evaluation of data from randomized controlled trials (RCTs), balanced studies, and all studies separately and in a hierarchical manner. Thirteen controlled studies, including six RCTs involving 2603 patients, were included. Overall pooled analysis revealed a disease-free survival benefit of CRT (odds ratio (OR): 1.264, p = 0.053), which was more evident in the subgroup analysis of RCTs (OR: 1.440, p = 0.006) and balanced studies (OR: 1.417, p < 0.001). Overall survival was insignificantly different in the overall pooled analysis (OR: 1.124, p = 0.347). However, the difference was marginally significant in the subgroup analysis of balanced studies (OR: 1.279, p = 0.055) and significant in the subgroup analysis of studies involving stage ≥III patients only (OR: 1.663, p = 0.005). Locoregional recurrence (LRR) reduction was noted in the overall pooled analysis (OR: 0.559, p = 0.012; pooled rate: 11.3% vs. 18.1%) and was more robust in the subgroup analyses. Grade ≥3 leukopenia was higher in the CRT arm (OR: 1.387, p = 0.004; pooled rate: 26.4% vs. 15.7%). CRT after D2 gastrectomy should be applied for patients with high risk of LRR (e.g., stage ≥ III), along with efforts to reduce leukopenia.

Highlights

Gastric cancer is responsible for up to 800,000 deaths annually and is the third leading cause of cancer-related death [1]
In the subgroup analyses of randomized controlled trial (RCT) alone, the pooled overall pooled analysis (OR) increased to 1.440, and heterogeneity was significantly diminished (p = 0.964, I2 = ~0.0%)
Our study clearly demonstrated the benefits of CRT after D2 gastrectomy in terms of disease-free survival (DFS) and Locoregional recurrence (LRR) and a possibility of decreased distant recurrence rate (DRR)

Summary

Introduction

Gastric cancer is responsible for up to 800,000 deaths annually and is the third leading cause of cancer-related death [1]. The mainstay curative modality for gastric cancer is surgical resection. Except for early-stage cases that are amenable to endoscopic resection Adjuvant chemotherapy (CT) was previously found to benefit western patients, in whom D2 gastrectomy is less commonly performed [7,8]. Recent landmark randomized controlled trials (RCTs) confirmed the oncologic benefit of S-1 or capecitabine plus oxaliplatin for Asian patients; adjuvant CT is widely administered to these patients (including those who underwent D2 gastrectomy) [9,10]. The Intergroup-0116 trial revealed the benefit of adjuvant chemoradiotherapy (CRT) [11], it was heavily criticized for its insufficient extent of surgery, as fewer than 10% of patients underwent. Analysis; John Wiley & Sons: Hoboken, NJ, USA, 2011. J.P.T.; Thompson, S.G. Quantifying heterogeneity in a meta-analysis.

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