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OBJECTIVES: To evaluate the efficacy of SOX combined with a programmed cell death protein-1 (PD-1) inhibitor compared with SOX alone in the perioperative management of locally advanced gastric cancer and to explore biomarkers that may predict response to anti-PD-1 therapy. METHODS: Data of patients with clinical stage T3-4aN0-3M0 (IIb-III) gastric cancer were reviewed to create a primary database. Patients treated with perioperative SOX combined with sintilimab were included in Group A, while those treated with SOX alone were included in Group B. After one-to-one propensity score matching, pathological response and short-term survival outcomes were compared between the two groups. In addition, potential efficacy-related biomarkers were analyzed. RESULTS: Between January 2018 and December 2022, a total of 150 patients were included in the analysis, with 75 patients in each group. The rates of pathological complete response (21.3% vs. 4.0%; P = 0.001) and major pathological response (45.3% vs. 22.7%; P = 0.003) in Group A were statistically higher than those in Group B. There was no significant difference in 1-year overall survival (92.8% vs. 92.0%; P = 0.392) and disease-free survival (88.9% vs. 88.0%; P = 0.357) between the two groups. Subgroup analysis of Group A showed that the pathological complete response (40.6% vs. 8.6%; P = 0.002) and major pathological response (65.6% vs. 28.6%; P = 0.002) rates were significantly higher in programmed death ligand-1-positive patients with a combined positive score of ≥ 5. A pathological complete response was achieved in 42.9% patients (3/7) with mismatch repair deficiency. For the two patients confirmed as Epstein-Barr virus-positive, one patient achieved a pathological complete response and the other achieved a major pathological response. CONCLUSIONS: The adoption of SOX combined with a PD-1 inhibitor may improve the pathological response rate of patients with locally advanced gastric cancer, especially those with programmed death ligand-1 combined positive score ≥ 5, Epstein-Barr virus-positivity and mismatch repair deficiency. However, further prospective studies are still warranted to confirm the long-term survival benefit.
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Infecciones por Virus de Epstein-Barr , Neoplasias Primarias Secundarias , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/tratamiento farmacológico , Neoplasias Gástricas/cirugía , Estudios Prospectivos , Puntaje de Propensión , Herpesvirus Humano 4 , Neoplasias Primarias Secundarias/tratamiento farmacológico , Biomarcadores , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéuticoRESUMEN
BACKGROUND: Currently, there is a lack of an effective strategy for the prevention of peritoneal metastasis (PM) from locally advanced gastric cancer (AGC). This randomized-controlled study aimed to evaluate the outcome of D2 radical resection with hyperthermic intraperitoneal chemotherapy (HIPEC) plus systemic chemotherapy versus systemic chemotherapy alone in locally AGC patients. METHODS: All enrolled patients were randomly assigned to receive HIPEC plus systemic chemotherapy (HIPEC group) or systemic chemotherapy alone (non-HIPEC group) after radical gastrectomy. HIPEC was performed intraperitoneally with cisplatin (40 mg/m2) within 72 h after surgery, while systemic chemotherapy based on the SOX regimen (S-1 combined with oxaliplatin) was administered 4-6 weeks after radical surgery. Patterns of recurrence, adverse events, 3-year disease-free survival (DFS), and overall survival (OS) were analyzed. RESULTS: A total of 134 patients were enrolled in the present study. The 3-year DFS rate was 73.8% in the HIPEC group, which was significantly higher than that in the non-HIPEC group (61.2%, P = 0.031). The 3-year OS rate was 73.9% in the HIPEC group and 77.6% in the non-HIPEC group, with no significant difference (P = 0.737). PM was the most common distant metastasis in both groups. The occurrence rate of PM in the HIPEC group was statistically lower than that in the non-HIPEC group (20.9% vs. 40.3%, P = 0.015). Grade 3 or 4 adverse events occurred in 19 (14.2%) patients, and there was no significant difference between the two groups. CONCLUSION: Radical surgery followed by HIPEC combined with systemic chemotherapy is a safe and feasible strategy for locally AGC patients and could effectively improve DFS and reduce the occurrence of PM. However, more prospective randomized studies with a large sample size are warranted. TRIAL REGISTRATION: This study was registered with www.medresman.org.cn as ChiCTR2200055966 on 10/12/2016.
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Hipertermia Inducida , Neoplasias Peritoneales , Neoplasias Gástricas , Humanos , Quimioterapia Intraperitoneal Hipertérmica , Neoplasias Gástricas/patología , Estudios Prospectivos , Neoplasias Peritoneales/terapia , Neoplasias Peritoneales/secundario , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Terapia CombinadaRESUMEN
BACKGROUND: Ovarian metastasis from gastric cancer (GC) is characterized by aggressive biological behavior and poor outcome. Currently, there is no standard treatment mode for such patients. Thus, we evaluated the efficacy of conversion therapy in patients with synchronous ovarian metastasis from GC in this study. METHODS: About 219 GC patients with ovarian metastasis in 2011-2020 were enrolled. Two groups were established based on the different treatment: the conversion therapy group (chemotherapy combined with surgical resection, CS group) and the non-conversion therapy group (NCS group). Propensity score matching (PSM) was used to analyze the efficacy of different treatment modes on the prognosis of these patients. RESULTS: Ninety-two patients were included according to PSM results, with 46 patients each in CS and NCS groups. The median overall survival (OS) in the CS group was notably better than that in the NCS group (p < 0.001). Twenty-six patients (56.52%) in the CS group achieved R0 resection, and they had a better prognosis (p = 0.003). Compared with patients who underwent simultaneous gastrectomy and ovarian metastasectomy (CSb group), those who underwent ovarian metastasectomy before systemic chemotherapy (CSa group) had a higher R0 resection rate (p = 0.016) and longer survival time (p = 0.002). A total of 38 patients (41.30%) across both groups received hyperthermic intraperitoneal chemotherapy (HIPEC), and these patients had a better survival (p = 0.043). CONCLUSION: The conversion therapy is safe and effective for patients with synchronous ovarian metastasis from GC and can improve their prognosis. However, our results need to be confirmed by more randomized controlled clinical studies.
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Neoplasias Ováricas , Neoplasias Gástricas , Humanos , Femenino , Neoplasias Gástricas/tratamiento farmacológico , Neoplasias Gástricas/cirugía , Puntaje de Propensión , Pronóstico , Quimioterapia Intraperitoneal Hipertérmica , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/cirugía , Estudios Retrospectivos , Terapia Combinada , Tasa de SupervivenciaRESUMEN
OBJECTIVE: The peritoneal cancer index (PCI) is used to evaluate the peritoneal metastasis of gastric cancer. A higher value indicates more widespread and/or larger tumors in the peritoneal cavity. The neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) are representative blood markers of systemic inflammatory responses, and D-dimer (DDI) is the final stable product of fibrin. This study explores the association of NLR, PLR, and DDI with PCI and assesses the clinical utility of a new blood score combining the NLR, PLR, and DDI (NPD score) for PCI and the prognosis prediction of gastric cancer. METHODS: This was a single-center, nonrandomized, retrospective, cohort study. We evaluated the risk factors for high PCI (≥15) using univariate and multivariate analyses. According to the findings of the ROC analysis, we determined the cut-off values of NLR, PLR and DDI and created the NPD score. The patients were grouped into high-risk and low-risk groups based on their NPD score (<2 and ≥2, respectively). RESULTS: Univariate and multivariate analysis demonstrated that the NLR, PLR, and DDI were independent risk factors for high PCI (P < 0.05). The NPD score of the high-risk group was ≥2, and the NPD score of the low-risk group was <2. The median survival time was 14.2 in the high-risk group and 25.6 in the low-risk group. The NPD score was significantly higher in the high-PCI group than that in the low-PCI group. The survival of the high-risk group was significantly worse than that of the low-risk group (P = 0.003). NPD score decrease was an independent predictive factor for PCI decrease. CONCLUSION: NLR, PLR, and DDI are potential independent risk factors for high PCI in patients with peritoneal metastasis of gastric cancer. The NPD scoring system can help in predicting PCI and the prognosis of patients with peritoneal metastasis of gastric cancer.
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Interleukin (IL)-17 have been reported to be associated with the pathogenesis of colorectal cancer (CRC). Few studies investigated the association between IL-17 gene polymorphisms and risk of CRC with inconsistent findings. Thus, we recruited 352 CRC cases and 433 controls in a Chinese population and their genotyping was done using polymerase chain reaction-restriction fragment length polymorphism method. Our data showed that IL-17A rs2275913 polymorphism was associated with the increased risk of CRC, while no association was observed for IL-17F rs763780 polymorphism. Stratified analyses revealed that the significant association was also obtained in the females, smokers, drinkers and age ≥ 60 years groups for rs2275913 polymorphism. Moreover, the CC and/or GC genotype of rs2275913 polymorphism were correlated with TNM stage and lymph node metastasis. No association was shown between IL-17F rs763780 polymorphism and clinical characteristics of CRC. In conclusion, our data indicate that IL-17A rs2275913 polymorphism but not IL-17F rs763780 polymorphism contributes to increased risk for CRC patients in this Chinese population.