Lauren Classification Is A Predictor For Pathological Response Of Preoperative Chemoradiotherapy Compared With Preoperative Chemotherapy In Patients With Locally Advanced Gastric Cancer

Abstract

To investigate the predictive value of Lauren classification to tumor pathological response after preoperative chemoradiotherapy (CRT) vs. preoperative chemotherapy (ChT) in locally advanced gastric adenocarcinoma (LAGC). From June 2013 to Dec, 2019, 182 patients in our hospital were enrolled into an ongoing multicentric phase III clinical trial comparing preoperative CRT (induction XELOX × 1 + 45Gy/25f with concurrent dose-reduced XELOX × 2) with preoperative ChT (XELOX × 3) in LAGC (NCT01815853). The clinical stage should be cT3N2-3M0, cT4aN+M0, or cT4bNanyM0. There were 124 males and 58 females, median age was 60 yrs (range 26-75 yrs). The interval between end of RT and surgery was 6-8 weeks. 65 out of 91 patients in the ChT group and 61 out of 91 patients in the CRT group had completed the preoperative treatments and the following radical D2 gastrectomy. Pathological response of primary tumor was categorized with NCCN tumor regression grade (TRG). Favorable pathological response (FPR) was defined as TRG0-1 with ypN0. At enrollment, patients’ baseline and tumor characteristics were well-balanced between the two groups. Proximal GC was in 58.2% (53/91) and 50.5(46/91) of the CRT and ChT group, respectively. Intestinal type (IT) GC was identified in 33(36.3%) patients of the ChT group, and in 36(39.6%) patients of the CRT group (X2 = 0.51, p = 0.916). After D2 gastrectomy, proportions of IT were 32.3% (21/65 pts) in the ChT group, and 50.8% (31/61 pts) in the CRT group, showing obvious shift towards resectability favoring IT vs. non-intestinal (n-IT, diffused plus mixed) type (X2 = 8.61, P = 0.035) after CRT. CRT group achieved higher rate of pCR (21.3% vs 3.1%, P = 0.002). There were 30, 37, and 22 patients obtained TRG0-1, ypN0, and FPR, respectively in the CRT group, while only 10, 14, and 5 patients did in the ChT group (P<0.001 for all). In the CRT group, ypN0 and FPR were observed in 80.6% and 45.2% of patients with IT tumor, but only in 35.7% and 21.4% with n-IT tumors (ypN0:P<0.001; FPR: P = 0.054), respectively. Logistic regression revealed IT tumor with higher probability of achieving ypN0 (OR = 7.500, 95%CI: 1.838-30.730; P = 0.005) than n-IT tumors. In contrast, no such differences were observed in the ChT group. Primary tumor locations were not predictive for ypN0 or TRG. In all patients with IT tumors, CRT was associated with higher rates of TRG0-1 (51.6% vs. 14.3%, P = 0.006), ypN0 (80.6% vs. 19.0%, P<0.001), FPR (45.2% vs. 0%, P<0.001) , pCR (22.6% vs. 0%, P = 0.033), and upstage 0-II (93.5% vs. 50.0%, P = 0.001) than ChT, while in patients with n-IT GC, only TRG showed significant improvement favoring CRT than ChT(TRG0-1: 42.9% vs. 15.9%, P = 0.011). Intestinal type gastric adenocarcinomas showed better responses to preoperative CRT vs. preoperative ChT than diffuse or mixed type GC did. This is the first set of data to date suggesting the predictive value of Lauren classification to tumor response after preoperative treatment in gastric cancer.