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The combined positive score (CPS) and tumor proportion score (TPS) have been developed to evaluate programmed death ligand-1 (PD-L1) expression, especially due to the potential benefit of the targeted therapy. However, the prognostic value of PD-L1 scoring systems in gastric cancer (GC) remains unclear. This study aimed to evaluate PD-L1 expression according to CPS and TPS in curative resected GC patients and its correlation with prognosis. We retrospectively evaluated 284 GC patients who underwent D2-gastrectomy by tissue microarray. PD-L1 expression was analyzed by immunohistochemistry. PD-L1 positivity by CPS and TPS was observed in 45 (15.8%) and 34 (12%) patients, respectively. Larger tumor size (p = 0.028), undetermined Lauren type (p < 0.001), and heavy inflammatory infiltrate (p = 0.009) were associated with CPS-positive GC. TPS-positive were more frequent in patients with larger tumor size (p = 0.004), undetermined type (p < 0.001), moderate/severe inflammatory infiltrate (p = 0.001), total gastrectomy (p = 0.036), and poorly differentiated histology (p = 0.025). No differences were observed in the pT, pN, and pTNM status according to the PD-L1 scores. Both scores were associated with Epstein-Barr virus positivity, microsatellite instability and p53-normal expression. The disease-free survival (DFS) was worse for CPS-negative compared to CPS-positive group (p = 0.052). No difference was observed between TPS-positive and negative groups (p = 0.436). Total gastrectomy, advanced pT status, and CPS-negative were independent factor for worse survival in GC. CPS was an independent prognostic factor for survival and could be used as a prognostic biomarker in patients with resectable GC. [ABSTRACT FROM AUTHOR]

Purpose: The importance of targeted therapy and interest in the study of predictive markers in gastric cancer (GC) have increased in recent years with the use of anti-HER2 therapy and immunotherapy with anti-PD1/PD-L1 for microsatellite instability (MSI) and PD-L1 + tumors. However, the behavior of remnant GC (RGC) in this scenario is poorly reported. Thus, this study aims to evaluate the clinicopathological characteristics and prognosis of RGC and its association with the expression of current markers for targeted therapy. Methods: All RGC resections performed in a single center from 2009 to 2019 were retrospectively reviewed. As a comparison group, 53 primary proximal GC (PGC) who underwent total D2-gastrectomy were selected. HER2, MSI status and PD-L1 expression were analyzed by immunohistochemistry. Combined Positive Score (CPS) was used to determine PD-L1 positivity. Results: A total of 40 RGC were included. RGC patients were older (p = 0.001), had lower BMI (p = 0.001) and number of resected lymph nodes (p < 0.001) compared to the PGC. Regarding markers expression, MSI was higher in RGC than PGC (27.5% vs 9.4%, p = 0.022). The frequency of CPS-positive was 32.5% and 26.4% in RGC and PGC, respectively (p = 0.522). HER2 positivity was 17.5% and 22.6% for RGC and PGC, respectively (p = 0.543). In survival analysis, DFS was better for RGC CPS-positive than RGC CPS-negative (p = 0.039) patients. There was no difference in survival considering MSI status. Conclusion: RGC had higher incidence of MSI than PGC, and CPS-positive RGC was associated with better survival. The immunological profile of RGC patients suggests that they would be good candidates for immunotherapy. [ABSTRACT FROM AUTHOR]

Background: Concurrent chemoradiotherapy followed by surgery is the standard treatment for locally advanced esophageal cancer (EC), and the role of induction chemotherapy (IC) remains unclear. We aimed to study if the addition of IC to standard treatment increases the rate of pathologic complete response (pCR). Methods: We assembled a retrospective analysis of patients (pts) diagnosed with locally advanced EC and treated with preoperative chemoradiotherapy followed by esophagectomy (CRT+S), preceded or not by IC, between 2009 and 2017. Patients' characteristics, tumor variables, and treatment outcomes were evaluated. The Kaplan-Meier method was used to estimate overall survival and the Cox proportional hazard model to evaluate prognostic factors. Results: One hundred and three patients were studied, with a median age of 62 years (range 37–84). Seventy-five patients (73%) were male, 67 (65%) had squamous cell carcinoma, and 31 (30%) had adenocarcinoma. Forty-three patients (41.7%) received IC followed by CRT+S (IC+CRT+S). The most frequent IC consisted of paclitaxel and platinum chemotherapy (90%), and the median number of cycles was 2. All patients received CRT+S. Concurrent chemotherapy was a combination of paclitaxel and platinum in 94 patients (91%). There was no statistically significant difference in pCR between the IC group and the standard CRT+S group. The pCR was 41.9% and 46.7% in the IC+CRT+S and CRT+S groups (p = 0.628), respectively. In the multivariate analysis, pCR was an independent prognostic factor for time to treatment failure (TTF) (HR 0.35, p = 0.021), but not for overall survival (OS) (p = 0.863). The factor that significantly affected OS in the multivariate analysis was positive lymph node (HR 5.9, 95%, p = 0.026). Conclusions: Our data suggest that the addition of IC to standard CRT + S does not increase the pCR rate in locally advanced EC. No difference in OS was observed between pts. that received or not IC. Regardless of the treatment received, pts. achieving a pCR presented improved TTF. [ABSTRACT FROM AUTHOR]

Background: The assessment of human epidermal growth factor receptor 2 (HER2), microsatellite instability (MSI) and programmed cell death-ligand 1 (PD-L1) expression is relevant for the selection and effectiveness of targeted therapy in gastric cancer (GC). Objective: We aimed to investigate the clinicopathological characteristics and prognosis of GC patients according to these profiles. Methods: GC patients who underwent gastrectomy with D2 lymphadenectomy were eligible. HER2, MSI status and PD-L1 expression were analyzed by immunohistochemistry (IHC). Patients were grouped as follows: HER2+ group, immunotherapy (IT) group (MSI and/or PD-L1+), and non-targeted therapy (NTT) group (stable microsatellite and HER2/PD-L1−). Results: Among 282 patients, 50 (17.7%) were HER2+ and 79 (28%) MSI/PD-L1+. Fifteen had HER2+ and MSI/PD-L1+, while 168 (59.6%) were in the NTT group. HER2+ GCs were related to male gender (p = 0.007), intestinal type (p = 0.001) and less advanced pTNM stage (p = 0.029). Older age (p = 0.003), subtotal gastrectomy (p = 0.025), intestinal type (p = 0.008), pN0 status (p = 0.002) and less advanced pTNM stage (p = 0.001) were associated with the IT group. IT GC had better disease-free survival (DFS) and overall survival than the NTT group (p = 0.015 and p = 0.027, respectively). Concerning patients eligible for the standard adjuvant therapy, the treatment impacted positively on DFS for HER2+ and NTT groups (p = 0.003 and p = 0.042, respectively). No difference in DFS was seen between IT patients who received perioperative/adjuvant therapy and those treated only with surgery (p = 0.160). Conclusions: GC patients who exhibited markers that can serve as an indication for known targeted therapy represent 40.4% of cases. The IT group was associated with a better prognosis. No benefit with standard adjuvant treatment appears to be achieved in MSI/PD-L1+ GCs. [ABSTRACT FROM AUTHOR]