bluuebunny/crossref_metadata_2025_split huggingface dataset:
Minimally invasive or open oesophagectomy for localized oesophageal cancer: Results of the ROMIO phase 3 randomized controlled trial.
Authors: Blazeby Jane M. ,   The ROMIO Group
Published: June 2021

e16057 Background: Patients with localised oesophageal adenocarcinoma or squamous cell cancer are frequently offered surgery, usually with neoadjuvant treatment. Whether minimally invasive surgical approaches are superior to standard open procedures in terms of patient recovery and survival benefit is unclear. Well-designed and well-conducted pragmatic trials are limited. The ROMIO study compared laparoscopic abdominal surgery and thoracotomy (LAO) with open oesophagectomy (OO), to test the hypothesis that LAO allows faster recovery than OO whilst maintaining the survival benefit of surgery. Methods: A pragmatic multi-centre randomised controlled trial (1:1 LAO vs. OO) was conducted in 9 major cancer centres in the UK. Included were patients with localised adenocarcinoma or squamous cell cancer selected by a multi-disciplinary team for oesophagectomy with or without neoadjuvant treatment. Surgery was quality assured by provision of a protocol, pre-operative video assessment of the 40 participating surgeons and intra-operative photographs of key agreed surgical components. The primary outcome was the physical function scale of the EORTC QLQ-C30 assessed during the first 3 months. Results: At enrolment to ROMIO 447 (85%) of 526 participants were male, mean age was 67 years (SD 9), 469 (89%) had an adenocarcinoma, 368 (70%) had a clinically staged T3 or T4a tumour, 295 (56%) had clinically positive nodes, and 438 (83%) underwent neoadjuvant treatment. 263 were randomly allocated to each of the two procedures, with 241 (92%) undergoing their allocated open surgery and 237 (91%) undergoing their allocated LAO (hybrid) surgery. Analyses are underway and this presentation will include the primary outcome measure and other short-term clinical outcomes including key complications and survival during the first 90 days (clinical data >95% complete). Conclusions: ROMIO is the largest multi-centre randomised controlled surgical trial of minimal access versus open surgical approaches for oesophageal cancer. The provision of a surgical quality assessment tool will supplement trial data to provide for the first-time evidence of surgical standards of both approaches. Clinical trial information: ISRCTN10386621.
Phase 2 study of zolbetuximab plus mFOLFOX6 in claudin 18.2-positive locally advanced or metastatic gastric or gastroesophageal junction adenocarcinoma (G/GEJ): ILUSTRO cohort 2.
Authors: Klempner Samuel J , Lee Keun-Wook , Metges Jean-Philippe , Catenacci Daniel V.T. , Loupakis Fotios , Ilson David H. , Shah Manish A. , Shitara Kohei , Arozullah Ahsan , Park Jung Wook , Raizer Jeffrey J. , Bang Yung-Jue 
Published: June 2021

e16063 Background: One accepted treatment for patients (pts) with advanced HER2-negative G/GEJ is mFOLFOX6 (5-FU, folinic acid, oxaliplatin). Despite treatment options, 5-year survival is poor, and limited biomarkers exist to inform treatment selection. Claudin 18.2 (CLDN18.2), a tight junction protein normally confined to gastric mucosa of healthy tissue, is often retained in G/GEJ. Zolbetuximab, a chimeric IgG1 monoclonal antibody, binds to CLDN18.2 and mediates cancer cell death via antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC). Nonclinical results showed that cytotoxic chemotherapy increased CLDN18.2 expression, improving ADCC/CDC activity of zolbetuximab. Phase 2 results (NCT01630083, FAST) showed prolonged survival with zolbetuximab+EOX (epirubicin, oxaliplatin, capecitabine) vs EOX in G/GEJ. This study assessed antitumor activity and safety/tolerability of first-line zolbetuximab+mFOLFOX6 (Cohort 2 in NCT03505320) in G/GEJ with high CLDN18.2 expression. Methods: Cohort 2 of this multicohort study enrolled adult pts with metastatic or locally advanced unresectable G/GEJ. Patients had measurable disease (RECIST v1.1), HER2-negative disease, and high CLDN18.2 expression (≥75% of tumor cells demonstrating moderate-to-strong membranous staining by central IHC testing). Patients received zolbetuximab 800 mg/m2 IV on Cycle 1 Day 3 then 600 mg/m2 Q3W. Zolbetuximab and mFOLFOX (Q2W from Cycle 1 Day 1) were administered in 42-day cycles. Key endpoints were safety/tolerability and objective response rate by independent central review (ORRICR RECIST v1.1). Results: As of Jan 26, 2021, Cohort 2 had enrolled 21 pts; median age was 63 years (range, 36-74), 57% were male, 43% were Asian, and 38% were white. Of 19 evaluable pts, 12 had confirmed partial responses; ORRICR was 63.2% (95% CI: 38.4-83.7) (Table). Median PFS was 13.7 months (95% CI: 7.4-not estimable); 12-month PFS rate was 58%. Common adverse events (AEs) were nausea (90.5%; grade 3, 4.8%) and vomiting (61.9%; grade 3, 9.5%). Common grade 3/4 AEs were decreased neutrophil count (33.3%) and neutropenia (28.6%). There were no fatal AEs. Conclusions: Results suggest promising antitumor activity with zolbetuximab+mFOLFOX6 in metastatic or locally advanced G/GEJ. The safety profile was manageable and no new safety signals were identified. Clinical trial information: NCT03505320. [Table: see text]
Chemothery (pacitaxol or irinotecan), plus apatinib and sintilimab as second-/third-line treatment for advanced gastric cancer.
Authors: Deng Ting , Zhang Le , Duan Jingjing , Li Hongli , Ge Shaohua , Bai Ming , Ning Tao , Yang Yuchong , Ji Zhi , Liu Rui , Wang Xia , Zhang Haiyang , Ba Yi 
Published: June 2021

e16080 Background: Patients with advanced gastric or gastro-esophageal junction cancer have poor prognosis after progression on first-line chemotherapy. We investigated to combine second-line chemotherpy with third-line drugs, apatinib and anti-PD-1 antibody in these patients. Methods: This study is a single center, exploratory study in China. Eligible patients are adults with histologically confirmed advanced gastric or GEJ adenocancinoma, who were failure of first-line or second-line chemotherapy. Subjects receive chemotherapy, pacitaxol or iritecan (investigator choice), apatinib 250mg po qd, sintilimab 200mg ivd q3w. Response was assessed every 6 weeks. (RECIST version1.1) Primary endpoint was progression free survival (PFS). Results: Between May 30, 2019 and November 5, 2020, a total of 26 patients were enrolled in this study, and 4 (15.4%) patients were failure of second-line chemotherapy. There were 21 males and 5 females, and the median age was 61. The total number of treatment cycles was 140 and the median number was 5.5. Among 24 patients who were evaluated, partial response (PR) was obtained in 12 cases, stable disease (SD) in 8 cases and progressive disease (PD) in 4 cases. Objective response rate was 50.0%，and disease control rate was 83.3%. The median PFS was 7.06 months (95% CI 5.52-8.60), and the median overal survival has not yet been reached. The most common adverse events (AE) were leukopenia (61.5%), anemia (57.7%), neutropenia (53.8%), proteinuria (42.3%), alopecia (42.3%), hypothyroidism (38.5%), elevated alanine aminotransferase (34.6%), elevated aspartate aminotransferase (34.6%) and elevated alkaline phosphatase (34.6%), but most of them were grade 1 or 2, and the most common grade 3 or 4 treatment-related adverse events was neutropenia (11.5%). Conclusions: Chemotherapy, plus apatinib and sintilimab demonstrated promising activity and manageable safety profile as second- even third-line treatment in advanced gastric or GEJ cancer. Demographics and baseline characteristics.[Table: see text]
Transjugular intrahepatic portosystemic shunt plus sequential systemic therapy for advanced hepatocellular carcinoma with tumor thrombus-related symptomatic portal hypertension: A multicenter retrospective study.
Authors: Qiu Zhenkang , Wang Guobao , Zhang Fujun , Xue Jingbing , Yan Huzheng , Wang Guisong , Feng Kai , Wu Xuan , He Zhijiang , Jiang Weiwei , Yang Guang , Chen Zixiong , Gao Fei 
Published: June 2021

e16116 Background: Portal vein tumor thrombus (PVTT) and symptomatic portal hypertension severely affect the survival and quality of life of hepatocellular carcinoma (HCC) patients. The aim of this study was to evaluate the clinical outcomes of the transjugular intrahepatic portosystemic shunt (TIPS) plus sequential systemic therapy in advanced HCC patients with tumor thrombus-related symptomatic portal hypertension. Methods: This multi-center retrospective study explored 142 advanced HCC patients with PVTT and symptomatic portal hypertension who received either TIPS plus sequential systemic therapy (group A) or only symptomatic and supportive treatment (group B) for from April 2016 to January 2020. The Kaplan-Meier method and log-rank test were performed to determine the survival differences of variables. Univariable and multivariable Cox proportional hazards regression analyses were used to identify prognostic factors of overall survival (OS). We used independent factors for the nomogram to predict OS. Results: The median OS of group A was significantly better than that of group B (7.6 [95% CI: 4.6, 10.6] vs. 4.5 [95% CI: 2.7, 6.4], months, P < 0.001). Multivariable analysis also showed that PVTT degree (I/II) (Hazard ratios [HR] = 0.679; 95% CI: 0.465, 0.994; P = 0.046), variceal bleeding (HR = 1.686; 95% CI: 1.059, 2.684; P = 0.028), Child-Pugh Class A (HR = 0.450; 95% CI: 0.272, 0.746; P = 0.002), and BCLC stage C (HR = 0.434; 95% CI: 0.222, 0.850; P = 0.015) were significant predictors of OS. These five indicators were included in the nomogram model to predict survival probabilities in 6- and 12-months OS. Conclusions: TIPS plus sequential systemic therapy is safe and feasible for the treatment of advanced HCC with tumor thrombus-related symptomatic portal hypertension.
A real-world study of camrelizumab in the treatment of hepatocellular carcinoma.
Authors: Zeng Yong-Yi , Guo Wu-hua , Zhang Zhibo , Shi Xi , Su Yongjie , Cai Qinghe , Peng Jianyang 
Published: June 2021

e16121 Background: Programmed cell death protein‐1(PD-1) targeted immunotherapy is a promising treatment strategy for advanced hepatocellular carcinoma. Anti-PD-1 inhibitor camrelizumab showed antitumour activity in phase II studies of advanced hepatocellular carcinoma, with manageable toxicities. This study evaluates safety and efficacy of camrelizumab in patients with advanced hepatocellular carcinoma. Methods: This is a multicentre, real‐world trial done at thirty-three centres in Fujian Province, China. Eligible patients were aged 18 to 75 years was diagnosed by China Liver Cancer Staging(CNLC) 2019 clinical diagnostic criteria or with a histological or cytological diagnosis of advanced hepatocellular carcinoma, unresectable or had progressed on or were intolerant to previous systemic treatment, and had an Eastern Cooperative Oncology Group performance score of 0-1. Patients were received camrelizumab 200 mg intravenously every 2 weeks plus other treatments, such as molecular targeted drug, transcatheyer artetial chemoembolization, radiotherapy and chemotherapy. The primary endpoints were progression-free survival. Safety was analysed in all treated patients. Follow-up is ongoing. Results: Between Mar 12, 2020, and Dec 25, 2020, 63 patients were screened for eligibility, of whom 41 eligible patients received camrelizumab were recruited and among whom 15 received apatinib, 16 received lenvatinib, 2 received sorafenib and 1 received regorafenib. Median followup was 5.28 months (IQR 1.63–10.20). Objective response was reported in 12 (29.3%; 95% CI 16.1–45.5) of 41 patients. Disease control was reported in 34 (82.9%; 95% CI 67.9–92.8) of 41 patients. The median PFS was not reached, and expected more than 9 months. Grade 3 or 4 treatment-related adverse events occurred in 21 (51.2%) of 41 patients; the most common were increased gamma-glutamyltransferase (15 [36.6%]) and increased aspartate aminotransferase (7 [17%]). One death was judged by the investigators to be potentially treatment-related (due to upper gastrointestinal bleeding). Conclusions: Camrelizumab showed promising efficacy and safety in pretreated Chinese patients with advanced hepatocellular carcinoma, and might represent a new treatment option for these patients. Clinical trial information: ChiCTR2000041405. Research Sponsor: Jiangsu Hengrui Medicine Co., Ltd. Clinical trial information: ChiCTR2000041405.
Molecular characteristics of patients with resectable hepatocellular carcinoma.
Authors: Zeng Daobing , Wang Menglong , Wu Jushan , Lin Dongdong , Guo Qingliang , Li Chuanyun , Zhang Haitao , Di Liang , Zhao Xiaofei , Ma Chao , Gao Daming , Liu Zhaobo , Fu Zhi , Sun Libo , Zhang Qikun , Li Guangming , Guo Rongyun , Wang Huina , Zhang Yanrui 
Published: June 2021

e16140 Background: Hepatocellular carcinoma (HCC) is one of the most common malignancies and leading cause of cancer deaths worldwide. Biomarkers contribute to predict the response of targeted treatments and immunotherapy. Therapy directed toward homologous recombination deficiency (HRD) is now approved in ovarian and breast cancer, but the pattern of HRD is not clear in HCC. The HRD phenotype has been defined as the presence of a non-silent somatic mutation in homologous recombination-related (HRR) genes. Thus, we aimed to analyze the molecular characteristics of resectable HCC, including HRR genes. Methods: Matched tumor/normal DNA from resectable HCC patients (N = 53) were analyzed by whole exome sequencing (WES) or Acornmed panel with 808 cancer-related genes. Results: Overall, 94.3% (50/53) patients exhibited genetic alterations. TP53, ARID1A, PTEN and NBPF1 were the most commonly mutated genes in resectable HCC. In addtion, 35.9% patinets harbored at least one HRR genes mutation. The frequently mutated genes were BRCA2 (4.4%), BRCA1(4.0%), ATM (3.9 %), and RAD50 (3.8%). Interesting, frequency of HRR genes mutation in the Chinese cohort was higher than that in TCGA (35.9 % vs 20.9%). Analysis of carcinogenic pathways shown that ERBB and PI3K-AKT signaling pathway were the common signaling pathway. In resectable HCC, 32.08% (17/53) patients disclosed high TMB (highest 25%). Further analysis found that PTEN mutations were remarkably associated with low TMB (p < 0.05). Conclusions: This study contributes to understand the molecular characteristics of patients with resectable HCC, which will be useful to guide personalized therapy and promote the clinical management in this population. Furthermore, the study suggested that it is feasibility for resectable HCC patients received PARP inhibitors, DNA-damaging chemotherapies, and immune checkpoint blockade therapy.
Impact of lenvatinib (LEN) dose-intensity and starting dose on survival among patients with advanced hepatocellular carcinoma (HCC): Results from a Canadian multicenter database (HCC CHORD).
Authors: Amaro Carla Pires , Allen Michael J , Knox Jennifer J. , Tsang Erica S. , Lim Howard John , Lee-Ying Richard M. , Chan Kelvin K. , Qian Jessica , Meyers Brandon M. , Thawer Alia , Al-Saadi Sulaiman Mohammed Saif , Hsu Tina , Ramjeesingh Ravi , Karachiwala Hatim , Abedin Tasnima , Tam Vincent C. ,   HCC CHORD Consortium
Published: June 2021

e16142 Background: The REFLECT trial established LEN as a first-line treatment option for HCC. However, decreased LEN exposure is common due to adverse events leading to dose reductions and treatment discontinuations. The aim of this study was to evaluate whether starting dose or dose-intensity of LEN affects survival. To our knowledge, this is the first study to examine dosing of LEN and survival in HCC patients treated outside of Asia. Methods: From July 2018 to December 2019, HCC patients treated with first-line LEN from 10 different Canadian cancer centers were included. Overall survival (OS), progression-free survival (PFS), disease control rate (DCR) and objective response rate (ORR) were retrospectively analyzed and compared across different mean dose-intensities (> 66.7% vs <=66.7%) and starting dose groups (Full vs reduced). Survival outcomes were assessed with Kaplan-Meier curves and Cox proportional hazards models. DCR and ORR were determined radiographically according to the treating physician´s assessment in clinical notes and not RECIST 1.1 or mRECIST. Results: A total of 173 patients were included. Median age was 67 years, 77% were men and 23% East Asian. The most frequent causes of liver disease were hepatitis C (38%) and B (20%). 56% of patients received localized treatment prior to LEN. Of those, 24% had TACE, 6% TARE and 8% had liver transplant. Before starting LEN 31% of patients were ECOG 0 and 57% were ECOG 1. Most patients were Child-Pugh A (81%) and BCLC stage C (73%). Main portal vein invasion was present in 15% of the patients. Median follow-up was 4.5 months. LEN was started at full dose in 54% of patients and 60% had a mean dose intensity greater than 66.7%. ORR, PFS and OS results and their comparison between the different starting dose and dose-intensities are shown in the table. In a multivariate model that adjusted for age, gender, stage, ECOG, Child-Pugh, BCLC, cirrhosis, liver etiology disease (hepatitis B, C and non-viral), presence of tumor thrombus, prior transplant and localized treatment, dose intensity (>66.7 vs <=66.7% [HR 0.70, 95% CI 0.42-1.18; p=0.18]) was not a predictor of survival. Conclusions: In HCC patients starting LEN at a reduced dose does not appear to compromise survival. LEN dose-intensity of > 66.7% was associated with improved survival, but not after controlling for potential confounders.[Table: see text]
Epigenomic analysis of biliary tract cancer identifies subtypes with different immune characteristics and clinical outcomes.
Authors: Qiu Zhiquan , Ji Jun , Xu Yu , Zhu Yan , Gao Chun-Fang , Wang Guoqiang , Li Chengcheng , Zhang Yuzi , Zhao Jing , Wang Chenyang , Wen Xiaofang , Zhang Zhou , Li Bingsi , Han-Zhang Han , Liu Hao , Cai Shangli , Zhang Zhihong , Li Bin , Jiang Xiaoqing 
Published: June 2021

e16153 Background: Biliary tract cancer (BTC) is an aggressive malignancy with poor prognosis and limited treatment options. The epigenome-associated multi-dimensional studies for BTC are limited. Here, we proposed a DNA methylation-based classification scheme and investigated the associations between methylation and multi-dimensional data including clinicopathological features, genetic aberrations, and prognosis. Methods: Multi-dimensional data concerning mutation, DNA methylation, and clinical data from 105 BTC patients who received surgical resection (gallbladder cancer [GBC], n=48, cholangiocarcinoma [CCA], n=57) were analyzed. Differentially methylated blocks (DMBs) in GBCs and CCAs were identified by comparing tumors and adjacent tissues. Methylation-based subtyping was performed via non-supervised consensus clustering. Results: The differentially methylated blocks (DMBs) in GBCs and CCAs are highly overlapping. Based on the common DMBs of GBCs and CCAs, the classifier yielded high sensitivity of 95.2% and specificity of 96.0%. Hypomethylated genes were enriched in pathways of transmemberane receptor and ion binding, while hypermethylation occurred in genes concerning DNA binding transcription activity. By non-supervised clustering of common DMBs, 6 clusters with different degrees of methylation change were identified. Higher methylation alteration (cluster risk-high) was associated with more copy number variation and shorter OS. By LASSO regression, a 12-gene prognostic model was trained and validated (Table). As for immune characteristics, the methylation of CD8A gene was lower in the cluster risk-high group, and this association was validated in the TCGA-cholangiocarcinoma cohort. In addition, lower methylation change was associated with higher BCR/TCR diversity, immune cell infiltration, and PD-L1 and CTLA4 mRNA expression. Conclusions: In BTC, methylation patterns may serve as a robust indicator of immune-related features and prognosis. Our integrative analysis highlights the association between genomic and epigenomic features, and provides insights into the molecular heterogeneity, and the potential therapeutic significance in biliary tract malignancies. Included methylation sites in the LASSO model.[Table: see text]
Phase II study of lenvatinib in combination with GEMOX chemotherapy for advanced intrahepatic cholangiocarcinoma.
Authors: Shi Guo-Ming , Jian Zhou , Fan Jia , Huang Xiao-Yong , Wu Dong , Liang Fei , Lu Jia-Cheng , Yang Guo-Huan , Chen Yi , Ge Ning-Ling , Ji Yuan , Hou YY , Sun Hui-Chuan , Qiu Shuang-Jian , Ye Qing-Hai , Huang Xiao-Wu , Shi Ying-Hong , Gao Qiang , Yang Xin-Rong , Wang Zheng 
Published: June 2021

e16163 Background: The prognosis of advanced intrahepatic cholangiocarcinoma (ICC) remains dismal with gemcitabine-based first-line chemotherapy. This study is to evaluate the safety and efficacy of lenvatinib in combination with gemcitabine and oxaliplatin (Gemox) chemotherapy in the advanced ICC. Methods: Locally advanced or metastatic ICC patients (pts) were given lenvatinib 12 mg/day (body weight ≥60 kg) or 8 mg/day (body weight <60 kg) oral administration, once daily. They also received 1g/m² gemcitabine on Day 1 and Day 8, and 85 mg/m² oxaliplatin Q3W by IV for 6-8 cycles. The primary outcome was objective response rate (ORR) and secondary outcomes included safety, disease control rate (DCR), progression-free survival (PFS) and overall survival (OS). ORR, DCR and PFS were measured according to RECIST 1.1. Treatment would be terminated by confirmed disease progression, unacceptable toxicity, or voluntary withdrawal. Results: From March 2020 to Sep. 2020, 30 pathologically-confirmed advanced ICC pts with a mean age of 59.2 (range, 33-74) years, including 14 women (46.7%), were enrolled at Zhongshan Hospital, Fudan University. At the end of last follow-up (February 10, 2021), the ORR was 30.0% (9/30; 95% CI: 14.7%-49.4%). The disease control rate (DCR) was 86.7% (26/30; 95% CI: 69.3%-96.2%). Median follow-up was 6.8 months. One pt with locally advanced disease was down-staged and then underwent resection. This patient remained disease-free survival at the end of last follow-up. 11 pts experienced disease progression and 8 pts have died. The median PFS and OS have not been reached. Median duration of response (DOR) has not been reached and responses were ongoing in 6/9 (66.7%) pts. 6-months OS rate was 92.6%. No grade 5 adverse event (AE) was observed in present study. 40.0% (12/30) of pts experienced grade 3 or higher AEs and 5 pts discontinued the treatment owing to fatigue (3 pts), jaundice (1 pt) and vomiting (1 pt). Conclusions: Addition of lenvatinib to Gemox chemotherapy provided modest efficacy with reasonable tolerability in advanced ICC patients. Clinical trial information: (NCT04361331). Clinical trial information: NCT04361331.