Who benefits from adjuvant radiation therapy for gastric cancer? A meta-analysis

Abstract

Purpose: Large randomized trials have demonstrated significant survival benefits with the use of adjuvant chemotherapy or chemoradiation therapy for gastric cancer. The importance of adjuvant radiation therapy (RT) remains unclear. We performed an up-to-date meta-analysis of randomized trials testing the use of RT for resectable gastric cancer.

Methods and materials: We searched MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials for randomized trials testing adjuvant (including neoadjuvant) RT for resectable gastric cancer. Hazard ratios describing the impact of adjuvant RT on overall survival (OS) and disease-free survival (DFS) were extracted directly from the original studies or calculated from survival curves. Pooled estimates were obtained using the inverse variance method. Subgroup analyses were performed to determine whether the efficacy of RT varies with chemotherapy use, RT timing, geographic region, type of nodal dissection performed, or lymph node status.

Results: Thirteen studies met all inclusion criteria and were used for this analysis. Adjuvant RT was associated with a significant improvement in both OS (HR = 0.78, 95% CI: 0.70-0.86, P<.001) and DFS (HR = 0.71, 95% CI: 0.63-0.80, P<.001). In the 5 studies that tested adjuvant chemoradiation therapy against adjuvant chemotherapy, similar effects were seen for OS (HR = 0.83, 95% CI: 0.67-1.03, P=.087) and DFS (HR = 0.77, 95% CI: 0.91-0.65, P=.002). Available data did not reveal any subgroup of patients that does not benefit from adjuvant RT.

Conclusion: In randomized trials for resectable gastric cancer, adjuvant RT provides an approximately 20% improvement in both DFS and OS. Available data do not reveal a subgroup of patients that does not benefit from adjuvant RT. Further study is required to optimize the implementation of adjuvant RT for gastric cancer with regard to patient selection and integration with systemic therapy.

Figure 1

Trial Selection. RCT – randomized controlled trial.

Figure 2

Fixed effects meta-analysis of the impact of adjuvant radiotherapy on overall survival. Trials are grouped by study design with respect to chemotherapy use. Hazard ratios for each trial are represented by the squares, the size of each square represents the weight of that trial in the meta-analysis, and the horizontal line crossing the square represents the 95% confidence interval (CI). The diamonds represent the estimated overall effect based on meta-analysis. * - included intraoperative radiotherapy.

Figure 3

Fixed effects meta-analysis of the impact of adjuvant radiotherapy on disease-free survival. Trials are grouped by study design with respect to chemotherapy use. Hazard ratios for each trial are represented by the squares, the size of each square represents the weight of that trial in the meta-analysis, and the horizontal line crossing the square represents the 95% confidence interval (CI). The diamonds represent the estimated overall effect based on meta-analysis.

Figure 4

Fixed effects meta-analysis of the impact of adjuvant radiotherapy on overall survival. Trials are grouped by type of nodal dissection performed. Hazard ratios for each trial are represented by the squares, the size of each square represents the weight of that trial in the meta-analysis, and the horizontal line crossing the square represents the 95% confidence interval (CI). The diamonds represent the estimated overall effect based on meta-analysis. * - included intraoperative radiotherapy.

Figure 5

Scatter plot of OS hazard ratio against DFS hazard ratio for the six trials that provided data for both endpoints. The best-fit line has a slope of 0.94 and an R² value of 0.87, indicating a strong correlation between OS and DFS results.