D2 Gastrectomy Research Articles

154P A multicenter, prospective study of apatinib plus chemotherapy as neoadjuvant treatment for locally advanced gastric cancer

Apatinib, a novel treatment option for chemotherapy-refractory advanced gastric cancer (AGC), has not yet been evaluated in patients with locally AGC. This trial investigated the efficacy and safety of apatinib combined with S-1 plus oxaliplatin (SOX) as a neoadjuvant treatment for locally AGC. Patients with M0 and either T2-T4 or N+ disease received apatinib (500 mg orally once daily on days 1-21 and discontinued in the last cycle) plus SOX (S-1, 40-60 mg orally twice daily on days 1-14; oxaliplatin, 130 mg/m2 intravenously on day 1) given every 3 weeks for 2-5 cycles. D2 gastrectomy was performed 2-4 weeks after the last cycle. To further compare the efficacy and safety between apatinib plus SOX (ASOX group) and SOX alone (SOX group), we reviewed historical control patients receiving SOX as neoadjuvant chemotherapy at the central center. The primary end point was the R0 resection rate. Between July 2017 and June 2019, 48 and 58 patients were enrolled in the ASOX and SOX groups, respectively. Forty patients in the ASOX group (83.3%) and 47 patients in the SOX group (81.0%) underwent surgery, with R0 resection rates of 75.0% and 67.2%, respectively (P=0.382). The proportion of patients with T downstaging in the ASOX group was significantly higher than that in the SOX group (36.4% vs 18.5%, P=0.036). For patients with target lesions, the radiological response rate was significantly higher in the ASOX group (75.0% vs 38.5%, P=0.015). Moreover, the ASOX group was associated with significantly higher proportions of patients achieving major pathological response (25.0% vs 10.3%, P=0.046). Grade 3 toxicities occurred in 33.3% of the ASOX patients, and no grade 4 toxicities or drug-related deaths were observed. Apatinib combined with SOX showed promising efficacy with an acceptable safety profile as the first-line neoadjuvant treatment for locally AGC.

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

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.

Prognosis of Adjuvant SOX vs XELOX Chemotherapy for Gastric Cancer After D2 Gastrectomy in Chinese Patients.

IntroductionTo compare the prognosis of adjuvant SOX (S-1 and oxaliplatin) vs XELOX (capecitabine and oxaliplatin) chemotherapy in Chinese patients with gastric cancer (GC) after D2 gastrectomy.MethodsThis was a real-world study of patients with GC (stages II–III) who underwent D2 gastrectomy and received adjuvant SOX or XELOX between 01/2010 and 06/2017 in Zhongshan Hospital affiliated to Fudan University. The patients were matched by propensity score matching. The primary and secondary endpoints were disease-free survival (DFS) and overall survival (OS), respectively. Adverse events (AEs) were compared.ResultsA total of 552 patients were included. The median follow-up time was 24.9 months. There were no differences in DFS (median, 44.4 vs 41.2 months; HR=1.17, 95% CI: 0.92–1.48) and OS (median, 61.5 vs 65.3 months; HR=1.01, 95% CI: 0.73–1.39) between the XELOX and SOX groups. Both DFS and OS had no significant differences between SOX and XELOX for all subgroups based on sex (P=0.949, P=0.990), age (P=0.303, P=0.392), Lauren type (P=0.362, P=0.573), type of gastrectomy (P=0.607 P=0.989), and pathological TNM stage (P=0.899, P=0.888). A total of 86 patients in the SOX subgroup (34.2%) experienced AEs, similar to the rate found in the XELOX subgroup (104 patients or 41.4%; P=0.098).DiscussionThe results suggested that adjuvant SOX chemotherapy has similar survival benefits compared to XELOX chemotherapy in Chinese patients with pathological stage II or III GC after D2 gastrectomy.

Immunophenotype based on inflammatory cells, PD-1/PD-L1 signalling pathway and M2 macrophages predicts survival in gastric cancer

BackgroundImmune response against cancer has prognostic impact but its role in gastric cancer is poorly known. The aim of the study was to assess the prognostic significance of immune cell score (CD3+, CD8+), tumour immune escape (PD-L1, PD-1) and immune tolerance (Clever-1).MethodsAfter exclusion of Epstein-Barr virus positive (n = 4) and microsatellite instable (n = 6) tumours, the study included 122 patients with GC undergoing D2 gastrectomy. CD3+ and CD8+ based ICS, PD-L1, PD-1 and Clever-1 expressions were evaluated. Differences in survival were examined using Cox regression adjusted for confounders. The primary outcome was 5-year survival.ResultsThe 5-year overall survival rate was 43.4%. High ICS was associated with improved overall survival (adjusted HR 0.48 (95% CI 0.26–0.87)) compared to low ICS. In the high ICS group, patients with PD-L1 expression (5-year survival 69.2 vs. 53.1%, p = 0.317), high PD-1 (5-year survival 70.6 vs. 55.3% p = 0.312) and high Clever-1 (5-year survival 72.0% vs. 45.5% (p = 0.070) had poor prognosis.ConclusionsHigh ICS was associated with improved survival. In the high ICS group, patients with high PD-L1, PD-1 and Clever-1 had poor prognosis highlighting the importance of immune escape and immune tolerance in GC.

Laparoscopic-assisted distal radical gastrectomy for gastric cancer

: Gastric cancer (GC) is a common malignant tumor and surgical resection remains the main treatment for GC. D2 lymphadenectomy is considered as the standard operation for GC, and laparoscopic radical gastrectomy has been widely used in clinics because of its minimal invasiveness. We herein report a case of gastric antrum carcinoma who was successfully treated with a standard laparoscopic-assisted distal radical gastrectomy. The lymphadenectomy is performed as required in the standardized D2 gastrectomy of distal GC, followed by a the Billroth II plus Braun’s anastomosis through a small incision in the upper abdomen. The operation was successful with a time of 212 minutes and a bleeding amount of 50 mL. As a result, the patient recovered very well and was discharged on the 5th day after surgery. This demonstrated that standard laparoscopic-assisted distal radical gastrectomy was feasible and safe for patient with gastric antrum carcinoma, which should be popularized in clinics.

Abstract CT237: A phase I study to assess the safety, tolerability, and immunogenicity of personalized neoantigen/cancer testis antigen nanovaccine (PVAC) for high-risk resected gastric cancer

Abstract Background: 35% of stage IIIB/C Gastric cancer patients will recurrent after D2 gastrectomy within one year. Mutation-derived epitopes (neoantigens) has been demonstrated to induce tumor cell specific immune responses controlling the tumor growth. Nanovaccine can increase antigen presentation efficiency and elicit potent antitumor T cell responses with robust therapeutic efficacy. We hypothesized that vaccination with neoantigens/cancer testis (CT) antigens could expand pre-existing and induce antigen-specific T-cells populations, favouring of tumor control enhancement. Here, we report the first-in-human application of this concept in gastric cancer. Methods: Patient-specific mutation-containing neoantigens were selected on the basis of tumour-specific mutations whole-exome sequencing (WES) and RNA sequencing. Cancer testis antigens were obtained according to immunohistochemical staining and HLA-binding affinity prediction. PVAC is an amphiphiles nanovaccine loaded with multiple personalized neoantigens/cancer testis antigens designed to induce antigen specific T cells and associated antitumor responses. PVAC will be administrated to stage IIIB/IIIC gastric carcinoma after six cycles of adjuvant chemotherapy (S-1/Oxaliplatin or S-1/docetaxel). Each patient received PVAC by subcutaneous injection on Days 1, 4, 8, 15, 22, 43, 64, 85, 169, administrated with the adjuvant montanide ISA 51 VG. Safety, immunogenicity and clinical efficacy will be evaluated. Results: 25 stage IIIB or IIIC gastric cancer patients were enrolled in this study. Mean age was 54.3 years old (range: 34-70), and ECOG performance scores were 0 or 1. Repeated dosing has been well tolerated with mild local discomfort and no DLTs. 10 of the 25 patients developed grade 1 local skin reactions with redness, swelling or subcutaneous indurations in the injection sites. Three patients were observed grade 2 local skin reactions in the injection sites. Four had grade 1 to 2 fever. No SAEs related to PVAC have been observed. Among median follow up time of 11.6 months (range: 7.5-24.0 months), only one patient had local recurrence at 10.5 months after surgery. The rest 24 patients remain disease free on study. Neoantigen specific T cell responses have been detected by IFN-γ Elispot from PBMCs. Conclusions: PVAC is a multiple neoantigens/CT antigens nanovaccine that personalizes tumor specific antigens and the individual patient's capacity to respond. Addition of PVAC may prolong progression-free survival (PFS) after the standard of care chemotherapy. Clinical trial information: ChiCTR1800017319. Citation Format: Qin Liu, Hanqing Qian, Jie Shao, Qiuping Xu, Huizi Sha, Yang Yang, Weifeng Wang, Lixia Yu, Baorui Liu, Jia Wei. A phase I study to assess the safety, tolerability, and immunogenicity of personalized neoantigen/cancer testis antigen nanovaccine (PVAC) for high-risk resected gastric cancer [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr CT237.

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

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.

Oncologic feasibility of D1+ gastrectomy for patients with cT1N1, cT2N0-1, or cT3N0 gastric cancer

IntroductionD2 gastrectomy has shown a survival benefit in patients with highly advanced gastric cancer; however, it remains unclear whether D2 gastrectomy is required for patients with early-stage advanced gastric cancer or early gastric cancer with limited lymph node metastasis. This analysis aimed to clarify the oncologic feasibility of D1+ gastrectomy in patients with cT1N1, cT2N0-1, or cT3N0 gastric cancer. MethodsThis retrospective cohort analysis included 466 patients with cT1N1, cT2N0-1, or cT3N0 gastric cancer who received curative gastrectomy with either D2 or D1+ dissection. Surgical outcomes were compared between the D2 group (n = 406) and the D1+ group (n = 60). ResultsThe number of patients with higher age and higher comorbidity index was greater in the D1+ group than in the D2 group. Postoperative complications were significantly lower in the D1+ group than in the D2 group (10.0% vs. 26.8%, p = 0.004). No statistically significant difference in 5-year overall survival (p = 0.146) and disease-specific survival (p = 0.807) between the groups was noted. The incidence of local recurrences (p = 0.500) and that of lymph node recurrences (p = 1.000) were also similar between the groups. Multivariable analysis for overall survival identified age, clinical node-positive status, high Charlson score (≥3), advanced pathological stage (≥III), and postoperative complication (grade ≥ II) as independent prognostic factors. The propensity score-matched analysis showed very similar survival outcomes between the groups. ConclusionD1+ gastrectomy may be oncologically feasible for patients with cT1N1, cT2N0-1, or cT3N0 stage gastric cancer.

Primary results of a randomized two-by-two factorial phase II trial comparing neoadjuvant chemotherapy with two and four courses of cisplatin/S-1 and docetaxel/cisplatin/S-1 as neoadjuvant chemotherapy for advanced gastric cancer.

AimNeoadjuvant chemotherapy (NAC) is promising to improve the survival of resectable gastric cancer. However, suitable regimen and treatment duration for NAC have not yet been established.MethodsWe conducted a randomized phase II trial to compare two and four courses of neoadjuvant S‐1/cisplatin (SC) and S‐1/cisplatin/docetaxel(DCS) using a two‐by‐two factorial design for locally resectable advanced gastric cancer. Patients with M0 and either T4 or T3 in case of junctional cancer or scirrhous‐type cancer received two or four courses of SC or DCS. Then, patients underwent D2 gastrectomy and adjuvant S‐1 chemotherapy for 1 year. The primary endpoint was 3‐year overall survival. The planned sample size was 120 eligible patients.ResultsBetween October 2011 and September 2014, 132 patients were assigned to CS (n = 66; 33 in 2‐courses and 33 in 4‐courses) and DCS (n = 66; 33 in 2‐courses and 33 in 4‐courses). The 3‐year OS was 58.1% in CS and 60.0% in DCS with hazard ratio of 0.80 (95% CI, 0.48‐1.34), while it was 53.1% in the two courses and 65.0% in the four courses with hazard ratio of 0.72 (95% CI, 0.43‐1.22). In the survival analysis by duration in each regimen, the 3‐year OS was 58.1% for both two and four courses in CS, while it was 48.5% for two courses of DCS and 71.9% for four courses of DCS.ConclusionsConsidering high 3‐year OS, four courses DCS has a value to be tested in a future phase III study to confirm superiority of neoadjuvant chemotherapy for locally advanced gastric cancer.

P-60 Tolerability of adjuvant chemotherapy with TS-1 or XELOX regimen in elderly patients with stage II or III gastric cancer after D2 gastrectomy

Compared to surgery, adjuvant TS-1 and XELOX regimen in gastric cancer (GC) has shown survival benefit after D2 gastrectomy. As the elderly population continues to grow, adjuvant chemotherapy (AC) has become important. Clinicians hesitate to offer chemotherapy to elderly patients because of comorbidities and intolerability. This study aims to investigate the efficacy, safety, and compliance of AC with TS-1 and XELOX regimen in patients aged >70 years.

Resectable locally advanced gastric adenocarcinoma: interim analysis

Background: The MAGIC and ACCORD 07 trials have established the role of perioperative chemotherapy in locally advanced gastric adenocarcinoma. A more recent study has demonstrated the superiority of the FLOT perioperative regimen. The best strategy to improve outcomes has yet to be determined. Aims of the study were to evaluate perioperative chemotherapy in terms of morbidity and tolerance of FLOT regimen with modification and histopathological responseMethods: This prospective study was started after ethical committee approval in February 2019 at a tertiary cancer center in South India for a period of 1 year up till February 2020. Patients fulfilling inclusion criteria were enrolled. Perioperative chemotherapy was given as scheduled regimen and adverse effects and response to preoperative chemotherapy were recorded. Radical D2 gastrectomy and histopathology assessed analysed by using IBM SPSS statistics ver. 21 and descriptive statistics used.Results: From February 2019 till February 2020, a total of 24 patients of newly diagnosed adenocarcinoma of the stomach of which 18 patients were nonmetastatic on workup. Moderately different (38.8%), well-differentiated in 11.2%, poorly differentiated in 50%. Total 66.7% were diagnosed as metastatic on staging laparoscopy, peritoneal wash cytology in 50% was negative. The cardiopulmonary resuscitation was seen in two patients.Conclusions: Even though it is an interim analysis with less number of patients enrolled, so far it can be concluded that all patients where surgery is planned should undergo peritoneal lavage cytology and FLOT regimen can be practised with acceptable morbidity. Long term results after completion of study will definitely throw more light.

Observational Study of Peritoneal Washing Cytology-Positive Gastric Cancer without Gross Peritoneal Metastasis in Patients who Underwent Radical D2 Gastrectomy

Background The clinical features and therapeutic strategies for gastric cancer with positive peritoneal washing cytology but without visible gross peritoneal metastasis have not been defined. The aim of this study was to evaluate the effect and clinical prognostic value of postoperative chemotherapy in gastric cancer patients with positive peritoneal washing cytology without gross peritoneal metastasis who underwent radical D2 gastrectomy in terms of disease-free survival (DFS) and overall survival (OS). Materials and Methods Intraoperative peritoneal washing cytology was performed in 285 patients who underwent radical D2 gastrectomy between April 2004 and May 2016. Of them, 88 patients with positive cytology but without gross peritoneal metastasis were included in the study. In total, 64 patients received postoperative chemotherapy, whereas 24 patients underwent surgery only. Results Most gastric cancer patients with positive cytology without gross peritoneal metastasis demonstrated pT4 and/or pN3 disease. Postoperative chemotherapy improved DFS and OS compared to surgery only in gastric cancer patients with positive cytology without gross peritoneal metastasis (median DFS 11.63 vs. 6.98 months, p < 0.001; median OS 25.50 vs. 12.11 months, p < 0.001). In multivariate analyses of gastric cancer patients with positive cytology without gross peritoneal metastasis, no chemotherapy was the strongest clinical factor for poorer DFS (hazard ratio [HR] 3.76, p < 0.001) or OS (HR 4.37, p < 0.001). Conclusion Postoperative chemotherapy improves the survival outcome compared to surgery alone in gastric cancer patients with positive peritoneal washing cytology but without visible gross peritoneal metastasis who underwent radical D2 gastrectomy.

FLOT Neoadjuvant Chemotherapy Followed by Laparoscopic D2 Gastrectomy in the Treatment of Locally Resectable Advanced Gastric Cancer.

Background The prognosis of patients with advanced gastric cancer remains unsatisfactory, highlighting the need for improved therapeutic strategies. We analyzed 23 resectable advanced gastric cancer patients who received FLOT followed by laparoscopic gastrectomy with D2 lymphadenectomy to evaluate the efficacy and safety. Methods Patients aged 18–75 years with gastric adenocarcinoma (stage cT3–4 and/or N + M0) underwent neoadjuvant FLOT therapy (four preoperative and four postoperative 2-week cycles) at Shanghai East Hospital. Laparoscopic gastrectomy was scheduled 3-4 weeks after completion of the last cycle of preoperative chemotherapy. The type of surgical procedure was determined by the location and extent of the primary tumor. Results 23 patients were reviewed in the study. 20 patients (81.2%) received four courses of FOLT therapy, while 3 patients (18.8%) received three courses of treatment. There were 3 (13.0%) complete responses, 13 (56.5%) partial responses, 4 (26.1%) of stable disease, and 1 (4.3%) of progressive disease. The clinical efficacy response rate was 69.6%. The R0 resection rate was 91.3%. Only one patient exhibited grade III postoperative complications. The pathologic complete remission was 13%. The common grade 3/4 adverse events from chemotherapy were leucopenia (17.4%), neutropenia (30.4%), anemia (13%), anorexia (13%), and nausea (17.4%). Postoperative complications occurred in 5 patients (26.1%). There was no treatment-related mortality or reoperation. The most reason for not completing chemotherapy was the patient's request. Conclusions These findings suggest that FLOT neoadjuvant chemotherapy, followed by laparoscopic D2 gastrectomy, is effective and safe in advanced, resectable advanced gastric cancer.

Chemoradiation versus chemotherapy after D2 gastrectomy: A meta-analysis including randomized and real-world trials.

e16590 Background: The ARTIST trial failed to achieve positive result regarding benefit of chemoradiation (CRT) after D2 gastrectomy. In most of clinical guidelines and practices, postoperative CRT has been recommended only for those with R1 resection or lesser extent surgery than D2. Our study is to evaluate oncologic benefit of CRT after D2 gastrectomy, integrating data from randomized clinical trials (RCTs) and real-world studies so far. Methods: Systematic searches for Medline and Embase were performed for controlled trials comparing CRT and chemotherapy (CT) arms after D2 gastrectomy with R0 resection, for gastric cancer. Subgroup analyses were performed including RCTs, and balanced studies without significant difference regarding major clinical indicators. Primary endpoint was disease free survival (DFS), and secondary endpoints included overall survival (OS), locoregional recurrence rate (LRR), distant recurrence rate (DRR), and grade ≥3 complications. Results: A total of 13 studies, comprised of 6 RCTs and 7 non-RCTs, involving 2,603 patients were included. DFS benefit was found in overall pooled analysis [odds ratio (OR): 1.264, p = 0.053, I2= 37.5%], and more evident in subgroup analyses using RCTs (OR: 1.440, p = 0.006, I2= ~0%) and balanced studies (OR: 1.417, p &lt; 0.001, I2= ~0%). OS benefit was not significant. LRR reduction was noted in overall pooled analysis (OR: 0.559, p = 0.012, I2 = 46.1%), and clearer in the subgroup analyses with RCTs (OR: 0.495, p &lt; 0.001, I2= ~0%) and balanced studies (OR 0.472, p &lt; 0.001, I2= 9.2%). Pooled LRR rates were 11.3% (95% confidence interval: 7.5-16.8) and 18.1% (13.1-24.4) in CRT and CT arms. DRR was lower in CRT arms (OR: 0.768, p = 0.023, I2= ~0.0%), but the difference was less significant in subgroup analyses. A grade 5 complication was found in each of the two arms among all studies. Comparison of complications varies and will be shown descriptively in the manuscript. Conclusions: Benefit of DFS and LRR with CRT after D2 gastrectomy was well shown in the present study. Identifying subgroup population mostly benefitable from CRT might yield positive results regarding OS and DRR in future studies.

Personalized neoantigen/cancer testis antigen nanovaccine (PVAC) mobilize specific therapeutic immunity for high-risk resected gastric cancer.

4535 Background: 35% of stage IIIB/C Gastric cancer patients will recurrent after D2 gastrectomy within one year. Mutation-derived epitopes (neoantigens) has been demonstrated to induce tumor cell specific immune responses controlling the tumor growth. Nanovaccine can increase antigen presentation efficiency and elicit potent antitumor T cell responses with robust therapeutic efficacy. We hypothesized that vaccination with neoantigens/cancer testis (CT) antigens could expand pre-existing and induce antigen-specific T-cells populations, favouring of tumor control enhancement. Here, we report the first-in-human application of this concept in gastric cancer. Methods: Patient-specific mutation-containing neoantigens were selected on the basis of tumour-specific mutations whole-exome sequencing (WES) and RNA sequencing. Cancer testis antigens were obtained according to immunohistochemical staining and HLA-binding affinity prediction. PVAC is an amphiphiles nanovaccine loaded with multiple personalized neoantigens/cancer testis antigens designed to induce antigen specific T cells and associated antitumor responses. PVAC will be administrated to stage IIIB/IIIC gastric carcinoma after six cycles of adjuvant chemotherapy (S-1/Oxaliplatin or S-1/docetaxel). Each patient received PVAC by subcutaneous injection on Days 1, 4, 8, 15, 22, 43, 64, 85, 169, administrated with the adjuvant montanide ISA 51 VG. Safety, immunogenicity and clinical efficacy will be evaluated. Results: 25 stage IIIB or IIIC gastric cancer patients were enrolled in this study. Mean age was 54.3 years old (range: 34-70), and ECOG performance scores were 0 or 1. Repeated dosing has been well tolerated with mild local discomfort and no DLTs. Three patients were observed grade 2 local skin reactions in the injection sites. No SAEs related to PVAC have been observed. Among median follow up time of 12.6 months (range: 8.5-25.0 months), only two patients had local recurrence at 24.0 months and 10.5 months after surgery, respectivelt. The rest 23 patients remain disease free on study. Neoantigen specific T cell responses have been detected by IFN-γ Elispot from PBMCs. Conclusions: PVAC is a multiple neoantigen/CT antigens nanovaccine that personalizes tumor specific antigens and the individual patient’s capacity to respond. Addition of PVAC may prolong progression-free survival (PFS) after the standard of care chemotherapy. Clinical trial information: ChiCTR1800017319 .

Randomized phase III trial to evaluate omentum preserving gastrectomy for patients with resectable advanced gastric cancer: JCOG1711 (ROAD-GC).

TPS4646 Background: Standard surgery for resectable advanced gastric cancer is D2 (standardized extended lymph node dissection) gastrectomy with omentectomy. The reason why omentectomy has been performed is as follows; (1) principal surgery for gastrointestinal cancers is en-block resection of mesothelium including regional lymph nodes. Omentum is a part of the mesothelium of the stomach. (2) Cancer cells implanted into the peritoneal cavity aggregated in the milky-spot of the omentum and formed peritoneal dissemination in an animal model. (3) By special staining, micrometastasis detected in the omentum. There is some arguments for this theory. (1) no prospective study showed survival benefit of omentectomy as compared with omentum preservation. (2) anatomically, milky-spot is found not only in the omentum but also in other mesothelium or Douglas pouch. (3) JCOG1001 phase III study showed no survival benefit of bursectomy against non-bursectomy although bursa is a part of mesothelium of the stomach. (4) Anti-immunity is accelerated by antigen presentation by macrophage in the milky-spot of the omentum. Preservation of the omentum may have several benefits; (1) decrease in blood loss and operation time, (2) preservation of physical function by omentum such as reaction to peritonitis and prevention of adhesion, and (3) overcoming difficulties in laparoscopic omentectomy and avoidance of organ injury during surgery. Methods: The study is multicenter randomized phase III trial designed to confirm non-inferiority of omentum preservation to omentectomy for resectable advanced gastric cancer. Patients aged 20-79 years, histologically proven gastric adenocarcinoma, clinical subserosal/serosal invasion, and expected R0 (curative) resection are randomly assigned (1:1) during surgery to either omentum preservation or omentectomy. Total or distal gastrectomy with D2 dissection is performed in both arms. Laparoscopic gastrectomy is not allowed. Intraoperative photographs of the dissected field are centrally reviewed for all patients for quality control. The primary endpoint is relapse-free survival (RFS) and the secondary endpoints are overall survival, blood loss, operation time, and adverse events. Sample size was set at 1050 considering expected 3-year RFS of 77% in both arms with non-inferiority margin of 5%, one-sided alpha of 5%, and power of 80%. Planned accrual and follow up period are 6.5 years and 3 years respectively. The trial was activated in March 2019, and 177 patients are enrolled as of January 2020. Clinical trial information: UMIN000036253 .

Immunogenomic classification of gastric cancer based on the tumor microenvironments expression of PD-L1 and CD8+ T-cell infiltration.

e16578 Background: Previous data has shown that a positive response to immunotherapy usually relies on active interactions between tumor cells and immunomodulators inside the tumor microenvironment (TME). The aim of this study was to classify gastric cancer (GC) subsets based on the TME immune status according to the expression of PD-L1 and infiltration of CD8+ T cells. Methods: One hundred and eighty-six tumor tissue from gastric cancer patients with a curative D2 gastrectomy were examined for evaluating PD-L1 and CD8+ T cells status using histopathologic analysis. The molecular characteristics of 289 GC samples in TCGA network were further analyzed to distinguish the genetic features of four immune subtypes depending on the presence of PD-L1/CD8+T cell. Results: GC samples were categorized into four types, type I (CD8+/PD-L1+, 60.3%), II (CD8-/PD-L1-, 11.8%), III (CD8-/PD-L1+, 0%), and IV (CD8+/PD-L1-, 27.9%), basing on PD-L1/CD8 expression. The PD-L1 expressing level was geographically associated with the intensity of CD8+ T cell infiltration which was significantly associated with disease-free survival (DFS) and overall survival (OS) (p = 0.003 and p = 0.006). Distinct patterns of genetic profile were described in four types of GC from TCGA database. Type I and III which PD-L1 were overly expressed had comparatively higher MSI and TMB, with EBV mainly enriched in Type I, whereas CIN was more likely to occur in PD-L1 aberrant types II and IV. SNV analysis illustrated higher gene mutations in oncogenes (PIK3CA and ERBB2), and in DNA damage repair related pathway, such as PRKDC, ATM, and SWI/SNF complexes (e.g. ARID1A) in Type I. However, TP53 mutations tend to enrich in Type II and IV. Similar results were obtained by transcriptome analysis. Conclusions: The genetic features of four immune subtypes proof that PD-L1 and CD8+ T cells status are reasonable immunogenomic classification of gastric cancer. SNV analysis prompts a potential mechanism for effectiveness of immunotherapy in Type I patients. Overall, the results may be useful for the development of clinical treatments for the blockade of immune checkpoints.

Surgeon Quality Control and Standardization of D2 Lymphadenectomy for Gastric Cancer: A Prospective Multicenter Observational Study (KLASS-02-QC).

To qualify surgeons to participate in a randomized trial comparing laparoscopic and open distal D2 gastrectomy for advanced gastric cancer. No studies have sought to qualify surgeons for a randomized trial comparing laparoscopic and open D2 gastrectomy for advanced gastric cancer. We conducted a multicenter prospective observational study evaluating unedited videos of laparoscopic and open D2 gastrectomy performed by 27 surgeons. Surgeons performed 3 of each laparoscopic and open distal gastrectomies with D2 lymphadenectomy for gastric cancer. Five peers reviewed each unedited video using a video assessment form. Based on experts' review of videos, a separate review committee decided surgeons as "Qualified" or "Not-qualified." Twelve surgeons (44.4%) were qualified on initial evaluation whereas the other 15 surgeons were not. Another 9 surgeons were finally qualified after re-evaluation. The median score for Qualified was significantly higher than Not-qualified (P < 0.001).Significant differences between Qualified and Not-qualified were noted both in operation type and in all evaluation area of surgical skill, perigastric, and extra-perigastric lymphadenectomy, although the inter-rater variability of the assessment score was low (kappa = 0.285). However, Not-qualified surgeons' scores improved upon re-evaluation of resubmitted videos.When compared laparoscopy with open surgery, median scores were similar between the 2 groups (P = 0.680). However, open gastrectomy scores for surgical skills were significantly higher than for laparoscopic surgery (P = 0.016). Our surgeon quality control study for gastrectomy represents a milestone in surgical standardization for surgical clinical trials. Our methods could also serve as a system for educating surgeons and assessing surgical proficiency.

Impact of the histological regression grade of the primary tumor and regional lymph nodes after neoadjuvant chemoradiotherapy on survival of patients with gastric cancer: two case reports

Background . Stomach cancer remains one of the most common malignancies worldwide, with high incidence rates and low rates of long-term treatment outcomes. Neoadjuvant therapy currently is increasingly being considered the standard therapy for locally advanced gastric and cardioesophageal cancers. A complete pathological response of the tumor has been reported to be observed in 8-20 % of patients. However, there is no guarantee that the evidence of pathological complete response will improve the cure results in all patients, and very little is known about prognostic factors after neoadjuvant therapy. Case descriptions . Two clinical cases of locally advanced gastric cancer were described. The patients were treated with neoadjuvant chemoradiotherapy followed by D2 gastrectomy. Accelerated hyperfractionated radiotherapy (1 + 1.5 Gy/ day) to a total dose of 45 Gy at intervals of 4-5 hours was administered concurrently with chemotherapy (capecitabine: 1850 mg/m 2 orally twice daily at 12-hour interval; oxaliplatin: 85 mg/m 2 intravenously on days 1 and 21). Histological examination revealed complete histological regression of the primary tumor in two cases. However, in one of the cases, metastases in regional lymph nodes with grade 2 histological tumor regression were revealed. In the first case, the patient is still alive with no evidence of disease recurrence at over 6-years after treatment. In the second case, the patient died of the disease progression 3 years after treatment. Conclusion. The data obtained are consistent with the few published studies reporting that pathological complete response to neoadjuvant therapy of not only the primary tumor but also regional lymph nodes is the key point determining the effectiveness of the combined modality treatment.

Efficacy and Safety of Apatinib Combined with S-1 Plus Oxaliplatin as Neoadjuvant Treatment for Locally Advanced Gastric Cancer: A Multicenter, Prospective Study

Background: Apatinib, a tyrosine kinase inhibitor targeting vascular endothelial growth factor receptor 2 (VEGFR-2), is a novel treatment option for advanced gastric cancer (AGC) refractory to two or more lines of prior chemotherapy but has not yet been evaluated in patients with locally AGC. This trial investigated the efficacy and safety of apatinib combined with S-1 plus oxaliplatin (SOX) as a neoadjuvant treatment for locally AGC. Methods: Patients with M0 and either T2-T4 or N+ disease received apatinib (500 mg orally once daily on days 1-21 and discontinued in the last cycle) plus SOX (S-1, 40-60 mg orally twice daily on days 1-14; oxaliplatin, 130 mg/m2 intravenously on day 1) given every 3 weeks for 2-5 cycles. D2 gastrectomy was performed 2-4 weeks after the last cycle. To further compare the efficacy and safety between apatinib plus SOX (ASOX group) and SOX alone (SOX group), we reviewed historical control patients receiving SOX as neoadjuvant chemotherapy at the central center. The primary end point was the R0 resection rate. Findings: Between July 2017 and June 2019, 48 and 58 patients were enrolled in the ASOX and SOX groups, respectively. Forty patients in the ASOX group (83.3%) and 47 patients in the SOX group (81.0%) underwent surgery, with R0 resection rates of 75.0% and 67.2%, respectively (P=0.382). For patients proceeding surgery, the R0 resection rates were 90.0% (36/40) and 82.3% (39/47), respectively (P = 0.534). The proportion of patients with T downstaging in the ASOX group was significantly higher than that in the SOX group (36.4% vs 18.5%, P=0.036). For patients with target lesions, the radiological response rate was significantly higher in the ASOX group (75.0% vs 38.5%, P=0.015). Moreover, the ASOX group was associated with significantly higher proportions of patients achieving major pathological response (25.0% vs 10.3%, P=0.046). Grade 3 toxicities occurred in 33.3% of the ASOX patients, and no grade 4 toxicities or drug-related deaths were observed. Interpretation: Apatinib combined with SOX showed promising efficacy with an acceptable safety profile as the first-line neoadjuvant treatment for locally AGC. Trial Registration: The trial is registered with ClinicalTrials.gov, number NCT03192735. Funding Statement: This study was supported by Scientific and technological innovation joint capital projects of Fujian Province, China (No.2017Y9011, No.2017Y9004). Minimally invasive medical center of Fujian Province (No. [2017]171). National natural science foundation of China (No.81871899). The second batch of special support funds for Fujian Province innovation and entrepreneurship talents (No.2016B013). Declaration of Interests: There are no conflicts of interest or financial ties to disclose from any authors. Ethics Approval Statement: The informed consent form and study protocol were approved by the Institutional Review Boards of each participating institution. The study was conducted in accordance with the International Conference on Harmonization Good Clinical Practice guidelines, the Declaration of Helsinki, and Chinese law. All patients provided written informed consent before enrollment.