The Impact of Gastric Anatomical Subdivisions on the Response to Neoadjuvant Chemotherapy in Gastric Cancer.

BACKGROUNDGastric cancer is a malignant tumor with high morbidity and mortality worldwide. Neoadjuvant chemotherapy (NAC), defined as chemotherapy administered before the primary treatment (usually surgery) to reduce tumor size and control micrometastases, has emerged as a crucial therapeutic strategy for locally advanced gastric cancer. Pathological complete response (pCR), characterized by the absence of viable tumor cells in the resected specimen after neoadjuvant treatment, is recognized as a strong predictor of favorable prognosis. However, the factors influencing the achievement of pCR remain incompletely understood.AIMTo identify and analyze the predictive factors associated with achieving pCR after NAC in gastric cancer patients, thereby providing evidence-based guidance for clinical decision-making.METHODSA retrospective analysis was performed on 215 patients from Shandong Cancer Hospital and Tai’an Central Hospital with locally advanced gastric cancer who underwent NAC followed by radical surgery at our hospital between January 2015 and December 2023. Comprehensive clinical and pathological data were collected, including age, gender, tumor location, Lauren classification, clinical staging, chemotherapy regimens, number of chemotherapy cycles, and baseline hematological indicators. The baseline hematological indicators included neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio, albumin level, carcinoembryonic antigen (CEA), and carbohydrate antigen 19-9. Univariate and multivariate logistic regression analyses were employed to determine the independent predictive factors for pCR.RESULTSAmong 215 gastric cancer patients, 41 (19.1%) achieved pCR after NAC. Multivariate analysis identified five independent predictive factors for pCR: Lauren intestinal type [odds ratio (OR) = 3.28], lower clinical T stage (OR = 2.75), CEA decrease ≥ 70% after NAC (OR = 3.42), pre-treatment NLR < 2.5 (OR = 2.13), and ≥ 4 chemotherapy cycles (OR = 2.87). The fluorouracil, leucovorin, oxaliplatin, docetaxel regimen achieved the highest pCR rate (27.5%), and oxaliplatin-containing regimens were superior to cisplatin-containing regimens (22.3% vs 12.7%, P = 0.034). Patients with both low NLR and platelet-to-lymphocyte ratio had the highest pCR rate (33.8%), while those with both high inflammatory markers had the lowest rate (10.7%). Earlier clinical stage disease (cT3N+ vs cT4N+: 28.6% vs 13.0%) and lower lymph node burden were associated with higher pCR rates.CONCLUSIONThe achievement of pCR after NAC in gastric cancer patients is closely associated with Lauren intestinal type, lower clinical T stage, a significant decrease in CEA after chemotherapy, low pre-treatment NLR, and an adequate number of chemotherapy cycles.

Tumor regression grade (TRG) and ypTNM are primarily employed to evaluate the efficacy of Neoadjuvant chemotherapy (NAC) in gastric cancer (GC) patients, however, have limited prognostic value. In this study, we established a clinical-radiomic fusion model, without TRG information, for better prognosis assessment of patients following NAC. A retrospective multicenter study comprising 875 GC patients from three centers was conducted. Cox hazard regression model was used for variable screening and risk weight assignment. Lasso regression was applied for dimensionality reduction and screening of radiomic features. Models were constructed for better prognosis assessment, and were verified in external cohorts. Survival analysis showed that dynamic T/N staging changes after NAC could effectively distinguish patients based on prognosis. Moreover, the Clinical SCORE model based on the dynamic T/N staging changes and other clinicopathological data had also been found in internal and external validations to be capable of effectively stratifying patients' risks. For CT images, the identified radiomics features were employed to establish the CT SCORE model, which was subsequently integrated with the Clinical SCORE model to construct the Final SCORE model for prognostic evaluation. In the training and validation cohorts, the prognostic discrimination performance of the Final SCORE model exceeded that of TRG and ypTNM. Furthermore, the final model might also be helpful for the screening of the population benefiting from postoperative adjuvant therapy. The developed clinical-radiomic Final SCORE model showed superior prognostic assessment performance than TRG and ypTNM for prognostic assessment of GC patients following NAC.

Despite optimal neoadjuvant chemotherapy only 40% of gastric cancer tumours achieve complete or partial treatment response. In the absence of treatment response, neoadjuvant chemotherapy in gastric cancer contributes to adverse events without additional survival benefit compared to adjuvant treatment or surgery alone. Additional strategies and methods are required to optimize the allocation of existing treatment regimens such as FLOT chemotherapy (5-Fluorouracil, Leucovorin, Oxaliplatin and Docetaxel). Predictive biomarkers detected using immunohistochemistry (IHC) methods may provide useful data regarding treatment response. To investigate the utility of CD4, CD8, Galectin-3 and E-cadherin in predicting neoadjuvant FLOT chemotherapy tumour response in gastric adenocarcinoma. Forty-three adult patients with gastric adenocarcinoma, of which 18 underwent neoadjuvant chemotherapy, were included in a prospective clinical cohort. Endoscopic biopsies were obtained from gastric cancer and normal adjacent gastric mucosa. Differences in expression of Galectin-3, E-cadherin, CD4+ and CD8+ molecules between tumours with and without treatment response to neoadjuvant chemotherapy were assessed with IHC. Treatment response was graded by clinical pathologists using the Tumour Regression Score according to the College of American Pathologists criteria. Treatment response was defined as complete or near complete tumour response, whereas partial or poor/no response was defined as incomplete. Digital IHC images were annotated and quantitatively assessed using QuPath 0.3.1. Biomarker expression between responsive and incomplete response tumours was assessed using a two-sided Wilcoxon test. Biomarker expression was also compared between normal and cancer tissue and between 15 paired tumour samples before and after chemotherapy. We performed a preliminary multivariate analysis and power analysis to guide future study. Statistical analyses were completed using R 4.1.2. The ratio between CD4+ and CD8+ lymphocytes was significantly greater in treatment responsive tumours (Wilcoxon, P = 0.03). In univariate models, CD4+/CD8+ ratio was the only biomarker that significantly predicted favourable treatment response (Accuracy 86%, P < 0.001). Using a glmnet multivariate model, high CD4+/CD8+ ratio and low Galectin-3 expression were the most influential variables in predicting a favourable treatment response. Analyses of paired samples found that FLOT chemotherapy also results in increased expression of CD4+ and CD8+ tumour infiltrating lymphocytes (Paired Wilcoxon, P = 0.002 and P = 0.008, respectively). Our power analysis suggests future study requires at least 35 patients in each treatment response group for CD8 and Galectin-3 molecules, whereas 80 patients in each treatment response group are required to assess CD4 and E-cadherin biomarkers. We demonstrate that an elevated CD4+/CD8+ Ratio is a promising IHC-based biomarker to predict favourable treatment response to FLOT neoadjuvant chemotherapy in locally advanced gastric cancer.

Gastric cancer (GC) remains a significant global health challenge, with high incidence and mortality rates. Neoadjuvant chemotherapy is increasingly used to improve surgical outcomes and long-term survival in advanced cases. However, individual responses to treatment vary widely, and current imaging methods often fall short in accurately predicting efficacy. Advanced imaging techniques, such as computed tomography (CT) 3D reconstruction and texture analysis, offer potential for more precise assessment of therapeutic response. To explore the application value of CT 3D reconstruction volume change rate, texture feature analysis, and visual features in assessing the efficacy of neoadjuvant chemotherapy for advanced GC. A retrospective analysis was conducted on the clinical and imaging data of 97 patients with advanced GC who received S-1 plus Oxaliplatin combined chemotherapy regimen neoadjuvant chemotherapy from January 2022 to March 2024. CT texture feature analysis was performed using MaZda software, and ITK-snap software was used to measure the tumor volume change rate before and after chemotherapy. CT visual features were also evaluated. Using postoperative pathological tumor regression grade (TRG) as the gold standard, the correlation between various indicators and chemotherapy efficacy was analyzed, and a predictive model was constructed and internally validated. The minimum misclassification rate of texture features in venous phase CT images (7.85%) was lower than in the arterial phase (13.92%). The volume change rate in the effective chemotherapy group (75.20%) was significantly higher than in the ineffective group (41.75%). There was a strong correlation between volume change rate and TRG grade (r = -0.886, P < 0.001). Multivariate analysis showed that gastric wall peristalsis (OR = 0.286) and thickness change rate ≥ 40% (OR = 0.265) were independent predictive factors. Receiver operating characteristic curve analysis indicated that the volume change rate [area under the curve (AUC) = 0.885] was superior to the CT visual feature model (AUC = 0.795). When the cutoff value was 82.56%, the sensitivity and specificity were 85.62% and 96.45%, respectively. The CT 3D reconstruction volume change rate can serve as a preferred quantitative indicator for evaluating the efficacy of neoadjuvant chemotherapy in GC. Combining it with a CT visual feature predictive model can further improve the accuracy of efficacy evaluation.

SO-11 Response evaluation after neoadjuvant chemotherapy for resectable gastric cancer: Downsizing vs downstaging

Simple SummaryResponse evaluation following neoadjuvant chemotherapy for gastric cancer has been widely debated. Following a full course of preoperative cycles, response evaluation can guide the vigor in delivering postoperative chemotherapy, indicate for whom a shift in regimen following a later relapse may be prudent, and be a tool for scientific use. In the everyday setting, the terms downsizing and downstaging are often used synonymously with response to treatment, but any abilities and limitations in this respect need to be proven. The aim of the present study was to investigate downsizing and downstaging as methods of response evaluation following NAC in gastric cancer. We evaluated whether the response mode translated into strata of long-term survival rates, a prerequisite for a useful method in a neoadjuvant setting.Background: The method of response evaluation following neoadjuvant chemotherapy (NAC) in resectable gastric cancer has been widely debated. An essential prerequisite is the ability to stratify patients into subsets of different long-term survival rates based on the response mode. Histopathological measures of regression have their limitations, and interest resides in CT-based methods that can be used in everyday settings. Methods: We conducted a population-based study (2007–2016) on 171 consecutive patients with gastric adenocarcinoma who were receiving NAC. Two methods of response evaluation were investigated: a strict radiological procedure using RECIST (downsizing), and a composite radiological/pathological procedure comparing the initial radiological TNM stage to the pathological ypTNM stage (downstaging). Clinicopathological variables that could predict the response were searched for, and correlations between the response mode and long-term survival rates were assessed. Results: RECIST failed to identify half of the patients progressing to metastatic disease, and it was unable to assign patients to subsets with different long-term survival rates based on the response mode. However, the TNM stage response mode did achieve this objective. Following re-staging, 48% (78/164) were downstaged, 15% (25/164) had an unchanged stage, and 37% (61/164) were upstaged. A total of 9% (15/164) showed a histopathological complete response. The 5-year overall survival rate was 65.3% (95% CI 54.7–75.9%) for TNM downstaged cases, 40.0% (95% CI 20.8–59.2%) for stable disease, and 14.8% (95% CI 6.0–23.6%) for patients with TNM progression, p < 0.001. In a multivariable ordinal regression model, the Lauren classification and tumor site were the only significant determinants of the response mode. Conclusions: Downsizing, as a method for evaluating the response to NAC in gastric cancer, is discouraged. TNM re-staging by comparing the baseline radiological CT stage to the pathological stage following NAC is suggested as a useful method that may be used in everyday situations.

Background: Neoadjuvant chemotherapy (NAC) was increasingly used for early-stage gastric cancer (GC) treatment to reduce the recurrence and mortality. However, clinical practices demonstrated that not all the patients underwent NAC prior to surgery could benefit from it. Current available methods for assessing the response to NAC, such as Tumor Regression Grading (TRG), CT, or serum tumor markers, can only evaluated after NAC or surgery. Novel markers for predicting the effect of neoadjuvant chemotherapy on prognosis before NAC is in urgent need. Gastric Cancer is featured by frequent somatic copy number alterations (SCNA) and high chromosomal instability. In addition, chromosomal instability has been demonstrated to effectively predict the therapeutic response to radiotherapy, chemotherapy, and targeted therapy. In this work, we investigated the chromosomal instability in GC patients undergoing NAC as a prognosis predictor. Methods: From Jan 2016 to Jun 2017, a cohort of 25 patients with Stage II/III gastric adenocarcinoma after surgical treatment at Department of Gastrointestinal Oncology, Peking University Cancer Hospital were enrolled in our study. ctDNA was collected before (pre-NAC) and after NAC (post-NAC). We analyzed the mutation profiles of 50 plasma samples collected from 25 patients using a 179 cancer-related gene panel (GenetronHealth; Beijing, China). Copy number instability (CNI) scores of ctDNA were calculated to reflect chromosome instability in ctDNA. Results: Based on the clinical evaluation of a combination of TRG, CT and serum tumor markers, 60% (15/25) patients were responsive to NAC. The pre-NAC CNI scores of ctDNA were significantly higher than that of post-NAC (median 127 vs. 113, Paired t test P=0.0403), which correlated well with the response rates and prognosis in the GC patients treated with NAC. 73.7% (14/19) patients with higher pre-NAC CNI score (CNI score &amp;gt;90) were responsive to NAC, while the response rate of the lower pre-NAC CNI score (CNI score &amp;lt;90) was only 16.7%(1/6). And the pre-NAC CNI scores of response group were much higher than that of the non-Response. (median 129 vs 86.5). Furthermore, comparing with the patients with lower pre-NAC CNI (CNI score &amp;gt;90), the higher ones had obviously better prognosis after NAC treatment (P=0.037, HR=9.358). Conclusions: To our knowledge, this is the first time demonstrating that the chromosomal instability quantification measured by CNI score of pre-NAC ctDNA may become a novel promising markers of response and prognosis to NAC in gastric cancer patients before NAC treatment. Additional larger cohort study aimed at understanding relationship between response to therapy and ctDNA instability are further required. Citation Format: Yongning Jia, Honglin Zhu, Fei Pang, Fei Shan, Shuangxi Li, Danhua Wang, Lin Li, Tonghui Ma, Ziyu Li. Chromosomal instability of circulating tumor DNA predicts response to neoadjuvant chemotherapy in 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 1991.

Although randomized controlled trials on neoadjuvant chemotherapy for gastric cancer have included some T1-staged tumors, overall survival (OS) has not been analyzed for this subset. Due to the low negative predictive value of clinical staging and the benefits of neoadjuvant chemotherapy for locally advanced disease, identifying patient groups with early-stage gastric cancer that may benefit from neoadjuvant chemotherapy is of merit. The objective of this study was to evaluate the relationship between OS and sequence of surgical therapy for clinical T1 gastric cancer. The 2017 National Cancer Database was used to compare patients who had surgery-first and those who received neoadjuvant chemotherapy for T1-stage gastric cancer. OS was analyzed using a parametric regression survival-time model adjusted for covariates. The effects of these covariates on OS based on surgical sequence were examined. 11,219 patients were included, of which 10,191 underwent surgery as their first or only treatment. When adjusted for covariates, neoadjuvant chemotherapy followed by curative-intent surgery was significantly associated with increased risk of death (HR 1.15, 95% CI 1.01-1.31, P = .030). In multivariate analysis, clinical N0 stage, non-minorities, and patients with high socioeconomic status had improved OS if they did not have neoadjuvant chemotherapy and instead had upfront surgery. Neoadjuvant chemotherapy is associated with decreased OS for early-stage gastric adenocarcinoma, even for patients with clinically positive nodal disease. In addition, the lack of survival improvement with a surgery-first approach in patients with disparities deserves further study.

Objective: To investigate the value of tumor perfusion parameter measured by using double contrast-enhanced ultrasound (DCEUS) QontraXt three-dimensional pseudocolor quantitative analysis to the therapeutic effect evaluation of preoperative neoadjuvant chemotherapy (NAC) in advanced gastric cancer (AGC) patients. Methods: Eighty-nine AGC patients underwent 3 cycles of preoperative NAC (XELOX) followed by complete resection of lesion. The DCEUS QontraXt three-dimensional pseudocolor was performed one or two weeks before the NAC and operation were applied, respectively. The peak enhancement (PE), time to peak (TP), sharpness of the bolus (β) and area under the enhancement curve (AUC) of primary gastric tumor were measured by QontraXt three-dimensional pseudocolor quantitative analysis. These DCEUS parameters between respond and non-respond groups before and after NAC therapy were compared. The prediction accuracy of DCEUS to the therapeutic effect evaluation of preoperative NAC was determined by the receive operating characteristic (ROC) curves. Results: Among 89 AGC patients, 52 patients responded to NAC therapy, while 37 patients resisted to NAC therapy. Twelve cases in respond group and 26 cases in non-respond group were mucinous carcinoma. Forty cases in respond group and 11 cases in non-respond group were non-mucinous carcinoma (P<0.05). In responder group, the PE and TP before NAC were (53.7±9.3)% and (14 521±2 667) ms, and (32.2±5.5)% and (17 235±1 898) ms after NAC. The ratio of changes of PE (ΔPE) and TP (ΔTP) were 0.43±0.17 and 0.36±0.14, respectively. In non-respond group, the PE and TP before NAC were (54.4±7.2)% and (13 869±3 247) ms, and (45.3±6.1)% and (15 127±1 423) ms after NAC therapy. The ratio of ΔPE and ΔTP were 0.24±0.20 and 0.22±0.12. The PE and TP after NAC, the ratio of ΔPE and ΔTP were significant different among these two groups (all of P<0.05). The ROC curves showed that the ratio of ΔPE in assessing the respond of gastric cancer patients to NAC was superior compared to other parameters (AUC=0.784, P=0.004). The optimal cut-off value of the ratio of ΔPE was 24% and its sensitivity and specificity to the therapeutic effect evaluation of NAC in gastric cancer were 82.7% and 64.9%. Conclusion: DCEUS QontraXt three-dimensional pseudocolor quantitative analysis might be a novel, noninvasive and reliable method to evaluate the therapeutic effect of preoperative NAC in AGC patients.

4102 Background: Prognosis for stage III gastric cancer was not satisfactory even by D2 gastrectomy and adjuvant chemotherapy. Neoadjuvant chemotherapy is another promising approach. This study investigated the outcomes of two and four courses of neoadjuvant S-1/cisplatin (SC) and paclitaxel/cisplatin (PC) using a two-by-two factorial design for locally advanced gastric cancer. Methods: Patients with stage II schirrhous/junctional tumors, stage III, or resectable stage IV, received S-1 (80 mg/m2 for 21 days with 1 week rest)/cisplatin (60 mg/m2 at day 8) or paclitaxel/cisplatin (80 mg/m2 and 25 mg/m2, respectively, on days 1, 8, and 15 with 1 week rest). The primary endpoint was 3-year OS. Key secondary endpoints included pathological/clinical response, R0 resection, and adverse events. Sample size was set at 60 to 80 to achieve 10% improvement of 3-year OS by four courses or by PC with approximately 80% probability of the correct selection. Results: Between Oct 2009 and July 2011, 83 patients were assigned to arm A (2 courses of SC, n=21), arm B (4 courses of SC, n=20), arm C (2 courses of PC, n=21), and arm D (4 courses of PC, n=21). Clinical response (arm A/B/C/D) was 29%/40%/33%/24%. R0 resection (arm A/B/C/D) was 76%/75%/57%/76%. Pathological response (arm A/B/C/D), defined as tumor regression more than two third in the primary tumor, was 43%/40%/29%/38%. Pathological complete response (arm A/B/C/D) was 0%/10%/0%/10%. Major grade 3/4 toxicities (arm A/B/C/D) were anemia (14%/15%/0%/28.6%), neutropenia (10%/15%/14%/33%), nausea (0%/10%/5%/5%), and appetite loss (5%/10%/0%/5%). Pathological complete response by per-protocol analysis (arm B/D) was 17% and 12%. Treatment discontinuation (number of patients, arm A/B/C/D) was disease progression (1/3/0/1), toxicities (1/4/0/3), and others (0/1/0/0). No surgical mortality was observed. Grade 3 morbidity classified by Clavien-Dindo was leakage in 5% (arm A), pancreatic fistula in 5% (arm C), and postoperative hemorrhage in 5% (arm B). Conclusions: Pathological complete response could be induced by four courses of neoadjuvant chemotherapy without a marked increase of toxicities, regardless of a SC or PC regimen. Clinical trial information: UMIN000002595.

Neoadjuvant chemotherapy combined with radical gastrectomy is one of the most important parts of the multimodality therapy strategies for locally advanced gastric cancer. With the development of laparoscopic technique in recent decades, laparoscopic technique plays a more and more important role in the surgical treatment of gastric cancer. Neoadjuvant chemotherapy, as a part of comprehensive treatment of gastric cancer, has gained more and more clinical supports and been recommended for guidelines. With the development of laparoscopic technique and clinical evidence, laparoscopic operation for advanced gastric cancer has been applied more and more widely. However, the safety and efficacy of laparoscopic resection following neoadjuvant chemotherapy, as a new treatment modality, still needs prospectively high-level researches to verify. Therefore, we will discuss some key points of laparoscopic gastrectomy after neoadjuvant chemotherapy based on the CLASS 03a trial, which is led by the Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, the Department of Gastrointestinal Surgery, Peking University Cancer Hospital and Institute, and Chinese Laparoscopic Gastric Surgery Study Group. The CLASS 03a trial aims to confirm surgical and oncological safety of laparoscopy distal D2 radical gastrectomy for locally advanced stage gastric cancer patients (cT3~4a, N-/+, M0) who completed neoadjuvant chemotherapy. On the base of CLASS 03a trial, this article elucidates the choice of neoadjuvant chemotherapy for gastric cancer and proposes some associated problems about neoadjuvant chemotherapy combined with laparoscopic gastric cancer operation.

The prognosis for stage 3 gastric cancer is not satisfactory, even with S-1 adjuvant chemotherapy. A randomized phase II trial was conducted to compare two and four courses of neoadjuvant S-1/cisplatin (SC) and paclitaxel/cisplatin (PC) using a two-by-two factorial design for locally advanced gastric cancer. The primary endpoint was overall survival. We clarified the impact of these regimens on the secondary endpoints, including the clinical and pathological responses, chemotherapy-related toxicities, and surgical results. Patients received S-1 (80 mg/m(2) for 21 days with 1 week's rest)/cisplatin (60 mg/m(2) at day 8) or paclitaxel/cisplatin (80 and 25 mg/m(2), respectively, on days 1, 8, and 15 with 1 week's rest) as neoadjuvant chemotherapy. Eighty-three patients were assigned to arm A (two courses of SC, n = 21), arm B (four courses of SC, n = 20), arm C (two courses of PC, n = 21), and arm D (four courses of PC, n = 21). Pathological response rate was 43 % in arm A, 40 % in arm B, 29 % in arm C, and 38 % in arm D. Pathological complete response was only observed in arms B (10 %) and D (10 %). Most bone marrow toxicities, nausea, vomiting, alopecia, and fatigue were slightly higher but acceptable in arms B and D. Grade 3/4 surgical morbidities were not commonly observed in all four arms. Pathological complete response could be induced by four courses of neoadjuvant chemotherapy without a marked increase of toxicities, regardless of a SC or PC regimen.

71 Background: Prognosis for stage III gastric cancer was not satisfactory even by D2 gastrectomy followed by S-1 adjuvant chemotherapy. Neoadjuvant chemotherapy will be another promising approach to improve the survival as demonstrated in some European trials, however, optimal duration and regimen have not been clarified yet. Methods: This trial compared efficacy of neoadjuvant chemotherapy using two and four courses of SC regimen; S-1 (80 mg/m2 for 21 days with 1 week rest) / cisplatin (60 mg/m2 at day 8), or PC regimen; paclitaxel / cisplatin (80 mg/m2 and 30 mg/m2, respectively at days 1, 8, and 15 with 1 week rest), by a two by two factorial design for stage II schirrhous / junctional tumors, stage III, or resectable stage IV. The primary endpoint was 3-year OS. Key secondary endpoints included pathological / clinical response, R0 resection, and adverse events. Sample size was set at 60 to 80 to achieve 10% improvement of 3-year OS by four courses or by PC with approximately 80% probability of the correct selection. Results: Between Oct 2009 and July 2011, 83 patients were assigned to arm A (2 courses of SC, n=21), arm B (4 courses of SC, n=20), arm C (2 courses of PC, n=21), and arm D (4 courses of PC, n=21). Clinical response (arm A/B/C/D) was 29%/40%/33%/24%. R0 resection (arm A/B/C/D) was 76%/75%/57%/76%. Pathological response (arm A/B/C/D), defined as tumor regression more than two third in the primary tumor, was 43%/40%/29%/38%. Pathological complete response (arm A/B/C/D) was 0%/10%/0%/10%. Major grade 3/4 toxicities (arm A/B/C/D) were anemia (14%/15%/0%/28.6%), neutropenia (10%/15%/14%/33%), nausea (0%/10%/5%/5%), and appetite loss (5%/10%/0%/5%). No surgical mortality was observed. Grade 3 morbidity classified by Clavien-Dindo was leakage in 5% (arm A), pancreatic fistula in 5% (arm C), and postoperative hemorrhage in 5% (arm B). Conclusions: This randomized phase II study suggested that pathological complete response could be induced by long-term neoadjuvant chemotherapy without increase of toxicities regardless of SC or PC regimen. Clinical trial information: UMIN000002595.

Objective: The aim of the present study is to investigate the relationship between microRNA-27a (miR-27a) and the efficacy of neoadjuvant chemotherapy in gastric cancer (GC) and its mechanism in the growth and metastasis of GC cells.Methods: The expression of miR-27a in serum of 74 GC patients received neoadjuvant chemotherapy was detected by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). Clinical value and prognosis of miR-27a expression in predicting the efficacy of neoadjuvant chemotherapy in GC were evaluated. Besides, GC cells with low miR-27a expression were transfected with miR-27a mimics, and cells with high miR-27a expression were transfected with miR-27a inhibitors and secreted frizzled-related protein 1 (SFRP1) siRNA. A series of experiments were applied for the determination of cell viability, invasion and migration of GC cells.Results: After neoadjuvant chemotherapy, the expression of miR-27a in serum of GC patients decreased significantly. Additionally, the expression of miR-27a in GC cell line was significantly higher than that in normal gastric mucosa cell line. Meanwhile, after down-regulating the expression of miR-27a in GC cells, the mRNA and protein expression of SFRP1 increased, the proliferation rate of cells slowed down, and the ability of invasion and migration decreased. Furthermore, combined with low expression of miR-27a and SFRP1, the proliferation rate of GC cells increased and the ability of invasion and migration increased.Conclusion: Collectively, our study highlights that the high expression of miR-27a indicates the poor efficacy and prognosis of neoadjuvant chemotherapy in GC patients. Down-regulation of miR-27a can inhibit the growth and metastasis of GC cells via up-regulation of SFRP1.

We report on a case of a 65-year-old Chinese male with locally advanced gastric adenocarcinoma achieving pathological complete response after neoadjuvant chemotherapy with capecitabine and oxaliplatin (XELOX) regimen. He underwent esophagogastroduodenoscopy, which revealed a 6x5cm gastric ulcer. Biopsy of gastric ulcer revealed adenocarcinoma. Further workups with abdominal enhancement computed tomography (CT) staged his cancer as T4N2M0. He received 2 cycles of neoadjuvant chemotherapy with XELOX without severe toxicity. Afterwards, he underwent curative surgery consisting of total gastrectomy with extended D2 lymph node dissections and a Roux-en-Y esophagojejunostomy. On microscopic examination, no tumor cells were detected in the ulcer scar of the resected stomach and in the regional lymph nodes. The benefit of XELOX regimen as neoadjuvant chemotherapy in gastric cancer is worth further investigation.