Correlation Analysis Between Tumor Deposit and Clinicopathologic Characteristics and Prognosis of Gastric Cancer: A Multicenter Retrospective Study.

BACKGROUND: The mechanism underlying the formation of gastric tumor deposits (TDs) is unclear. We aimed to explore the risk factors for the formation and prognostic value of TDs. METHODS: This retrospective analysis included 781 locally advanced gastric cancer (LAGC) patients from four medical institutions in China, from June 2014 to June 2018. The risk factors for TD formation and prognostic value were determined through univariate and multivariate analyses. RESULTS: Univariate analysis revealed that TD positivity was closely related to tumor diameter, Borrmann classification, differentiation degree, pT stage, pN stage, pTNM stage, and nerve and vascular invasion (p < 0.05). Multivariate logistic regression revealed that tumor diameter ≥ 5 cm (odds ratio [OR] 1.836, 95% confidence interval [CI] 1.165-2.894, p = 0.009) and vascular invasion (OR 2.152, 95% CI 1.349-3.433, p = 0.001) were independent risk factors for TD positivity. Multivariate Cox analysis revealed that TD positivity (OR 1.533, 95% CI 1.101-2.134, p = 0.011), tumor diameter ≥ 5 cm (OR 1.831, 95% CI 1.319-2.541, p < 0.001), pT4a stage (OR 1.652, 95% CI 1.144-2.386, p = 0.007), and vascular invasion (OR 1.458, 95% CI 1.059-2.008, p = 0.021) were independent risk factors for GC prognosis. The 5-year overall and disease-free survival of the TD-positive group showed significant effects among patients in the pT4a and pN3b stages (p < 0.05). CONCLUSIONS: TDs are closely related to tumor diameter and vascular invasion in LAGC patients, and TD positivity is an independent prognostic factor for LAGC patients, especially those at pT4a and pN3b stages.

DNA mismatch repair deficiency and outcomes of patients with locally advanced gastric cancer treated with preoperative docetaxel, oxaliplatin, and S-1 plus surgery and postoperative S-1 or surgery plus postoperative S-1: a sub-analysis of the phase 3 PRODIGY trial.

BACKGROUND: The benefit of adjuvant chemotherapy for locally advanced gastric cancer (LAGC) patients with DNA mismatch repair (MMR) deficiency (D-MMR) is controversial due to concerns about its potential detrimental effect. The PRODIGY trial showed the survival benefit of adding preoperative docetaxel, oxaliplatin, and S-1 (DOS) to surgery plus postoperative S-1 for LAGC patients. In this sub-analysis, we evaluated the benefit of preoperative DOS according to MMR status. METHODS: Among patients enrolled in the PRODIGY trial treated with either preoperative DOS followed by surgery and postoperative S-1 (CSC arm), or surgery and postoperative S-1 (SC arm) at Asan Medical Center (n = 249), those in the full analysis set with available tissue to assess MMR status were included in the present analysis. RESULTS: A total of 231 patients (CSC arm, n = 108; SC arm, n = 123) were included (median age, 58 years [range, 27-75]), and 21 patients (CSC arm, n = 8 [7.4%]; SC arm, n = 13 [10.6%]) had D-MMR tumors. Progression-free survival and overall survival tended to be superior in the CSC arm than in the SC arm among D-MMR patients (HR 0.48 [95% CI 0.09-2.50]; log-rank P = 0.37 and HR 0.55 [95% CI 0.11-2.86]; log-rank P = 0.46, respectively), as well as among proficient MMR (P-MMR) patients (HR 0.68 [95% CI 0.46-1.03]; log-rank P = 0.07 and HR 0.75 [95% CI 0.49-1.14]; log-rank P = 0.17, respectively). CONCLUSION: Preoperative DOS followed by surgery and postoperative S-1 may be considered a treatment option for LAGC patients regardless of MMR status.

Effect of sarcopenia on short-term and long-term outcomes of older patients with locally advanced gastric cancer: a multicenter study.

OBJECTIVE: To assess the effect of preoperative sarcopenia on the short-term and long-term outcomes in older patients with locally advanced gastric cancer (LAGC). METHODS: Clinicopathological data of older patients with LAGC who underwent radical surgery were retrospectively analyzed. Sarcopenia was defined as a skeletal muscle index of less than 36.4 cm2/m2 for men and less than 28.4 cm2/m2 for women. Comparing the postoperative complications and survival between sarcopenia and non-sarcopenia groups using multicenter data. RESULTS: A total of 406 older patients with LAGC were included in the analysis, including 145 (35.7%) with sarcopenia and 261 (64.3%) with non-sarcopenia. Multivariate logistic regression analysis showed that sarcopenia was an independent risk factor for postoperative complications with CD grade ≥ II (OR 1.616; P < 0.05). Kaplan-Meier survival curve analysis showed that the 5-year overall survival (OS) and 5-year recurrence-free survival (RFS) in the sarcopenia group were lower than those in the non-sarcopenia group (P both < 0.05). Multivariate Cox regression analyses showed that sarcopenia was an independent prognostic factor for 5-year OS and RFS (P both < 0.05). The 5-year recurrence rate in the sarcopenia group was 57.2%, which was significantly higher than that in the non-sarcopenia group (46.4%; P = 0.036). Recurrence pattern analysis showed that the incidence of distant metastases in patients with sarcopenia (42.8%) was significantly higher than non-sarcopenia (31.4%; P = 0.022). CONCLUSION: Sarcopenia serves as a valuable predictor of both short-term and long-term outcomes in older patients with LAGC. Therefore, the significance of assessing preoperative nutritional status and implementing thorough postoperative follow-up for older LAGC patients with sarcopenia should be emphasized.

Development and validation of nomograms for predicting overall survival and cancer-specific survival in elderly patients with locally advanced gastric cancer: a population-based study.

OBJECTIVE: To evaluate the multiple factors influencing the survival of elderly patients with locally advanced gastric cancer (LAGC) and develop and validate the novel nomograms for predicting the survival. METHODS: The clinical features of patients treated between 2000 and 2018 were collected and collated from the Surveillance, Epidemiology, and End Results (SEER) database and three medical centres in China, and the patients were randomly divided into a training cohort (3494), internal validation cohort (1497) and external validation cohort (841). Univariate and multivariate analyses of the prognostic values were performed to identify independent prognostic factors associated with overall survival (OS) and cancer-specific survival (CSS), and two nomogram models were developed. Harrell's concordance index (C-index) and calibration curves were employed to assess discrimination and calibration. Decision curve analysis (DCA) and receiver-operating characteristic (ROC) curves were utilized to investigate the clinical usefulness. RESULTS: In the SEER database, the 5-year OS of the patients was 31.08%, while the 5-year CSS of the patients was 44.09%. Furthermore, in the external validation set, the 5-year OS of the patients was 49.58%, and the 5-year CSS of these patients was 53.51%. After statistical analysis, nine independent prognostic factors of OS and CSS were identified, including age, race, tumour size, differentiation, TNM stage, gastrectomy type, lymph node metastasis (LNM), lymph node ratio (LNR) and chemotherapy. The C-index (approximately 0.7) and calibration curve (close to the optimal calibration line) indicated satisfactory discrimination and calibration of the nomogram. DCA and ROC curves showed that the developed nomogram was superior to TNM stage. CONCLUSION: The novel validated nomogram could accurately predict the prognosis of individual elderly patients with LAGC and guide the selection of clinical treatment measures.

Long-term survival outcome of locally advanced gastric cancer patients who achieved a pathological complete response to neoadjuvant chemotherapy.

BACKGROUND: Long-term outcome of patients with locally advanced gastric cancer (LAGC) who achieved a pathological complete response (pCR) was scarcely discussed, and never had the factors affecting the prognosis of pCR patients been investigated. METHODS: We retrospectively reviewed all patients who achieved a pCR to neoadjuvant chemotherapy (NAC) in Jinling Hospital. The 3- and 5-year overall survival (OS) and progression-free survival (PFS) were calculated with the Kaplan-Meier method. Meanwhile, univariate and multivariate COX regression analysis was applied to identify prognostic factors affecting patients' survival. RESULTS: A total of 37 consecutive LAGC patients with pCR were included. The 3- and 5-year OS rates were 88.8% and 78.6%, and the 3- and 5-year PFS rates were 86.5% and 75.8%. In the multivariate COX model, NAC duration of more than 3 cycles (HR 0.11 [0.02-0.62], P = 0.013) and poorly differentiated tumor at diagnosis (HR 0.17 [0.03-0.95], P = 0.043) were detected as protective factors for patients OS. Whereas for PFS, NAC duration (HR 0.12 [0.02-0.67], P = 0.015) was the only protective factor confirmed, with tumor differentiation at diagnosis exhibiting marginal significance (HR 0.21 [0.04-1.09], P = 0.063). CONCLUSIONS: Patients with LAGC who achieved a pCR displayed favorable long-term survival outcome, especially those with adequate cycles (≥ 3) of NAC. Besides, poor differentiation at diagnosis might also predict the better OS when pCR achieved.

Using Normalized Carcinoembryonic Antigen and Carbohydrate Antigen 19 to Predict and Monitor the Efficacy of Neoadjuvant Chemotherapy in Locally Advanced Gastric Cancer.

Carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) are established prognostic biomarkers for patients with gastric cancer. However, their potential as predictive markers for neoadjuvant chemotherapy (NACT) efficacy has not been fully elucidated. METHODS: We conducted a retrospective analysis to determine values of CEA and CA19-9 prior to NACT (pre-NACT) and after NACT (post-NACT) in 399 patients with locally advanced gastric cancer (LAGC) who received intended NACT and surgery. RESULTS: Among the 399 patients who underwent NACT plus surgery, 132 patients (33.1%) had elevated pre-NACT CEA/CA19-9 values. Furthermore, either pre-NACT or post-NACT CEA /CA19-9 levels were significantly associated with prognosis (p = 0.0023) compared to patients with non-elevated levels. Moreover, among the patients, a significant proportion (73/132, 55.3%) achieved normalized CEA/CA19-9 following NACT, which is a strong marker of a favorable treatment response and survival benefits. In addition, the patients with normalized CEA/CA19-9 also had a prolonged survival compared to those who underwent surgery first (p = 0.0140), which may be attributed to the clearance of micro-metastatic foci. Additionally, the magnitude of CEA/CA19-9 changes did not exhibit a statistically significant prognostic value. CONCLUSIONS: Normalization of CEA/CA19-9 is a strong biomarker for the effectiveness of treatment, and can thus be exploited to prolong the long-term survival of patients with LAGC.

Multidisciplinary treatment for locally advanced gastric cancer: A systematic review and network meta-analysis.

Introduction: This study aimed to evaluate the efficacy of multidisciplinary treatment for patients with locally advanced gastric cancer (LAGC) who underwent radical gastrectomy. Patients and Methods: Randomised controlled trials (RCTs) comparing the effectiveness of surgery alone, adjuvant chemotherapy (CT), adjuvant radiotherapy (RT), adjuvant chemoradiotherapy (CRT), neoadjuvant CT, neoadjuvant RT, neoadjuvant CRT, perioperative CT and hyperthermic intraperitoneal chemotherapy (HIPEC) for LAGC were searched. Overall survival (OS), disease-free survival (DFS), recurrence and metastasis, long-term mortality, adverse events (grade ≥3), operative complications and R0 resection rate were used as outcome indicators for meta-analysis. Results: Forty-five RCTs with 10077 participants were finally analysed. Adjuvant CT had higher OS (hazard ratio [HR] = 0.74, 95% credible interval [CI] = 0.66-0.82) and DFS (HR = 0.67, 95% CI = 0.60-0.74) than surgery-alone group. Perioperative CT (odds ratio [OR] = 2.56, 95% CI = 1.19-5.50) and adjuvant CT (OR = 0.48, 95% CI = 0.27-0.86) both had more recurrence and metastasis than HIPEC + adjuvant CT, while adjuvant CRT tended to have less recurrence and metastasis than adjuvant CT (OR = 1.76, 95% CI = 1.29-2.42) and even adjuvant RT (OR = 1.83, 95% CI = 0.98-3.40). Moreover, the incidence of mortality in HIPEC + adjuvant CT was lower than that in adjuvant RT (OR = 0.28, 95% CI = 0.11-0.72), adjuvant CT (OR = 0.45, 95% CI = 0.23-0.86) and perioperative CT (OR = 2.39, 95% CI = 1.05-5.41). Analysis of adverse events (grade ≥3) showed no statistically significant difference between any two adjuvant therapy groups. Conclusion: A combination of HIPEC with adjuvant CT seems to be the most effective adjuvant therapy, which contributes to reducing tumour recurrence, metastasis and mortality - without increasing surgical complications and adverse events related to toxicity. Compared with CT or RT alone, CRT can reduce recurrence, metastasis and mortality but increase adverse events. Moreover, neoadjuvant therapy can effectively improve the radical resection rate, but neoadjuvant CT tends to increase surgical complications.

A study protocol of a randomized phase II trial of perioperative chemoimmunotherapy verses perioperative chemoimmunotherapy plus preoperative chemoradiation for locally advanced gastric (G) or gastroesophageal junction (GEJ) adenocarcinoma: the NeoRacing study.

BACKGROUND: Perioperative chemotherapy (ChT) and preoperative chemoradiation (CRT) are both the standard treatments for locally advanced gastric cancer (LAGC). CRT can achieve a higher pathological complete regression (pCR) rate, but whether this higher pCR rate can be transformed into a long-term survival benefit remains inconclusive. Therefore, relevant studies are in progress. On the other hand, immunotherapy has been established for the first-line treatment of advanced gastric cancer (AGC) and has been widely explored in the perioperative setting. The combination of chemotherapy/radiotherapy and immunotherapy may have a synergistic effect, which will lead to a better antitumor effect. The preliminary reports of ongoing studies show promising results, including a further improved pCR rate. However, the preferred treatment combination for LAGC is still not established. To solve this problem, we are carrying out this randomized phase II trial, which aims to evaluate the efficacy and safety of perioperative chemotherapy plus the use of PD-1 antibody with or without preoperative chemoradiation for LAGC. METHODS: Eligible patients with LAGC or gastroesophageal junction (GEJ) adenocarcinoma were randomized to receive perioperative ChT, PD-1 antibody, surgery with (Arm A) or without preoperative CRT (Arm B), and PD-1 antibody maintenance until one year after surgery. The primary endpoint of this study is that the pCR rate of Arm A will be significantly higher than that of Arm B. The secondary endpoints include the pathological partial regression (pPR) rate, R0 resection rate, objective response rate (ORR), event-free survival (EFS), overall survival (OS), safety and surgical complications. Moreover, several explorative endpoints will be evaluated to find and validate the predictive biomarkers of immunotherapy. DISCUSSION: The results of the NeoRacing study will provide important information concerning the application of PD-1 antibody in LAGC patients during the perioperative setting. Meanwhile, the two treatment protocols will be compared in terms of efficacy and safety. TRIAL REGISTRATION: ClinicalTrials.gov , NCT05161572 . Registered 17 December 2021 - Retrospectively registered.

The validity of neoadjuvant chemotherapy with paclitaxel plus S-1 is not inferior to that of SOX regimen for locally advanced gastric cancer: an observational study.

BACKGROUND: Paclitaxel plus S-1(PTXS) has shown definite efficacy for advanced gastric cancer. However, the efficacy and safety of this regimen in neoadjuvant setting for locally advanced gastric cancer (LAGC) are unclear. This study aimed to compare the efficacy of neoadjuvant chemotherapy (NAC) PTXS and oxaliplatin plus S-1 (SOX) regime for patients with LAGC. METHODS: A total of 103 patients with LAGC (cT3/4NanyM0/x) who were treated with three cycles of neoadjuvant SOX regimen (n = 77) or PTXS regimen (n = 26) between 2011 and 2017 were enrolled in this study. NAC-related clinical response, pathological response, postoperative complication, and overall survival were analyzed between the groups. RESULTS: The baseline data did not differ significantly between both groups. After NAC, the disease control rate of the SOX group (94.8%) was comparable with that of the PTXS group (92.3%) (p = 0.641). Twenty-three cases (29.9%) in the SOX group and 10 cases (38.5%) in the PTX group got the descending stage with no statistical difference (p = 0.417). No significant differences were observed in the overall pathological response rate and the overall postoperative complication rate between the two groups (p > 0.05). There were also no differences between groups in terms of 5-year overall and disease-free survival (p > 0.05). CONCLUSIONS: The validity of NAC PTXS was not inferior to that of SOX regimen for locally advanced gastric cancer in terms of treatment response and overall survival. PTXS regimen could be expected to be ideal neoadjuvant chemotherapy for patients with LAGC and should be adopted for the test arm of a large randomized controlled trial.

Combined systemic immune-inflammatory index (SII) and prognostic nutritional index (PNI) predicts chemotherapy response and prognosis in locally advanced gastric cancer patients receiving neoadjuvant chemotherapy with PD-1 antibody sintilimab and XELOX: a prospective study.

BACKGROUND: Previous studies have confirmed that systemic immune-inflammatory index (SII) and prognostic nutritional index (PNI) can predict the prognosis and chemotherapy efficacy of various malignant tumors. However, to the best of our knowledge, no study investigated the SII combined with PNI score to predict the efficacy of anti-programmed death 1 (anti-PD-1) antibody sintilimab and XELOX regimen (capecitabine plus oxaliplatin) in the treatment of locally advanced gastric cancer. This study aims to evaluate the predictive value of pre-treatment SII-PNI score on the sensitivity of sintilimab immunotherapy combined with XELOX chemotherapy in patients with locally advanced gastric cancer. METHODS: We registered a prospective clinical study involving 30 locally advanced gastric cancer patients from March 2020 to July 2021. The pre-treatment SII and PNI were calculated from peripheral blood samples, and the cut-off value was calculated by receiver operating characteristic. The SII-PNI score ranged from 0 to 2 and were categorized into the following: score of 2, high SII (≥ 568.5) and low PNI (≤ 52.7); score of 1, either high SII or low PNI; score of 0, no high SII nor low PNI. RESULTS: All patients were evaluated by RECIST1.1 criteria after four cycles of sintilimab immunotherapy combined with XELOX chemotherapy, including 5 patients with TRG 3 and 25 patients with non-TRG 3. The SII-PNI score of non-TRG 3 patients was significantly lower than that of TRG 3 patients (P = 0.017). The medial progression free survival of patients with low SII-PNI score was significantly better than that of patients with high SII-PNI score (P < 0.001). Multivariate analysis showed that SII-PNI score was an independent prognostic factor for predicting progression-free survival (P = 0.003). CONCLUSION: The pre-treatment SII-PNI score is a significant indicator for predicting chemosensitivity of locally advanced patients after sintilimab immunotherapy combined with XELOX chemotherapy, which can help to identify high-risk groups and predict prognosis. TRIAL REGISTRATION: The registered name of the trial is "Prospective clinical study of sintilimab combined with chemotherapy for neoadjuvant therapy in locally advanced gastric cancer". Its Current Controlled Trials number is ChiCTR2000030414. Its date of registration is 01/03/2020.

Deep learning predicts resistance to neoadjuvant chemotherapy for locally advanced gastric cancer: a multicenter study.

BACKGROUND: Accurate pre-treatment prediction of neoadjuvant chemotherapy (NACT) resistance in patients with locally advanced gastric cancer (LAGC) is essential for timely surgeries and optimized treatments. We aim to evaluate the effectiveness of deep learning (DL) on computed tomography (CT) images in predicting NACT resistance in LAGC patients. METHODS: A total of 633 LAGC patients receiving NACT from three hospitals were included in this retrospective study. The training and internal validation cohorts were randomly selected from center 1, comprising 242 and 104 patients, respectively. The external validation cohort 1 comprised 128 patients from center 2, and the external validation cohort 2 comprised 159 patients from center 3. First, a DL model was developed using ResNet-50 to predict NACT resistance in LAGC patients, and the gradient-weighted class activation mapping (Grad-CAM) was assessed for visualization. Then, an integrated model was constructed by combing the DL signature and clinical characteristics. Finally, the performance was tested in internal and external validation cohorts using area under the receiver operating characteristic (ROC) curves (AUC). RESULTS: The DL model achieved AUCs of 0.808 (95% CI 0.724-0.893), 0.755 (95% CI 0.660-0.850), and 0.752 (95% CI 0.678-0.825) in validation cohorts, respectively, which were higher than those of the clinical model. Furthermore, the integrated model performed significantly better than the clinical model (P < 0.05). CONCLUSIONS: A CT-based model using DL showed promising performance for predicting NACT resistance in LAGC patients, which could provide valuable information in terms of individualized treatment.

Laparoscopic versus open surgery for locally advanced and metastatic gastric cancer complicated with bleeding and/or stenosis: short- and long-term outcomes.

BACKGROUND: Laparoscopic surgery has justified its efficacy in the treatment of early gastric cancer. There are limited data indicating the eligibility of laparoscopic interventions in locally advanced gastric cancer. Publications describing the safety of laparoscopic techniques in the treatment of local and metastatic gastric cancer complicated by bleeding and stenosis are scarce. METHODS: The study included patients with histologically confirmed locally advanced and disseminated gastric cancer and complicated with bleeding and/or stenosis who underwent gastrectomy with vital indications between February 2012 and August 2018. Surgical and oncologic outcomes after laparoscopic surgery (laparoscopic surgery) and open surgery (OS) were compared. RESULTS: In total, 127 patients (LS, n = 52; OS, n = 75) were analyzed. Baseline characteristics were similar between the groups. Forty-four total gastrectomies with resection of the abdominal part of the esophagus, 63 distal subtotal (43 Billroth-I and 20 Billroth-II), and 19 proximal gastrectomies were performed. The median duration of surgery was significantly longer in the LS group, 253 min (interquartile range [IQR], 200-295) versus 210 min (IQR, 165-220) (p < 0.001), while median intraoperative blood loss in the LS group was significantly less, 180 ml (IQR, 146-214) versus 320 ml (IQR, 290-350), (p < 0.001). Early postoperative complications occurred in 35% in the LS group and in 45 % of patients in the OS group (p = 0.227). There was no difference in postoperative mortality rates between the groups (3 [6 %] versus 5 (7 %), p = 1.00). Median intensive care unit stay and median postoperative hospital stay were significantly shorter after laparoscopy, 2 (IQR, 1-2) versus 4 (IQR, 3-4) days, and 8 (IQR, 7-9) versus 10 (IQR, 8-12) days, both p < 0.001. After laparoscopy, patients started adjuvant chemotherapy significantly earlier than those after open surgery, 20 vs. 28 days (p < 0.001). However, overall survival rates were similar between the group. Three-year overall survival was 24% in the LS group and 27% in the OS groups. CONCLUSIONS: Despite the technical complexity, in patients with complicated locally advanced and metastatic gastric cancer, laparoscopic gastrectomies were associated with longer operation time, reduced intraoperative blood loss, shorter reconvalescence, and similar morbidity, mortality rates and long-term oncologic outcomes compared to conventional open surgery.

[Topographic and anatomical landmarks for endoscopic navigation in surgery for complicated gastric cancer]. / Topografo-anatomicheskie orientiry endovideokhirurgicheskoi navigatsii pri vypolnenii operatsii po povodu oslozhnennykh form raka zheludka.

OBJECTIVE: To develop an algorithm for sequential visual navigation and imaging of the most permanent topographic and anatomical landmarks for safe laparoscopic surgery of complicated gastric cancer. MATERIAL AND METHODS: We analyzed 42 laparoscopic surgeries for complicated locally advanced gastric cancer. RESULTS: Anatomical navigational landmarks and technical aspects of their safe isolation during laparoscopic surgery for gastric cancer are recommended. CONCLUSION: The topographic-anatomical navigation system based on the most constant anatomical landmarks ensures safe laparoscopic interventions for complicated locally advanced gastric cancer.

The protocol of a prospective, multicenter, randomized, controlled phase III study evaluating different cycles of oxaliplatin combined with S-1 (SOX) as neoadjuvant chemotherapy for patients with locally advanced gastric cancer: RESONANCE-II trial.

BACKGROUND: Curing locally advanced gastric cancer through surgery alone is difficult. Adjuvant and neoadjuvant chemotherapy bring potential benefits to more patients with gastric cancer based on several clinical trials. According to phase II studies and guidelines, SOX regimen as neoadjuvant chemotherapy is efficient. However, the optimal duration of neoadjuvant chemotherapy has not been established. In this study, we will evaluate the efficacy and safety of different cycles of SOX as neoadjuvant chemotherapy for patients with locally advanced gastric cancer. METHODS: RESONANCE-II trial is a prospective, multicenter, randomized, controlled phase III study which will enroll 524 patients in total. Eligible patients will be registered, pre-enrolled and receive three cycles of SOX, after which tumor response evaluations will be carried out. Those who show stable disease or progressive disease will be excluded. Patients showing complete response or partial response will be enrolled and assigned into either group A for another three cycles of SOX (six cycles in total) followed by D2 surgery; or group B for D2 surgery (three cycles in total). The primary endpoint is the rate of pathological complete response and the secondary endpoints are R0 resection rate, three-year disease-free survival, five-year overall survival, and safety. DISCUSSION: This study is the first phase III randomized trial to compare the cycles of neoadjuvant chemotherapy using SOX for resectable locally advanced cancer. Based on a total of six to eight cycles of perioperative chemotherapy usually applied in locally advanced gastric cancer, patients in group A can be considered to have completed all perioperative chemotherapy, the results of which may suggest the feasibility of using chemotherapy only before surgery in gastric cancer. TRIAL REGISTRATION: Registered prospectively in the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP) with registration number ChiCTR1900023293 on May 21st, 2019.

Phase II trial of prophylactic hyperthermic intraperitoneal chemotherapy in patients with locally advanced gastric cancer after curative surgery.

BACKGROUND: HIPEC is an emerging procedure to treat peritoneal metastasis of gastric cancer. Data about HIPEC in locally advanced gastric cancer is scarce. The purpose of this trial is to evaluate the safety and toxicity of prophylactic HIPEC with cisplatin for patients with locally advanced gastric cancer. METHODS: From March 2015 to November 2016, a prospective, randomized phase II trial was conducted. After radical gastrectomy, patients in the experimental group underwent HIPEC with cisplatin followed by adjuvant chemotherapy with SOX regime. Patients in the other group were treated with SOX regime alone. Postoperative complications and patient survival were compared. RESULTS: In total, 50 patients were eligible for analyses. No significant difference was found in the incidence of postoperative complications including anastomotic/intestinal leakage, liver dysfunction, bone marrow suppression, wound infection and ileus (P > 0.05). Mean duration of hospitalization after radical gastrectomy was 11.7 days. 12.2 days in experimental group and 10.8 days in control group respectively (P = 0.255). The percentage of patients with elevated tumor markers was 12.1% in experimental group, which was significantly lower than 41.2% in control group (P = 0.02). 3-year RFS of patients who treated with or without prophylactic HIPEC were 84.8 and 88.2% respectively (P = 0.986). In the multivariate analysis, pathological T stage was the only independent risk factor for the RFS of patients (P = 0.012, HR =15.071). CONCLUSION: Additional intraoperative HIPEC with cisplatin did not increase postoperative complications for locally advanced gastric cancer after curative surgery. Prophylactic HIPEC with cisplatin was safe and tolerable, while it did not reduce the risk of peritoneal recurrence in this trial, supporting further studies to validate the efficacy of it. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR2000038331. Registered 18 September 2020 - Retrospectively registered, http://www.chictr.org.cn/showproj.aspx?proj=59692 .

Omentectomy Does Not Affect the Postoperative Outcome of Patients With Locally Advanced Gastric Cancer: A Systematic Review and Meta-Analysis.

OBJECTIVE: To explore the influence of omentectomy on postoperative outcomes in patients with locally advanced gastric cancer (LAGC). BACKGROUND: Although several meta-analyses have investigated the influence of bursectomy on postoperative outcomes in patients with LAGC, no meta-analyses have explored the influence of omentectomy on postoperative outcomes in such patients. METHODS: We performed a comprehensive electronic search of the literature up to December 2020 to identify studies that compared postoperative outcomes between patients with LAGC who did and did not undergo omentectomy. A meta-analysis was performed using random-effects models to calculate the risk ratio (RR) and 95% confidence interval (CI), and heterogeneity was analyzed using I2 statistics. RESULTS: Eight retrospective studies involving a total of 2658 patients with LAGC who underwent surgery were included in this meta-analysis. Among them, 3 propensity score matching (PSM) studies demonstrated that the 5-y recurrence-free survival (RFS) rate was 72.9% (314/431) in patients with LAGC who did not undergo omentectomy, whereas it was 70.3% (303/431) in those who did. The results revealed no significant difference in 5-y RFS between groups (RR, 0.91; 95% CI, 0.74-1.13; P = 0.41; I2 = 0%). Two PSM studies also revealed no significant difference in 5-y overall survival (OS) between groups (RR, 0.77; 95% CI, 0.52-1.13; P = 0.18; I2 = 47%). CONCLUSIONS: The results of these meta-analyses show that omentectomy had no significant influence on 5-y OS, especially 5-y RFS, in patients with LAGC.

Posttherapy topographical nodal status, ypN-site, predicts survival of patients who received neoadjuvant chemotherapy followed by curative surgical resection for non-type 4 locally advanced gastric cancer: supplementary analysis of JCOG1004-A.

BACKGROUND: Perioperative treatment is an accepted standard approach for treating locally advanced gastric cancer (LAGC). Histopathological tumor regression with < 10% residual tumor is a globally accepted prognosticator in LAGC patients who received neoadjuvant chemotherapy (NAC) and curative surgery. However, despite a response of the primary tumor, a significant percentage of patients dies from recurrence and identification of those at risk for relapse remains challenging. We re-estimated the value of histopathological tumor regression as a prognosticator alongside other factors, especially posttherapy topographical nodal status, ypN-site. PATIENTS AND METHODS: Individual patient data including clinicopathological variables were used from the four JCOG trials investigating NAC (JCOG0001, JCOG0002, JCOG0210, JCOG0405) for analyzing prognosticators in patients with curative surgery excluding those with type 4 AGC by univariable and multivariable Cox regression analyses. RESULTS: Among 85 patients, 5-year overall survival (OS) was 46.0% [95% confidence interval (CI) 35.0-56.4] with a median follow-up of 3.2 years. On univariable analysis, histopathological tumor regression with ≥ 10% residual tumor and ypN-site 2-3 were negatively associated with OS [≥ 10% residual tumor: hazard ratio (HR) 2.60; 95% CI 1.22-5.54; P = 0.014; ypN2-3: HR 3.59; 95% CI 1.60-8.06; P = 0.002). On multivariable analysis, only ypN-site 2-3 was predictive of OS (HR 3.67; 95% CI 1.55-8.69; P = 0.003), whereas histopathological tumor regression with ≥ 10% residual tumor was not (HR 2.24; 95% CI 0.98-5.10; P = 0.055). CONCLUSIONS: ypN-site may have greater impact on OS than histopathological tumor regression in patients who received NAC plus surgery for non-type 4 LAGC.

[Prognosis and Related Factors of Patients with Pathological Complete Response after Neoadjuvant Therapy for Gastric Cancer].

Objective To investigate the related factors of pathological complete response(pCR)of patients with gastric cancer treated by neoadjuvant therapy and resection,and to analyze the risk factors of prognosis. Methods The clinical and pathological data of 490 patients with gastric cancer who received neoadjuvant therapy followed by radical gastrectomy from January to December in 2008 were retrospectively analyzed.Univariate and multivariate analyses were performed to identify the risk factors affecting pCR and prognosis. Results Among the 490 patients,41 achieved pCR,and the overall pCR rate was 8.3%(41/490).The pCR rate was 16.0% in the neoadjuvant chemoradiation group and 6.4% in the neoadjuvant chemotherapy group.The results of multivariate analysis showed that neoadjuvant chemoradiation(OR=4.401,95% CI=2.023-9.574,P<0.001)and preoperative therapeutic response as partial response(OR=40.492,95% CI=5.366-305.572,P<0.001)were independent predictors of pCR after neoadjuvant therapy.Multivariate analysis of prognosis showed that poorly differentiated tumor(HR=1.809,95% CI=1.104-2.964,P=0.019),gastric cardia-fundus-body tumor(HR=2.025,95% CI=1.497-2.739,P<0.001),≤15 intraoperative dissected lymph nodes(HR=1.482,95% CI=1.059-2.073,P=0.022),and postoperative complications(HR=1.625,95% CI=1.156-2.285,P=0.005)were independent risk factors for prognosis,while pCR(HR=0.153,95% CI=0.048-0.484,P=0.001)and postoperative adjuvant chemotherapy(HR=0.589,95% CI=0.421-0.823,P<0.001)were independent protective factors of prognosis. Conclusions Patients who achieved pCR after neoadjuvant therapy for locally advanced gastric cancer might have promising long-term survival,and pCR is an independent predictor for overall survival.Compared with chemotherapy alone,preoperative chemoradiotherapy can significantly improve the pCR rate of patients with locally advanced gastric cancer.

Deep learning radiomic nomogram can predict the number of lymph node metastasis in locally advanced gastric cancer: an international multicenter study.

BACKGROUND: Preoperative evaluation of the number of lymph node metastasis (LNM) is the basis of individual treatment of locally advanced gastric cancer (LAGC). However, the routinely used preoperative determination method is not accurate enough. PATIENTS AND METHODS: We enrolled 730 LAGC patients from five centers in China and one center in Italy, and divided them into one primary cohort, three external validation cohorts, and one international validation cohort. A deep learning radiomic nomogram (DLRN) was built based on the images from multiphase computed tomography (CT) for preoperatively determining the number of LNM in LAGC. We comprehensively tested the DLRN and compared it with three state-of-the-art methods. Moreover, we investigated the value of the DLRN in survival analysis. RESULTS: The DLRN showed good discrimination of the number of LNM on all cohorts [overall C-indexes (95% confidence interval): 0.821 (0.785-0.858) in the primary cohort, 0.797 (0.771-0.823) in the external validation cohorts, and 0.822 (0.756-0.887) in the international validation cohort]. The nomogram performed significantly better than the routinely used clinical N stages, tumor size, and clinical model (P < 0.05). Besides, DLRN was significantly associated with the overall survival of LAGC patients (n = 271). CONCLUSION: A deep learning-based radiomic nomogram had good predictive value for LNM in LAGC. In staging-oriented treatment of gastric cancer, this preoperative nomogram could provide baseline information for individual treatment of LAGC.

Optimizing Therapies in the Perioperative Management of Gastric Cancer.

OPINION STATEMENT: Gastric cancer is a major health burden worldwide. Only about one-third of all the gastric cancer patients survive beyond 5-years. Management of this deadly disease has evolved over the last few decades due to the incorporation of better staging techniques, surgical approach, effective systemic treatment, and sequencing of different therapeutic modalities. There are some global differences in how local-regional gastric cancer is managed and treated. In the USA and some parts of Europe, perioperative chemotherapy is a preferred management approach. Adjuvant chemoradiation is considered if the surgical resection is performed upfront. However, in Asia, postoperative chemotherapy alone after D2 surgical resection is considered standard of care treatment. Based on recent evidence, perioperative treatment with triplet chemotherapy regimen FLOT (5FU, leucovorin, oxaliplatin, docetaxel) is the preferred regimen. However, doublet fluoropyrimidine/platinum combination is a reasonable alternative if triplet regimen cannot be given. At present, there are no approved targeted or immunotherapy agents in perioperative setting; however, there are a number of ongoing trials designed to examine the efficacy of targeted therapy and checkpoint inhibitors in various combinations with systemic therapy in perioperative setting.