bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neoadjuvant pembrolizumab plus chemotherapy for resectable locally advanced esophageal squamous cell carcinoma (ESCC): Interim results.
Authors: Wang Weiwei , He Jia , Wu Xi , Zhou Weixun , Zhao Luo , Li Li 
Published: June 2022

e16011 Background: Esophageal squamous cell carcinoma (ESCC) is the predominant subtype of esophageal cancer in China. Its prognosis remains poor and neoadjuvant treatment may improve the prognosis for resectable ESCC. The combination of immunotherapy with cytotoxic agents has shown encouraging antitumor activity in multiple tumors but data are lacking to support this approach as a neoadjuvant strategy for locally advanced ESCC. We conducted a prospective clinical trial of pre-operative pembrolizumab with chemotherapy in patients with locally advanced ESCC. Methods: Patients with clinical stage IIB-IVA ESCC eligible for resectable surgery were prospectively enrolled. Patients received neoadjuvant pembrolizumab (200mg) and chemotherapy (docetaxel 75mg/m2 plus cisplatin 75mg/m2 or carboplatin area under curve 4-5) every 3 weeks for four cycles before surgery. The primary endpoint was pathologic complete response (pCR) rate and radical (R0) resection rate. Secondary endpoints include Disease Free Survival (DFS), adverse events, and the correlation between biomarkers and immunotherapy efficacy. Results: From August 2020 to January 2022, 27 eligible patients participated the study. Twenty-four patients have completed four cycles of neoadjuvant therapy, among whom 22 patients were radiologically evaluable after neoadjuvant therapy. The objective response rate (ORR) was 68.2% and disease control rate was 100%. Among 22 patients with resectable tumors, 14 patients underwent McKeown MIE and 5 patients are still waiting for the surgery. Three other patients who achieved partial response (PR) refused surgery due to fear of complications. For 14 patients who underwent esophagectomy within 29-74 (median44) days after neoadjuvant treatment, all achieved radical resection. pCR (ypT0N0) was observed in 4 patients (4/14, 28.6%). Three patients (3/14,21.4%) had a College of American Pathologists (CAP) score of 1, one (1/14, 7.1%) had a CAP of 2, and 6 (6/14, 42.9%) had a CAP of 3. Most treatment-related AEs (TRAEs) were grade 1 or 2. Grade 3/4 TRAEs of leucopenia, decreased neutrophil count and dermatitis occurred in 9 (33.3%), 14 (51.9%), and 1 (3.7%) cases, respectively. No surgical complication was observed. Conclusions: Neoadjuvant pembrolizumab plus chemotherapy has achieved satisfactory initial efficacy and safety results in locally advanced ESCC. A phase III randomized controlled trial is required to confirm the clinical benefits of this neoadjuvant therapy.
Encouraging efficacy of sintilimab combined with nanoparticle albumin-bound paclitaxel and platinum as the first-line treatment for metastatic esophageal squamous cell carcinoma: A retrospective study.
Authors: Wang Chao-Jie , Feng Jiang-Shan , Zhao Wei-Feng 
Published: June 2022

e16013 Background: Esophageal squamous cell carcinoma (ESCC) is one of the common malignancies worldwide and associated with poor prognosis. More recently, immunotherapy, especially monoclonal antibodies of programmed death receptor 1 (PD-1) and its ligand (PD-L1), has provided new treatment options for patients with various tumors. But there was no study to investigate the efficacy and safety of sintilimab combined with nanoparticle albumin-bound paclitaxel (Nab-PTX) and platinum as the first line treatment of metastatic ESCC. Methods: This was a retrospective study, the eligible metastatic ESCC patients were given sintilimab in combination with Nab-PTX and cisplatin or nedaplatin for up to 4-6 cycles (every 3 weeks). After immunochemtherapy, patients without progressive disease (PD) continued to receive sintilimab every three weeks as maintenance treatment until unacceptable toxicity, PD, withdrawal of consent, or for up to 2 years. The primary end point was objective response rate (ORR), the secondary end points included progression-free survival (PFS), overall survival (OS), disease control rate (DCR), and safety. Results: A total of 22 patients diagnosed as metastatic ESCC were enrolled, one patient reached a complete response (CR), 15 patients reached a partial response (PR), 4 patients stable disease (SD) and 2 patients PD. The ORR was 72.7% (16/22), the DCR was 90.9% (20/22). The time to response (TTR) was 1.9 months (95% CI:1.7-2.2 months). The median PFS was 7.0 months (95% CI, 6.0-9.3 month), median OS was not reached (6.5 months to not reached). Treatment related adverse events (AEs) occurred in 21 patients (95.5%), and most of them were grade 1 and 2. AEs of grade 3 or 4 occurred in 10 (45.5%) patients, there was no treatment-related death in this study. Conclusions: The preliminary results of this study suggest that sintilimab combine with Nab-PTX and platinum for patients with metastatic ESCC had significant high ORR and encouraging median PFS, and the safety profile is manageable. Clinical trial information: ChiCTR2100051909.
APEC: Efficacy and toxicity of anlotinib plus PD-1 inhibitors as later-line therapy in advanced/metastatic esophageal squamous cell carcinoma (ESCC): A retrospective real-world study.
Authors: Liu Jun , Ma Xiumei , Wu Jianguo , Zhang Ming , Li Hongxuan , Cheng Yan , Fu Xiaolong 
Published: June 2022

e16014 Background: Anlotinib has been approved in ESCC treatment because of its good tolerance and efficacy. Antiangiogenic target therapy plus immunotherapy has been initially recognized, whereas the data on the third & above line is still unknown. We aimed to retrospectively analyze the effect of anlotinib plus PD-1 inhibitor as later-line therapy on the survival of ESCC in the real world. (APEC, NCT 04984096). Methods: Retrospective data analysis was performed on ESCC patients (pts) treated with anlotinib plus PD-1 inhibitors as later-line therapy between Sep 2019 and Nov 2021 at Shanghai Chest Hospital, China. Demography, previous treatment, performance status, pathological classification, comorbidities, and distant metastatic organ status were collected. Progression free survival (PFS) was the primary end point of this study. The secondary end points were objective response rate (ORR), disease control rate (DCR) and overall survival (OS). Tumor response was assessed per RECIST version 1.1 by the investigators. Adverse events were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0. Results: There were 21 pts in the cohort. The average age was 61.5 (range 48-77) years old, and 95.2% patients were male. 7 cases (33.3%) had comorbidities. 2 cases (9.5%) had other tumor history. In addition, 19 pts (90.5%) had received radiotherapy, 21 pts (100.0%) had received chemotherapy and 19 pts (90.5%) had received immunotherapy. Among all pts, 1 patient achieved complete response (CR), 6 pts partial response (PR), 10 pts stable disease (SD), illustrating an ORR of 33.3 % and a DCR of 81.0%. Median PFS reached 8.1 months (95%CI 3.8-12.4) while median OS was not reached. All grades of TRAEs occurred in 95.2% pts and 90.5% were grade 1-2. Of note, grade 3-4 hematological toxicity (lymphocytopenia) was reported in only 2 patient (9.5%). All AEs were resolved after symptomatic treatment. Conclusions: Our data suggest that treatment with anlotinib plus PD-1 inhibitors as later-line therapy can result in curative effect of ESCC, which can achieve promising ORR, DCR and PFS with mild toxicity. To our knowledge, this is the first analysis to demonstrate the benefits of anlotinib plus PD-1 inhibitors as later-line therapy in ESCC. The data suggests that anlotinib plus PD-1 inhibitor is a new treatment in ESCC pts, and further validation in a larger cohort is needed. Clinical trial information: 04984096.
Serological markers associated with response and adverse events in patients of esophageal squamous carcinoma with toripalimab combined with nab-paclitaxel and S-1 as neoadjuvant therapy.
Authors: Zhang Guoqing , Yuan Jing , Xu Qing , Zhang Jing , Liu Minglu , Song Zhigang , Wu Liang Liang , Yang Bo , Hu Yi , Jiao Shunchang , Luo Haitao , Cui Xiaoli , Pan Chaohu 
Published: June 2022

e16017 Background: Immune checkpoint inhibitor (ICI) combined with chemotherapy as a neoadjuvant therapy has been applied to the treatment of patients with esophageal squamous carcinoma (ESCC), however, there were a limited number of predictive biomarkers for response and adverse events. Methods: 60 patients diagnosed with ESCC and considered propable for surgical treatment were enrolled from October 2019 to September 2020 in the first medical center of Chinese PLA General Hospital and received Toripalimab combined with nab-Paclitaxel and S-1 as neoadjuvant therapy. Serum samples were collected at baseline and performed with 92 proteins using proximity extension assay technology. Results: In total, 50 patients were examined, and 3 patients did not pass quality control. Patients with IFN-Y-L, LAMP3-L and Gal.1-H at baseline were associated with longer overall survival. Furthermore, 21 proteins were found to be significantly lower in patients with severe side effects than in patients without serious adverse events. Conclusions: Our study found that serum levels of several proteins were associated with clinical benefit and severe side effects, and these proteins may be useful biomarkers for predicting response and severe side effects in ESCC treated with ICI and chemotherapy.
The advent of anti-PDL-1 antibodies in the treatment of advanced gastric carcinomas: A systematic review.
Authors: Vorla Mounica , Akbar Usman Ali , Ashraf Aqsa , Pusa Mounika , Barham Saman , Khan Adil , Sheikh Daniya , Dab Ammar Yaser , Qazi Shaheryar , Chaughtai Zeeshan , Anwer Faiz 
Published: June 2022

e16020 Background: The poor prognosis of systemic chemotherapy in advanced gastric adenocarcinoma (GC) and gastroesophageal (GE) carcinoma prompted the development of novel agents such as anti-PDL-1 antibodies, which have the potential to overcome drug resistance due to signaling pathway overlap. We study here the safety and efficacy of standalone and combination chemo-immunotherapy in the treatment of advanced GC & GE Carcinomas. Methods: Following the PRISMA guidelines, we searched the literature on PubMed, Cochrane, Embase & clinicaltrials.gov. A total of 300 articles were screened, and 7 studies were included. Results: With anti-PDL-1 inhibitors in phase III clinical trial, the overall survival (OS) was more remarkable in Chemotherapy (CTX) vs. Avelumab (AVE) (5 vs 4.6 mo). However, Nivolumab (NIVO 1mg and NIVO 3mg) significantly prolonged the OS when combined with Ipilimumab (IPI), but the grade > 3 adverse events were reported more in NIVO1 and NIVO3 regimen. Similarly, Pembrolizumab (P) increased both OS and progression-free survival (PFS) when used alone and as combination therapy compared to chemotherapy alone, as illustrated in the table. Conclusions: The anti-PDL-1 inhibitors show promising data to treat advanced or relapsed GC or GE Carcinomas with favorable side effect profiles. However, there is further need for high-quality large prospective randomized clinical trials.[Table: see text]
Intratumoral CD8+ t cell as a potential positive predictor for treatment of chemo-immunotherapy in PD-L1 negative advanced gastric cancer patients.
Authors: Tong Gangling , Zhu Meiqin , Chen Yaoxu , Wang Shubo , Cheng Boran , Wang Shubin , Liao Wangjun 
Published: June 2022

e16029 Background: It was demonstrated that CPS PDL1 positive patients of advanced gastric cancer (GC) could benefit from specific immune checkpoint inhibitors (ICI) for first-line, and second-line or subsequent therapy. However, whether the application of ICI could lead to better clinical outcome in advanced GC patients who were negative for PDL1 remains further explore. Some studies showed that patients with specific tumor immune microenvironment (TME) are more sensitive to immunotherapy. Therefore, TME may be a potential positive predictor for PDL1 negative patients treated with immunotherapy. Methods: We retrospectively enrolled 26 advanced GC patients who were treated by chemoimmunotherapy in Shenzhen Hospital of Peking University and evaluated for clinical characteristics. Peritumoral and intratumoral Tumour-infiltrating lymphocytes (TIL) were detected by mIHC (multiplex immunofluorescence) among these patients. The correlation between PFS and clinical characteristics including TIL was analyzed by univariate survival analysis and multivariate Cox proportional hazards analysis. Results: In 26 patients, 5 patients (19.2%) experienced complete response (CR), 9 patients (34.6%) experienced partial response (PR), while 7 patients (26.9%) experienced stable disease (SD). Compared with non-responders, higher intratumoral infiltrating CD8+ T cells instead of other subtypes were detected in CPS PDL1 negative Patients who respond to chemoimmunotherapy. Further analysis revealed that CD8+ TIL was a predictive biomarker for PFS to chemo-immunotherapy in CPS PDL1 negative patients. Conclusions: For CPS PDL1 negative advanced GC patients, intratumoral CD8+ TIL may be a potential positive predictor for treatment of chemo-immunotherapy.
Cambrelizumab plus chemotherapy as conversion therapy for unresectable metastatic gastric cancer: A single-arm, multicenter, prospective clinical trial.
Authors: Li Shuang , He Liang , Li Meng , Wang Quan 
Published: June 2022

e16032 Background: Although anti-PD-1 antibody in combination with chemotherapy has shown promising antitumor activity in advanced gastric or gastroesophageal junction adenocarcinoma (GC/GEJC), the evidence of conversion therapy for initially unresectable GC/GEJC is limited. Camrelizumab combined chemotherapy as conversion therapy for unresectable GC/GEJC was a prospective, single-arm, phase 2 study we conducted. Here, we updated the results of efficacy and safety of this study. Methods: Patients with HER-2 negative and PD-L1+ (CPS≥1) or MSI-H/dMMR, or EBV (+) unresectable gastric cancer were enrolled. Eligible patients must meet one of the following criteria: 1) peritoneal metastasis (CY1P0 or P1a, P1b or PCI < = 10); 2) liver metastasis (H1), < 3 metastatic sites; 3) para-aortic lymph node metastasis. For patients with lymph node metastasis or liver metastasis, they received 6 cycles of camrelizumab (200mg ivgtt on day1, q3w) plus SOX (Oxaliplatin, 130mg/m² ivgtt, d1, q3w, S-1 40/50/60 mg based on BSA, po, bid, d1-14, q3w) as conversion therapy. For patients with peritoneal metastasis, they received 6 cycles of camrelizumab (200mg ivgtt on day1, q3w) plus IP (Paclitaxel, 50mg/m², ivgtt, d1, d8, q3w. Paclitaxel, 20mg/m², intraperitoneal administration, d1, d8, q3w. S-1 40/50/60 mg based on BSA, po, bid, d1-14, q3w) as conversion therapy. Then patients without disease progression evaluated by imaging underwent gastrectomy of D2 lymph node dissection. The primary endpoint was R0 resection rate and 2 years survival rate, the secondary endpoints were objective response rate (ORR), pathological complete response (pCR) rate and overall survival. Results: Between December 30, 2020 and January 5, 2022, 31 patients were enrolled. 19 patients received SOX plus camrelizumab, 12 patients received IP plus camrelizumab. Unfortunately, 7 of them were confirmed PD by imaging. In addition, two patients refused gastrectomy and withdrew from the study. 12 patients underwent gastrectomy and 8 patients are in the process of conversion therapy. Among the 12 patients were evaluable, 9 of them gained R0 resection (75%), 1 patient (8.3%) achieved pCR and 2 patient (16.6%) reached TRG1. The most common grade 3 adverse events (AEs) were neutropenia (27.6%). No serious AEs resulted in termination of treatment or death. Conclusions: Camrelizumab combined with chemotherapy was an effective and safe conversion therapy strategy for patients with unresectable GC/GEJC. Furthermore, the analysis of biomarkers with clinical benefits is undergoing. Clinical trial information: NCT04694183.
Clinicopathological features, treatment outcome and survival of 115 cases of gastric adenocarcinoma with bone marrow metastasis and disseminated intravascular coagulation.
Authors: Xiao Jian , Cao Taiyuan , Du Ge , Zhai Xiaohui , Li Shanshan 
Published: June 2022

e16035 Background: Bone marrow (BM) infiltration is a special subtype of bone metastasis in gastric cancer (GC) and frequently complicated with disseminated intravascular coagulation (DIC) and other hematological disorders, which constitute a critical but poorly defined clinical syndrome (GBD syndrome). At present, only case reports are available about this peculiar disease. This pooled analysis was to describe its detailed clinicopathological features and treatment outcome. Methods: Cases reported in medical literatures or treated in our hospital from 2000 to 2021 were systemically scrutinized. The inclusion criteria were: adenocarcinoma in gastroesophageal junction or stomach, carcinomatosis in BM, and overt DIC. Detailed clinical and pathological data were reviewed. Based on the chronological order of the diagnosis of GC, BM infiltration and DIC, GBD syndromes could be classified as synchronous and metachronous type. Descriptive statistics, chi-square test, Fisher's exact tests, and survival analysis were performed as appropriate. Results: 115 cases of GBD syndrome were identified. 91 (79.1%) were synchronous and 24 (20.9%) were metachronous. Female patients were more than half in the study (61, 53.1%). The median age of 51 (9-87) was relatively younger than that of normal GC. ECOG PS 3-4 were present in 67 (58.3%) cases. 109 (94.8%) had poorly differentiated adenocarcinoma. Her-2 overexpression were only seen in 8 (6.9%) cases and none were d-MMR. 88.3% (53 out of 60) cases treated in our hospital showed remarkable CKMB elevation which was not mentioned in previous reports. Abnormal level of LDH and ALP were seen in 91.2% and 64.3% cases. Totally, 82 patients received anticancer therapy. 70 (85.3%) went through the first DIC strike. 5-FU and docetaxel were the most applied agents. Patients treated with BSC only survived 14 days (2-61). After the remission of DIC, patients with synchronous and metachronous BD syndrome achieved 168 and 182 days of overall survival, respectively (p = 0.932). Conclusions: CKMB might be a distinctive marker for GBD syndrome. Active chemotherapy achieved numerous remissions of DIC and a considerable survival. Further translational research and prospective trial are urgently needed.
The mortality of venous thromboembolism in hospitalized patients with different gastrointestinal malignancies.
Authors: Fatima Zainab , Darweesh Mohammad , Alhabhbeh Ammar , Abdel-Razeq Nayef Hikmat , Manthri Sukesh , Young Mark 
Published: June 2022

e16036 Background: Venous thromboembolism (VTE) is associated with significant morbidity and mortality in cancer patients. Our study compares the mortality in hospitalized VTE patients among the five most common Gastrointestinal (GI) malignancies which includes esophageal, gastric, pancreatic, colorectal, and hepatobiliary cancers. Methods: A retrospective study was conducted utilizing the Nationwide Inpatient Sample database (NIS) from 2016 to 2018. Patients with Venous thromboembolism (VTE) were identified using ICD 10 codes from all primary discharge diagnoses. Only deep venous thrombosis (DVT) and pulmonary embolism (PE) were considered. Patients with VTE were further divided into groups: esophageal cancer, gastric cancer, pancreatic cancer, colorectal cancer, hepatobiliary cancer, and compared with patients who did not have these malignancies. Patients younger than 18 years of age or patients with missing age, gender or race were excluded. Among the hospitalized patients with VTE, we investigated the difference in mortality with different gastrointestinal malignancies. Adjusted odds ratio (OR) was calculated using multivariate regression analysis. Results: Among 751,834 patients discharged with a VTE diagnosis, 0.24% had esophageal cancer, 0.25% had gastric cancer, 0.93% had pancreatic cancer, 1.10% had colorectal cancer, 0.35% had hepatobiliary cancer, and the other 97.14% did not have these malignancies. The study shows that adults admitted to the hospitals for VTE have higher mortality when compared to patients who did not have GI malignancies, with esophageal cancer having the highest inpatient mortality with an OR of 2.66 (95% CI 1.78-3.94, P of 0.00). For the remaining GI cancers, gastric cancer had an OR of 1.74 (95% CI 1.141-2.661, P of 0.010), pancreatic cancer had an OR of 1.74 (95% CI 1.402-2.178 P of 0.000), hepatobiliary cancer had an OR of 1.67 (95% CI 1.144-2.439 P-value of 0.002) and colorectal cancer had OR of 1.18 (95% CI 0.930-1.517 P of 0.169), which was not statistically significant. Conclusions: Pancreatic and gastric cancers have a higher risk of VTE and frequently score high in validated VTE risk assessment tools such as the Khorana score. This study shows that VTE in hospitalized patients with esophageal cancer is associated with greater mortality. More research is needed to analyze the outcomes of VTE in cancer patients and to identify those who would benefit from thromboprophylaxis. Due to the nature of the NIS database, one of the study's limitations was the difficulty in identifying patients receiving DVT prophylaxis.
A study of neoadjuvant sintilimab combined with chemotherapy TP for locally advanced esophageal squamous cell carcinoma (ESCC).
Authors: Li Zhao , Xu Peng-Fei , Mao Wei-Min , Kuang YuKang , Fan Hai-Yin , Zou Bin , Zhu Jian-Feng , Li Chao , Cheng Xiao-Liang , Liu Xing-Fei , Guo Changying 
Published: June 2022

e16038 Background: Although preoperative chemoradiotherapy is the standard of care for patients with locally advanced esophageal cancer, ESCC still has a dismal prognosis. Sintilimab, a humanized IgG4 monoclonal antibody with high affinity and specificity for PD-1, has shown promising efficacy with overall survival in ESCC in a phase II study (ORIENT-02, NCT03116152)1. KEEP-G 03 given the encouraging MPR and favorable tolerability of preoperative sintilimab in combination with triplet chemotherapy in resectable ESCC (KEEP-G 03, NCT03946969)2. This trial evaluates the feasibility and safety of preoperative sintilimab in combination with chemotherapy of TP in ESCC. Methods: This is a single-arm, single center research, phase 2 trial to assessment the efficacy and safety of asintilimab and chemotherapy of TP(Q3W 2-4 cycle) as neoadjuvant treatment of locally advanced ESCC. The key eligibility criteria was locally advanced ESCC, ECOG PS 0 or 1, and at least one measurable lesion per RESIST v1.1. aSintilimab: 200mg for 60kg, 3mg/kg for body weight < 60kg; TP: pacilitaxel 175mg/m2 plus cisplatin 75mg/m2. Primary Objectives: pCR, MPR. Secondary Objectives: R0 rate, RFS, OS, Safety (CTCAE 5.0). Exploratory Objectives: The alteration of molecular biomarkers to neoadjuvant treatment including PD-L1, TMB, DDR, etc. Results: From 1/2020 to 12/2021, 20 eligible patients were recruited in the Jiangxi Tumor Hospital, NanChang, China. Conclusions: Given the encouraging MPR and favorable tolerability, the combination of sintilimab and chemotherapy of TP could be a potentially feasible and safe neoadjuvant option for locally advanced ESCC. The trial will be continued to evaluate the feasibility of this regimen.[Table: see text][Table: see text][Table: see text]