Resectable Advanced Gastric Cancer Research Articles

P-312 Perioperative chemotherapy versus surgery alone on resectable advanced gastric cancer in a Moroccan population

Gastric cancer represents the fifth most common tumor and the third-leading cause of cancer-related death worldwide. The results of surgical treatment of locally advanced gastric cancer remain generally poor due to the high rate of relapse after surgery. In the last decade, neoadjuvant chemotherapy has become the standard of care for patients with stage ≥IB resectable advanced gastric cancer. The benefit in progression-free and overall survival was confirmed by several randomised trials and meta-analyses compared to immediate surgery.

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.

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 .

Immune checkpoint molecule V-set Ig domain-containing 4 (VSIG4) expression is associated with poor prognosis in advanced gastric cancer patients

Abstract Background New therapeutic approaches are needed for the treatment of advanced gastric cancer (AGC). V-set Ig domain-containing 4 (VSIG4) is an immune checkpoint molecule that may have prognostic or predictive utility in the treatment of AGC. The aim of this study was to investigate expression of VSIG4 and its clinical significance in AGC and other major cancers. Methods We analyzed VSIG4 expression and its correlation with survival rate in various carcinomas including 1,034 surgically resected AGCs from two academic hospitals. Patients were divided into a discovery (N = 572), internal validation (N= 230), and external validation (N= 232) sets. Results VSIG4-positive AGC tumors were significantly associated with overall survival (OS) (hazard ratio (HR) = 3.02, 95% confidence interval (CI) = 2.32–3.94, P<0.001,) and event-free survival (HR = 2.8, 95% CI=2.18–3.72, P <0.001). These findings was successfully validated in the independent cohorts. VSIG4-positive status was also significantly correlated with low intratumoral CD8+ T-cell infiltration (P = 0.036) and high FoxP3+/CD8+ intratumoral T-cell infiltration ratios (P = 0.016). VSIG4 expression in other cancers was not associated with higher 5-year OS rates (colon, P = 0.459, lung, P = 0.275, kidney, P = 0.121, breast, P = 0.147). Conclusions VSIG4 is an independent prognostic factor in AGC. Notably, VSIG4 expression was significantly associated with low CD8+ T-cell infiltration and high regulatory T cell/CD8+T cell ratios, implying a cancer tolerating immune environment. Our results may be an important basis for future gastric cancer-specific immunotherapeutic drug development.

Is Laparoscopic Gastrectomy More Advantageous for Elderly Patients Than for Young Patients with Resectable Advanced Gastric Cancer?

Laparoscopic gastrectomy (LG) is now practiced widely, but it is unclear whether LG is the appropriate approach for elderly patients with resectable advanced gastric cancer. The aim of this study was to examine whether LG is more or less advantageous for elderly patients than for young patients. We collected data on 571 consecutive patients who underwent gastrectomy for pT2-4 gastric cancer between January 2001 and December 2015. After adjustment with one-to-one propensity score matching, short-term and long-term outcomes were compared between the LG and open gastrectomy (OG) groups among young (age < 70years) and elderly (age ≥ 70years) patients. The LG group had a significantly longer operative time (P < 0.001) and less blood loss (P < 0.001) than the OG group among young and elderly patients. There were no significant differences regarding complications. Although disease-specific survival was similar between the LG and OG groups among young and elderly patients, LG was associated with more favorable overall survival than OG only among elderly patients (hazard ratio 0.67; 95% confidence interval 0.35-1.26). Death from respiratory diseases occurred more frequently in the OG group (10.9%) than in the LG group (0%) for elderly patients (P = 0.012). LG for resectable advanced gastric cancer was not inferior to OG in terms of both short-term and long-term outcomes regardless of patient age. In elderly patients, LG may improve overall survival by reducing mortality from respiratory diseases.

Diagnosis of invasion depth in resectable advanced gastric cancer for neoadjuvant chemotherapy: An exploratory analysis of Japan clinical oncology group study: JCOG1302A

BackgroundNeoadjuvant chemotherapy (NAC) is increasingly used for resectable locally advanced gastric cancer (LAGC). JCOG1302A investigated the diagnostic criteria of LAGC patients with cT3–4/N1–3 to minimize contamination of pathological stage I as a candidate for NAC. In JCOG1302A, 77.2% of cT3–4 tumors diagnosed via a combination of endoscopy and computed tomography (CT) were pT3–4. However, the role of endoscopic ultrasonography (EUS) and additional diagnostic procedures/modalities remains unclear. Here, we investigated whether EUS, thin-slice CT, and foaming agent (FA) in CT contribute to accurate diagnosis of AGC invasion depth. MethodsUsing JCOG1302A study data, we compared positive predictive value (PPV), negative predictive value (NPV), and kappa index (KI) between conventional and additional diagnostic procedures to identify pT3–4: conventional endoscopy (CE) with versus without EUS, 1-mm versus 5-mm CT slice, and CT with versus without FA. ResultsWe analyzed 1232 patients’ data. PPV, NPV, and KI were 79.2%/73.7%, 59.2%/58.8%, and 0.38/0.39 (CE alone/CE with EUS), 77.8%/75.5%, 62.9%/71.2%, and 0.38/0.39 (5-mm CT/1-mm CT), and 78.6%/75.1%, 60.9%/69.7%, and 0.38/0.40 (CT without FA/CT with FA), respectively. Overall, there were no remarkable differences in any comparison. More specifically, PPV and KI were slightly higher with CE alone rather than CE with EUS. Although NPV was higher for 1-mm CT and CT with FA, PPV was rather higher for 5-mm CT and CT without FA. ConclusionAdditional diagnostic procedures/modalities, like EUS, 1-mm slice CT, or FA in CT may not improve the diagnostic accuracy of invasion depth in resectable LAGC.

High compliance to ERAS protocol does not improve overall survival in patients treated for resectable advanced gastric cancer.

IntroductionThe ERAS (Enhanced Recovery after Surgery) protocol revolutionized perioperative care for gastrointestinal surgical procedures. However, little is known about the association between adherence to the ERAS protocol in gastric cancer surgery and the oncological outcome.AimTo explore the relation between adherence to the ERAS protocol and the oncological outcome in gastric cancer patients.Material and methodsWe performed a retrospective analysis of a prospectively collected database of patients treated for gastric cancer between 2013 and 2016. All patients were treated perioperatively with a 14-item ERAS protocol. Every patient underwent regular follow-up every 3 months for 3 years after surgery. 80% compliance to the ERAS protocol was the goal during perioperative care. Based on the level of compliance, patients were divided into group 1 and group 2 (compliance of ≥ 80% and < 80%, respectively).ResultsCompliance to the ERAS protocol was not a risk factor for diminished overall survival – probability of 3-year survival was 63% in group 1 and 56% in group 2 (p = 0.75). The proportional Cox model revealed that only stage III gastric cancer was a risk factor of poor prognosis in patients operated on for gastric cancer (HR = 7.89, 95% CI: 2.96–20.89; p = 0.0001).ConclusionsHigh adherence to the ERAS protocol did not improve overall survival in our 3-year observation. Only the stage of the disease, according to the AJCC classification, was identified as a risk factor for poor prognosis.

Feasibility and pathological response of TAS-118 + oxaliplatin as perioperative chemotherapy for patients with locally advanced gastric cancer (APOLLO-11).

351 Background: TAS-118 is a novel oral agent, containing S-1 and leucovorin. In the SOLAR study (NCT02322593), TAS-118 + oxaliplatin (OHP) significantly improved overall survival compared to S-1 + cisplatin for patients (pts) with advanced gastric cancer (GC). We conducted this open-label study to assess feasibility of perioperative adjuvant chemotherapy with TAS-118 + OHP in pts with locally advanced resectable GC with lymph node metastasis. (Clinical trial information: UMIN000024688). Methods: Eligible pts who had histopathologically confirmed GC with clinical T3-4N1-3M0 on image findings (14th Japanese classification of gastric carcinoma), age 20 to 79 years, were enrolled in this study. The protocol treatment consisted of preoperative 4 courses of TAS-118 (80-120 mg/body, days 1-7) + OHP (85 mg/m2, day 1) every 2 weeks, and gastrectomy with D2 lymphadenectomy, followed by postoperative 12 courses of TAS-118 alone (step1) or 8 cycles of TAS-118 + OHP (step2). The primary endpoints were tolerability of preoperative chemotherapy, gastrectomy and postoperative chemotherapy with TAS-118 plus OHP. Here, we report the feasibility of preoperative chemotherapy and gastrectomy, and pathological response. Results: Between December 2016 and April 2018, 45 pts with a median age of 61 years were enrolled. The numbers of pts with T stage (cT3/4a) and those with N stage (cN1/2/3) were 13/32 and 25/17/3, respectively. The completion rate of preoperative chemotherapy and gastrectomy was 88.9% ( 95% CI 78.0-95.5) and 95.6% (95% CI 86.7-99.2). The relative dose intensity of TAS-118 and OHP was 86.0% and 90.6%. During the 4 cycles of preoperative TAS-118 + OHP, 2 pts discontinued the treatment due to adverse event (AE). Major grade 3-4 AEs were diarrhea (17.8%) and neutropenia (8.9%). R0 resection rate was as high as 95.6%. One pts experienced grade 4 postoperative bleeding, but no treatment-related death was reported. pCR was achieved in 6/45 pts (13.3%) and other 7 pts (28.9%) showed near complete regression (&lt;10 % residual tumor cells). Conclusions: Preoperative TAS-118 + OHP followed by D2 gastorectomy was well tolerated and showed promising efficacy. Clinical trial information: 000024688.

SOX Neoadjuvant Chemotherapy Followed by Surgery for Resectable Advanced Gastric Cancer with Multiple Lymph-node Metastasis

高度リンパ節転移を伴う進行胃癌に対する術前補助化学療法（neoadjuvant chemotherapy，以下NAC）は有効な治療法の一つである．対象は2015年より2019年までに当院で経験した術前にS-1，オキサリプラチン併用療法（SOX療法）を施行した高度リンパ節転移を伴う切除可能cStage Ⅲ進行胃癌の８例である．結果は，SOX療法施行後のRECIST version1.1基準による臨床的評価ではPRが６例，SDが２例でPDは認めなかった．病理組織学的病期はⅠBが３例，ⅡAが１例，ⅡBが２例，ⅢAが２例であり，downstagingになった症例は８例中７例（87.5％）であった．病理組織学的効果はGrade １aが３例，Grade １bが２例，Grade ２aが２例，Grade ２bが１例でGrade ３の症例はなかった．CTCAE基準によるNACの副作用はGrade １の貧血，嘔気，末梢神経障害が１例ずつ，Grade ２の貧血が２例で，Grade ３以上の副作用は認めなかった．術式はD2郭清を伴う幽門側胃切術が３例，胃全摘術が５例であった．術後合併症は認められず，全例無再発生存中である．

A real-life analysis on the indications and prognostic relevance of perioperative chemotherapy in locally advanced resectable gastric adenocarcinoma.

Perioperative chemotherapy (periCTX) based on the "MAGIC" scheme has become a standard treatment in Europe for locally advanced oesophagogastric cancer. We assessed implementation and long-term oncological outcomes of MAGIC periCTX for locally advanced gastric cancer. Population-based cohort study of all patients with locally advanced gastric cancer undergoing surgical resection with curative intent in Catalonia and Navarra (the first two autonomous communities included in the EURECCA Upper GI Spanish Working Group) between January 2011 and December 2013. The main variable was the percentage of patients treated with MAGIC periCTX. Kaplan-Meier analysis and Cox proportional hazards model were used to assess the survival benefit of periCTX. Among 814 patients, 217 (26.6%) received periCTX (especially patients more likely to receive it: aged < 70years, with proximal tumors, low anesthetic risk, and cT3-4/cN+ clinical stage). 35% did not complete perioperative chemotherapy, with no relationship with age. PeriCTX showed no effect on postoperative morbimortality. Histological tumor regression was more often absent or poor (38.2%) than total or almost total (27.8%), although clinico-pathological lymph-node downstaging was higher than expected by staging inaccuracy (38.7% vs. 24.2%). PeriCTX was associated with a better survival only in cT3-4 and cN+ patients, showing less prognostic relevance than optimal oncological surgery with D2 lymphadenectomy. Only 26.6% of locally advanced resectable gastric cancer patients received PeriCTX. Pathological response was poor, although some degree of nodal downstaging was observed. Survival benefit of periCTX was limited to cT3-4 and cN+ patients, being less relevant than D2 lymphadenectomy.

Influential factors and prognostic analysis of blood vessel invasion in advanced gastric cancer

The purpose of this study was to analyze the influencing factors of BVI in advanced gastric cancer and explore the factors affecting the prognosis of advanced gastric cancer, so as to accurately evaluate the disease status and enable patients to receive effective treatment. We retrospectively analyzed 622 cases with complete data and successful follow-up. BVI was found in 144 of the 622 patients with advanced gastric cancer, with a detection rate of 23.15%. BVI was closely related to the differentiation degree, infiltration depth and lymph node metastasis of advanced gastric cancer, (P < 0.05). Gender, age, tumor location, tumor size, Lauren classification, tumor M stage, and clinical TNM stage were not the influencing factors of BVI in patients with advanced gastric cancer (P > 0.05). The 5-year survival rate of patients in the positive group of BVI was 34.72%. The 5-year survival rate of patients with advanced gastric cancer was correlated with BVI, Lauren classification, depth of invasion, lymph node metastasis, and clinical TNM staging, (P < 0.05). The 5-year survival rate was independent of gender, age, tumor location, tumor size, tumor tissue differentiation, and M stage (P > 0.05). The results of multi-factor analysis showed that BVI, N stage and clinical TNM stage were independent predictors of prognosis in patients with advanced radical gastric cancer. By analyzing the stage and related prognostic factors of resectable advanced gastric cancer, we found that BVI was not only closely related to lymph node metastasis, but also an independent predictor of prognosis of advanced gastric cancer. As this study was only a single-center retrospective study, there may be a selective bias in clinical data. So large-scale and multi-center collaboration is needed to further explore the influencing factors of BVI in the progression of gastric cancer.

Immune checkpoint molecule V-set Ig domain-containing 4 (VSIG4) expression is associated with poor prognosis in advanced gastric cancer patients

Abstract Background New therapeutic approaches are needed for the treatment of advanced gastric cancer (AGC). V-set Ig domain-containing 4 (VSIG4) is an immune checkpoint molecule that may have prognostic or predictive utility in the treatment of AGC. The aim of this study was to investigate expression of VSIG4 and its clinical significance in AGC and other major cancers. Methods We analyzed VSIG4 expression and its correlation with survival rate in various carcinomas including 1,034 surgically resected AGCs. Patients were divided into a discovery (N = 572), internal validation (N = 230), and external validation (N = 232) sets. Tumor microarrays using multiple tumor pieces were made considering intratumoral heterogeneity. A quantitative image analysis was applied. Digital slide images were obtained using the Pannoramic 250 Flash III and analyzed using the CellProfiler v2.2.0. The region of interest was manually selected within the TMA scanned image and extracted as 2 – 10 JPEG images in each case. Single cell segmentation and quantification of staining intensity were performed using a CellProfiler v2.2.0 pipeline. Results VSIG4-positive AGC tumors were significantly associated with overall survival (OS) (hazard ratio (HR) = 3.02, 95% confidence interval (CI) = 2.32-3.94, P Conclusions VSIG4 is an independent prognostic factor in AGC. Notably, VSIG4 expression was significantly associated with low CD8+ T-cell infiltration and high regulatory T cell/CD8+T cell ratios, implying a cancer tolerating immune environment. Our results may be an important basis for future gastric cancer-specific immunotherapeutic drug development. Legal entity responsible for the study The authors. Funding Grant (2019IP0408) from the Asan Institute for Life Sciences, Asan Medical Center, Seoul, Korea, and grant (NRF-2017R1D1A1B03033660) from the National Research Foundation of Korea. Disclosure All authors have declared no conflicts of interest.

Preoperative Plasma Fibrinogen and Serum Albumin Score Is an Independent Prognostic Factor for Resectable Stage II-III Gastric Cancer.

Background Radical gastrectomy with D2 lymphadenectomy is recognized as the standard treatment for resectable advanced gastric cancer. Preoperative fibrinogen and albumin measurements may bring clinical benefits in terms of providing advanced notice of a poor prognosis or recurrence in patients undergoing radical resection. The aim of this study was to identify markers that are predictive of a poor prognosis prior to surgery. Methods Eight hundred forty-two consecutive patients who underwent curative radical gastrectomy at our hospital between 2008 and 2012 were retrospectively reviewed. Based on plasma fibrinogen and serum albumin levels, preoperative fibrinogen and albumin scores (Fib-Alb scores) were investigated, and the prognostic significance was determined. Results The patients were classified according to a Fib-Alb score of 0 (n = 376), 1 (n = 327), or 2 (n = 139). When the correlation between the response rate and the change in the Fib-Alb score was investigated, the response rate was significantly lower in patients with an increased Fib-Alb score than in the other patients. In the survival analysis, patients in the Fib-Alb high-score group exhibited significantly worse recurrence-free survival (RFS) (P = 0.030) than patients in the other groups. A multivariate analysis using clinical stage and the change in the Fib-Alb score as covariates revealed that a change in the Fib-Alb score (Fib-Alb score 1, HR: 1.31, 95% CI: 1.03-1.66, P = 0.028; Fib-Alb score 2, HR: 1.61, 95% CI: 1.20-2.17, P = 0.001) was a significant independent predictive factor for RFS. Conclusions The prognosis of patients with high fibrinogen and low albumin levels is poor. The Fib-Alb score was shown to be an independent prognostic factor for postoperative recurrence in gastric cancer patients who underwent radical gastrectomy.

LBA41 - Phase III randomized study of neoadjuvant chemotherapy (CT) with docetaxel(D), oxaliplatin(O) and S-1(S) (DOS) followed by surgery and adjuvant S-1, vs surgery and adjuvant S-1, for resectable advanced gastric cancer (GC) (PRODIGY)

BackgroundAdjuvant CT after D2 gastrectomy is standard therapy for resectable advanced GC in Asia. We investigated whether added neoadjuvant (NA) CT can further improve outcomes. Methods530 pts with newly diagnosed locally advanced gastric or gastroesophageal junction (GEJ) adenocarcinoma (cT2,3/N[+]M0 or cT4/N[any]M0, AJCC 7th ed), ECOG PS 0-1, were randomized 1:1 to NA DOS then surgery and adjuvant S-1 (CSC; n=266), or surgery and adjuvant S-1 (SC; n=264). NA CT was D 50mg/m2 iv and O 100mg/m2 iv on day 1, S 40mg/m2 twice po on days 1–14 every 3 weeks for 3 cycles. Standard surgery was D2 gastrectomy. Adjuvant CT was S 40mg/m2 twice po on days 1–28 every 6 weeks for 8 cycles. Primary endpoint: 3-year progression free survival (PFS) in full analysis set (FAS). ResultsWith 46 pts excluded due to ineligibility or consent withdrawal, FAS was 484 pts (238 in CSC, 246 in SC). Baseline characteristics were balanced. In CSC arm, 214 pts (90.0%) completed 3 cycles of NA DOS. Main ≥grade3 toxicities: neutropenia in 12.6%, febrile neutropenia 9.2%, diarrhea in 5.0%, 1 treatment related death. 222 CSC (93.3%) and 246 SC (100%) pts underwent surgery. R0 resection rates: 96.4% vs 85.8%, p<0.0001; lower pathologic stage in CSC with pathologic CR 10.4% vs 0%, p<0.0001. Major surgical complication rates: 6.3% vs 8.5% with 1 surgical mortality in CSC arm. 204 CSC pts started adjuvant S-1, 170 (83.3%) completed 8 cycles; SC arm: 187 started, with completion of 8 cycles in 157 (84.0%). Main ≥grade3 toxicities: neutropenia (6.4% CSC, 5.4% SC), diarrhea (2.9% CSC, 3.2% SC). With median follow up of 37.4 months and 37.8% of PFS events, 3-year PFS rate (FAS) was 66.3% for CSC, 60.2% for SC; hazard ratio (HR) 0.70 (95% CI 0.52–0.95), stratified log-rank p=0.023. Sensitivity analyses (intent to treat set and landmark analysis) confirmed these results. ConclusionsAddition of NA DOS to D2 gastrectomy and adjuvant S-1 led to significant tumour downstaging and improved PFS with acceptable safety in PRODIGY study. Neoadjuvant DOS chemotherapy followed by D2 gastrectomy and adjuvant S-1 should be considered as a treatment option for resectable advanced GC. Clinical trial identificationNCT01515748. Legal entity responsible for the studySanofi Korea. FundingSanofi Korea. DisclosureY. Kang: Advisory / Consultancy: Ono; Advisory / Consultancy: BMS; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Merck Serono; Research grant / Funding (institution): Roche; Advisory / Consultancy, Research grant / Funding (institution): Novartis; Advisory / Consultancy: Daehwa; Advisory / Consultancy: LSKBiopharma; Advisory / Consultancy: Taiho; Advisory / Consultancy: Blueprint; Advisory / Consultancy: Macrogenics; Advisory / Consultancy: Zymeworks; Advisory / Consultancy: Hengrui. G. Kim: Shareholder / Stockholder / Stock options, Full / Part-time employment: Sanofi. Y. Lee: Shareholder / Stockholder / Stock options, Full / Part-time employment: Sanofi. All other authors have declared no conflicts of interest.

Real-life data on improvement of survival after perioperative chemotherapy versus surgery alone on resectable adenocarcinoma of the stomach - a single-center study.

In the last decade, neoadjuvant chemotherapy has become the standard of care also for curatively resectable advanced gastric cancer. Prospective randomized studies have shown a significant benefit in disease free and overall survival rate after perioperative chemotherapy as compared to immediate surgery. However, data in the "real-life" setting are rare. In our retrospective study, we wanted to clarify the question whether this benefit is achievable under real-life conditions. A total of 81 patients with resected adenocarcinoma of the stomach or distal esophagogastric junction (AEG III) clinical stage II-IIIc according to UICC (eighth edition) were enrolled. Forty-two patients received perioperative chemotherapy (cohort 1) and 39 patients were operated on immediately (cohort 2). Chemotherapy was carried out according to the ECF, EOX, or FLOT protocols. Overall 5-year survival was 35.7 % in cohort 1 and 23.7 % in cohort 2. Thus, the relative 5-year overall survival benefit was 51 %, and 12 % in absolute numbers (p = 0.083). For patients receiving perioperative chemotherapy per protocol (n = 20), a more marked absolute improvement in 5-year overall survival of 16.3 % as compared to immediately operated on patients was achieved (p = 0.05). Progression-free survival in this analysis was shown to be improved by perioperative chemotherapy also without statistical significance (p = 0.03). Patients with curatively resectable gastric adenocarcinoma or type III AEG tumor benefit from perioperative chemotherapy in terms of overall survival even under real-life conditions. Moreover, a benefit in progression-free survival can be demonstrated.

History of Peritoneal Surface Malignancy Treatment in Japan.

In this review, Japanese experience of cytoreductive surgery and perioperative chemotherapy is described. The new concept of peritoneal metastasis (PM) type, i.e., trans-mesothelial, trans-lymphatic, and superficial growing metastasis type was proposed in 2012. Surgeons should perform peritonectomy according to the type of PM. Since 1980, Japanese surgical oncologists have been spearheading the use of cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemoperfusion (HIPEC) as treatment for PM from gastric cancer. Two RCTs were conducted to verify the effect of HIPEC for the prophylaxis of peritoneal recurrence after curative resection of advanced gastric cancer. These two studies indicated that HIPEC is effective in preventing peritoneal recurrence of gastric cancer with serosal invasion. In 2002, intraperitoneal chemotherapy using taxans was developed for the treatment of PM from gastric cancer and led to the development of neoadjuvant intraperitoneal/systemic chemotherapy (NIPS), which was reported in 2006. In 2009, extensive intra-operative peritoneal lavage (EIPL) was developed, and contributed to the remarkable improvement in survival of patients with positive lavage cytology as demonstrated by prospective randomized clinical trials. In 2017, the Peritoneal Surface Oncology Group International proposed the value of complete cytoreduction and peritoneal cancer index cut-off as independent prognostic factors after CRS for gastric cancer with PM. Founded in 2016, the Japanese/Asian School of Peritoneal Surface Oncology (JASPSO) trains beginners to perform CRS and HIPEC safely. Sixteen students have already graduated from JASPSO and started to perform the treatment in their home countries.

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

93 Background: Neoadjuvant chemotherapy is promising to improve the survival of resectable gastric cancer. Cisplatin/S-1 (CS) and docetaxel/cisplatin/S-1 (DCS) are both active for metastatic gastric cancer. Methods: We conducted a randomized phase II trial to compare two and four courses of neoadjuvant S-1/cisplatin (SC) and docetaxel/cisplatin/S-1 (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 schirrhous type received two or four courses of cisplatin (60 mg/m2 at day 8)/S-1 (80 mg/m2 for 21 days with 1 week rest) or docetaxel (40 mg/m2 at day 1)/cisplatin (60 mg/m2 at day 1)/S-1 (80 mg/m2 for 14 days with 2 weeks rest) as neoadjuvant chemotherapy. 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 in total so that the treatment group with the superior observed 3-year OS rate by more than 60% as compared with 50% of the control group was to be selected with a probability of 85% or higher. Results: Between 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% (95% CI, 45.8-70.3%) in CS and 60.0% (95% CI, 48.0-71.9%) in DCS with hazard ratio of 0796 (95% CI, 0.475-1.335), while that was 53.1% (95% CI, 40.9-65.4%) in the two courses and 65.0% (95% CI, 53.2-76.8%) in the four courses with hazard ratio of 0.722 (95% CI, 0.429-1.216). In the survival analysis by duration in each regimen, the 3-year OS was 58.1% (95% CI, 45.8-70.3%) both for two and four courses in CS, while that was 48.5% (95% CI, 31.4-65.5%) for two courses of DCS and was 71.9% (95% CI, 56.3-87.5%) for four courses of DCS. Conclusions: Considering 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. Clinical trial information: UMIN000006378.

Surgical treatment strategy for advanced gastric cancer

There are large amount of gastric cancer patients in China, and because of current medical care situation in China, most of the patients have been diagnosed with advanced stage. Surgery is still an important method for patients with advanced gastric cancer, to cure or improve their survival. For lymph node dissection of resectable advanced gastric cancer, D2 radical resection as a standard progressive lymph node dissection of gastric cancer is gradually accepted by East Asian countries and more and more western countries. As recommended by the 8th AJCC-TNM staging, ≥16 lymph nodes for pathological examination are needed to provide better survival, and ≥30 lymph nodes allows better evaluation for prognosis. After years of research, surgical experts have found that D1+ is not suitable for advanced gastric cancer. The III phase clinical trials for advanced gastric cancer, JLSSG 0901 in Japan and KLASS-02 in Korea, have been carried out to confirm that the long-term survival of laparoscopic surgery is no worse than traditional open surgery. CLASS-01 III phase study performed by Chinese laparoscopic gastroenterological study group compared the efficacy between laparoscopic and open distal gastrectomy with D2 lymph node dissection for advanced gastric cancer. The short-term report showed that the laparoscopic surgery has favorable safety, effectiveness, and satisfactory oncologic effect. With the development of conversion therapy, IV stage gastric cancer was divided into 4 types: potential resectable metastasis, borderline resectable metastasis, incurable metastasis and unresectable metastasis. And it is proposed that patients of the 2nd, and some of the 3rd and 4th types are suitable for conversion therapy. Surgery should be performed when tumor has maximal response to chemotherapy. In addition, palliative resection or short circuited surgery may be selected for patients who are refractory to conversion therapy or have some complications such as pyloric stenosis or obstruction, perforation of the tumor, or massive hemorrhage that cannot be alleviated.

Prognostic impact of preoperative prognostic nutritional index in resected advanced gastric cancer: A multicenter propensity score analysis

BackgroundAdvanced gastric cancer (AGC) causes debilitating malnutrition and leads to deterioration of the immune response. However, the concept of the prognostic nutritional index (PNI) is controversial when applied to patients with AGC. The aim of the present study was to evaluate the effect of the PNI after gastrectomy in patients with AGC. Materials and methodsA multicenter retrospective study was conducted using propensity score matching (PSM) in gastric adenocarcinoma patients who underwent resection via laparoscopic or open surgery between 2014 and 2017. To overcome selection bias, we performed 1:1 matching using 5 covariates. ResultsThe resection margins (P < 0.001) and LNM (P = 0.004) were significantly different between the two groups. In univariate analysis, poor tumor differentiation (P = 0.038) (R1+R2, P = 0.004), vascular and neural invasion (P < 0.001), and a PNI<50 (P < 0.001) were associated with poor recurrence-free survival (RFS). In multivariate analysis, a PNI<50 (hazard ratio (HR), 12.993; P < 0.001) was a risk factor for RFS. Univariate analysis for overall survival (OS) revealed that a PNI<50 (P < 0.001) (R1+R2,P = 0.006) and vascular and neural invasion (P < 0.001) were risk factors. In subsequent multivariate analysis, a PNI<50 (HR, 24.501; P < 0.001) was a significant risk factor for OS. Clinical assessments performed during a 12.34 (±5.050) month follow-up revealed that OS (P < 0.001) and RFS (P < 0.001) were worse in patients with a low PNI (<50) than in matched patients with a high PNI. ConclusionA low PNI is a strong predictor of unfavorable RFS and OS in patients with AGC.

656P - Diagnosis of invasion depth in resectable advanced gastric cancer for neoadjuvant chemotherapy: An exploratory analysis of JCOG1302A

656P - Diagnosis of invasion depth in resectable advanced gastric cancer for neoadjuvant chemotherapy: An exploratory analysis of JCOG1302A