Comparison of efficacy and safety of nab-paclitaxel and oxaliplatin + S-1 and standard S-1 and oxaliplatin chemotherapy regimens for treatment of gastric cancer.

BACKGROUNDGastric cancer (GC) remains a major global health burden, particularly in East Asia, due to its high incidence, aggressive progression, and poor prognosis in advanced stages. Although surgery is the mainstay of curative treatment, outcomes for locally advanced cases remain unsatisfactory despite perioperative chemotherapy. In recent years, immune checkpoint inhibitors, especially anti-PD-1 antibodies like sintilimab, have shown promise in improving survival when combined with chemotherapy. However, the comparative efficacy and safety of SOX plus sintilimab vs established regimens such as P-SOX and SOX alone in the neoadjuvant setting have not been fully explored.AIMTo compare the efficacy and safety of three neoadjuvant chemotherapy regimens—SOX combined with sintilimab (SOX + PD-1), albumin-bound paclitaxel plus oxaliplatin and S-1 (P-SOX), and SOX—in patients with advanced GC.METHODSA retrospective analysis was conducted on 299 patients with advanced GC who received both neoadjuvant and adjuvant chemotherapy along with standard D2 radical gastrectomy. Among them, 81 patients received SOX plus sintilimab, 118 received the P-SOX regimen, and 100 received the SOX regimen. All patients were randomly assigned to training (70%) or validation (30%) cohorts using the R software sample function. Short-term efficacy, long-term survival outcomes, and adverse events were assessed across the three groups. Additionally, clinical factors associated with progression-free survival (PFS) were further investigated.RESULTSIn terms of short-term efficacy, the SOX + sintilimab group had higher objective response rates [91.4% and 70.4% according to the tumor regression grade (TRG) and Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria, respectively] than did the P-SOX (88.1% and 59.3%) and SOX groups (84.0% and 55.0%), although the intergroup differences were not statistically significant (P = 0.167). For long-term outcomes, the SOX + sintilimab group demonstrated significantly better OS rates at 1 year (98.8%), 18 months (92.6%), 2 years (84.0%), and 3 years (48.1%) than did the P-SOX (93.2%, 86.4%, 71.2%, 30.5%) and SOX (91.0%, 84.0%, 72.0%, 29.0%) groups, with the 3-year overall survival (OS) difference being statistically significant (P = 0.007). Similarly, PFS rates in the SOX + sintilimab group (1 year: 92.6%; 18 months: 77.8%; 2 years: 65.4%; 3 years: 35.8%) were significantly greater than those in the P-SOX (82.2%, 68.6%, 53.4%, 26.3%) and SOX (77.0%, 66.0%, 43.0%, 27.0%) groups, with significant differences at 1 year (P = 0.021) and 2 years (P = 0.011). In terms of safety, grade 1-2 gastrointestinal reactions, peripheral neuropathy, and alopecia were the main TRAEs across groups. The P-SOX group had a significantly greater incidence of alopecia (54.2% vs 53.0% vs 23.5%, P = 0.009) and more cases of grade 2 alopecia (6.8% vs 1.2%), potentially due to the accumulation of triple-agent toxicity. No significant intergroup differences were observed in hematologic toxicity or liver dysfunction (all P > 0.05).CONCLUSIONCompared with the SOX and P-SOX regimens, the SOX plus sintilimab combination demonstrated significantly improved short- and long-term efficacy with favorable safety, with superior advantages in terms of 2- and 3-year OS and early PFS, suggesting that this combination is a more promising therapeutic option for patients with advanced GC. Patients who achieved good perioperative chemotherapy responses (meeting the TRG and RECIST 1.1 criteria) and had tumor diameters ≤ 2 cm, well-differentiated histology, earlier cTNM stages, and no lymph node metastasis had a better prognosis.

Understanding mechanisms of primary resistance to checkpoint inhibitors will lead to precision immunotherapy of advanced gastric cancer

Preoperative neoadjuvant chemotherapy is one of the most common treatments for patients with advanced gastric cancer that cannot be completely removed by surgery. Nab‐paclitaxel is a nano‐formulation of paclitaxel that has been shown to be effective in treating stomach cancer. In addition, oxaliplatin + S‐1 (SOX) has been a first‐line chemotherapy regimen for gastric cancer, and it has the effect of tumor downstaging, improving the R0 resection rate, and reducing the postoperative recurrence rate, but the side effects are significant. During the application of oxaliplatin, obvious gastrointestinal reactions such as nausea and vomiting can be observed. There may also be blood system side effects such as leukopenia and thrombocytopenia, as well as serious adverse reactions such as peripheral neuropathy. Therefore, we reduced the amount of oxaliplatin in SOX and added nab‐paclitaxel on the basis of this, in order to increase the efficacy while reducing the side effects of SOX regimen. We selected 192 patients with advanced gastric cancer admitted to the Department of Gastrointestinal Oncology of Qinghai University Hospital from July 2019 to February 2022, and all were treated with nab‐paclitaxel plus oxaliplatin + S‐1 neoadjuvant chemotherapy regimen, and underwent further surgery after chemotherapy. The tumor regression grade (TRG grade) and response evaluation criteria of solid tumor 1.1 (RECIST1.1) were taken as the dependent variables. According to TRG classification, 120 patients were effective (grade 0, 1, 2 = 62.50%, age: 55.63 ± 9.02 years), 72 patients were ineffective (grade 3 = 37.50%, 55.82 ± 9.21 years), and the effective rate of chemotherapy was 62.50%. According to RECIST1.1, 116 patients were effective (CR + PR = 60.42%, mean age 55.84 ± 9.02 years), 76 patients were ineffective (SD + PD = 39.58%, 55.47 ± 9.19 years), and the effective rate was 60.42%. The factors p < 0.2 in univariate logistic regression analysis were included in multivariate logistic regression analysis, and p < 0.05 was the statistical difference, and statistically significant factors were screened out for modeling and plotted the nomogram. Among them, in the tumor regression grade, the final factors related to effective chemotherapy are the degree of differentiation, cT. stage, tumor diameter, chemotherapy cycle, and the final factors related to effective chemotherapy in the solid tumor response evaluation criteria are the degree of differentiation, cT. stage, tumor diameter. Therefore, we conclude that the regimen of nab‐paclitaxel combined with oxaliplatin and S‐1 has certain positive significance in the treatment of advanced gastric cancer.

Introduction. Perioperative FLOT chemotherapy has improved prognosis in patients with locally advanced resectable gastric cancer (GC). However, in 80 % of cases, the tumor is resistant to the therapy, resulting in unnecessary toxicity and delayed surgical treatment.Aim. Evaluation of clinico-morphological patterns of microsatellite instability, HER2 gene amplification, changes in gene copy number and their relationship with the response to perioperative FLOT chemotherapy in patients with locally advanced resectable GC.Materials and methods. The retrospective study included 185 patients. All tumor samples were assessed for HER2 and microsatellite instability status. Among all cases there were 45 patients with locally advanced T2–4N1–2 M0 GC, who underwent a total or subtotal gastrectomy with D2 lymphadenectomy and perioperative chemotherapy with FLOT. Microsatellite instability detection was performed using fragment analysis, HER2 gene amplification testing – fluorescent in situ hybridization. Also 19 patients were tested for copy number changes of the FGFR1, FGFR2, KRAS, MET, EGFR, CCND1, MYC genes using Multiplex ligation-dependent probe amplification. The endpoints were progression-free survival and objective response rate.Results. Microsatellite instability was detected in 4.8 % (9/185) of GC cases. Microsatellite instability was associated with advanced age (p = 0.005), low grade of differentiation (p = 0.011), presence of tumor-infiltrating lymphocytes (p = 0.0004), and high preoperative CA 72–4 levels (p = 0.025). Prevalence of HER2 amplification was 7.5 % (14/185). It was associated with low grade of differentiation (p = 0.048) and metastasis in regional lymph nodes (p = 0.037). PFS in patients with HER2-positive (HER2 – human epidermal growth factor receptor 2) GC treated with perioperative FLOT chemotherapy (4/45) was significantly lower than in patients with HER2-negative GC: the median was 156 and 317 days, respectively (hazard ratio 0.49; 95 % confidence interval 0.16–1.47; p = 0.0006). There was no correlation between the presence of the alteration and ORR (p = 1.0). Progression-free survival in GC patients with KRAS amplification (3/19) was significantly lower comparing with patients without it: the median was 98 and 327 days, respectively (hazard ratio 0.29; 95 % confidence interval 0.07–1.19; p 0.0001). There was no association between an increase in KRAS copy number and objective response rate (p = 1.0). For microsatellite instability and other studied markers no statistically significant correlation with progression-free survival and objective response rate was found (p 0.05).Conclusion. The presence of HER2 and KRAS amplification have been shown as promising predictive markers of the treatment failure in patients treated with perioperative FLOT chemotherapy for locally advanced resectable GC.

Perioperative chemotherapy (PC) with radical surgery represents the gold standard of treatment for resectable advanced gastric cancer (GC). The prognostic value of pathological tumor regression grade (TRG) induced by neoadjuvant chemotherapy (NACT) is not clearly established. This study aimed to investigate the correlation between TRG and survival in GC. Patients affected by advanced GC undergoing PC and radical surgery were considered. TRG was assessed for each patient according to Becker's grading system. The correlation between TRG and survival was investigated. One-hundred patients were selected; 25 showed a good response (GR) (TRG 1a/1b), while 75 had a poor response (PR) (TRG 2/3) to NACT. GR patients showed better disease-free survival (DFS) (52 vs. 19 months, p < .001) and disease-specific survival (DSS)(57 vs. 25 months, p < .0001) when compared to PR patients. On univariate analysis, TRG, lymph node ratio (LNR), tumor size, grading, and post-neoadjuvant therapy TNM stage were significantly correlated with survival. On multivariate analysis, TRG, LNRand tumor size were independent prognostic factors for DFS and DSS. TRG, LNR, and tumor size are independent prognostic factors for DFS and DSS in patients with advanced GC undergoing NACT.

486 Background: Management of locally advanced gastric and gastroesophageal junction (GOJ) cancer relies on peri-operative chemotherapy and radical surgery. Response to neoadjuvant chemotherapy can be evaluated by Mandard Tumor Regression Grade (TRG) performed on the removed specimens. The aim of this study was to investigate the prognostic value of TRG, in terms of post-surgical disease-free survival (DFS) and overall survival (OS). Methods: Retrospective analysis of all consecutive patients (Jan 2010 to Dec 2021) who underwent oncological gastrectomy for gastric or GOJ adenocarcinoma after neoadjuvant chemotherapy was performed. TRG was evaluated according to Mandard classification, ranging from 1 (complete pathological response) to 5 (absence of response), TRG 1-2 being considered as “good responders” and TRG 3-5 as “bad responders”. Univariate and multivariate analysis were performed for DFS and OS. Results: One hundred and ninety-nine patients were included, 157 treated with FOLFOX and 42 with FOLFOX + Taxanes (either FLOT or FOLFOX + Abraxane). TRG 1-2 was observed in 30% in patients (pts) treated with FOLFOX and 24% in pts treated with FOLFOX + Taxanes. With a median follow-up over 5 years (yrs), median DFS and OS were not reached (DFS rates at 3, 5 and 10yrs of 66.5%, 64.1% and 55.7%, respectively; OS rates at 3, 5 and 10yrs of 75.6%, 66.8% and 60.4%, respectively). In univariate analysis, TRG 1-2 was significantly associated with favorable outcome compared to TRG 3-5 in terms of DFS (HR 2.4, p-value 0.0056) and OS (HR 2.6, p-value 0.0061), as well as ECOG at diagnosis (0 vs. 1), ypT stage (yp T0-2 vs. yp T3-4), ypN stage (ypN- vs. ypN+), tumor localization (antrum + body vs. cardia + esophagus), and lymphatic, vascular and peri nervous embolisms (negative vs. positive) for both DFS and OS. However, in multivariate analysis (selection backward Cox-model), only ypT stage and vascular embolisms for DFS, and ypT and ypN stages for OS were found to be independent prognostic factors. Conclusions: Although TRG is a prognostic factor in patients with gastric or GOJ cancer, it does not appear as an independent factor for DFS and OS in this series of 199 pts. These results raise the issue of “good responder” definition, especially for TRG 3. Prognostic impact of TRG needs to be investigated for patients treated with combination of immune checkpoint inhibitors and chemotherapy in neoadjuvant regimens.

The ratio of positive lymph nodes (LNs) to the total LN harvest is called the LN ratio (LNR). It is an independent prognostic factor in gastric cancer (GC). The aim of the current study was to evaluate the impact of neoadjuvant chemotherapy (NAC) on the LNR (ypLNR) in patients with advanced GC. We retrospectively analyzed the data of patients with advanced GC, who underwent gastrectomy with N1 and N2 (D2) lymphadenectomy between August 2011 and January 2019 in the Department of Surgical Oncology at the Medical University of Lublin. The exclusion criteria were a lack of preoperative NAC administration, suboptimal lymphadenectomy (<D2 and/or removal of less than 15 lymph nodes), and a lack of data on tumor regression grading (TRG) in the final pathological report. A total of 95 patients were eligible for the analysis. A positive correlation was found between the ypLNR and tumor diameter (p < 0.001), post treatment pathological Tumour (ypT) stage (p < 0.001), Laurén histological subtype (p = 0.0001), and the response to NAC (p < 0.0001). A multivariate analysis demonstrated that the ypLNR was an independent prognostic factor in patients with intestinal type GC (p = 0.0465) and in patients with no response to NAC (p = 0.0483). In the resection specimen, tumor diameter and depth of infiltration, Laurén histological subtype, and TRG may reflect the impact of NAC on LN status, as quantified by ypLNR in advanced GC.

To investigate the value of prognostic nutrition index (PNI) and systemic immunoinflammatory index (SII) for predicting pathological responses of patients with advanced gastric cancer (GC) after neo-adjuvant chemotherapy (NACT). The clinicopathological data of 326 patients with advanced GC who received NACT in Xiangya School of Medicine, Central South University (The First People's Hospital of Changde City) from January 2017 to December 2021 were retrospectively collected. The SII and PNI of patients were calculated. The receiver operating characteristics (ROC) curve was leveraged for getting the optimal cutoff values of SII and PNI. The pathological response of patients after NACT, as obtained from their postoperative pathological examinations, was evaluated based on the tumor regression grade (TRG) criteria. Multivariate regression analysis was employed for identifying factors that led to various pathological responses after NACT in advanced GC patients. The log-rank test was utilized for between-group comparison of patients' survival curves. The SII and PNI were 507.45 and 48.48 respectively, and their levels were divided into high and low groups. Pathological response (TRG 0-1) was observed in 66 cases (20.25%), while non-pathological response (TRG 2-3) was observed in 260 cases (79.75%). The results of multivariate logistic regression analysis showed that tumor diameter < 5 cm, ypT T0-T2, ypN N0, chemotherapy regimen XELOX (capecitabine combined with oxaliplatin), SII < 507.45 (P=0.002), PNI > 48.48 were all independent factors affecting the pathological responses of advanced GC patients after NACT (all P < 0.05). With SII and PNI being included, the AUC was 0.821 (95% CI: 0.765-0.876), and the specificity was 87.90% and the sensitivity was 64.20%. The Kaplan-Meier survival curve analysis showed that NACT patients with tumor diameter < 5 cm, ypT T0-T2, ypN N0, XELOX chemotherapy regimen, SII < 507.45 and SII ≥ 507.45 had a higher survival rate. (P < 0.001). Before treatment, tumor diameter < 5 cm, ypT T0-T2, ypN N0, chemotherapy regimen XELOX, SII < 507.45, PNI > 48.48 were all independent factors affecting the pathological response of advanced GC patients after NACT. Moreover, the inclusion of SII and PNI increased the accuracy of predicting the pathological response of patients after NACT.

Simple SummaryMultimodal treatment of locally advanced gastric cancer is still debated today due to controversial results in different trials. Nevertheless, perioperative chemotherapy with radical surgery certainly shows a better long-term outcome than surgery alone, so much so it is the main multimodal treatment offered in Europe, at the present. Tumor regression grade is the objective response to preoperative chemotherapy and its extent, in terms of reduction of neoplastic cells in the resected specimen, is strongly affected by Lauren’s classification, TNM stage, and tumor grading. Therefore, since this information can be achieved only after surgical resection, the return of chemotherapy is quite unpredictable in advance and, in about half cases, it is definitely ineffective. Naples Prognostic Score, that mirrors the immune–nutritional conditions, tested on 59 consecutive advanced gastric cancer patients undergoing multimodal treatment, showed a strong power in predicting tumor regression grade and therefore is strictly correlated with long-term outcome and survival.Despite recent progresses, locally advanced gastric cancer remains a daunting challenge to embrace. Perioperative chemotherapy and D2-gastrectomy depict multimodal treatment of gastric cancer in Europe, shows better results than curative surgery alone in terms of downstaging, micrometastases elimination, and improved long-term survival. Unfortunately, preoperative chemotherapy is useless in about 50% of cases of non-responder patients, in which no effect is registered. Tumor regression grade (TRG) is directly related to chemotherapy effectiveness, but its understanding is achieved only after surgical operation; accordingly, preoperative chemotherapy is given indiscriminately. Conversely, Naples Prognostic Score (NPS), related to patient immune-nutritional status and easily obtained before taking any therapeutic decision, appeared an independent prognostic variable of TRG. NPS was calculated in 59 consecutive surgically treated gastric cancer patients after neoadjuvant FLOT4-based chemotherapy. 42.2% of positive responses were observed: all normal NPS and half mild/moderate NPS showed significant responses to chemotherapy with TRG 1–3; while only 20% of the worst NPS showed some related benefits. Evaluation of NPS in gastric cancer patients undergoing multimodal treatment may be useful both in selecting patients who will benefit from preoperative chemotherapy and for changing immune-nutritional conditions in order to improve patient’s reaction against the tumor.

355 Background: Perioperative chemotherapy is the standard of care for locoregional gastric cancers in western populations. However, the impact of response to therapy as a biomarker of cancer survival has not been fully defined. This study focuses on the pathological response to neoadjuvant chemotherapy, as measured by tumor regression grade (TRG), for gastric cancer and its impact on patient outcomes, primarily overall survival. Methods: Patients undergoing gastrectomy for nonmetastatic invasive gastric adenocarcinoma following perioperative chemotherapy (clinical T2+/N+cM0) were identified from an institutional database (2000-2021). Demographics, clinical staging including histologic grade, surgical factors and survival outcomes were included. The association between TRG and overall survival from time of surgery was assessed. OS was estimated using the Kaplan Meier method with adjustment for covariates using Cox regression. Results: One hundred seventeen patients were identified. Median age was 65 years (IQR 57–73). The majority of the patients were male (n = 64, 55%). Seventy-six patients underwent total gastrectomy, 22 subtotal gastrectomy, and 19 distal gastrectomy. Six patients (5.1%) had a TRG of 0, 18 patients (15.4%) had a TRG of 1, 25 patients (21.4%) had a TRG of 2, and 68 patients (58.1%) had a TRG of 3. Median survival overall was 40.9 months (95% CI 28.7–66.4). TRG status was not significantly different between chemotherapy regimens (doublet vs triplet, p = 0.96). Median survival was longest in the TRG 0 group (86.9 months), followed sequentially by TRG 1 (74.5 months), TRG 2 (51.5 months), and lastly, TRG 3 group with 27.0 months. Increased tumor regression (lower TRG) was significantly associated with prolonged survival (p &lt; 0.01 by log-rank for trend). After adjustment for clinical patient factors and tumor factors, TRG remained significantly associated with overall survival (Table; TRG hazard ratio 1.62, p = 0.007). In addition to TRG status, clinical T4 tumors and diffuse histology were associated with poor survival (cT4 hazard ratio 2.09, p = 0.039, diffuse histology hazard ratio 1.82 (p = 0.071). Conclusions: In patients receiving perioperative chemotherapy for treatment of gastric cancer, response to therapy as defined by TRG is independently prognostic of survival.[Table: see text]

The overall survival benefits of perioperative chemotherapy (PCT) and perioperative chemoradiotherapy (PCRT) for patients with locally advanced gastric cancer (GC) have not been fully explored. The aim of this study was to compare the benefits of PCT and PCRT in GC patients and determine the factors affecting survival rate using directed acyclic graphs (DAGs). The data of 1,442 patients with stage II-IV GC who received PCT or PCRT from 2000 to 2018 were retrieved from the Surveillance, Epidemiology, and End Results (SEER) database. First, the least absolute shrinkage and selection operator (LASSO) was used to identify possible influencing factors for overall survival. Second, the variables that were selected by LASSO were then used in univariate and Cox regression analyses. Third, corrective analyses for confounding factors were selected based on DAGs that show the possible association between advanced GC patients and outcomes and evaluate the prognosis. Patients who received PCRT had longer overall survival than those who received PCT treatment (P = 0.015). The median length of overall survival of the PCRT group was 36.5 (15.0 - 53.0) months longer than that of the PCT group (34.6 (16.0 - 48.0) months). PCRT is more likely to benefit patients who are aged ≤ 65, male, white, and have regional tumors (P<0.05). The multivariate Cox regression model showed that male sex, widowed status, signet ring cell carcinoma, and lung metastases were independent risk factors for a poor prognosis. According to DAG, age, race, and Lauren type may be confounding factors that affect the prognosis of advanced GC. Compared to PCT, PCRT has more survival benefits for patients with locally advanced GC, and ongoing investigations are needed to better determine the optimal treatment. Furthermore, DAGs are a useful tool for contending with confounding and selection biases to ensure the proper implementation of high-quality research.

The overall survival benefits of perioperative chemotherapy (PCT) and perioperative chemoradiotherapy (PCRT) for patients with locally advanced gastric cancer (GC) have not been fully explored. The aim of this study was to compare the benefits of PCT and PCRT in GC patients and determine the factors affecting survival rate using directed acyclic graphs (DAGs). The data of 1,442 patients with stage II-IV GC who received PCT or PCRT from 2000 to 2018 were retrieved from the Surveillance, Epidemiology, and End Results (SEER) database. First, the least absolute shrinkage and selection operator (LASSO) was used to identify possible influencing factors for overall survival. Second, the variables that were selected by LASSO were then used in univariate and Cox regression analyses. Third, corrective analyses for confounding factors were selected based on DAGs that show the possible association between advanced GC patients and outcomes and evaluate the prognosis. Patients who received PCRT had longer overall survival than those who received PCT treatment (P = 0.015). The median length of overall survival of the PCRT group was 36.5 (15.0 − 53.0) months longer than that of the PCT group (34.6 (16.0 − 48.0) months). PCRT is more likely to benefit patients who are aged ≤ 65, male, white, and have regional tumors (P<0.05). The multivariate Cox regression model showed that male sex, widowed status, signet ring cell carcinoma, and lung metastases were independent risk factors for a poor prognosis. According to DAG, age, race, and Lauren type may be confounding factors that affect the prognosis of advanced GC. Compared to PCT, PCRT has more survival benefits for patients with locally advanced GC, and ongoing investigations are needed to better determine the optimal treatment. Furthermore, DAGs are a useful tool for contending with confounding and selection biases to ensure the proper implementation of high-quality research.

Optimising treatment regimens for the management of advanced gastric cancer

Perioperative chemotherapy is the standard treatment for locally advanced gastric or gastro-esophageal junction cancer, and the addition of programmed cell death 1 (PD-1) inhibitor is under investigation. In this randomized, open-label, phase 2 study (NEOSUMMIT-01), patients with resectable gastric or gastro-esophageal junction cancer clinically staged as cT3-4aN + M0 were randomized (1:1) to receive either three preoperative and five postoperative 3-week cycles of SOX/XELOX (chemotherapy group, n = 54) or PD-1 inhibitor toripalimab plus SOX/XELOX, followed by toripalimab monotherapy for up to 6 months (toripalimab plus chemotherapy group, n = 54). The primary endpoint was pathological complete response or near-complete response rate (tumor regression grade (TRG) 0/1). The results showed that patients in the toripalimab plus chemotherapy group achieved a higher proportion of TRG 0/1 than those in the chemotherapy group (44.4% (24 of 54, 95% confidence interval (CI): 30.9%-58.6%) versus 20.4% (11 of 54, 95% CI: 10.6%-33.5%)), and the risk difference of TRG 0/1 between toripalimab plus chemotherapy group and chemotherapy group was 22.7% (95% CI: 5.8%-39.6%; P = 0.009), meeting a prespecified endpoint. In addition, a higher pathological complete response rate (ypT0N0) was observed in the toripalimab plus chemotherapy group (22.2% (12 of 54, 95% CI: 12.0%-35.6%) versus 7.4% (4 of 54, 95% CI: 2.1%-17.9%); P = 0.030), and surgical morbidity (11.8% in the toripalimab plus chemotherapy group versus 13.5% in the chemotherapy group) and mortality (1.9% versus 0%), and treatment-related grade 3-4 adverse events (35.2% versus 29.6%) were comparable between the treatment groups. In conclusion, the addition of toripalimab to chemotherapy significantly increased the proportion of patients achieving TRG 0/1 compared to chemotherapy alone and showed a manageable safety profile. ClinicalTrials.gov registration: NCT04250948 .

The neoadjuvant therapeutic effects of various chemotherapeutic drugs on gastric cancer have reached the corresponding plateau. Whether the combination of sindilizumab and albumin-bound paclitaxel+oxaliplatin+S-1 chemotherapy (SAPO-S1 therapy) regimen can bring better efficacy and observe the incidence of adverse reactions in the neoadjuvant treatment of Gastric Cancer (GC) may be the direction of our research. This study aimed to evaluate the efficacy of S1 chemotherapy regimen combined with multiple chemotherapy drugs sindilizumab (PD-1 inhibitor), albumin-bound paclitaxel and oxaliplatin) for neoadjuvant therapy in locally advanced Gastric Cancer (LA-GC). The patients were given 4 cycles of sindilizumab combined with albumin paclitaxel+oxaliplatin+S-1 chemotherapy (SAPO-S1) before surgery. The R0 resection rate, surgical complications, pathologic complete response, complete pathologic response (pCR) the main pathological response rates (residual tumor cells≤10%, major pathological response) were observed. MPR and postoperative pathological tumor regression grade (TRG), using the response evaluation criteria in solid tumors (RECIST1.1) to evaluate the efficacy of new adjuvant therapy and record the short-term adverse events (adverse event, AE) of patients after medication to evaluate safety. The overall response rate (ORR) was achieved to 53.3% and disease control rate (DCR) was achieved in 28 patients (93.3%), and the descending phase was achieved in 17 patients (56.7%). The tumor resolution grades of TRG 0, TRG 1, TRG 2 and TRG 3 were 16.7%, 13.3%, 43.3% and 16.7%, respectively. The pCR rate was 16.7%, the MPR rate was 30.0%, and the R0 resection rate was 90.0%. In addition, SAPO-S1 therapy has fewer side effects. Overall, SAPO-S1 therapy has a good therapeutic effect and safety in LA-GC.