bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparative effectiveness of nonsurgical therapies for localized hepatocellular carcinoma: Analysis of the National Cancer Database.
Authors: Rajyaguru Devalkumar , Borgert Andrew , Polewski Peter James , Smith Angela 
Published: January 2019

425 Background: Data guiding selection of optimal nonsurgical therapies for management of localized hepatocellular carcinoma (HCC) are lacking. Because there are limited prospective comparative data for these treatment modalities, we aimed to compare the effectiveness of chemotherapy (systemic or arterial directed) versus radiofrequency ablation (RFA) versus radioembolization (RE) in nonsurgically managed patients with stage I and II HCC using the National Cancer Database. Methods: We identified patients who received chemotherapy, RFA or RE for nonsurgically managed Stage I (T1N0M0) and II (T2N0M0) HCC between 2008 and 2013. Patients excluded included those who received upfront lobectomy or resection or extended lobectomy or hepatectomy or transplant, and if they had Ishak fibrosis score of 5-6 or total bilirubin > 3 mg/dl or international normalized ratio (INR) of > 3. Overall survival (OS) was compared between treatment groups using propensity score matched (1:1:1) and weighted analyses. We also verified balance of all available confounders, and assessed sensitivity to unobserved confounding. Results: Overall 2622 (73.2%), 837 (23.3%) and 125 (3.5%) patients with nonsurgically managed stage I and II HCC received chemotherapy, RFA and RE, respectively. RE treated patients tend to be older, live in the areas with a higher median income and higher percentage of high school- educated residents, and have stage II disease. The propensity matched cohort included 303 patients with baseline characteristics well balance between all arms. After propensity matching, 5-year OS was 17.4% (95% CI, 6.6% to 32.3%) in the chemotherapy group, 27.2% (95% CI, 14.2% to 42%) in the RFA group and 36.6% (95% CI, 23.1% to 50.1%) in RE group (p = 0.48). Conclusions: To our knowledge, this is the first study comparing various different nonsurgical therapies for localized HCC. All chemotherapy, RFA and RE are effective treatment options for nonsurgically managed patients with stage I and II HCC. Although these data are retrospective, RE appears to be a reasonable first-line treatment of nonsurgically managed stage I and II HCC in carefully selected patients.
Racial disparities in the initial treatment of hepatocellular carcinoma in the population 65+ years in the United States.
Authors: Costa Stephanie , Delgado David J. , Kaufman Michael Ross , George Brandon , Mitchell Edith P. 
Published: January 2019

431 Background: Insufficient evidence exists regarding the initial management of elderly patients with hepatocellular carcinoma (HCC). The purpose of this study was to describe racial differences in initial treatment of 65+ year old patients with HCC diagnosed in the United States (2004-2014). Methods: A retrospective cohort study was conducted using the 1973-2014 Surveillance, Epidemiology and End Results Program (SEER) database of the National Cancer Institute. Patients with primary hepatocellular carcinoma, diagnosed between 2004 and 2014, and with complete information on race, gender, year of diagnosis, age, marital status, region, tumor status at diagnosis and initial treatment were included. Descriptive statistics were used to compare race with sociodemographic and clinical variables. Univariate and multivariate logistic regressions were performed to describe the association of race with receiving any treatment for HCC (local hepatic therapy and surgical treatment versus no treatment). Results: The sample consisted of 25,499 HCC patients: 70.0% White, 9.1% Black, 19.8% API, 1.0% AI; 68.6% male; 46.8% diagnosed in 2004-2009; 54.8% age 65-74, 45.2% 75 and older; 54.7% married, 7.3% Midwest, 13.8% Northeast, 15.7% Southeast; 81.3% first malignant primary indicator, 13.8% metastasis, 49.3% localized site, and 20.9% receiving initial treatment. After controlling for confounding variables, as compared to White patients, African American patients (OR:0.739 95% CI:0.652, 0.839) had decreased odds of receiving initial treatment; and Asian/Pacific Islander patients (OR:1.490 95% CI:1.371,1.618) had increased odds of receiving initial treatment. Conclusions: Racial disparities exist at the presentation of HCC in the 65+ population. African American patients are less likely to receive treatment and Asian/Pacific Islander patients are more likely to receive treatment. Further research is needed to understand these relationships in subpopulations.
Clinical outcomes of FOLFIRINOX and gemcitabine/nab-paclitaxel in the real world setting.
Authors: Franco Fernando Franco , Juan C Camara , Martin Valades Jose Ignacio , Marrupe David , Gutierrez Abad David , Leon Ana , Juez Ignacio , De Torres Maria Victoria , Sánchez-Ruiz Antonio Carlos , Bernal Elsa , Garcia Adrian Silvia , Moreno Diana , Cardena Ana , Hernández Roberto , Ruiz-Casado Ana 
Published: January 2019

440 Background: The incidence of pancreatic cancer is increasing in developed countries. Though FOLFIRINOX (FFX) and gemcitabine plus nab-paclitaxel (GNP) are associated with increased toxicity and are addressed to a well selected population, there seems to have been a rapid incorporation of these regimens in the real world. Overall survival (OS) was 11.1 months for FFX and 8.5 months for GNP. Survival rate at 18 m with FFX was 18.6%; at 24 m with GNP was 9%. Questions have arisen about external validity of original trials and how could these regimens impact overall survival since they are available nowadays for second line settings. Methods: This is a retrospective study. The Departments of Pharmacy of 5 Spanish hospitals generated the listings of patients (pts) treated in first line with the new regimens, namely FFX or GNP. To avoid bias related to non-prospective data collection, we restricted the analysis to survival data, serious toxicity and 2nd line options. Results: From Jan 2012 to Dec 2016, a total of 136 pts (M/F 52/48 %) were treated. Med age 63 y (38-83 y), 95% adenocarcinoma. 48% head of pancreas. ECOG 88% 0-1. 36 % locally advanced and 64% metastatic. 88% had liver mets. In the 1st line 64% were treated with FFX and 36% with GNP. 5 (3,7%) pts died in the first 3 months of treatment, because of infectious complications. 16 pts were operated after chemotherapy. 60% of the pts could receive a 2nd line (43% GNP, 25% FFX, 32% other). 27 pts (19.8%) were treated with a 3rd line. More pts treated with FFX required G-CSF (85% vs 15%). The median OS was 13 months with no differences between regimens. Survival rate at 30 months was 25% for both regimens. Elevated Ca 19.9 levels and Neutrophil-Lymphocyte ratio (NLR) increased the risk of death during the first-line. Conclusions: Originally reported OS is not only reproduced but improved in the real world despite a less strict inclusion of pts. 25% of patients remain alive 30 months after diagnosis. Superiority could not be demonstrated for any of the schemes. The availability of both regimens seems to dilute the potential differences and it is not so important the election of the 1st line. Both NLR and Ca 19.9 level predicted risk of death during the 1st line impairing the possibility of being treated in 2nd line.
ALBI-RT: A novel radiation therapy specific hepatotoxicity prediction model for hepatocellular carcinoma patients.
Authors: Schaub Stephanie K , Bowen Stephen R. , Chapman Tobias Robert , Nyflot Matthew J. , Apisarnthanarax Smith 
Published: January 2019

444 Background: The albumin-bilirubin (ALBI) grade system was optimized to predict survival in hepatocellular carcinoma (HCC) patients; however, its applicability to patients treated with radiation therapy (RT) is unclear. We propose a novel analysis of the ALBI equation, designated ALBI-RT, to assess hepatotoxicity risk after RT. Methods: We retrospectively reviewed 48 consecutive HCC patients treated with RT (2013-2016). Raw ALBI values and Child-Pugh (CP) scores were calculated. Any patient deaths were examined for radiation induced liver disease (RILD). Raw ALBI was assessed as a continuous variable to perform ROC analyses to identify cutoffs for overall survival (OS) and RILD-specific survival (RILD-SS). Univariate predictors of OS and RILD-SS were evaluated using Cox regression to determine hazard ratios (HR). Results: Patient cohort was comprised of 60% CP-A and 39% CP-B/C. Median follow-up and OS was 13 and 10 months, respectively. There were 18 deaths with 6 ascribed to RILD. We identified a raw ALBI cutoff at -1.70 (AUC = 0.94, p = 0.008) that was predictive of RILD-SS with a sensitivity of 100% and specificity of 71%. Dichotimization of RILD-SS cutoff generated two ALBI-RT risk categories: low-risk A < -1.70 (n = 29) and high-risk B ≥ -1.70 (n = 18). ALBI-RT subdivided CP-A patients, identifying 14% at increased risk of RILD; conversely, ALBI-RT grade A identified 21% of CP-B/C patients at a decreased risk of RILD. For OS, raw ALBI as a continuous variable (HR 3.0, p = 0.02), and to a lesser degree ALBI-RT Grade B (HR 2.4, p = 0.06), performed similarly to traditional ALBI grade (HR 3.0, p = 0.01), and CP score (HR 1.4, p = 0.03). In contrast for RILD-SS, raw ALBI as a continuous variable (HR 25.1, p = 0.01) and ALBI-RT Grade B (HR 9.9, p = 0.04) were associated with an elevated relative risk of RILD than traditional ALBI grade (HR 5.8, p = 0.02) and CP score (HR 2.3, p = 0.003). Conclusions: ALBI-RT is a promising metric for pre-treatment assessment of HCC patients for predicting RILD-related death after RT with an elevated relative-risk compared to both CP and conventional ALBI grades. Future prospective evaluation and validation in independent data sets will strengthen the generalizability and utility of ALBI-RT.
Assessing the effectiveness of adjuvant chemoradiotherapy after cholecystectomy in patients with gallbladder cancer.
Authors: Van der Voort Grant McLeod , Martin Brendan , Thomas Tarita 
Published: January 2019

455 Background: The study was conducted to compare the overall survival for patients receiving concurrent chemoradiotherapy (CCRT) versus radiotherapy (RT) or chemotherapy (CT) alone after cholecystectomy in patients with gallbladder cancer. Methods: Patients with gallbladder cancer who had surgical resection from 2004 to 2015 were identified in the National Cancer Database. The proportional hazards assumption for each predictor was assessed using Martingale residuals. Significance was then determined using univariable and multivariable Cox proportional hazards frailty models that allow for clustering of patients within their treatment facility type. Results: A total of 7,258 gallbladder cancer patients who had undergone cholecystectomy met eligibility criteria: 1,509 (20.8%) received CCRT, 283 (3.9%) received RT alone, 1,368 (18.9%) received CT alone, and 4,098 (56.5%) received no adjuvant therapy. The median survival for this patient sample was 29.11 months with median follow-up of 59.10 months. On multivariable analysis, the hazard of death at any given time for patients who received adjuvant CCRT following surgery was 20% (HR = 0.80, 95 CI: 0.73-0.87) lower than those who only underwent surgery alone (p < .0001). By contrast, the hazard of death at any given time for patients who received CT following surgery was 33% (HR = 1.33, 95 CI: 1.22-1.44) higher than those who only underwent surgery (p <.0001). Conclusions: CCRT is associated with improved OS compared with CT or RT alone after cholecystectomy in patients with gallbladder cancer, suggesting that adjuvant CCRT should be used in this population although prospective data is needed to validate these findings.
Markov decision analysis of neoadjuvant treatment pathway versus surgery first pathway for resectable pancreatic cancer.
Authors: Bradley Alison , McKay Colin , Jamieson Nigel , Dickson Euan , Carter Ross , Van der Meer Robert 
Published: January 2019

456 Background: Surgery first (SF) versus neoadjuvant approach (NAT) to management of potentially resectable pancreatic ductal adenocarcinoma (PDAC) is controversial. This study is unique in utilizing institutional data to offer Markov decision-analysis of overall treatment pathways for resectable PDAC. Methods: An advanced Markov decision analysis model was constructed and populated with data from a retrospective institutional database. Patients presenting with resectable PDAC from 2008-2012 were included in the SF arm. Those presenting with resectable PDAC from 2012-2016 and treated within NAT pathway populated the NAT arm. Model uncertainties were tested with one and two-way deterministic sensitivity analysis and probabilistic Monte Carlo sensitivity analysis set to 1000 cycles with variables altered between highest and lowest observed values. Results: NAT pathway gave an additional 0.58 QALMs (22.43 vs. 21.85 QALMs). Monte Carlo analysis reported indifference between treatment strategies. One-way deterministic sensitivity analysis showed that probability of resection in the SF pathway must be greater than 0.82, or below 0.72 in NAT pathway, and probability of receiving adjuvant therapy above 0.6 to alter pathway superiority. Two-way deterministic sensitivity analysis demonstrated treatment superiority depended on resection rate in each pathway and receiving adjuvant therapy in SF pathway. Markov cohort analysis demonstrated superiority of neoadjuvant pathway (Table). Conclusions: Optimal treatment pathway remains debatable on an intention-to-treat Markov decision analysis. Markov cohort analysis of treatment received demonstrated benefit with NAT pathway. [Table: see text]
Prescribing patterns for FOLFIRINOX in the real world.
Authors: Guenther Chad Michael , Bhulani Nizar , Korenke Adam , Li Jenny Jing , Khosama Leticia , Syed Samira K. , Kazmi Syed Mohammad Ali , Cheedella Naga Koteswari , Karri Sirisha , Lohrey Jay , Sanjeevaiah Aravind , Verma Udit N. , Cox John Vernon , Arriaga Yull Edwin , Beg Muhammad Shaalan 
Published: January 2019

463 Background: FOLFIRINOX therapy is associated with improved outcome in patients with gastrointestinal cancers. The regimen can be associated with significant toxicity and empiric dose modifications are often used. We analyzed 1) real-world prescribing patterns of FOLFIRINOX and 2) toxicity of therapy. Methods: Patients undergoing FOLFIRINOX chemotherapy at an academic, NCI-Designated Comprehensive Cancer Center were identified and electronic medical records reviewed. Patients who received at least one dose of FOLFIRINOX were included. Chemotherapy dose, growth factor use and toxicity data was abstracted for the first 8 weeks. ‘Standard FOLFIRNOX’ was defined as the regimen utilized by Conroy et al (NEJM 2011). Any empiric reduction/withholding of drug dose for cycle 1 was classified as ‘modified FOLFIRINOX’. Bivariate analysis was performed on the data. Results: There were 111 patients seen between 5/2011-3/2017 and 94% had pancreatic cancer. Age range was 29-87 years and 52% were female. 59% received ‘modified FOLFIRINOX’ and 20% received empiric growth factors. Line of therapy for standard vs modified respectively was 71.1% vs 45.5% for 1st, 17.8% vs 36.4% for 2nd, and 11.1% vs 18.2% for beyond 2nd (p = 0.03). Patients with ‘modified FOLFIRINOX’ were more likely to have metastatic disease (p = 0.01), have received second line or beyond, and higher ECOG score (p = 0.03). Patients with ‘modified FOLFIRINOX’ had a trend toward fewer treatment-related ED visits or hospitalization vs ‘standard FOLFIRINOX’ (27.2% vs 42.2% p = 0.10) and fewer treatment delays (25.8% vs 42.2% p = 0.07). Conclusions: In the real world setting, a majority of patients on FOLFIRINOX receive empiric dose modifications. Although modified dose did not translate to a significant difference in ED visits, hospitalizations or treatment delays, there was a trend toward fewer events.
The effect of socioeconomic factors on the outcome of hepatocellular carcinoma.
Authors: Sellers Cortlandt , Ludwig Johannes M , Uhlig Johannes , Stein Stacey , Taddei Tamar Hamosh , Kim Hyun S 
Published: January 2019

466 Background: To investigate the impact of socioeconomic factors on overall survival (OS) for patients with hepatocellular carcinoma (HCC) at an inner-city tertiary care hospital. Methods: Consecutive patients treated for HCC diagnosed between 2005 and 2016 in the cancer registry were studied. Patients were stratified by demographic, socioeconomic variables and treatment course. Kaplan-Meier curves and Cox proportional hazard modeling were performed. Results: Patients were 79% male (770 pts) with mean age of 62.8 yrs (SD 10.2 yrs). 25% of patients (239 pts) had private insurance, 38% (363 pts) with Medicare, and 34% (239 pts) with Medicaid. Median OS stratified by primary insurance demonstrated a survival benefit for private insurance with 27.8 mo (95% CI 23.1–33.1) vs 21.0 mo (95% CI 16.5–26.5) for Medicare (HR 0.82, p = 0.0344) vs 13.3 mo (95% CI 10.2–19.7) for Medicaid (HR 0.80, p = 0.0002) (p = 0.0007). When further stratified by AJCC Stage, median OS in Stage II was 55.3 mo (95% CI: 32.4–67.1 mo) for private insurance vs 26.0 mo (95% CI: 18.7–36.3 mo) in Medicare vs 13.2 mo (95% CI: 9.0–38.1 mo) in Medicaid (p = 0.0309). Private insurance in Stage III had a median OS of 23.8 mo (95% CI: 10.9–39.8 mo) vs 14.6 mo (95% CI: 7.5–30.8 mo) in Medicare vs 6.7 mo in Medicaid (95% CI: 2.5–12.2 mo) (p = 0.0069). No differences were seen in Stage I and Stage IV. Cancer-directed treatments were utilized in 91% of private insurance vs 84% in Medicare vs 78% in Medicaid (p < 0.0001). Median OS stratified by marital status showed 23.7 mo (95% CI: 21.0–28.1 mo) for married (720 pts, 76%) vs 5.2 mo (95% CI: 9.6–20.1 mo) for never-married (227 pts, 24%) (p = 0.0009) (HR 1.4, p = 0.0013). Cancer-directed treatments were utilized by 87% of married vs 77% of never-married (p = 0.0016). Increased age was associated with decreased median OS (correlation -0.14, p < 0.0001). No differences in OS were seen with ethnicity or gender. Multivariate Cox proportional analysis demonstrated survival advantage for private insurance versus Medicaid (HR 1.3, p = 0.0435) and Medicare (HR 1.2, p = 0.0472). Conclusions: Primary insurance and social support appear to affect the OS of patients with HCC. Further investigations to elucidate the socioeconomic determinants to enhance survivals are warranted.
Modified CLIP score with albumin-bilirubin grade in relation to prognostic value in HBV-related hepatocellular carcinoma patients treated with transcatheter arterial chemoembolization therapy.
Authors: Cai Xiu-Rong , Chen Zhan-Hong , Lin Qu , Dong Min , Ma Xiao-kun , Chen Jie , Wen Jing-yun , Wu Xiang-yuan 
Published: January 2019

480 Background: Child-Pugh grade is widely used to assess hepatic function reserve, but it is relatively subjective for assessment of hepatic encephalopathy. A newly developed scoring system combining albumin and bilirubin, called ALBI grade, aims to assess liver function objectively. In prognosis prediction of hepatocellular carcinoma (HCC), The Cancer of the Liver Italian Program (CLIP) score is commonly used in clinical practice and includes Child-Pugh evaluation. We substituted ALBI grade for Child-Pugh grade to establish ALBI-CLIP system and conducted this study to validate the prognostic value of ALBI -CLIP in HBV-related HCC patients after TACE therapy. Methods: We retrospectively analyzed HBV-related HCC patients who received TACE therapy. Baseline data were collected and evaluated. Child-Pugh grade and ALBI grade were integrated into CLIP and ALBI-CLIP systems, respectively. Univariate and multivariate analyses were conducted to identify independent prognostic factors for overall survival. Comparisons of receiver operating characteristic (ROC) curves and likelihood ratio test (LRT) were used to compare the value of ALBI-CLIP, CLIP and TNM staging systems in predicting survival. Results: A total of 207 patients were included. 153 (73.9%) and 54 (26.1%) patients were classified as Child-Pugh grade A and B, respectively. But according to ALBI grade, 57 (27.5%), 136 (65.7%) and 14 (6.8%) of them were correspondingly divided into Grade 1, 2 and 3. Comparisons of ROC curves showed that ALBI-CLIP and CLIP had similar areas under the curve, both of which were larger than that of TNM system in predicting 3-month, 6-month, 1-year and 2-year survival. LRT indicated that both ALBI-CLIP and CLIP had larger χ2 values and smaller values of Akaike information criterion (AIC), compared with TNM system (χ2 = 29.771, 29.479, 9.105; AIC = 858.215, 858.069, 879.410 for ALBI-CLIP, CLIP and TNM, respectively). Conclusions: Our current study suggested that modified CLIP score with albumin-bilirubin grade retained prognostic value in HBV-related HCC treated with TACE therapy.
Nivolumab in advanced hepatocellular carcinoma (HCC) and Child Pugh B (CPB) cirrhosis: Safety and clinical outcomes in a retrospective case series.
Authors: Kambhampati Swetha , Bauer Kelly , Hwang Jimmy , Bocobo Andrea Grace , Gordan John Dozier , Kelley Robin Kate 
Published: January 2019

496 Background: HCC patients (pts) with Child Pugh B (CPB) cirrhosis have poor prognosis and limited treatment (Tx) options. Nivolumab demonstrated durable responses and acceptable safety in Child Pugh A (CPA) HCC in the CheckMate-040 trial with rates of hepatotoxicity similar to non-HCC populations. The safety and efficacy of nivolumab has not been established in pts with CPB cirrhosis. Methods: Design: Retrospective case series with IRB approval. Key eligibility: HCC with CPB cirrhosis; treated with nivolumab as standard Tx; enrolled in the UCSF Hepatobiliary Tissue Bank and Registry. Study endpoints: Safety during nivolumab Tx including all-cause grade(Gr) ≥ 3 adverse events (AE), serious AE (SAE), any grade immune-related (ir)AE, and systemic steroid (SS) requirement; clinical outcomes including time on Tx (TOT) with nivolumab and overall survival (OS). Results: Thirteen pts were included: male 77%; Asian 38%, white 54%; median age 66 (range: 26-86); HCV Ab+ 31%, HBsAg+ 23%; BCLC B/C 31%/69%; median Child-Pugh score 8; median prior systemic Tx 1 (range: 0-6); prior sorafenib 69%, median duration on prior sorafenib 137 days (range 10-341). The Table depicts safety outcomes on nivolumab. Median TOT on nivolumab: 44 days (95% CI: 32, 98) (range: 17-811+). Median OS from start of nivolumab: 119 days (95% CI: 40, 247) (range: 40-811+). Best response of at least stable disease occurred in 3/13 (23%) of patients, including prolonged stable disease (SD) for 6+ months and complete response (CR) for 24+ months on nivolumab (1 pt each). Conclusions: CPB HCC pts treated with nivolumab experienced high rates of all-cause Gr ≥ 3 AE and SAE and short OS, similar to prior studies in CPB HCC. Rates of irAE attributed to nivolumab were similar to rates reported in CheckMate-040 CPA population, without unexpected AE. A subset of pts experienced prolonged stable disease and CR. Nivolumab warrants further study in CPB HCC.[Table: see text]