bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficacy and safety of first-line immunotherapy for advanced gastric or gastroesophageal cancer: System review network meta-analysis.
Authors: Qin Qiong , Sun Yongkun , Yang Lin , Zhong Diansheng 
Published: June 2023

e16014 Background: In advanced gastric or gastroesophageal cancer, a series of randomized controlled trials had investigated different first-line immunotherapy compared with chemotherapy. However, the optimal immunotherapy strategy is yet to be established. We compared the efficacy and safety of first line immunotherapy for patients with advanced, HER2-negative gastric or gastroesophageal junction cancer. Methods: We performed systematic review and a network meta-analysis (NMA) of immune checkpoint inhibitors (ICIs) monotherapy or combined with chemotherapy for gastric or gastroesophageal cancer with HER2 negative. We searched PubMed, Embase, Cochrane Central Register of Controlled Trails, ClinicalTrials.gov, and several international conference databases, from 1 January 2012 to 1 March 2022.Published and unpublished randomized controlled trials compared different first-line immunotherapy with chemotherapy were included. This study was registered in the Prospective Register of Systematic Reviews (CRD 42021291609) to ensure transparency. Results: We analyzed a total 5 studies including 5279 patients and involving 5 immunotherapies. In patients without programmed death-ligand 1(PD-L1) selection, ICIs combined with chemotherapy improved progression free survival (PFS) and overall survival (OS). Sintilimab plus chemotherapy provided the best OS benefit (HR=0.77, 95% CI 0.63-0.94) and the best PFS benefit (HR=0.64, 95%CI 0.53-0.77) compared with standard chemotherapy. Furthermore, pembrolizumab plus chemotherapy seemed to provide the best objective response rate (OR= 1.81, 95%CI 1.44-2.28). Pembrolizumab monotherapy was the safest first-line treatment for grade equal or more 3 AEs (OR= 0.09, 95% CI 0.06-0.14). Subgroup analysis showed that sintilimab plus chemotherapy was associated with the best OS in CPS PD-L1≥1 (HR=0.73,95%CI 0.59-0.91) and PD-L1 ≥10 (HR=0.56, 95% CI 0.41-0.77). Pembrolizumab monotherapy improved OS in PD-L1 ≥10 (HR=0.69, 95% 0.49-0.97). Conclusions: Our results indicate that Sintilimab combined chemotherapy were associated with the best PFS and OS for patients with advanced GC or GEJC with HER2 negative.
Efficacy and safety of anlotinib hydrochloride combined with nivolumab in the treatment of advanced upper gastrointestinal tumor as second-line or later-line therapy: The results of gastric cancer cohort.
Authors: Cui Yuehong , Yu Yiyi , Wu Jing , Li Qian , Liang Li , Wang Yan , Yu Shan , Liu Tianshu 
Published: June 2023

e16015 Background: The upper gastrointestinal tumors, such as gastric adenocarcinoma (GAC) and esophageal squamous cell carcinoma (ESCC), have high rates of incidence and poor prognosis in our country, lacking of efficient therapy after failure of first-line regimen. Despite available treatment, there are still huge unmet medical needs of second-line or later-line therapy for patients with GAC or ESCC. Therefore, we will investigate the efficacy and safety of Anlotinib Hydrochloride (a multi-target tyrosine kinase inhibitor) combined with Nivolumab (PD-1 antibody) in GAC and ESCC. Methods: Patients with unresectable or metastatic GAC or ESCC who have failed standard therapy were treated by Anlotinib Hydrochloride 12mg/day orally for two weeks and Nivolumab 360mg every 3 week until the disease progression or intolerable adverse effects occurring. The study protocol was registered on ClinicalTrial.gov (NCT04503967,07/08/2020). The primary endpoint of this study was ORR (Objective Response Rate). The secondary endpoints were PFS (Progression-Free Survival), OS (Overall Survival), DCR (Disease Control Rate), and safety. Results: Gastric adenocarcinoma cohort would be reported only. From December 2020 to September 2022, 45 patients were enrolled in gastric adenocarcinoma cohort. There were 34 male patients and 11 female patients. The median age was 59 years. The percentage of gastric cancer patients with second-line and later-line treatment were 62.2% and 37.8%, respectively. 2 patients (4.4%) achieved complete remission (CR), 11 patients (24.4%) got partial remission (PR), and 15 patients (33.3%) got stable disease (SD). The ORR (CR+PR) was 28.9%, and DCR (CR+PR+SD) was 62.2%. Among 28 patients (62.2%) treated as second-line therapy, ORR was 32.1%, and DCR was 57.0%. As for later-line therapy of 17 patients, ORR and DCR were 23.5% and 70.6%, respectively. The median follow-up duration was 15.0 months (95% CI 8.17~21.83), then median PFS was 3.80±0.94 months, and median OS was 11.10±3.04 months. When the patients were treated as second-line therapy, median PFS was 3.0±0.97 months, and median OS was 14.50±3.89 months. Median PFS and OS in later-line patients of gastric adenocarcinoma were 3.80±1.30 months and 8.0±0.68 months, respectively. 36 patients (80%) had treatment-related adverse events (TRAEs). More than 10% of incidence rate included hypothyroidism (n=8), liver dysfunction (n=6), and rash (n=6). G3-4 of TRAEs were hypothyroidism (n=1), liver dysfunction (n=1), palmar-plantar erythrodysesthesia (n=1), rash (n=1), and hypophysitis (n=1). Conclusions: Anlotinib hydrochloride combined with Nivolumab showed effective clinical response and tolerable safety in second-line or later-line treatment of advanced gastric adenocarcinoma. Clinical trial information: NCT04503967 .
The prognostic value of metastasectomy among patients with gastric, pancreatic, and colorectal cancer accompanied by isolated liver metastasis: A SEER analysis.
Authors: Fahmawi Suhib , Abu heija Usama , Abdelhay Ali , Al-Ani Abdallah , Manthri Sukesh 
Published: June 2023

e16026 Background: It is well acknowledged that the poor prognosis of gastrointestinal (GI) cancer is largely due to distant metastasis. It’s been reported previously that metastasectomy, particularly with liver metastasis in colorectal cancer patients, have survival benefit. Multidisciplinary management of distant metastatic cancer mandates the consideration of all treatment options, and in selected patients with hepatic metastasectomy can be performed with curative intent. There is no consensus on the ideal management strategy for synchronous disease. The purpose of this study was to analyze the prognostic value of metastasectomy in patients with certain GI cancers associated with isolated liver metastasis. Methods: A total of 14,204 patients who underwent primary site resection along with metastasectomy for isolated liver metastases from gastric, pancreatic, and colorectal were extracted from the Surveillance, Epidemiology, and End Results database between 2010 and 2019. Patients younger than 18 years, and cases with missing information including age, gender, race, unknown stage, and unknown metastasis site were excluded. Cox-regression analysis estimated the prognostic value of metastasectomy, presented by hazard ratios (HR), among different GI cancers. Survival ratios were controlled for age, race, and gender. All analyses were performed on STATA v17. Results: Study sample included 3% of patients with gastric cancer, 4.2% with pancreatic cancer, and 92.8% were colorectal cancer patients. Incidence of metastasectomy was 19.9% among gastric cancer, 30.69% of pancreatic cancer and 25.76% of colorectal cancer patients. Cox-regression analysis demonstrated survival benefit for patients with gastric (HR 0.65, CI 0.45 - 0.94, p = 0.02), pancreatic (HR 0.51, CI 0.39 – 0.67, p < 0.001), and colorectal cancer (HR 0.58, CI 0.55 – 0.62, p < 0.001) patients undergoing metastasectomy. Conclusions: Aggressive approach with primary site resection along with metastasectomy for isolated liver metastases from gastric, pancreatic, and colorectal cancers significantly improved survival. Prospective data from evidence-based protocols is missing, and therefore optimal management of hepatic metastasis should be personalized and determined by a multi-disciplinary team. [Table: see text]
A retrospective cohort study examining the effects of anti–PD-1 antibody in combination with apatinib in patients previously treated for HER2-negative advanced gastric/gastroesophageal junction cancer.
Authors: Hou Xinfang , Li Shuai , Wu Chen 
Published: June 2023

e16048 Background: Combining immune checkpoint inhibitors with vascular endothelial growth factor (VEGF)/VEGF receptor (VEGFR) inhibitors are effective in treating a number of solid tumors; however, evidence in advanced gastric/gastroesophageal junction (G/GEJ) cancer is limited. Methods: This retrospective study included consecutive patients who received a programmed cell death protein 1 (PD-1) inhibitor plus the VEGFR-2 inhibitor apatinib, second-line or later to treat unresectable advanced or metastatic, histologically-proven, human epidermal growth factor receptor 2 (HER2)-negative G/GEJ cancer in a single center between November 1, 2018 and March 31, 2021. Treatment was continued until the disease progressed or the toxicity became intolerable. Results: Data from 52 patients (median age 64 years; 38 men) were analyzed. The primary tumor site was the stomach in 29 patients (56%) and the GEJ in 23 patients (44%). The number of previous line(s) of therapy was one in 22 patients (42%) and two or more in 30 patients (58%). Liver metastasis was present in 22 patients (42%) and 33 patients (63%) had two or more metastatic sites. PD-1 inhibitors taken included camrelizumab (n=28), sintilimab (n=18), pembrolizumab (n=3) and tislelizumab (n=1), all given 200 mg every 3 weeks (Q3W), and toripalimab (240 mg Q3W) and nivolumab (200 mg every 2 weeks) in 1 patient each. The objective response rate was 15.4% (95% confidence interval [CI] 6.9–28.1), the disease control rate was 61.5% (95% CI 47.0–74.7). After a median follow-up of 14.8 months (range 11.8–23.5), median progression-free survival was 4.2 months (95% CI 2.6–4.8), overall survival was 9.3 months (95% CI 7.9–12.9). Grade 3–4 treatment-related adverse events occurred in 12 patients (23.1%). There was no unexpected toxicity or death. Conclusions: Combination therapy with an anti-PD-1 antibody and apatinib was effective in patients with previously treated, unresectable advanced or metastatic G/GEJ cancer, with a manageable safety profile.
Association of PIWI-interacting RNA-23210 with tumor metastasis in esophageal squamous cell carcinoma.
Authors: Peng Wei , Zhu Jinghua , Cao Guochun , Zhang Qin 
Published: June 2023

e16060 Background: his study aimed to analyze the expression, clinical significance of PIWI-interacting RNA-23210 (piRNA-23210) in esophageal squamous cell carcinoma (ESCC) and the biological effect in its cell line by piRNA-23210 overexpression. Methods: Quantitative real-time RT-PCR (qRT-PCR) was used to analyze piRNA-23210 expression in 60 cases of ESCC and 60 cases of normal tissues to study the relationship between piRNA-23210 expression and clinical factors. Recombinant lentiviral vector was constructed to overexpress piRNA-23210 and then infect ESCC TE-1 cell line. qRT-PCR was used to detect the level of piRNA-23210. 3-[4,5-dimethylthiazol -2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay, cell apoptosis, cell cycle, and migration and invasion assays were also conducted as to the influence of the upregulated expression of piRNA-23210 that might be found on TE-1 cells biological effect. Results: The level of piRNA-23210 expression was found to be significantly lower in ESCC tissue than normal tissues (P < 0.05). Decreased expression of piRNA-23210 was significantly correlated with lymph node metastasis, clinic stage, and histological grade of patients with ESCC (P < 0.05). Meanwhile, loss of piRNA-23210 expression correlated significantly with poor overall survival time by Kaplan–Meier analysis (P < 0.05). The result of biological function show that TE-1 cell transfected piRNA-23210 had a lower survival fraction; higher percentage of the G0/G1 phases; higher cell apoptosis; significant decrease in migration and invasion; and lower cyclin D1, Bcl-2, and MMP-7 protein expression compared with TE-1 cell untransfected piRNA-23210 (P < 0.05). Conclusions: piRNA-23210 expression decreased in ESCC and correlated significantly with lymph node metastasis, clinical stage, poor overall survival, cell proliferation, cell cycles, cell apoptosis and migration and invasion in ESCC cell by regulating cyclinD1, Bcl-2, and MMP-7 expression, suggesting that piRNA-23210 may play important roles as a negative regulator to ESCC cell.
Phase I clinical trial using a unique immunotherapeutic combination of MUC1-targeted CAR-T cells with PD-1-knockout in the treatment of patients with advanced esophageal cancer.
Authors: Chen Size , Lin Yiguang 
Published: June 2023

e16061 Background: Combining CAR-T with programmed cell death-1 (PD-1) inhibition may be a more efficacious approach for treatment of solid tumors. This clinical study was designed to assess the safety and tolerability of PD-1 knockout MUC1-Targeted CAR-T engineered Cells to treat advanced esophageal cancer. Methods: Patients with advanced esophageal cancer were recruited according to the criteria in NCT03706326. PD-1 gene knockout (KO) MUC1-targeted CAR-T cells were prepared by constructing MUC1-specific CARs using the SM3 scFv in patient-derived T-cells, and PD-1 gene KO was achieved in these CAR positive T cells using the CRISPR-Cas9 system. Efficiency and validation were confirmed by sequencing and flow cytometry. MUC1-CAR+/PD-1- KO engineered T cells at a starting dose of 5x107 were infused over 60 min. The dose was escalated to 5x109 cells. Following treatment, the safety and tolerability of dose of the therapeutic cells were assessed using CTCAE v4.0. Patients’ general condition, levels of lymphocytes, IL-6, hs-CRP, PCT, CYFRA21, NSE(E), and SCC were monitored at regular intervals. Circulating CART cells were checked regularly. Tumor size were examined by MRI/CT scans. Efficacy was also assessed. Results: A total of 9 patients (aged 48 to 80) diagnosed with esophageal cancer/esophageal squamous cell carcinoma (IIIb to IV), were included in this study. All participants received at least one cycle of CART cell treatment. Among the 9 treated patients, 4 received 1 cycle, other 5 received 2, 3, 4, 7 and 10 cycles, respectively. The most common adverse events (AE) were acute fever (8 patients, 38.0-40.5 C◦), chills (5 patients, occurred in the subsequent cycle of infusion), skin rash (4 patient). No grade 3-5 AEs were found, and no cytokine release syndrome (CRS) was observed. Of the 9 assessed patients, 6 had stable disease (SD) while 3 had progressive disease. All patients had significant symptom improvements after infusion. Circulating CART cells gradually declined after infusion; the number dropped down to approximately 25% in 4 months after one cycle treatment indicating the necessity of receiving more cycles. Patients who received multiple cycles of infusion showed long-term and steady SD status. Two patients who received a multiple cycle of CAR-T cells had an overall survival (OS) of 24 months. Conclusions: Our data suggests that the treatment of patients with advanced esophageal cancer with PD-1 disrupted MUC1-targeted CAR-T cells is safe and well-tolerated by all patients. No CRS and other serious EAs were observed throughout the study. The efficacy of this unique combined therapy is currently being assessed. Our limited data indicate that the OS of the patients extended significantly in the treated patients. Two out of 6 patients with an OS of greater than 24 months, an outstanding clinical outcome. Clinical trial information: NCT03706326 .
Fruquintinib plus oxaliplatin combined with S-1 (SOX) as neoadjuvant therapy for locally advanced gastric adenocarcinoma (FRUTINEOGA): A multicenter, phase II study.
Authors: Wu Liucheng , Qin Yuzhou , Huang Mingwei , Long Di 
Published: June 2023

e16063 Background: Neoadjuvant chemotherapy (NCT) has become the standard treatment for patients (pts) with locally advanced GC, and SOX is the most common neoadjuvant regimen in China. Fruquintinib is a VEGFR inhibitor that blocks new blood vessel growth associated with tumor proliferation. It is a potent, highly selective small-molecule inhibitor of VEGFR-1,-2, and -3. The generally good tolerability in pts and fruquintinib’s low potential for drug-drug interaction suggest that it may be highly suitable for combinations with other antineoplastic therapies. We aimed to investigate the efficacy and toxicity of fruquintinib plus SOX as neoadjuvant treatment for locally advanced GC. Methods: It was a prospective, multicenter, phase II study in pts with stage III (cT3/4aN+M0) GC. Pts received 2 to 4 cycles of fruquintinib (5mg qd D1-14, Q3W) plus SOX (oxaliplatin 130mg/m2 D1, S-1 40-60mg bid D1-14 depending on body surface area (BSA), Q3W). Pts underwent D2 gastrectomy after neoadjuvant treatment. The primary endpoint was pathological response rate (pRR), and the secondary endpoints were disease-free survival (DFS), overall survival (OS), objective response rate (ORR), major pathological response rate (MPR), and R0 resection rate. Results: Up to February 3, 2023, 19 pts were eligible for the study. Median age was 62 years (29-73), 68.4% were male, and 21.1% were ECOG 1. Seven pts dropped out of clinical trial for AEs (2 pts), violation of treatment protocol (1 pt), staging error (2 pts), and refusal of surgery (2 pts). Twelve pts underwent surgery, 1 patient was found with peritoneal implantation, 11 patients underwent gastrectomy. Among the 11 pts, 9 pts achieved pRR (81.8%) and 3 pts achieved MPR (27.3%). The pathologic CR rate was 27.3% (3 of 11 pts). Moreover, 11 pts had curative intended operations and R0 resection rate was 90.9%. Among all the 19 pts, 16 pts received at least one dose of the combination treatment. A total of 2 pts had target lesions, 1 patient had complete response and 1 had partial response. Among the other 14 pts without target lesions, 1 (7.1%) had progressive disease with peritoneal implantation metastasis, and none had complete response. Furthermore, the most common TEAEs of grade ≥ 3 occurred in 19 pts were decreased appetite (21.1%), hypertension (21.1%), nausea (15.8%), vomiting (10.5%), oral mucositis (10.5%), fatigue (5.3%), diarrhea (5.3%) and respiratory infections (5.3%). There were neither new safety signals nor AEs inducing treatment deaths. Conclusions: The combination of fruquintinib and SOX as neoadjuvant treatment in patients with locally advanced GC is safe. The combination demonstrates promising evidence of anti-tumor efficacy in terms of pathological response. Clinical trial information: NCT05122091 .
Comparison of adjuvant capecitabine plus oxaliplatin (CAPOX) versus S-1 in patients with gastric cancer after gastrectomy based on the registry data base on the National Health Insurance Service (NHIS) database in Korea.
Authors: Maeng Chi Hoon , Kim Hoseob , Kim Mina 
Published: June 2023

e16069 Background: The standard of care for locally advanced gastric cancer in Asia is still upfront gastrectomy with D2 lymph node dissection followed by adjuvant chemotherapy (AC). Both capecitabine plus oxaliplatin (CAPOX) and S-1 are accepted. Which of the two types of chemotherapy is better is still controversial. Methods: For this retrospective nationwide cohort study, data were obtained from the NHIS of Korea. As the NHIS is a single-payer healthcare system, it covers the entire population in the Republic of Korea and it also provides comprehensive information which contains demographic data, healthcare utilization, pharmaceutical prescriptions, and death for each patient. In study population, we included patients who received gastrectomy with a primary diagnosis of gastric cancer which were certified by international classification of disease (ICD) 10th codes of C16.x from January 1st 2013 to December 31th 2018. Survival outcomes of patients who received postoperative chemotherapy were compared based on S-1 (Arm S) vs. CAPOX (Arm C) as well as other relevant clinical variables such as age, sex, co-morbidity and completion of planned treatment. Results: During the study period, 98,556 patients were identified to have undergone both gastric cancer and surgery. After excluding ineligible subjects, a total of 6,602 patients were included in the analysis. Of these, there were 4,199 in Arm S and 2,403 in Arm C, respectively. After propensity score matching, final study population were identified 2,067 in each arm. Arm C showed statistically inferior survival (OS) compared to Arm S (5-year OS rate, 84.0% vs 90.0%, p < 0.0001). Disease-free survival (DFS) was also shorter in Arm C than Arm S (5-year DFS, 78.4% vs 86.1%, p < 0.0001). Age (65 ≥ vs. < 65) and incompleteness of the planned treatment had also significant negative effect on both OS and DFS. Charlson co-morbidity index (≥4 vs. 0-3) was not associated with the difference of OS or DFS. After adjusting with multivariable analysis, Arm C still showed worse OS (HR 1.609, 95% CI, 1.339-1.934, p < 0.0001) and DFS (HR 1.552, 95% CI, 1.333-1.807, p < 0.0001) compared to Arm S. Conclusions: Both S-1 and CAPOX showed excellent efficacy. This nation-wide cohort study suggests that S-1 can be a better option in some clinical situations.
A prospective analysis of robotic three-stage esophagectomy for carcinoma of the esophagus in a tertiary care cancer centre.
Authors: Bathala Udayee Teja 
Published: June 2023

e16078 Background: This study is to evaluate the safety and technical feasibility of total robot-assisted three-stage esophagectomy in terms of: Completeness of surgery, margin status, lymph nodes harvested, learning curve, docking time and total operating time, and associated morbidity and mortality. Methods: It is a prospective non-randomised study from Nov 2016 to Nov 2022 with a total of 168 patients. Inclusion criteria: Histologically proven squamous cell carcinoma, adenocarcinoma of the intrathoracic esophagus surgically resectable (T1-3,N0 -1,M0); ECOG performance status: 0,1 or 2. Exclusion criteria: Carcinoma of cervical esophagus; patients unfit for general anesthesia; stage IV disease. Results: In a total of 168 patients, 52% had Squamous cell carcinoma and 48% had Adenocarcinoma; 8% had upper thoracic, 44.5% mid thoracic and 47% lower thoracic lesions. Mean docking time of 33 mins and mean operating time of 321 min. Average hospital stay of 7 days with average of 44 lymph nodes retrieved and mean blood loss of 280 ml. Intra operative complications of RLN injury in 2%, Thoracic duct injury in 1.6%, and Azygous vein injury in 1%.Post operative complications such as delayed gastric emptying in 3.5%, anastomotic leak in 2.9%, pleural effusion in 2.4%, wound infection in 0.6% and re-exploration in 1.7%. Conclusions: Robotic-assisted esophagectomy has its own unique benefits of very low conversion rates, short learning curve, good quality lymphadenectomy in supra-azygous and bilateral recurrent laryngeal nerve area, less painful with faster recovery even in aged patients with significant co-morbidities. Future RCT may confirm the lower incidence of major complications, and similar OS and DFS compared to open approaches.[Table: see text][Table: see text]