Serum basic fibroblast growth factor and interleukin-1ß predict the effect of first-line chemotherapy in patients with advanced gastric cancer.

BACKGROUND: The incidence and mortality rates of gastric cancer in China are the second-highest in the world, and most patients with gastric cancer lose their chance of surgery by the time of their diagnosis. AIM: To explore the predictive potential of serum basic fibroblast growth factor and interleukin-1ß levels for the effect of first-line chemotherapy in patients with advanced gastric cancer. METHODS: From the gastric cancer patients admitted to our hospital from May 2019 to April 2023, 84 patients were selected and randomly and equally assigned to the experimental or control group. The FLOT group received the FLOT chemotherapy regimen (composed of oxaliplatin + calcium folinate + fluorouracil + paclitaxel), while the SOX group received the SOX chemotherapy regimen (composed of oxaliplatin + tiga capsules). The clinical efficacy, tumor marker levels, adverse reactions, and survival rates of the two groups were compared 7 days after the end of the relevant treatments. RESULTS: The target effective rate of the FLOT group was 54.76%, which was much higher than that of the SOX group (33.33%; P < 0.05). After treatment, both the groups demonstrated lower levels of cancer antigen (CEA), carbohydrate antigen 199 (CA199), and peptide tissue antigen (TPS). For several patients before treatment (P < 0.05). Third and fourth grades. In terms of adverse reactions, the level of white blood cells in both the groups was lower. Moreover, the incidence of hand-foot skin reactions in these two study groups was lower (P < 0.05), while those of peripheral neuritis, vomiting, diarrhea, and abnormal liver function were significant (P < 0.05). No statistically significant difference was noted between the two groups (P < 0.05). The 1-year survival rate was higher in the FLOT group (P < 0.05). CONCLUSION: The FLOT regimen was effective in reducing the serum CEA, CA199, and TPS levels as well as in improving the 1-year survival rate of patients with good tolerability, making it worthy of clinical promotion and application.

Survival Advantages in Gastric Cancer Patients Receiving Preoperative SOX Regimen Chemotherapy.

Objective: This study addressed whether preoperative chemotherapy (PECT) plus surgery prolongs overall survival (OS) compared with surgery plus postoperative chemotherapy (POCT) among gastric cancer (GC) patients in Northwest China. Materials and Methods: The authors included 157 GC patients confirmed histologically or by gastroscopic pathological examination treated at the General Hospital of Ningxia Medical University of China between 2012 and 2018. All patients were followed up by telephone in January 2019 within a 2-week period. The endpoint was death due to GC or its complications. Results: Thirty-eight patients received PECT, 41 patients received POCT, 40 patients received surgery alone, and 38 patients received chemotherapy alone. Surgery was performed with R0 resection and subsequent extended lymph node dissection. Chemotherapy was performed with the S-1, oxaliplatin capecitabine regimen. Patients who received PECT had longer OS than those with POCT treatment (hazard ratio = 2.409, p = 0.037). The 5-year OS rate was 32.7% higher in the PECT group than in the POCT group. Conclusions: PECT was associated with better OS in GC patients and should be considered by clinicians in GC treatment, although prospective studies are needed for confirmation.

Clinical efficacy of Compound Kushen Injection combined with SOX regimen in the treatment of elderly patients with advanced gastric cancer / 国际肿瘤学杂志

Objective:To explore the clinical efficacy and influence on quality of life of Compound Kunshen Injection combined with SOX regimen (Tigio + Oxaliplatin) in the treatment of elderly patients with advanced gastric cancer.Methods:A total of 76 elderly patients with advanced gastric cancer admitted to Caidian District People's Hospital of Wuhan from May 2017 to December 2021 were retrospectively analyzed. Patients were divided into study group ( n=38) and control group ( n=38) according to different treatment methods. The study group was treated with Compound Kunshen Injection combined with SOX regimen, and the control group was treated with SOX regimen. All patients received at least 2 cycles of chemotherapy. The disease control rate (DCR) , the changes of serum carcinoembryonic antigen (CEA) and carbohydrate antigen 199 (CA199) before and after treatment of the two groups were compared. The occurrence of adverse reactions to chemotherapy and the improvement of quality of life related indicators before and after treatment were observed in the two groups. Results:The DCR of the study group was 84.2% (32/38) and that of the control group was 63.2% (24/38) , with a statistically significant difference ( χ2=4.34, P=0.037) . After treatment, CEA levels in both study group and control group were decreased compared with those before treatment [7.92 (5.00, 50.23) ng/ml vs. 40.08 (6.37, 68.18) ng/ml, Z=3.53, P<0.001; 40.24 (20.12, 53.69) ng/ml vs. 41.32 (11.50, 63.90) ng/ml, Z=2.06, P=0.044], and CEA level in the study group was decreased more significantly than that in the control group ( Z=1.99, P=0.048) . After treatment, CA199 levels in both study group and control group were decreased compared with those before treatment [20.23 (17.34, 71.31) U/ml vs. 70.14 (12.75, 96.95) U/ml, Z=2.70, P=0.007; 54.25 (30.54, 76.75) U/ml vs. 62.28 (23.00, 84.80) U/ml, Z=2.37, P=0.018], with no statistically significant difference in the reduction level of CA199 between the two groups ( Z=0.73, P=0.463) . Most of the adverse reactions in the two groups during chemotherapy were grade 1-2, which disappeared after symptomatic treatment. Compared with the control group, the study group had lower incidence of gastrointestinal reaction [26.3% (10/38) vs. 52.6% (20/38) , χ2=5.50, P=0.019], myelosuppression [18.4% (7/38) vs. 44.7% (17/38) , χ2=6.09, P=0.014] and peripheral neurotoxicity [21.1% (8/38) vs. 44.7% (17/38) , χ2=4.83, P=0.028]. The improvements of QOL score [78.9% (30/38) vs. 55.3% (21/38) , χ2=4.83, P=0.028], Karnofsky performance status score [71.1% (27/38) vs. 47.4% (18/38) , χ2=4.41, P=0.036], hemoglobin [73.7% (28/38) vs. 50.0% (19/38) , χ2=4.52, P=0.034] and pain control [65.8% (25/38) vs. 24.1% (16/38) , χ2=4.29, P=0.038] of the study group were better than those of the control group, with statistically significant differences. Conclusion:Compound Kunshen Injection combined with SOX regimen in the treatment of elderly patients with advanced gastric cancer can not only improve the DCR of patients, but also reduce the serum levels of tumor markers CEA and CA199, among which the CEA decline is more obvious, reduce the incidence of adverse reactions of chemotherapy and improve the quality of life of patients.

The efficacy and safety of continuous intra-arterial infusion neoadjuvant chemotherapy with surgery for locally advanced gastric cancer: a preliminary pilot study.

Background: Neoadjuvant chemotherapy (NAC) followed by R0 resection is regarded as a standard treatment strategy for locally advanced gastric cancer (GC); however, the response to systemic chemotherapy remains unsatisfactory. Continuous intra-arterial infusion chemotherapy (CAIC) is a new method, compared with systematic chemotherapy, it can deliver chemotherapy drugs more accurately, so as to achieve higher surgical conversion rate. This study aimed to explore the efficacy and safety of CAIC in locally advanced GC patients. Methods: In this retrospective pilot study, four patients with histologically confirmed locally advanced GC were identified from a tertiary hospital between May 2018 and December 2018. Clinic stage was belonged to T4N1-3M0 in all cases with potential probability for surgery. All cases received three cycles of NAC by CAIC with oxaliplatin (100 mg on day 1) plus oral S-1 (80 mg/m2/day twice daily for 14 days) (SOX). Contrast-enhanced computed tomography (CT) scans and pathological examinations were performed to evaluate chemotherapeutic response based on the tumor regression grade (TRG) and post-neoadjuvant pathological Tumor Node Metastasis (ypTNM) staging. All cases were regularly followed up with face-to-face interviews at outpatient, abdominal enhanced CT scan and serum tumor markers were be requested at 3-month intervals for up to 1 year postoperatively. Results: The obstruction was significantly alleviated after three cycles of CAIC. Contrast-enhanced CT scans showed decreased tumor volume to some extent, along with lymph node shrinkage after treatment. Radical (R0) resection was achieved in all cases. Histopathological analysis showed tumor downstaging in three cases and upstaging in one case. The tumor response to treatment demonstrated TRG1a in one case, TRG1b in one case, and TRG2 in two cases, with an overall tumor regression rate of 100%. No obvious adverse events or perioperative complications were observed during or following treatment. All cases were alive without tumor recurrence or progression after the 1-year postoperative follow-up. Conclusions: Our study may shed light on super-selective CAIC as an effective method for improving the NAC response in locally advanced GC. Future studies with a larger sample sizes and long-term outcomes are required for a final conclusion.

Comparisons of effects of SOX and mFOLFOX6 chemotherapy regimens on patients with locally advanced gastric cancer.

The neoadjuvant chemotherapy plays an important role in locally advanced gastric cancer, but its efficacy, safety profiles and clinical outcomes among different regimens still remain controversial. In this study, totally 231 eligible patients with locally advanced gastric cancer were enrolled. These patients were divided into the observation group (SOX regimen, n = 123) and control group (mFOLFOX6 regimen, n = 108) according to different chemotherapy regimens. Then, the differences in chemotherapy efficacy, adverse reactions, surgical characteristics, complications and survival condition were compared. No significant differences were observed in clinical efficacy of chemotherapy, the rate of D2 lymph node clearance, R0 resection, complications, responses of neoadjuvant chemotherapy and survival condition between two groups (P > 0.05). The incidence of abdominal pain, diarrhoea, nausea and vomiting in the observation group were significantly lower than those in the control group (16.26% vs 29.63%, χ2 = 5.893, P < 0.05; 11.38% vs 26.85%, χ2 = 9.084, P < 0.05; 35.77% vs 53.70%, χ2 = 7.499, P < 0.05). The SOX regimen and mFOLFOX6 regimen have similar chemotherapy efficacy for locally advanced gastric cancer, but SOX regimen has a lower risk of gastrointestinal adverse reactions comparing with mFOLFOX6 regimen.

Low-dose apatinib combined with camrelizumab and the SOX regimen in the neoadjuvant treatment of locally advanced gastric/gastroesophageal junction adenocarcinoma (SPACE-neo): a protocol for an open-label, single-arm, clinical trial.

Background: Neoadjuvant chemotherapy with S-1 plus oxaliplatin (SOX regimen) has shown promising results in pathological response rate and survival rate in patients with locally advanced resectable gastric cancer (LAGC). We previously carried out the SPACE study to assess efficacy and safety of low-dose apatinib combined with camrelizumab and the SOX regimen as a first-line treatment of advanced gastric/gastroesophageal junction adenocarcinoma (AGC/GEJC). The preliminary results demonstrated a high objective response rate. However, the SPACE study was conducted in patients with AGC, but the efficacy of LAGC patients is not yet known. The SPACE-neo study is designed to investigate whether this combination could improve outcomes in patients with locally advanced gastric/gastroesophageal junction cancer (LAGC/GEJC) as neoadjuvant therapy. Methods: SPACE-neo is a prospective, open-label, single-arm study conducted in China at the First Affiliated Hospital of Nanjing Medical University (Jiangsu Province Hospital). Thirty-two patients with human epidermal growth factor receptor 2 (HER2)-negative or HER2-unknown LAGC/GEJC confirmed by histopathology or cytology will be recruited. Included patients shall be clinically staged as M0 and either T3 to T4 or N+ assessed by ultrasound endoscopy and thoracoabdominal-enhanced computed tomography or magnetic resonance imaging. The patients will receive three cycles of this combined regimen as a neoadjuvant treatment. Each patient will receive screening visits within 2 weeks before the first cycle and planned visits before every cycle of treatment. Key monitoring data include imaging data, pathological findings, and adverse events associated with neoadjuvant and surgical treatment. The primary endpoints are major pathological response (MPR) and safety. MPR is the proportion of patients whose residual tumor cells make up less than 10% of the primary tumor from among the total cohort. Clopper-Pearson method will be used to estimate the 95% confidence interval of MPR and safety data will be reported as descriptive statistical analysis. Discussion: The SPACE-neo trial aims to evaluate the safety and preliminary efficacy of this regimen in the neoadjuvant treatment of LAGC/GEJC. It is hoped that the study can achieve a higher pathological response rate and longer survival rate. Trial Registration: ChiCTR.gov.cn: ChiCTR2100049305.

Study on Efficacy and Safety of Low-Dose Apatinib Combined with Camrelizumab and SOX Regimen as First-Line Treatment of Locally Advanced and Unresectable Gastric/Gastroesophageal Junction Cancer: A Protocol for an Open-Label, Dose Escalation and Extension Phase Ib Clinical Trial.

BACKGROUND: The standard treatment for advanced gastric/gastroesophageal junction cancer (AGC/GEJC) is palliative chemotherapy combined with targeted therapy. The SOX regimen (S-1 plus oxaliplatin) is recommended as neoadjuvant or palliative first-line chemotherapy in Asian patients. Apatinib, an oral VEGFR tyrosine kinase inhibitor, is associated with additional survival benefit as third- or subsequent-line therapy. However, the median overall survival time of AGC/GEJC is only 8-11 months in the West and 13-17 months in East Asia/Japan, even with the application of anti-angiogenic agents. Hence, the multimodal and individual management of patients is challenging standards to improve prognosis, including the preferential use of low-dose anti-angiogenic drugs and immunotherapy, as well as the application of multi-disciplinary treatment (MDT)-directed conversion therapy. METHODS/DESIGN: This single-center study was designed to combine low-dose apatinib with camrelizumab plus the SOX regimen in diagnosed potentially resectable and initially unresectable AGC/GEJC. This a prospective, open-label, single-arm, dose escalation and extension phase Ib clinical trial, conducted in Jiangsu Province Hospital, beginning from June 2020. All patients will first receive this combined regimen (3 weeks/cycle) for at most eight cycles, then apatinib and camrelizumab in maintenance therapy until disease progression, intolerable toxicity, death, a maximum 2 years of treatment or discontinuation for any reason. Follow-up and evaluation will be carried out regularly. If surgery is allowed by MDT discussions, oral apatinib will be discontinued during the last preoperative cycle. The primary endpoints are the objective response rate and maximum tolerated dose according to the Response Evaluation Criteria In Solid Tumors (RECIST) criteria (version 1.1) and the Common Terminology Criteria for Adverse Events (CTCAE) criteria (version 5.0). DISCUSSION: This study will assess the response and side effects of AGC/GEJC patients in the use of low-dose apatinib combined with camrelizumab and the SOX regimen, and this combined therapy is expected to be a feasible and optimized first-line treatment option. In addition, this study will provide robust evidence and novel ideas for conversion therapy. TRIAL REGISTRATION: ChiCTR.gov.cn: ChiCTR2000034109.

Durable Response After Combination Of Concurrent Chemoradiotherapy And Anti-PD-1 Therapy In HER2-Negative Advanced Gastric Adenocarcinoma: A Case Report.

Advanced gastric cancer (AGC) is difficult to treat with poor prognosis. Despite various possible treatments, the median survival time of such patients remains unsatisfactory. Therefore, new therapeutic approaches or combinations need to be further explored. We herein reported a case of a 54-year-old male patient who was initially diagnosed with HER2-negative advanced gastric cancer. Based on previous studies and patient's desire, we made a therapeutic plan: the combination of concurrent radiochemotherapy and immune checkpoint blockade therapy. After about 4 months of combined therapy, the patient showed satisfactory complete response to tumor lesions even metastatic lesions (CR, disappearance of all target lesions). In summary, the combination of concurrent SOX regimen chemotherapy, stomach radiotherapy and PD-1 antibody immunotherapy is effective in the treatment of advanced gastric cancer.

Clinical significance of CD8+ T cell immunoreceptor with Ig and ITIM domains+ in locally advanced gastric cancer treated with SOX regimen after D2 gastrectomy.

Gastric cancer (GC) development and progression is significantly associated with tumour immune escape. T cell immunoreceptor with Ig and ITIM domains (TIGIT) inhibits T-cell responses and is associated with human cancers and T cell exhaustion phenotypes, but its role in cancers remains unclear. TIGIT and programmed cell death protein (PD)-1 levels were detected in 441 human GC specimens using histochemistry. We used flow cytometry to evaluate percentage of TIGIT+ constituting CD8+ T cells of 23 patients with GC who underwent D2 gastrectomy and the S-1 plus oxaliplatin (SOX) regimen. We investigated the influence of SOX regimen and TIGIT functional antibody on CD8 tumour-infiltrating lymphocytes (TILs). Results showed that PD-1 and TIGIT were significantly over expressed in GC and predicted poorer outcome, agreeing with bioinformatics analysis. Significantly reduced percentages of CD8+ TIGIT+ cells were observed in patients after D2 gastrectomy (pre- vs post-surgery, 38 ± 8.7% vs. 26.7% ± 5.2%, p < 0.0001). TIGIT expression on CD8+T cells was modulated by chemotherapeutics (pre- and post-chemotherapy, 31.3 ± 9% vs. 25.1 ± 4.5%, respectively, p = 0.0047) and higher TIGIT expression in post-chemotherapy group was associated with relapsed GC (p = 0.036). In vitro experiments revealed increased CD8+ TIL proliferation and interferon (IFN)-γ production following SOX regimen and TIGIT functional antibody treatments. In conclusion, TIGIT contributes to CD8+ TILs immune dysfunction in patients with GC. Combination of anti-TIGIT therapy and chemotherapy could be considered a therapy for GC.

Cost-effectiveness Analysis of SOX Regimen versus CapeOX Regimen for Metastatic Colorectal Cancer / 中国药房

OBJECTIVE:To evaluate the cost-effectiveness of SOX regimen(tegafur+oxaliplatin)vs. CapeOX regimen (capecitabine+oxaliplatin)in the treatment of metastatic colorectal cancer,and to provide reference for exploring more economical first-line regimen of metastatic colorectal cancer. METHODS:Based on published high-quality Ⅲ-phase randomized controlled trial,Markov model was established according to the process of disease development in patients with metastatic colorectal cancer. The model was divided into progression-free survival state,progressive disease state and death state. Combined with relevant data of our hospital,pharmacoeconomic cost-effectiveness analysis was conducted for SOX regimen and CapeOX regimen. Sensitivity analysis validation model was used to analyze the stability of the model. RESULTS:According to the results of Markov model operation,compared to standard CapeOX regimen,SOX regimen could increase 0.14 QALYs,and cost increased by 35 493.45 yuan;incremental cost-effectiveness ratio was 253 524.64 yuan/QALYs,which was higher than willingness-to-pay(WTP) threshold(168 201.201 yuan/QALYs). Single factor sensitivity analysis showed that cost of oxaliplatin had the most important impact on the result of cost-effectiveness analysis. Probabilistic sensitivity analysis depicted that with the increase of GDP per capita,the probability of SOX regimen with cost-effectiveness would increase. CONCLUSIONS:At present,compared with standard CapeOX regimen,SOX regimen has no cost-effectiveness for metastatic colorectal cancer,which is not recommended as the first choice for first-line treatment of metastatic colorectal cancer.

Efficacy analysis of CAPOX regimen and SOX regimen in the treatment of advanced gastric cancer / 中国现代普通外科进展

Objective:To study the effect of CAPOX regimen and SOX regimen in the treatment of advanced gastric cancer.Methods:140 patients with advanced gastric cancer who received chemotherapy from January 2010 to June 2011 in the hospital were enrolled in this study.The patients were divided into observation group (CAPOX regimen) 72 cases and control group(SOX regimen) 68 cases according to the different chemotherapy protocols,two groups were treated with central venous catheter,and in the course of chemotherapy for the given antiemetic,hepatoprotective and Acid suppression related drugs.The observation group was treated with CAPOX regimen,and the control group was treated with SOX regimen,and the 21d was used as the 1 chemotherapy cycle,and the effect was evaluated after 2 cycles of chemotherapy.Results:The effective rate of observation group was 33.33％ (24/72),compared with the control group of 33.82％(23/68),the difference was not statistically significant (P＞0.05).The incidence of hand foot syndrome in the observation group was 16.67％ (12/72),was significantly higher than the control group of 2.94％(2/68),the difference was statistically significant(P＜0.05).The total incidence of adverse reactions in the observation group was 58.33％ (42/72),compared with the control group of 57.35％(39/68),the difference was not statistically significant(P＞0.05).The 1 to 5 year survival rate of the observation group compared with the control group was not statistically significant(P＞0.05).The two groups before and after treatment of CD3+,CD3+CD4+ and CD3+/CD8+ compared,the difference was not statistically significant (P＞0.05).Conclusion:Using CAPOX scheme and the SOX regimen can be better in the treatment of advanced gastric cancer,curative effect and short and long term survival rate was almost equal and influence of immune function of patients with no significant difference,but CAPOX scheme may exist higher hand foot syndrome probability,it is worth clinical optic.

CT imaging evaluation analysis of preoperative SOX regimen neoadjuvant chemotherapy in the treatment of advanced gastric cancer / 中国生化药物杂志

Objective To evaluate and analyze the CT imaging of preoperative SOX regimen neoadjuvant chemotherapy in the treatment of advanced gastric cancer.Methods A total of 33 patients with advanced gastric cancer treated in our hospital from January 2010 to February 2015 were enrolled for the study and given tegafur gimeracil oteracil potassium capsule plus oxaliplatin for injection as preoperative adjuvant chemotherapy.And all the patients were given surgery after 3 cycles of SOX regimen chemotherapy, and surgical resection of the tumor was taken as the final pathology gold standard.The CT imaging data of the patients before and after the chemotherapy was counted and then analyzed and compared with the pathological data to clarify the value of CT imaging in the evaluation of SOX regimen neoadjuvant chemotherapy for advanced gastric cancer.Results The effective rate was 33.33% and the ineffective rate was 66.67% in the preoperative SOX regimen neoadjuvant chemotherapy for advanced gastric cancer through clear surgical pathology.The correlation between tumor volume reduction and pathological grading was the strongest(r=0.581, P<0.001).By ROC analysis, the best area value(AUC) of the tumor volume reduction rate was 0.834.When the tumor volume reduction rate with 36.94% was taken as the effective threshold for SOX regimen neoadjuvant chemotherapy, the sensitivity and specificity of the evaluation were the best with 74.62% and 83.01% respectively.Conclusion sCT volume measurement can be used as a reliable clinical data to evaluate the efficacy of preoperative SOX regimen neoadjuvant chemotherapy in the treatment of advanced gastric cancer and have certain guiding significance in the late treatment of patients with advanced gastric cancer.