Abstract
BackgroundDue to negative results in clinical trials of postoperative chemoradiation for gastric cancer, at present, there is a tendency to move chemoradiation therapy forward in gastric and gastroesophageal junction (GEJ) adenocarcinoma. Several randomized controlled trials (RCTs) are currently recruiting subjects to investigate the effect of neo-adjuvant radiotherapy (NRT) in gastric and GEJ cancer. Large retrospective studies may be beneficial in clarifying the potential benefit of NRT, providing implications for RCTs.MethodsWe retrieved the clinicopathological and treatment data of gastric and GEJ adenocarcinoma patients who underwent surgical resection and chemotherapy between 2004 and 2015 from Surveillance, Epidemiology, and End Results (SEER) database. We compared survival between NRT and non-NRT patients among four clinical subgroups (T1–2N−, T1–2N+, T3–4N−, and T3–4N+).ResultsOverall, 5272 patients were identified, among which 1984 patients received NRT. After adjusting confounding variables, significantly improved survival between patients with and without NRT was only observed in T3–4N+ subgroup [hazard ratio (HR) 0.79, 95% confidence interval (CI): 0.66–0.95; P = 0.01]. Besides, Kaplan-Meier plots showed significant cause-specific survival advantage of NRT in intestinal type (P < 0.001), but not in diffuse type (P = 0.11) for T3–4N+ patients. In the multivariate competing risk model, NRT still showed survival advantage only in T3–4 N+ patients (subdistribution HR: 0.77; 95% CI: 0.64–0.93; P = 0.006), but not in other subgroups.ConclusionsNRT might benefit resectable gastric and GEJ cancer patients of T3–4 stages with positive lymph nodes, particularly for intestinal-type. Nevertheless, these results should be interpreted with caution, and more data from ongoing RCTs are warranted.
Highlights
Due to negative results in clinical trials of postoperative chemoradiation for gastric cancer, at present, there is a tendency to move chemoradiation therapy forward in gastric and gastroesophageal junction (GEJ) adenocarcinoma
Considering nodal status and tumor stage can influence the benefit of neo-adjuvant radiotherapy (NRT) in gastric cancer patients [1], we divided the cohort into four subgroups to perform subgroup analysis: T1–2N−, T1–2N+, T3–4N−, and T3–4N+ (Fig. 1)
Since a previous study reported that patients with intestinal type of Lauren classification were more likely to benefit from adjuvant Radiation therapy (RT) in advanced GC [2], we explored whether there was a survival difference between NRT and no NRT groups based on Lauren classification in T3–4N+ patients (Fig. 2)
Summary
Due to negative results in clinical trials of postoperative chemoradiation for gastric cancer, at present, there is a tendency to move chemoradiation therapy forward in gastric and gastroesophageal junction (GEJ) adenocarcinoma. Large retrospective studies may be beneficial in clarifying the potential benefit of NRT, providing implications for RCTs. Radiation therapy (RT) has gained increasing attention in adjuvant treatment of resectable gastric cancer or gastroesophageal junction (GEJ) adenocarcinoma in the past two decades, since the landmark study of INT-0116 in US [1]. In Asian population, ARTIST trial targeting patients after D2 lymph node dissection showed negative results; but subgroup analysis implicated that adjuvant RT could potentially benefit a subset of patients with nodal involvement or intestinal histology type [3]. CRITICS-II [8] and TOPGEAR [9] studies are actively investigating the effects of neo-adjuvant radiotherapy (NRT) in patients with stomach adenocarcinoma; the safety of preoperative chemoradiation has been proven according to interim analysis of preliminary results from TOPGEAR trial [10]. In China, two phase III RCTs, PREACT study [11] and NEOCRAG (registration number NCT01815853), are currently underway to provide more evidence for efficacy of preoperative chemoradiation compared with preoperative chemotherapy in locally advanced gastric and GEJ adenocarcinoma
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