bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of a prognostic signature model for predicting disease-free survival of hepatocellular carcinoma.
Authors: Li Guangming , Liu Huanhuan , Zeng Daobing , Wang Menglong , Guo Qingliang , Wu Jushan , Fu Zhi , Zhang Haitao , Wang Huina 
Published: June 2022

e16128 Background: Hepatocellular carcinoma (HCC) is a type of aggressive disease with poor prognosis. Although surgery is the most effective therapy for early liver cancer, recurrence rate is up to 50%. Therefore, it is crucial to predict the recurrence for improvement of prognosis of liver cancer. This study aim is to establish a prognostic model using for the prediction of recurrence in HCC. Methods: We collected the genomic and clinical data of 372 patients from the cancer genome atlas (TCGA) database. Mutational signature were established based on univariate Cox analysis and least absolute shrinkage and selection operation (LASSO) Cox regression analysis. A prognostic signature model were developed. Results: The patients with higher pathological T stage (p < 0.001) and old age (p = 0.05) were associated with a worse DFS. In addtion, patients with a HRD score over 24 had a worse DFS compared to those in patients with HRD score less than 24 (p < 0.001). Based on the 1 year DFS, 112 differential mutation gene (DMEs) and 326 differential expressed genes (DEGs) were identified. The univariate Cox and LASSO Cox regression models were employed to select 47 DMEs and 9 gene expression construct an prognosis model. The AUC is 0.612. A nomogram of DFS was established based on the prognosis model, HRD, and tumor stage. The AUC is 0.812 in training set and 0.842 in validation set. Conclusions: We established and validated a novel nomogram model based the genomic and clinical factors for predict DFS in Hepatocellular Carcinoma patients. This model has good predictive value for prognosis, which could improve the risk stratification and individual treatment of Hepatocellular Carcinoma patients.
Prevalence of underlying cirrhosis etiologies in hepatocellular carcinoma patients of Hispanic versus non-Hispanic ethnicity.
Authors: Chang Jeremy , Ajmera Veeral , Fowler Kathryn J , Ting Stephanie , Tamayo Pablo , Burgoyne Adam 
Published: June 2022

e16163 Background: While the incidence and rates of mortality are in decline for the vast majority of cancers, those of hepatocellular carcinoma (HCC) continue to increase. Forecasts from the Surveillance, Epidemiology, and End Results (SEER) database suggest that the Hispanic population will have the highest incidence rate of HCC in the United States by the end of this decade. As a result, further studies are needed to identify specific risk factors for the development of HCC in this ethnic group. Methods: This was a retrospective, single center study conducted in Southern California to identify the prevalence of underlying cirrhosis etiologies in HCC patients of Hispanic versus non-Hispanic ethnicity. Causes of cirrhosis included nonalcoholic fatty liver disease (NAFLD), viral hepatitis, alcohol, and other chronic liver disease. The designation of NAFLD cirrhosis was assigned to patients in whom there was an exclusion of viral hepatitis B, viral hepatitis C, significant alcohol consumption, other etiology of chronic liver disease, and who had the presence of fatty liver on imaging or were diagnosed with cirrhosis with a concomitant metabolic risk factor (diabetes mellitus, hypertension, hyperlipidemia, or obesity). Results: A total of 165 patients were included in this study. There were 57 patients of Hispanic ethnicity and 108 patients of non-Hispanic ethnicity. No significant differences in age or gender were found between the two groups. When analyzing the prevalence of cirrhosis etiologies, 17 patients (29.8%) of Hispanic background were found to have underlying NAFLD cirrhosis compared to 10 patients (9.3%) of non-Hispanic background (p = 0.001). In contrast, 67 patients (62%) in the non-Hispanic group had diagnoses of cirrhosis associated with viral hepatitis B or C compared to 22 patients (38.6%) in the Hispanic group (p = 0.005). There was no significant difference in the prevalence of alcoholic cirrhosis (24.6% vs 13%, p = 0.08), cirrhosis due to other chronic liver disease (1.8% vs 2.8%, p = 1), or HCC without cirrhosis (5.3% vs 13%, p = 0.178) between Hispanic and non-Hispanic patients, respectively (Table). Conclusions: There were significantly higher rates of NAFLD cirrhosis identified in HCC patients of Hispanic ethnicity compared to those of non-Hispanic ethnicity. With the continually rising incidence rate of HCC in this patient group, it is important for providers to be aware of this association so that appropriate surveillance and prevention strategies may be pursued.[Table: see text]
Outcomes of hepatocellular carcinoma in obese patients: Insights from a nationwide database.
Authors: Farooq Umer , Franco Diana , Tarar Zahid , Anwer Faiz 
Published: June 2022

e16178 Background: Obesity is associated with hepatocellular carcinoma (HCC), affecting mortality and post-surgical outcomes. Growing epidemiological obesity trends parallel the constant rise of HCC incidence. Therefore, we sought to examine outcomes of HCC in obese patients. Methods: We investigated the National Inpatient Sample and National Readmission Database 2018-2019 using International Classification of Diseases-10 codes for adult patients with HCC. Analyses were performed using STATA (v 14.2), considering 2 sided P< 0.05 as statistically significant. Proportions were compared using Fisher exact test and continuous variables using Student’s t-test. Confounding variables were adjusted using multivariate logistic and linear regression analyses. Results: Obese patients with HCC had lower odds of inpatient mortality and higher odds of hospice discharge ( P< 0.05). Obesity was associated with a higher length of stay (LOS) by 0.90 days and hospital cost by 5,453 USD ( P< 0.01). We found higher odds of acute renal failure (Adjusted odds ratio (aOR) 1.37, P< 0.01) and a higher prevalence of HCV, smoking, and alcohol use in obese patients. There were no differences in lobectomy, partial hepatectomy, or transarterial radioembolization; however, higher odds of liver transplant were observed (aOR 1.82, P< 0.01). A higher proportion of obese HCC patients had lymph nodes metastasis (6.43% vs. 6.08%, P:0.64). Rates of respiratory problems, ICU admission, cardiac arrest, HIV, DVT, myocardial infarction, and stroke were not different between the two groups ( P> 0.05). Conclusions: Obese patients with HCC appear to have an advanced stage at presentation leading to lower rates of lobectomy, partial hepatectomy, and TARE and higher rates of liver transplant and hospice utilization. Future studies need to address the barriers leading to delays in diagnosis.[Table: see text]
Comprehensive genomic analysis of early and late-onset hepatocellular carcinoma.
Authors: Shao Yang , Chen Xin , Pang Jiaohui , Zhang Yaru , Ou Qiuxiang , Yin Jiani , Wu Xue 
Published: June 2022

e16186 Background: Hepatocellular carcinoma (HCC) accounts for 90% of primary liver cancer and is a leading cause of cancer-related death worldwide. HCC is highly therapy-resistant, and biomarker-driven therapies are emerging as important treatment options. Risk factors have been implied to distinguish early and late-onset patients. A high prevalence of non-cirrhotic HCC attributed to hepatitis B virus infection was found in young Asian patients. In late-onset patients, genetic aberrations accumulated with age in liver cirrhosis and other chronic liver diseases could provide the basis of tumorigenesis. Thus, diverse genomic alteration modes may underlie HCC of different onset ages, but the analysis is lacking. This study aims to explore genomic distinctions underlying early and late-onset HCC, thus facilitating personalized biomarker-driven treatments. Methods: The plasma and tumor samples from 222 Chinese HCCs underwent genomic profiling with hybridization capture-based targeted next-generation sequencing. The patients were categorized into early (male < 40 years or female < 50 years) or late (male ≥ 40 years or female ≥ 50 years) onset in accordance with the American Association for the Study of Liver Diseases guideline. We compared the clinical and molecular characteristics and explored differences between the early and late-onset cohorts. Results: The late-onset cohort accounts for 83.3% (185/222) of all HCC cases, and its male incidence rate is significantly higher than that of early-onset (88.6% vs 56.8%, p< 0.0001). More younger cases have a family history of HCC (21.6% vs 14.6%). The mean somatic alteration numbers per patient are comparable between early and late-onset (8.30 vs 9.92). While TP53, TERT, and MCL1 are the most frequently mutated genes in both cohorts, we identified eight genes with significantly higher mutation frequencies in early-onset. OncoKB Levels 1 to 4 actionable alterations are present in 48.7% and 44.3% of younger and older patients, respectively, whereas the early-onset cohort has a significant enrichment of actionable MDM2 alterations (10.8% vs 1.1%, p= 0.0078). The prevalence of DNA Damage Response and Repair (DDR) gene mutations (35.1% vs 48.6%) and tumor mutation burden (TMB, mean: 4.17 muts/Mb vs 8.11 muts/Mb) are elevated in older patients. Notably, individuals harboring DDR mutations are associated with higher TMB in late-onset (mean TMB in DDR-mutated: 10.44 vs DDR- wildtype: 5.90, p= 0.0016) but not early-onset (mean TMB in DDR-mutated: 3.47 vs DDR- wildtype: 4.54, p= 0.280). Conclusions: Tumors from early and late-onset HCC demonstrated differences in genes and other biomarkers relevant to cancer biology and response to therapy. Specifically, DDR-mutated patients in the late-onset cohort are associated with higher TMB and may benefit from combining targeted and immunotherapy. Future studies are warranted to examine the response to biomarker-driven treatment strategies.
Combination of transarterial chemoembolization (TACE) and tyrosine kinase inhibitors (TKIs) compared to TACE alone as bridging therapy transplant recipients with hepatocellular carcinoma: An update.
Authors: Esmail Abdullah , Victor David , Kodali Sudha , Graviss Edward A. , Nguyen Duc T. , Moore Linda W. , Saharia Ashish , McMillan Robert , Fong Joy N. , Uosef Ahmed , Elshawwaf Mahmoud , Heyne Kirk , Ghobrial Rafik Mark , Abdelrahim Maen 
Published: June 2022

e16201 Background: Hepatocellular carcinoma (HCC) is the world's sixth most prevalent cancer and the third leading cause of cancer-related death. For patients with advanced HCC, trials combining TACE with tyrosine kinase inhibitors (TKIs) such as Sorafenib have given mixed outcomes. (TACE) plus lenvatinib led showed significant improvement in OS compared to lenvatinib alone in the first-line setting in patients with advanced HCC according to phase 3 LAUNCH trial which was presented at the 2022 ASCO Gastrointestinal Cancers Symposium. This study was aimed to compare the outcome of HCC patients who received TACE plus TKI agent versus TACE alone. Methods: Retrospectively all subjects with unresectable HCC were included in this study, who underwent liver transplantation (LT) and were treated by either TACE alone (TA) or TACE plus Sorafenib (TandS) between July 2008–December 2021. For categorical factors, HCC recurrence after LT was reported as frequencies and proportions, while for continuous variables, the median and interquartile range (IQR) or mean was used. For categorical variables, Chi-square or Fisher's exact tests were used, while for continuous variables, Kruskal-Wallis test was used. Results: Seven hundred patients were screened; only 128 patients in total underwent LT with most being males (77%); the median age of 61.5 years. The TA group included 79 (77%) subjects who matched Milan Criteria (MC) and 24 (23%) who did not, but the TandS group had a greater number of cases who did not meet MC: 16 (64%) versus 9 (36%); p = 0.01. There was a significant variation in five-year disease-free survival (DFS) across the therapy groups investigated, with 100% DFS in the TandS group vs 67.2 percent in the TAne group (p = 0.07). The TandS group had a five-year patient survival rate of 77.8% compared to 61.5 percent in the TA group (p = 0.51). However, beyond the MC, patients who were treated with TA had the average percentage of necrotic tumor on resected histology of 43.8 %, 32 % compared to 69.6 %, 32.8 % for cases treated with TandS, p = 0.03. Conclusions: We have found that using TandS is generally well tolerated and demonstrated improved OS compared to TA in patients with unresectable HCC. A prospective clinical study (NCT05171335) is ongoing at our institution to further investigate this concept.
Salvage 177Lu-dotatate therapy in patients with progressive metastatic neuroendocrine tumors.
Authors: Hoe Hui Jing , Wyld David 
Published: June 2022

e16212 Background: 177Lu-dotatate (LuPRRT) is effective in selected patients with metastatic neuroendocrine tumours (NETs). Most of these patients will subsequently have progressive disease with limited treatment options available. We analyzed the outcomes and toxicities of salvage LuPRRT in this study. Methods: This is a retrospective cohort study. Patients who had salvage LuPRRT at Royal Brisbane and Women’s Hospital (RBWH) from November 2016 to January 2021 were identified and included in this study. We manually reviewed the hospital electronic medical records and radiology databases to review patient characteristics, outcomes, and toxicities from salvage LuPRRT. Results: Of the 37 patients included, 37.8% (14/37) had small bowel primary, 27.0% (10/37) had pancreatic primary and 10.8% (4/37) had pulmonary primary. 83.8% (31/37) received 4 cycles of initial LuPRRT (I-PRRT) with a median dose of 32.0 GBq. The median duration of response to I-PRRT was 31 months. These patients had salvage LuPRRT (R-PRRT) on progression with 83.8% (31/37) received 2 cycles with a median cumulative 177LuTate dose of 48.0 GBq. Partial response, stable disease and progressive disease were observed in 10.8% (4/37), 40.5% (15/37) and 27.0% (10/37) of patients respectively. Median duration of response with R-PRRT was 8 months. 2.7% (1/37) developed Grade 3 anaemia and 2.7% (1/37) developed Grade 3 thrombocytopenia with R-PRRT. 8.1% (3/37) developed nephrotoxicity Grade 1 nephrotoxicity. 21.6% (8/37) of patients had re-retreatment with further LuPRRT (RR-PRRT) on progression. The median retreatment cycles were 2 and the median cumulative 177LuTate dose received was 58.8 GBq. Partial response, stable disease and progressive disease were seen in 25% (2/8), 12.5% (1/8) and 62.5% (5/8) of patients respectively. Median duration of response with RR-PRRT was 4 months. There were no reported Grade 3 haematologic toxicities with RR-PRRT. 1 patient developed Grade 1 nephrotoxicity with RR-PRRT. At time of data analysis in April 2021, 27% (10/37) had ongoing response while 73% (27/37) had progressed. Conclusions: Salvage LuPRRT is an effective and safe treatment option for selected patients with progressive metastatic NETs.
Fecal metagenome analysis in long-term survivors (LTS) of pancreas cancer.
Authors: Kharofa Jordan , Hussein Walaa , Sohal Davendra , Olowokure Olugbenga Olanrele , Ahmad Syed A. , Patel Sameer H. , Wilson Gregory , Weiss Alison , Haslam David , Apewokin Senu 
Published: June 2022

e16298 Background: Despite improvements in median survival in pancreas adenocarcinoma (PCa), the 5 year overall survival remains less than 10%. Clinical and tumor genomic characteristics have not differentiated PCa long term survivors (LTS) from unselected patients, however specimens in LTS show enhanced tumor immune response. In preclinical studies, fecal transplant experiments from LTS of PCa reveal delayed tumor growth through unknown mechanisms involving the fecal microbiota (Riquelme Cell 2019). However, features of the fecal microbiome in patients with LTS are unknown. Methods: In this cross-sectional study, comprehensive shotgun metagenomics were performed on stool from PCa patients with LTS (n = 16). LTS was defined as > 4 years from pancreatectomy and all therapy without evidence of recurrence. LTS were compared to control patients with PCa who completed pancreatectomy and chemotherapy (n = 6). Stool was sequenced using an Illumina NextSeq500. Raw reads were processed with Kneaddata for trimming, Kracken2 for taxonomic profiling, Bracken for abundance estimation, and Humann3 for metabolic pathway analyses. Statistical analyses were performed in R with MicrobiomeSeq and Phyloseq for comparison of LTS and controls. Results: At diagnosis, the median age of LTS was 60 with a median time from pancreatectomy of 6 years (4-14 years) at donation. The median age of control patients was 65 with a median disease-free survival of 17 months from pancreatectomy. All patients underwent pancreatectomy and chemotherapy prior to sample donation. No material differences were observed in overall microbial diversity for LTS and controls using Shannon/Simpson indexes. The overall composition of bacteria, eukaryotes, viruses and archaea were similar in LTS relative to controls. Lefse analyses revealed significant enrichment of species relative abundance in LTS for the Ruminococacceae family and the Faecalobacterium genus including the Faecalobacterium prausnitzii species. Enriched species in control patients included Clostridium perfringes. Metabolic pathway analyses of the fecal metagenome of LTS revealed several gene families enriched in Faecalobacterium prausnitzii responsible for starch degradation, ribonucleotide biosynthesis, and thiamin degradation as well gene products from Akermannsia mucinophilia representing unknown pathways. Conclusions: Stool from patients cured from PCa share unique microbial features relative to control populations including enrichment of species in the Faecalobacterium genus and Ruminococacceae family . Interestingly, similar species enrichments are observed in metastatic melanoma patients who respond to PD-1 inhibition (Gopalakrishnan Science 2017). Additional studies are needed to explore underlying immune mediated mechanisms in which the fecal microbiota may influence long term survival in PCa.
Influence of type 2 diabetes mellitus and concomitant anti-diabetic medications in patients with metastatic pancreatic ductal adenocarcinoma.
Authors: Pretta Andrea , Cimbro Erika , Giampieri Riccardo , Spanu Dario , Lai Eleonora , Pecci Federica , Balconi Francesca , Lupi Alessio , Pozzari Marta , Murgia Sara , Bardanzellu Fabio , Maccioni Antonio , Contu Fabiana , Persano Mara , Donisi Clelia , Pusceddu Valeria , Puzzoni Marco , Ziranu Pina , Berardi Rossana , Scartozzi Mario 
Published: June 2022

e16301 Background: The association between pancreatic ductal adenocarcinoma (PDAC) and type 2 diabetes mellitus (DM2) has long been evaluated. Indeed, DM2 can be both an epiphenomenon of PDAC and a risk factor. However, the data on the influence of DM2 and concomitant drug therapy in the progression of pancreatic neoplasms are conflicting. The present study aimed to investigate the correlation between overall survival (OS) and antidiabetic drugs in patients with metastatic pancreatic ductal adenocarcinoma and DM2. Methods: Data from 232 patients were collected retrospectively from 2014 to 2021. 174 from the Department of Medical Oncology of the University Hospital of Cagliari and 58 from the Department of Medical Oncology, AOU Ospedali Riuniti of Ancona. All patients had stage IV disease and received gemcitabine plus nab-paclitaxel first-line chemotherapy. Statistical analysis was performed with the MedCalc package. We aimed to evaluate the correlation between DM2, anti-diabetic medications (ADMs) and median overall survival (mOS). Survival distribution was assessed by Kaplan-Meier curves. Finally, multivariate analysis was performed, taking into consideration the following prognostic factors: sex, ECOG-PS, LDH, Ca19.9, and metastatic sites. Results: The median age was 69 y.o. (range 40-84 y.o.), 127 (54,7%) were male. All patients received first-line treatment with gemcitabine plus nab-paclitaxel. 138 (59,4%) patients were not affected by DM2, 94/232 (40,6%) were affected by DM2. Among DM2 patients, 57 (%) were insulin-treated and 37 (%) were metformin-treated. DM2 patients showed a statistically significant higher median overall survival (26 versus 11 months, 95% CI, p = 0,0002). Furthermore, among DM2 patients insulin-treated and metformin-treated showed a mOS of 21 months and 33 months, respectively (95% CI, p = 0.0002). Finally, multivariate analysis showed that treated-DM2 is an independent prognostic factor ( p = 0.03). Conclusions: The results of our study showed a correlation between DM2 on treatment (with insulin or metformin) and higher mOSin patients with metastatic PDAC. However, the limitations due to retrospective data collection must be considered. The mechanisms underlying these findings could be explained by maintaining optimal insulin concentration and good glycemic control during treatments, or by the activity of anti-diabetic medication in neoplastic tissues. However, further studies in this setting are needed.
Body composition parameter as risk predictor in metastatic renal cell carcinoma (mRCC)?
Authors: Heetfeld Constantin , Hensen Bennet , Eggers Hendik , Peters Inga , Kuczyk Markus A , Grünwald Viktor , Ivanyi Philipp 
Published: June 2022

e16506 Background: Imaging-derived data for patient’s (pts) prognostication in advanced/metastatic (m)RCC remains scarce. Recently, imaging body composition parameters such as muscle radiation attenuation (MA) and skeletal muscle index (SMI) as prognostic markers for cancer became a matter of interest. Here, impact of MA and SMI in mRCC pts, treated in our tertiary center, were retrospectively investigated. Methods: During the observation period 01/03 – 05/16, 401 pts mRCC receiving first line medical treatment were identified and analyzed. Pts were included for MA- and SMI-analysis based on Computed tomography (CT) scan data and recorded height and bodyweight, respectively. SMI and MA were assessed by a self-designed software-module using MeVisLab. SMI- and MA-subgroups were established by cutoff points, established using an optimum risk stratification method. Descriptive statistics and overall survival (OS) with Log-rank analysis were administered. Parameters with differences in MA-subgroups (p < 0.2) were analyzed with univariable and multivariable Cox-Regression, once p < 0.2 at each subsequent step. Results: 133 pts were eligible for MA-, 123 pts for SMI-analysis. The median age was 62 (range: 39-84) years, and 65.4% of pts showed an ECOG = 0. 87/133 (65.4%) and 71/123 (57.7%) pts showed low MA and low SMI, respectively. At time of mRCC diagnosis pts with low MA were significantly older (mean: 65 vs. 58 years, p < 0,001), while T-, N-, and M-status, as well as MSKCC did not differ. Low MA was associated with a median OS of 27 (95% CI: 17,1-36.3) mo., compared to 60 (95% CI: 36.7-83.3) mo. for high MA (Log-Rank p = 0.001). Multivariable analysis identified low MA as an independent risk factor for OS (HR 2.07; 95% CI 1.24-3.48; p = 0.006). SMI did not reach significance (p = 0.1) (Tab.1). Conclusions: Here, MA provided a robust prognostic parameter regarding OS in mRCC pts. Interestingly, SMI showed no prognostic impact. CT-derived MA could be a promising addition to existing risk-scores. Further research is needed to validate these finding.[Table: see text]