bluuebunny/crossref_metadata_2025_split huggingface dataset:
Envafolimab plus chemotherapy in advanced gastric or gastroesophageal junction (G/GEJ) cancer.
Authors: Yin Xianli , Zhang Yun , Deng Yanhong , Xu Nong , Xu Jianming , Li Lei , Song Xiaotong , Lu Haolan , Gong John , Liu Dongfang 
Published: May 2020

e16585 Background: Envafolimab is a novel fusion protein of humanized anti-PD-L1 single domain antibody and human IgG1 Fc, formulated for subcutaneously (SC) injection. This study examined the feasibility of combining envafolimab with chemotherapy in advanced G/GEJ cancer. Methods: This study was a single arm, phase Ⅱ trial in adult subjects with previously untreated advanced G/GEJ cancer. Subjects received 8 cycles (2 weeks each) of envafolimab plus FOLFOX regimen followed by envafolimab and 5-FU until progression or unacceptable toxicity. Envafolimab was administrated SC at 5 mg/kg on day 1 of each cycle; FOLFOX consisted of 80 mg/m2 oxaliplatin, 400 mg/m2 5-FU and 400 mg/m2 leucovorin intravenous infusion on day 1, 2400 mg/m2 5-FU administered with a 48-hour continuous infusion on day 1 and 2. Tumor was assessed every 6 weeks per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1). Primary endpoints were safety and tolerability. Toxicity was graded using CTCAE v5.0. Secondary endpoints included objective response rate (ORR), duration of response (DoR). and progression free survival (PFS). Results: A total of 15 subjects were treated and evaluable for response. ECOG performance status was 1 in 80% of subjects. Majority had gastric cancer (86.7%). At the data cutoff, the minimum follow-up was 6 months. The treatment emergent adverse event (TEAE) occurrence was 100% (all grades) and 73.3% (grades 3-4). The most frequent grade 3-4 TEAE included neutrophil count decreased 46.7%, anemia 20.0%, and platelet disorder 20% (3/15). Confirmed ORR was 60% (unconfirmed ORR: 73.3%). Median DOR was not reached. Median PFS was 6.8 months. Conclusions: Envafolimab plus FOLFOX demonstrated a manageable safety profile with promising clinical efficacy as a first line therapy for advanced G/GEJ cancer. Clinical trial information: CTR20181124 .
Racial disparities in patients with unresectable stage III/IV esophageal cancer at time of diagnosis: A National Cancer Database Analysis.
Authors: Sadaps Meena , Mehta Neal , Zhao Ran , Wei Wei , Bhatt Amit , Khorana Alok A. 
Published: May 2020

e16589 Background: Significant racial disparities exist in the patterns of care and clinical outcomes for patients with early stage, non-metastatic esophageal cancer but data in advanced esophageal cancer are lacking. In this study, we aim to evaluate racial disparities in patients with locally advanced/metastatic, unresectable esophageal cancers. Methods: We identified patients in the National Cancer Database with esophageal cancer, from 2004 to 2016, with unresectable stage III/IV disease at time of diagnosis. We compared overall survival (OS) between different racial groups as well as other demographic and socioeconomic factors that may have contributed to this disparity. Secondary factors that were studied included age, sex, education, histology, and location of tumor. Results: 49,139 patients were included in this analysis. Median age was 64.5 years and 39,314 (80.0%) were male. 16,723 (34.0%) patients had stage III disease and 32,416 (66.0%) patients had stage IV disease. 16,208 patients (33.0%) had squamous cell carcinoma and 32,931 (67.0%) had adenocarcinoma. Patients were stratified into one of the following six categories for race: Caucasian (40,139; 81.7%), African American (5,571; 11.3%), Asian (907; 1.8%), Hispanic/Latino (1,793; 3.6%), Native American (145; 0.3%), and other (167; 0.3%). African Americans had worse median OS (Table) than Asians (p = 0.000), Hispanic/Latinos (p = 0.000), and Caucasians (p = 0.001) when analyzed in a pairwise comparison using log-rank testing. Within the African American subset, older age ( > 70 years) (p = 0.00), male gender (p = 0.00), and tumor location in the mid (p = 0.02) or upper third (p = 0.00) of the esophagus were associated with worse outcomes using Cox’s multivariate regression model. Conclusions: Racial disparities persist even in unresectable stage III/IV esophageal cancer patients with African Americans noted to have worse clinical outcomes as compared to most other races including Caucasian, Asian, and Hispanic/Latino patients. Further research is warranted to determine the cause for this disparity and to implement the necessary changes to improve outcomes for these patients. [Table: see text]
Effect of significant incidence of Braf p.V600E mutations in esophageal cancer on potential use of tyrosine kinase inhibitors.
Authors: Moorthy Thurai , Rajasooriyar Chrishanthi , Ginige Anusha , Ranatunge Niluka , Surenthirakumaran Rajendra 
Published: May 2020

e16591 Background: Routine diagnosis of esophageal cancer varies from locally advanced to metastatic at presentation. Most of these patients are cachectic at presentation and physically not suitable for radical tri-modality treatment as per the CROSS trial. Hence, the prognosis of esophageal cancer remains guarded. Presently, tyrosine kinase inhibitors (TKI) are successfully used in treating melanoma, non-small cell lung cancer, and a possibility for treating esophageal cancer. Allele Specific Multiplex Sequencing (ASMS) detects somatic mutations in samples with low mutant copies and in the presence of overwhelming wild type. Hence, we have re-evaluated and are reporting the findings of the incidence of Braf p.V600E in esophageal cancer using ASMS. Methods: DNA was extracted from 40 formalin fixed paraffin embedded tumor tissue (FFPE) samples that were collected from patients with squamous-cell carcinoma of the esophagus. The Braf p.V600E/K mutations were analyzed using ASMS. All positive results were confirmed by bi-directional ASMS. The results were correlated with patients’ demographic and pathological data. Results: Overall incidence of Braf p.V600E was 92.5% and was present in all stages (IB, IIB, IIIA, IIIB, IIIc and IV) of esophageal cancer. There was no difference in the incidence of Braf p.V600E between patients who smoke, consume alcohol, chew betel or any combination, and those who do not. There is also no gender difference in the incidence of Braf p.V600E. Conclusions: Braf p.V600E is a pivotal driver mutation in the MAPK pathway. Firstly, the data shows incidence of Braf. p.V600E is higher than what is reported in literature and paves the way for follow up with further studies for possible use of TKI targeted chemotherapies. Secondly, incidence of Braf p.V600E mutations could be independent of known cancer etiology (e.g. smoking, consumption of alcohol, chewing betel).
Real-world experience with Lenvatinib in the management of Hepatocellular Carcinoma: A single-center Indian experience.
Authors: Rauthan Amit , Somashekhar S.P. , Patil Poonam , Zaveri Shabber 
Published: May 2020

e16596 Background: Sorafenib has been the standard first line treatment for more than a decade in advanced Hepatocellular carcinoma (HCC) patients. Lenvatinib is a novel oral tyrosine kinase inhibitor which inhibits VEGF receptors 1-3, FGF receptors 1-4, PDGF receptor alpha, RET and KIT, and has activity in multiple cancers. In the recent phase III REFLECT trial, Lenvatinib was non-inferior to Sorafenib in the first line management of advanced HCC. It showed better response rates, improved progression free survival (PFS) with similar overall survival (OS). There is no data of Lenvatinib in Indian patients. Methods: This is a single center, retrospective study, which included patients with metastatic or unresectable HCC who received treatment with Lenvatinib at our center. The endpoints were objective response rate (ORR), PFS and toxicity. Results: 31 patients received Lenvatinib from Dec 2017 to Oct 2019. Patients greater than 60kg received 12mg/day and those less than 60kg received 8mg/day. There were 5 females and 26 males. Median age was 60 years (29-78 years). All patients were BCLC stage C. Child Pugh score was A in 20 patients, B in 9 patients and C in 2 patients. AFP was elevated in 25 (80.6%) patients. 26 patients received Lenvatinib as initial therapy, 3 received it after Sorafenib progression, and 2 received after Sorafenib and Nivolumab progression. 6 patients (19.35%) achieved partial response (PR), 12 (38.7%) had stable disease and 13 (41.9%) had progressive disease by recist criteria. ORR was 19.35% and disease control rate was 58%. 2 patients underwent TACE after achieving PR. The median PFS was 7 months. The common adverse events were hypertension, weight loss, palmar plantar rashes, dysphonia and fatigue. Grade 3 AEs occurred in 8 patients (25.8%). 10 patients (32.2%) required dose reduction due to side effects. Conclusions: Lenvatinib has demonstrated a high response rate and disease control rate in our patients. Achieving a PFS of 7 months is an improvement over our previous Sorafenib experience. Further followup will demonstrate the overall survival. It is well tolerated and most side effects can be managed with patient education. The major advantage has been that in contrast to Sorafenib, only 32.2% patients required dose reduction due to side effects. These results are practice changing and Lenvatinib has become our first line regimen in advanced HCC. Lenvatinib would provide a good backbone to combine immunotherapy as first line treatment in future.
Expression of the type 3 inositol 1, 4, 5-trisphosphate receptor according to the chronic liver disease etiology in hepatocellular carcinoma.
Authors: Diniz Paulo Henrique Costa , dos Santos Marcone Loiola , França Andressa , Filho Antônio Carlos Melo Lima , Vidigal Paula Vieira Teixeira , Ferrari Teresa Cristina de Abreu , Leite Maria de Fátima 
Published: May 2020

e16604 Background: The expression of type 3 isoform of the inositol 1, 4, 5-trisphosphate receptor (ITPR-3), an intracellular calcium (Ca2+) channel reported in liver cancer cells, is important in the Ca2+ signalling. Thus, it may be involved in the many events of hepatocarcinogenesis. Here, we investigated the ITPR-3 expression in hepatocellular carcinoma (HCC) and its association with clinicopathological parameters and long-term outcomes, according to the etiology of underlying chronic liver disease (CLD). Methods: Clinical and laboratory data from patients (n = 53) who underwent orthotopic liver transplantation for HCC treatment in a Brazilian referral center were retrospectively collected. After pathological reviewing of their explanted liver samples, ITPR-3 expression in both tumor and underlying cirrhosis were assessed by immunohistochemistry, and quantified using density histograms in the ImageJ software. Event (tumor recurrence or death from any cause) occurrence and event-free survival (EFS) were analysed. Results: Hepatitis C virus (HCV) (n = 31), alcohol abuse (n = 16) and cryptogenic cirrhosis (n = 6) were the underlying CLD etiology, and the groups were, in general, well balanced regarding clinicopathological indices. Median EFS was 78.9 months (range, 63.6-94.1). The ITPR-3 expression profile was cytoplasmatic, predominantly perinuclear, and was stronger in tumor than in adjacent cirrhosis, considering all etiologies together (intensity 9.1% higher in tumors, p < 0.001) However, analyzing each etiologic group, the cryptogenic was the only one in which there was no difference between tumor and underlying CLD. Comparing the ITPR-3 expression only in tumors, there was no difference regarding the etiology of CLD. The tumor ITPR-3 higher intensity was correlated with higher serum aspartate alanine-transferases (ALT) levels (p = 0.018) and lower mitotic index ( < 5 per 10 high power fields) (p = 0.009). There was no association between receptor expression and event occurrence or EFS. Conclusions: The ITPR-3 was expressed in HCC, regardless of the underlying CLD etiology. Its correlation with mitotic index, a cell proliferation marker, was demonstrated, but there were no associations with clinical outcomes. Apart from cryptogenic cirrhosis, ITPR-3 expression was more intense in tumors than in underlying cirrhosis. These findings suggest that ITPR-3 could have a role in carcinogenesis. However, the prognostic and therapeutic implications need to be investigated.
Outcome of FOLFOX based chemotherapy in advanced pancreatobiliary cancers presenting with hyperbilirubinemia.
Authors: Batra Sandeep , Jha Sanjeev Kumar , Bahl Ankur , Chaturvedi Harit , Taneja Satyam 
Published: May 2020

e16605 Background: Treatment of pancreatobiliary cancer patients with severe liver dysfunction including hyperbilirubinemia secondary to liver metastasis or biliary obstruction is challenging. A significant number of patients at presentation are in advanced/ locally advanced stage thus severely limiting chemotherapy options. FOLFOX (5 FU, Leucovorin, Oxaliplatin) represents a feasible option considering the pharmacokinetics. Clinical data on the dosage and tolerability of chemotherapy is limited and no recommendations are available to treat such patients in upfront setting with persistent hyperbilirubinemia. This observational study was done to find out safety and efficacy of FOLFOX based chemotherapy in these patients. Methods: Patients with advanced pancreatobiliary cancers with hyperbilirubinemia were treated with mFOLFOX6 based chemotherapy. Patients were treated till progression or 6 months or death (whichever occurred ealy) and assessed for toxicity and survival. Results: Only 13 out of 40 patients were able to complete all 12 cycle of chemotherapy. 12 patients were able to receive 2nd line chemotherapy of physician choice and 2 patients were able to received 3rd line chemotherapy. Total bilirubin of patients at start of chemotherapy ranged from 3 to 39.4 mg/dl with a mean value of 9.17±6.67 mg/dl and a median value of 7.5 mg/dl. Median progression free survival (PFS) of mFOLFOX6 was 5.97 months whereas median overall survival (OS) was 8.2 months. 6 patients were able to receive only one cycle of chemotherapy. 2 patients were able to receive only 2 cycles of chemotherapy. 26 patients completed 6 cycles of chemotherapy. Objective response rate was 45% after 6 cycles of chemotherapy. Of these 26 patients response assessment revealed progressive disease in 7 patients. 2 patient had complete metabolic response of which one of them had locally advanced disease. On laparotomy of this patient there were an extensive peritoneal disease curative surgery was not feasible. One patient successfully underwent Whipple’s procedure after 6 cycles of chemotherapy followed by adjuvant radiotherapy. Conclusions: FOLFOX based chemotherapy is a feasible option and a hope for patients of advanced pancreatobiliary cancers presenting with hyperbilirubinemia with a tolerable toxicity profile and providing comparable PFS and OS to other chemotherapy drugs/ regimens used in non hyperbilirubinemic patients.
Compliance to the American Association for the Study of Liver Diseases (AASLD) guidelines and its impact on overall survival in patients with hepatocellular carcinoma.
Authors: Manne Ashish , Mulekar Madhuri S , Escobar Daisy E , Prodduturvar Pranitha , Fahmawi Yazan , Henderson Phillip , Abdul-Rahim Osama , Hussain Zeiad , Liles Spencer , Fonseca Annabelle , Howard John Harrison , Mneimneh Wadad , Gilbert Robert , Pai Sachin Gopalkrishna , Nelson Cindy , Khushman Moh'd M. 
Published: May 2020

e16609 Background: The Barcelona-Clinic Liver Cancer (BCLC) staging based management proposed by AASLD depends on baseline liver function and performance status of the patient in addition to tumor characteristics. Low adherence to AASLD guidelines, especially in advanced staged tumors, can be ascribed to suboptimal revision/updates of the guidelines reflecting the advancements in hepatocellular carcinoma (HCC) management. Here, in addition to the adherence rate, we explored the overall survival of patients with HCC according to first-line treatment modality compliance to AASLD guidelines. Methods: This is a retrospective study conducted at the University of South Alabama/Mitchell Cancer Institute. Between 2017 and 2019, 148 unique treatment-naïve patients with HCC were identified. Patients were staged according to the BCLC staging system and their compliance with suggested first-line treatment modality according to AASLD guidelines was noted. Overall survival was explored and differences between overall survival rates of compliant and non-complaint patients were compared using the log-rank Wilcoxon test. Results: In our cohort, the median age was 72.5 years (range 38-90). Males represented 80%. Caucasians, African Americans, and other ethnicities (e.g. Asians) represented 68%, 30% and 2% respectively. The overall adherence rate was 83%. The adherence rate according to BCLC stage 0, A, B, C and D was 100%, 97%, 77%, 77% and 38% respectively. Compliance vs. non-compliance to AASLD guidelines showed no significant difference in overall survival of patients with BCLC stage 0-A, B and C. In patients with BCLC stage D (N = 13), compared to patients treated in compliance to AASLD guidelines (N = 5), patients treated in non-compliance (N = 8) had better overall survival (2.2 vs. 5.2 months, p = 0.0012). Conclusions: In our cohort, the adherence rate to AASLD treatment guidelines in patients with BCLC stage D was very low at 38%. Lack of adherence in this group of patients translated into better overall survival. The current AASLD guidelines for the management of HCC have several limitations, especially for advanced stages. In the last few years, the FDA approved several tyrosine kinase inhibitors, immune checkpoint inhibitors and the monoclonal antibody, ramucirumab. This expansion generated the need for periodic updates/revisions of consensus guidelines.
Comparison of mutational landscape of non-alcoholic fatty liver disease, viral hepatitis, and alcohol consumption related hepatocellular carcinoma.
Authors: Qiu Jinrong , Wang Weifeng , Li Yingmei , Chen Shifu 
Published: May 2020

e16614 Background: Hepatocellular cancer (HCC) is the seventh most common cancer and the fourth leading cause of cancer-related death worldwide. The most common risk factors of HCC have traditionally included hepatitis B virus (HBV), hepatitis C virus (HCV), and alcohol-related liver disease (ALD). Recently, Non-Alcoholic Fatty Liver Disease (NAFLD) has emerged as the fastest growing risk factor for the development of HCC. This study reports the mutation landscape of NAFLD-related hepatocellular carcinoma (HCC) versus other etiologies. Methods: Mutation data of 219 HCC samples were collected from TCGA database, including 13 NAFLD, 87 HBV, 37 HCV, and 82 ALD-related samples. We analyzed mutations for different type of HCC samples using GDC level 3 mutation data. Driver mutations were called by applying software MuSig2CV. Results: In 219 samples, a total of 32189 mutations were identified, including 3163 in NAFLD, 11430 in HBV, 6390 in HCV, and 11206 in ALD-related HCC samples. Driver genes shared by viral hepatitis and ALD-related samples were TP53 (32% for ALD, 33% for HBV, 42% for HCV) and CTNNB1(32 % for HCV, 26% for HBV,29% for ALD), while TP53 was not among the highest frequency of mutations in NAFLD-related samples. As lack of NAFLD-related HCC samples (n = 13), most frequently mutated genes in NAFLD-related HCC samples were computed instead of driver genes. Top 5 mutated genes in NAFLD-related HCC samples were TTN (36%), CACNA1B (27%), DSCAM (27%), GLI2 (27%), and BEB (27%). Conclusions: From our results, TP53 has a lower mutation frequency in NAFLD-related HCC samples than in other types of HCC. To further validate this finding, a larger size of NAFLD-related HCC samples is essential.
Mutational profile of hepatocellular carcinoma by liquid biopsy of Hispanics in central California.
Authors: Ali Mir , Chaudhary Uzair Bashir , Valliani Salimah , Kim Shirley , Moers Diana , Akabane Hugo , Fathi Amir 
Published: May 2020

e16621 Background: Hepatocellular carcinoma (HCC) when localized to liver is typically diagnosed with Characteristic radiographic features while tumor tissue sampling is not warranted anymore. Recently, circulating tumor DNA (ctDNA) has been used to evaluate mutational profile in solid tumors in order to personalize treatments. However, it is not established well in HCC, specifically in Hispanic patients. This study aims to describe the mutational profile of Hispanic patients with ctDNA analysis as a single center experience. Methods: We enrolled 33 patients with diagnosis of HCC from 1/2016 to 12/2019. Diagnosis of HCC was based on Characteristic radiological features, defined by Liver Imaging Reporting and Data System (LI-RADS category 5). 18 patients self-identified as Hispanic while remaining were mainly Caucasians. FoundationOne Liquid genomic testing by Foundation Medicine was used for profiling of 77 most commonly mutated genes of sampled blood. Results: Baseline patient characteristics were similar between Hispanic and non-Hispanic population. Median age of diagnosis was 64 in this cohort with 23(70%) males and 10(30%) females. 30 patients had underlying cirrhosis with hepatitis C present in 19(58%) and heavy alcohol abuse in 15(45%) of cirrhotic. 32 patients had liver-only disease, while we had one patient with extrahepatic disease. 22 of these 33 patients had a single HCC lesion while 11 had multifocal HCC. 20 patients (60.6%) had at least 1 pathogenic mutation. 13 patients (39.4%) did not have any pathogenic mutations. The frequency of commonly mutated genes for our Hispanics versus non-Hispanics were following: CTNNB1(45.5% vs 44.4%), TERT (45.5% vs 55.6%), TP53(36.4% vs 55%), CNK2A (18.2% vs 0). Median of Allele frequency percentage was 0.81%. Mutations in TP53 was commonly detected at codon 249(R249S). Presence of these pathogenic mutations were associated with poor clinical features such as multifocal disease and higher AFP values > 59 as compared to 15 without mutations. Other mutations present at lower percentage include ERBB2, PIK3CA, DNMT3A, GNAS, KDR, RB1, PTEN and their frequency was similar in both Hispanic and non-Hispanic groups. Conclusions: Genomic profiling of ctDNA by liquid biopsy in our Hispanic patients with HCC appears similar to established mutational profile of HCC in Caucasian and Asian populations. These findings can be verified in heterogeneous populations in order to serve as a potential prognostic tool and help with personalized medicine.