bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical predictors of progression of a hepatic lesion from Li-RADS (LR) 3 to LR5 among patients (pts) at risk of hepatocellular carcinoma (HCC).
Authors: Hannan Lindsay Marie , Harris William Proctor , Ojeda Patricia I. , Park James O. , Mieloszyk Rebecca , Bhargava Puneet , Johnson Guy E. 
Published: February 2020

481 Background: We sought to identify predictors of progression of LR3 lesions (i.e. indeterminate for HCC) to LR5 lesions (i.e. definitely HCC) on follow-up imaging among cirrhotic pts. Methods: Imaging reports with LR assignments were identified among pts seen at the University of Washington, 2013-2017. Cirrhotic pts with a LR3 lesion and follow-up scan within 1 year (yr) of LR3 lesion date were included (n = 313). Clinical features were abstracted from chart review. Survival analyses employing interval censoring were performed. Variables as potentially predictive of LR3 progression were identified in univariate analyses, with backwards elimination done (p < 0.05) to obtain the final multivariate model. Results: 20.4% of LR3 lesions progressed to LR5 within 1 yr; 73% were still LR3, 8% progressed to LR4. The population was predominantly male (61%), Caucasian (71%), older than 55 (63%). The most common cirrhotic etiologies were HCV (46.7%), alcohol (32.6%), and NASH (12.8%), not mutually exclusive. AFP at the time of LR3 scan was low if available (39% with AFP <5, 16% 5-10, 28% unknown). 22.7% had impaired liver function (ALBI grade 3); 19.5% lacked data to calculate ALBI grade. CT scan was the most common exam (56%). Multiple LR3 lesions were seen on 51% of scans. Most LR3 lesions were right sided (75%), < 1 cm (51%); 7% of lesions were > 2cm. Men (HR 2.0, p = 0.02), earlier scan yr (HR 0.47 per yr, p < 0.0001), older age (HR 1.42 per 15 yr, p = 0.047), lesion size (HR 1.21 for 2cm+, global p = 0.02) appeared as independent predictors of LR3 to LR5 progression based on the final model. Of 16 variables examined, men were more likely to have chronic HCV, history of alcohol use and less likely to have autoimmune hepatitis. No other differences were seen. In an a priori analysis, risk of male sex (HR 1.99, p = 0.03) persisted despite control for HCV, alcohol, age, race, scan yr, lesion size, and number of lesions. Conclusions: Identification of clinical factors associated with LR3 progression may allow for risk modeling tools that may assist in determining imaging frequency and timing of intervention. The increased risk among men vs women is not explained by clinical or radiographic features listed above.
Potential use of lenvatinib for patients with unresectable hepatocellular carcinoma beyond progression of sorafenib treatment: A real-world evidence and in vitro assessment with protein phosphorylation array.
Authors: Sato Yasushi , Tomonari Tetsu , Tanaka Hironori , Tanaka Takahiro , Hirao Akihiro , Okamoto Koichi , Miyamoto Hiroshi , Muguruma Naoki , Kagiwada Harumi , Kitazawa Masashi , Fukui Kazuhiko , Horimoto Katsuhisa , Takayama Tetsuji 
Published: February 2020

485 Background: No information is available on the efficacy and safety of lenvatinib (LEN) as a second/third-line treatment for unresectable hepatocellular carcinoma (HCC) after sorafenib (SOR) therapy. We evaluated the characteristics and the therapeutic efficacy and safety of LEN as a second- and third-line treatment as well as first- treatment for unresectable HCC patients in clinical settings. Moreover, to rationalize these clinical findings in vitro, we assessed the anti-tumor activity of LEN on SOR-resistant cell line and performed a comprehensive phosphorylated protein array analysis associated with 377 signal transduction pathways using SOR-resistant and parental HCC cells. Methods: We retrospectively enrolled 51 unresectable HCC patients. Radiologic responses in 41 patients were evaluated by modified RECIST. Active signal transduction pathways in the cells were identified by protein array analysis, including 1205 proteins. Results: The evaluated patients comprised 25 TKI-naive (first- line), 7 intolerant to SOR (second-line), and 9 patients resistant to regorafenib (third-line). The ORRs were 64% in first-line, 42.8% in second-line, and 22.2% in third-line groups (first-line vs. third-line p< 0.05). The OS in the first-line was significantly longer than that in third-line group ( p< 0.05). Patients with better liver functional reserve (Child score, ALBI grade) exhibited higher ORR and longer OS. LEN was well-tolerated in the second/third-line treatment. The IC50 value of LEN against PLC/PRF5-R2 (30 μM) was significantly higher than that against PLC/PRF5 (6.4 μM). LEN significantly inhibited more signal transduction pathways related to FRS2, a crucial FGFR downstream molecule, in PLC/PRF5 than in PLC/PRF5-R2 cells. Conclusions: Our study indicates that LEN was active and safe in the second/third-line treatment for unresectable HCC. LEN seems more effective for HCC patients with better hepatic reserve function, or before TKI-resistance is acquired because of the partial cross-resistance to SOR.
Randomized, open-label, perioperative phase II study evaluating nivolumab alone or nivolumab plus ipilimumab in patients with resectable HCC.
Authors: Kaseb Ahmed Omar , Duda Dan G. , Tran Cao Hop Sanderson , Abugabal Yehia I. , Vence Luis M. , Rashid Asif , Pestana Roberto , Blando Jorge M. , Singh Shalini , Vauthey Jean-Nicolas , Hassan Manal , Amin Hesham M. , Qayyum Aliya , Chun Yun Shin , Tzeng Ching-Wei David , Sakamuri Divya , Wolff Robert A. , Yao James C. , Allison James Patrick , Sharma Padmanee 
Published: February 2020

486 Background: In HCC, surgical resection is associated with high recurrence rates, and no effective neoadjuvant or adjuvant therapies currently exist. Immunotherapy using anti-PD-1 antibodies has shown promised but limited increase in survival in advanced disease. To maximize the benefit, we are studying the efficacy and safety of anti–PD-1 (nivolumab) and anti–CTLA-4 (ipilimumab) antibodies against HCC for resectable HCC. Methods: This is a randomized phase II trial of nivolumab (Arm A) or nivolumab + ipilimumab (Arm B) as pre-operative treatment for patients with HCC who are eligible for surgical resection. Pts are given nivolumab 240 mg every 2 weeks (wks) for a total of 6 wks. Pt in Arm B are treated concurrently with ipilimumab 1 mg/kg every 6 wks. Surgical resection occurs within 4 wks after last cycle of therapy. Pts continue adjuvant immunotherapy for up to 2 years after resection. The primary objective is the safety/tolerability of nivolumab +/- ipilimumab. Secondary objectives include overall response rate, complete response rate and time to progression. Exploratory objectives include evaluating the pre- and post-treatment immunological changes in tumor tissues and peripheral blood. Results: Twenty-six patients were enrolled at the time of this interim analysis, of which 20 have evaluable data. Most pts (55%) were between 60-70yo and male (75%). Four pts were HCV-positive, 6 had HBV and 10 had no hepatitis. 20 patients proceeded with resection as planned, surgery was aborted for 5 patients (1 for frozen abdomen and 2 development of contralateral liver nodule). Three are still receiving preoperative therapy. Pathologic complete response (pCR) was observed in 5/20 evaluable patients – 2 in Arm A and 3 Arm B (25% pCR rate). Five patients in Arm B and 1 in Arm A experienced grade 3 or higher toxicity prior to surgery. No grade 4 or higher toxicity were observed. Conclusions: We report a pCR rate of 25% for resectable HCC after preoperative immunotherapy in a randomized phase II pilot trial. Treatment was safe and surgical resection was not delayed. The study is ongoing. These promising results may contribute to a paradigm shift in the perioperative treatment of resectable HCC. Clinical trial information: NCT03510871.
Economic burden and patterns of care in patients with advanced hepatocellular carcinoma.
Authors: Aly Abdalla , Malangone-Monaco Elisabetta , Noxon Virginia , Henriques Caroline , Benavente Fernando , Kim Amy K. 
Published: February 2020

487 Background: Hepatocellular carcinoma (HCC) is often diagnosed in advanced stages. While sorafenib has been the standard of care for advanced HCC, treatment guidelines are not clearly defined. We studied real world systemic lines of therapy (LOT) and economic burden in HCC patients. Methods: The MarketScan database was used to identify patients newly diagnosed with HCC (ICD-9 155.0, ICD-10 C22.0, C22.8) from 2011-2018 and continuously enrolled for ≥6 months prior and ≥1 month post HCC diagnosis. Patients with prior liver transplantation or metastasis, or other primary cancers, pregnancy, or clinical trial participation at any time were excluded. Systemic LOT were identified and ended due to discontinuation, switch, or end of follow up. Transarterial procedures (chemoembolization [TACE], radioembolization [TARE]) were also reported. Results: A total of 1,558 patients (mean age, 62; 78% male; median follow up, 8.8 months) were studied. The first LOT was mostly sorafenib (78%). The median time from HCC diagnosis to start of sorafenib was 43 days. The median duration of therapy on sorafenib was 60 days, with patients ending sorafenib use due to discontinuation (40%) or switching (6%). Only 16% of patients received second LOT, of which 10% were PD-1 inhibitors. Use of TACE and TARE over the follow up period was 15% and 12%, respectively. TACE was more prevalent prior to first LOT (11%) compared to during first LOT (4%) and between first and second LOT (6%). This trend was also observed for TARE (7%, 3%, and 4%, respectively). Patients incurred a mean all-cause total cost of $181,036 and $17,235 per-patient per-month (PPPM), of which $9494 were HCC-specific (Table). Conclusions: Most patients received sorafenib as first line in advanced HCC, but only for 2 months. Only 16% of patients receive second line therapy. HCC patients have a high economic burden and there is a need for more effective and safe treatments. [Table: see text]
Primary liver angiosarcoma and factors associated with improved outcomes: An analysis of the National Cancer Database.
Authors: Jain Prantesh , Cioffi Gino , Patil Nirav , Opneja Aman , Alahmadi Asrar , Bajor David Lawrence , Saltzman Joel N. , Getty Patrick J. , Ammori John Brian , Bhatt Aashish D. , Mansur David B. , Lee Richard T. , Mangla Ankit 
Published: February 2020

498 Background: Primary liver angiosarcoma (LAS) is a rare and aggressive tumor of the liver. In this analysis of the national cancer database (NCDB) we sought the risk of mortality and factors associated with survival amongst patient diagnosed with LAS. Methods: Patients diagnosed with hepatocellular carcinoma (HCC) or LAS from 2004 – 2014 were identified in the NCDB. The Kaplan-Meier method with the log-rank test was used to calculate survival for HCC and LAS patients. Additional analyses were performed on the cohort with LAS to assess the impact of surgery, chemotherapy, radiation therapy (RT) and facility type on overall survival (OS). Multivariable analyses using cox proportional methods, adjusted for age, sex, Charlson/Deyo score, race, ethnicity, insurance status, facility location and type, surgery status, and chemotherapy status were performed to obtain adjusted hazard ratio (aHR). Results: Total of 118,066 patients with HCC and 346 patients with LAS were identified in the database. Median survival for HCC patients was 11.9 months (95% CI: 11.7-12.2) and 2.0 months for LAS patients (95% CI: 1.8 – 2.4). Risk of mortality was higher for patients with LAS compared to those with HCC (aHR (95% CI): 2.23 (1.97 - 2.53), p < .0001). Among the LAS patients, those who received surgery had a median survival of 8.6 months (95% CI: 5.6 - 17.3), and 1.8 months for those who did not (95% CI: 1.48 - 1.94). Risk of mortality was lower in patients who received surgery compared to those who did not (aHR (95% CI): 0.23 (0.15 - 0.37), p < .0001). Patients treated at and academic center had a higher median survival (3.3 months, 95% CI: 2.2 - 4.1) then those treated at a non-academic center (1.5 months, 95% CI: 1.2 - 1.8). Though, there was no significant difference in OS (aHR (95% CI): 0.48 (0.21 - 1.10), p = 0.082). A very small number of patients received chemotherapy or RT to conduct a meaningful analysis. Conclusions: Patients diagnosed with primary LAS have a worse OS compared to those with HCC. Amongst patients with primary LAS, surgical resection is associated with best survival outcomes. Treatment at an academic center is associated with better median survival, although OS did not reach statistical significance in our analysis.
Insurance status and cholangiocarcinoma: A NCDB analysis.
Authors: Ahmed Hibah , Law Nathan , Wolfe Katrina , Silberstein Peter T. 
Published: February 2020

500 Background: There is an increasing rise of cholangiocarcinoma though the cause is unclear. Cholangiocarcinoma is more often than not incurable at diagnosis and associated with a high mortality rate. Our goal was to compare survival of patients with differing insurance types diagnosed with cholangiocarcinoma identified in the National Cancer Database (NCDB). Methods: We identified 5,638 patients with cholangiocarcinoma in the NCDB diagnosed between 2004-2014. Patients included were categorized as having no insurance, private insurance, Medicaid, or Medicare were included. Between-insurance survival differences were estimated by the Kaplan-Meier method and associated log-rank tests; Tukey-Kramer adjusted p < .05 indicated statistical significance. Results: Statistically significant survival differences were indicated between all insurance groups (all adjusted p < 0.05), such that privately insured patients had the highest median survival. The discrepancy in survival between uninsured and privately insured patients was the largest (6.5 months vs 13.1 months, respectively). Medicaid patients on average had a survival of 7.5 months, while Medicare patients had a median survival of 7.8 months. 2.8% of uninsured patients presented with stage I cholangiocarcinoma, whereas 34% of privately insured patients presented with stage I cholangiocarcinoma. More Medicare patients were treated at community cancer programs compared to privately insured patients (56.7% vs 30.7%, respectively). Likewise, more Medicare patients were treated at academic/research programs compared to those with private insurance, Medicaid, or those who were uninsured (44.7% vs 38.7% vs 7.2% vs 3.7%, respectively). Conclusions: Our study shows the discrepancies in survival between patients with differing insurance statuses. Of all insurances, those privately insured had the largest median survival. [Table: see text]
Sociodemographic characteristics as predictors of outcomes in hepatocellular carcinoma: A retrospective cohort study.
Authors: Beutler Bryce David , Ulanja Mark Bilinyi , Aluru Vijay , Gullapalli Nageshwara 
Published: February 2020

503 Background: It has been established that race, insurance status, and socioeconomic class play an important role in predicting health care outcomes. However, the impact of these factors has yet to be investigated in the setting of hepatocellular carcinoma (HCC). Methods: We designed a retrospective cohort study utilizing data from the SEER program (2007-2015) to identify patients with resectable HCC (N = 28518). Exposures of interest were race (Asian [AS], Black [BL], Native American/Alaska Native [NA/AN], or White [WH]), insurance status (Medicare/Private Insurance [ME/PI], Medicaid [MAID], or No Insurance [NI]), and median household income. Endpoints included: (1) likelihood of surgical recommendation and (2) overall survival. Multinomial logistic regression for relative risk ratio (RRR) and Cox models were used to identify pertinent associations. Results: Race, insurance status, and socioeconomic class had statistically significant effects on the likelihood of surgical recommendation and overall survival. AS were more likely to receive a recommendation for hepatic resection (RRR = 1.60; 95% CI: 1.42 – 1.80; Reference Race: BL) and exhibited prolonged overall survival (HR = 0.77; 95% CI: 0.73 – 0.82) as compared to members of other ethnic groups; there was no difference in these endpoints between BL, NA/AN, or WH individuals. Patients who had ME/PI were more likely than those with MAID or NI to receive a surgical recommendation. ME/PI was also associated with superior overall survival. Individuals with a household income in the highest quintile were less likely to receive a surgical recommendation than those in the lower quintiles, but nevertheless demonstrated prolonged survival. Conclusions: Race, insurance status, and socioeconomic class have measurable effects on HCC management and outcomes. The underlying causes of these disparities warrant further investigation. [Table: see text]
Impact of facility type, insurance status, and income on use of single agent chemotherapy (SACT) for advanced hepatocellular carcinoma (AHCC): Analysis of National Cancer Database (NCDB).
Authors: Lee Richard T. , Cioffi Gino , Opneja Aman , Alahmadi Asrar , Patil Nirav , Jones Nelroy , Bajor David Lawrence , Saltzman Joel N. , Mohamed Amr , Mangla Ankit , Barnholtz-Sloan Jill 
Published: February 2020

504 Background: This study analyzes the pattern of use of SACT in the treatment and survival of AHCC before and after sorafenib was FDA approved in late 2007. Methods: Adult patients diagnosed with HCC and treated with only chemotherapy (CT) from 2004 – 2014 were identified in NCDB database. Patients were analyzed during 3 time frames: 2004–2006 (pre-sorafenib (PS), 2007–2011 (early sorafenib (ES) and 2012–2014 (late sorafenib (LS)). Cox proportional hazards models and Kaplan-Meier method were used for analyses. Results: The NCDB contained 31,107 patients with HCC diagnosed from 2004–2014 and treated with CT alone. Patients were generally men (77.3%), >50 years of age (92.5%), and with a variety of T-stages - T1 (31.0%), T2 (23.9%), T3 (28.3%), and T4 (16.9%). The use of SACT was only 6.2% in the PS period, increased to 15.5% in the ES period, and to 22.3% in the LS period (p<0.0001). During this later period, the highest proportion of SACT is among academic and integrated network facilities (23.4%) as compared to community facilities (16.4%, p<0.0001). The MS of patients with AHCC treated only with CT has improved significantly over the study periods from 10 months (m) (95% CI: 9.5-10.6) to 12.5m (12.0-12.9) to 16m (15.6-16.4, p< 0.001). Significant differences in MS were found between facility types in all time frames (Table). Multivariate analysis indicates worse outcomes for patients treated at community cancer programs (HR 1.66, 1.53-1.79) as compared to academic programs as well as for no insurance (HR 1.13, 1.05-1.22) and estimated household income of <$63,000 (HR 1.09, 1.05-1.13). Conclusions: Despite an overall improvement in survival for AHCC patients treated with only CT, significant differences in the utilization of SACT and survival exist by facility type, insurance status, and income. [Table: see text]
Celecoxib versus parecoxib versus oxycodone in pain control for transcatheter chemoembolization in patients with hepatocellular carcinoma.
Authors: Zhao Ming , Lyu Ning , Kong Yanan , Li Xiaoxian 
Published: February 2020

509 Background: Abdominal pain is one of the most common side effects of transarterial chemoembolization (TACE) in patients with unresectable hepatocellular carcinoma. Previous studies reported that perioperative controlled-release oxycodone (CRO) intake or administration of parecoxib resulted in adequate pain control after TACE. However, there are currently no studies comparing opioids with nonsteroidal anti-inflammatory drugs (NSAIDs) in controlling postoperative pain. Therefore, we conducted a clinical trial to compare the analgesic effect and safety among celecoxib (oral COX-2 inhibitor), parecoxib (injectable COX-2 inhibitor), and CRO (oral opioids) in patients undergoing TACE. Methods: The study was a prospective, randomized, paralleled trial in which 213 patients were enrolled between September 2016 and March 2019. Patients were randomly assigned at the ratio of 1:1:1 to receive celecoxib, parecoxib or CRO 1 h before TACE (T0) and once every 12 h for 2 days after TACE. Pain level, morphine consumption and adverse events were evaluated and compared among the three regimens. Results: Highest incidence of pain occurred within the first 12 hours (T12) after TACE. Analysis of pain control showed no significant difference among the mean highest pain scores, percentage distribution of pain categories and mean morphine consumption in the three groups at T0, T12, T24, T36, and T48. At T24, 11 patients (15.7%) in oxycodone group had fever, which was higher than parecoxib regimen (1 patient [1.5%], P = 0.003). At T36, 13 patients (18.6%) in oxycodone regimen had fever, which was higher than celecoxib regimen (2 patients [2.9%], P = 0.003) and parecoxib regimen (1 patient [1.5%], P < 0.001). At T48, 11 patients (15.7%) in oxycodone regimen had fever, which was higher than celecoxib regimen (2 patients [2.9%], P = 0.010) and parecoxib regimen (0 patients, P = 0.001). Conclusions: The results suggested that patients obtained celecoxib, parecoxib or CRO once every 12 hours can have the same level of analgesic effect during each time period of TACE. However, body temperature balance in oxycodone regimen was significantly worse than celecoxib regimen and parecoxib regimen. Clinical trial information: NCT03059238.
The comparison of mFOLFOXIRI with CAOX/SOX as neoadjuvant chemotherapy for locally advanced rectal cancer.
Authors: Terazawa Tetsuji , Kodama Hiroyuki , Yukami Hiroki , Aoki Masahiko , Miyamoto Takahiro , Asaishi Ken , Yamaguchi Toshifumi , Kii Takayuki , Goto Masahiro , Tanaka Keitaro , Okuda Junji , Higuchi Kazuhide 
Published: February 2020

51 Background: The standard therapy for the locally advanced rectal cancer (LARC) (Ra or Rb, T2Npsitive, T3/4Nany) is chemoradiotherapy (CRT) followed by surgery. The CRT prevents local recurrence, although problems such as complications or the improvement of distant recurrence still remain. Several studies about the neoadjuvant chemotherapy (NAC) without radiation showed favorable R0 resection rate and outcome, however the best regimen of NAC is unclear. The aim of this study is to investigate the efficacy and safety of mFOLFOXIRI and CAPOX/SOX as NAC. Methods: We examined the patients (pts) with LARC who were planned to receive mFOLFOXIRI (5FU 2400mg/m2/day1-2, leucovorin 200mg/m2, oxaliplatin 85mg/m2, irinotecan 150mg/m2, every 2 weeks) or CAPOX/SOX(capecitabine 2000mg/m2 or S-1 mg/m2 80day1-14, oxaliplatin 130mg/m2, day1, every 3weeks) for 8-12 weeks as NAC, retrospectively. Results: Forty-nine pts received mFOLFOXIRI and thirty-two pts received XELOX/SOX between Jan 2015 and Mar 2019. The characteristics of mFOLFOXIRI and XELOX/SOX were as follows; median age, 64 (37-80) and 65 (33-68); PS 0/1, 46(94%)/3(6%) and 14(44%)/18(56%); Ra/Rb-P, 4(8%)/45(92%) and 0/32; clinical T2/3/4, 4(7%)/27(55%)/19(39%) and 1(3%)/18(56%)/13(41%); clinical N0/1/2, 13(27%)/26(53%)/10(20%) and 7(22%)/17(53%)/8(25%). The pathological response rate which was defined as tumor affected area over one-third were 61.2% in mFOLFOXIRI and 65.6% in CAPOX/SOX including complete remission of 4.1% and 12.5%, respectively. Six of 49 pts withdrew from mFOLFOXIRI due to toxicities, whereas one of 32 pts from CAPOX/SOX. One pt received CRT after SOX because of lack of efficacy. The major grade 3/4 toxicities of mFOLFOXIRI were neutropenia (n = 22, 45%), thrombocytopenia and febrile neutropenia (n = 4, 8%) and anorexia (n = 3, 6%), whereas CAPOX/SOX neutropenia (n = 3. 9%), thrombocytopenia (n = 1, 3%) and hand-foot syndrome (n = 1, 3%). The one year of relapse free survival rate were 85.4% and 83.6%. Conclusions: Although the pathological response of mFOLFOXIRI was comparable with CAPOX/SOX, CAPOX/SOX was less toxic.The further investigation including 5 year overall survival rate rate was needed.