bluuebunny/crossref_metadata_2025_split huggingface dataset:
Importance of detoxification capacity of albumin for assessing state of gastric cancer patients and effective treatment planning.
Authors: Kit Oleg Ivanovich , Goroshinskaya Irina A. , Maslov Andrey A. , Medvedeva Dar'ja E. , Surikova Ekaterina Igorevna , Nemashkalova Ludmila A. , Kaminskiy Gennadiy V. , Tishchenko Irina , Malinin Sergey A. , Chilhahyan Lusegen 
Published: January 2019

34 Background: The aim of the study was measuring biochemical indices reflecting endotoxicosis syndrome in gastric cancer patients with adenocarcinoma of different grades and signet ring cell carcinoma. Methods: The study included 67 patients with gastric cancer divided into 4 groups depending on the tumor histotype: well- and moderately-differentiated adenocarcinoma (G1-2); poorly-differentiated adenocarcinoma (G3); signet ring cell carcinoma (SRCC); combined gastric tumors; and 12 healthy donors. The content of medium mass molecules (MMM254 and MMM280), total and effective albumin concentrations (TCA and ECA), toxicity index (IT = TCA/ECA-1) and intoxication factor (IF = MMM254/ECA⋅1000) were used to assess the level of endogenous intoxication. The Statistika 6.0 software package was used. Results: IT, reflecting the functional state of the albumin molecule, significantly exceeded the level in donors: by 2.3 times in G1-2, by 3.3 times in G3, by 3.2 times in SRCC (p < 0.01-0.001), by 2.2 times in mixed tumors (p < 0.05). The greatest increase in IT – by 4.6 times – was observed in patients with serosal invasion and tumor spread to the adjacent structures (T4 in the TNM classification). IF, which is an integral indicator of endotoxemia, in all groups of patients was significantly (p < 0.01-0.00001) higher than in donors. The increase was 55.2% in patients with G1-2, 132.7% for G3, 234.6% for T4, 66.8% for SRCC, and 59.6% for mixed tumors. The dynamic observation of patients showed that a sharp increase in the studied parameters was followed by relapses. Conclusions: The increase in IT and IF in all groups of patients indicated an enhancement of endotoxemia in gastric tumors, mainly due to the decreased detoxification capacity of albumin, as high levels of MMM were observed only in some patients. The changes were significantly more expressed in patients with G3, with the maximal changes in all the studied endotoxicosis parameters in T4. The results demonstrated the diagnostic significance of the detoxification ability of albumin for the evaluation of the state of gastric cancer patients and for the adequate treatment planning.
Early occurrence of hepatocellular carcinoma in patients with and without cirrhosis after HCV treatment with direct-acting antivirals.
Authors: Finkelmeier Fabian , Dultz Georg , Kronenberger Bernd , Peiffer Kai Henrik , Krauss Franziska , Zeuzem Stefan , Sarrazin Christoph , Vermehren Johannes , Waidmann Oliver 
Published: January 2019

356 Background: The aim of the study was to evaluate the risk of HCC development after treatment with direct-acting antivirals (DAA) and to compare hepatocellular carcinoma (HCC) occurrence to patients treated with interferon (IFN)-based therapies. Methods: We analyzed a large cohort with chronic HCV patients for the onset of new hepatocellular carcinoma after DAA treatment. A historic interferon treated cohort was investigated for comparison. Results: 819 patients were included in the DAA group, 269 (32.8%) had established cirrhosis. Median follow up was 263 days (0-1001). 25 patients (3.1%) were diagnosed with de novo HCC within the observation time. All of these patients had established cirrhosis. Patients with new HCC were mostly male, older, treatment experienced, had a lower SVR12 rate and higher levels of liver inflammation markers. Investigation of the subcohort of 269 cirrhotic patients yielded a HCC rate of 9.3% during the follow-up of approximately one year. Non-SVR12 was an independent risk factor for de novo HCC (OR 4.983, 1.39-17.88, 0.014). Most HCCs were diagnosed in early stage BCLC A. In the historical cohort of 351 IFN treated patients the rate of de novo HCC was 5.4% overall and 11.8% in patients with already established cirrhosis (n = 68). In the multivariate analysis failed SVR (OR 5.386, 1.155-25.108, p = 0.032) remained an independent risk factor for de novo HCC. In a combined analysis of all patients (DAA and IFN treated) in a multivariate approach male gender, failed SVR and cirrhosis were independent factors for HCC development. Conclusions: DAA treatment in cirrhotic patients does not seem to reduce the risk of HCC development in the short term. HCC rates were not different between DAA-treated patients and those who received interferon. Achievement of SVR seems to be the most important aim to prevent HCC development.
Clinical benefit of maintenance therapy for patients with advanced biliary tract cancer without progression on first-line gemcitabine plus cisplatin.
Authors: Hyung Jaewon , Yoo Changhoon , Kim Kyu-Pyo , Kim Bum Jun , Jeong Jae Ho , Chang Heung-Moon , Ryoo Baek-Yeol 
Published: January 2019

357 Background: Gemcitabine plus cisplatin (GP) is the standard first line chemotherapy for patients with advanced biliary tract cancer (BTC). In the pivotal ABC-02 study, patients received up to 24 weeks (6-8 cycles) of three-weekly GP. In daily practice setting, however, patients without progression often receive GP more than 6-8 cycles. It is uncertain whether maintenance treatment has clinical benefit in patients without progression on GP. Methods: Advanced BTC patients treated with GP between April 2010 and February 2015 in Asan Medical Center, Seoul, Korea, were retrospectively analyzed. Among the patients who did not progressed and stopped GP after 6-8 cycles, patients were stratified according to the further treatment; those with or without further cycles of GP (maintenance group vs observation group). Primary endpoint was overall survival (OS). Results: Among 740 patients, 231 patients (31.2%) were eligible for this analysis; 111 for observation group, 120 for maintenance group. In observation group, 76 patients (68.5%) stopped GP due to completion of scheduled chemotherapy and 27 patients (24.3%) due to the patients’ request or toxicity. There were no statistically significant differences in baseline characteristics between two groups. Median OS from the initiation of GP was 20.5 months [95% CI 15.4-25.6] and 22.4 months [95% CI 17.0-27.8] in the observation and maintenance group, respectively (p = 0.32). Median progression-free survival (PFS) was 10.4 months [95% CI 7.0-13.8] and 13.2 months [95% CI 11.3-15.2], respectively (p = 0.22). These were consistent in the multivariate analyses for OS and PFS after the adjustment of prognostic factors. Conclusions: In our analysis, maintenance therapy of GP was not associated with improved survival outcomes. Considering the potential disadvantages such as cumulative toxicities, maintenance therapy may not be beneficial in patients who did not progressed on 6-8 cycles of GP.
A phase II pilot trial of nivolumab (N) + albumin bound paclitaxel (AP) + paricalcitol (P) + cisplatin (C) + gemcitabine (G) (NAPPCG) in patients with previously untreated metastatic pancreatic ductal adenocarcinoma (PDAC).
Authors: Borazanci Erkut Hasan , Jameson Gayle S. , Borad Mitesh J. , Ramanathan Ramesh K. , Korn Ronald Lee , Caldwell Lana , Ansaldo Karen , Hendrickson Kristin , Marceau Katie , Von Hoff Daniel D. 
Published: January 2019

358 Background: Effective therapy for the treatment of PDAC remains one of the greatest unmet oncology clinical needs. The addition of C to G and AP has shown promising clinical data in a previously reported study [J Clin Oncol 35, 2017 (suppl 4S; abstract 341)]. In preclinical work, vitamin D (Vit D) analog therapy decreases myeloid derived suppressor cells and regulatory T cells, turning PDAC into a more immune-friendly microenvironment. This trial combines AP/C/G with Vit D analog P and the anti-PD-1 antibody N as a combination therapy for patients with previously untreated metastatic PDAC. This trial evaluates the efficacy and safety of NAPPCG in that patient population (NCT02754726). Methods: Eligibility criteria include Stage IV PDAC, no prior chemotherapy for systemic disease, KPS ≥ 70, and measurable disease. Doses are AP 125 mg/m2 undiluted, G 1000 mg/m2 in 250 ml of normal saline (NS), each infused over 30 minutes with C 25 mg/ m2 in 500 ml of NS infused over 60 minutes on days 1, 8, 22, and 29 of a 42-day cycle. N is given at a fixed dose of 240 mg as a 60 minute infusion on days 1, 15, and 29. P is given at a fixed dose of 25 µg IV twice weekly. Primary objective is to determine the efficacy of the combination for patients with previously untreated metastatic PDAC through determining CR, ORR, PFS, and OS. The secondary objective is to evaluate safety in patients with previously untreated metastatic PDAC. Results: Trial was initiated May 2016 and10 patients have been enrolled in the initial phase of the study and are evaluable (baseline and ≥1 follow up CT scan). Most common drug-related grade (Gr) 3-4 adverse events (AE’s), n = 10, are thrombocytopenia 100% (gr 3 = 50%, gr 4 = 50%) with no serious bleeding events, anemia 50% (gr 3 = 50%, gr 4 = 0%), and colitis 20% (gr 3 = 20%, gr 4 = 0%). By RECIST 1.1 criteria, the best response is 8 PR and 2 SD, yielding an 80% ORR. Median PFS is 8.2 months. Median OS has not been reached. Conclusions: Although a small study, the high response rate is encouraging. This regimen is being expanded to 25 patients with plans to include exploratory inflammatory biomarkers. Clinical trial information: NCT02754726.
Major arterial resection for stage 3 adenocarcinoma of the pancreas.
Authors: Loveday Benjamin , Tomiyama Koji , Zilbert Nathan , Tremblay St-Germain Amélie , Serrano Aybar Pablo Emilio , Fox Adrian , Segedi Maja , Scholtz Paul , O'Malley Martin , Borgida Ayelet , Bianco Teresa , Dodd Anna , Krzyzanowska Monika K. , Moore Malcolm J. , Kim Joon-Hyung J. , Wei Alice Chia-chi , Gallinger Steven , Dhani Neesha C. , McGilvray Ian M 
Published: January 2019

362 Background: Stage 3 pancreas ductal adenocarcinoma (PDAC) is defined by arterial involvement, and its resection remains controversial. The objective of this study was to evaluate clinical and oncologic outcomes for patients with stage 3 PDAC who entered a treatment program of neoadjuvant therapy (NAT) and pancreatic resection, with comparison between those who underwent arterial (AR) vs. standard resection (SR). Methods: This cohort study included patients from 2009-2016 in a single academic institution, with biopsy-proven potentially resectable stage 3 PDAC who entered a treatment program of NAT followed by surgical exploration if non-progressive disease on imaging. AR was performed if required to achieve R0 resection. Oncological outcomes were analyzed as intention to treat from diagnosis date. Results: Eighty-nine patients met inclusion criteria, of whom 87 (97.8%) received chemotherapy and 50 (56.2%) received radiotherapy. 46/89 (51.7%) underwent surgical exploration; 31 underwent pancreas resection (AR n = 20, SR n = 11), and 15 were found to have metastatic or unresectable disease. The AR group had a longer operative time (681 vs. 563 minutes, p = 0.0059) and more blood loss (1600 vs. 575 mL, p = 0.0004) compared with SR, with no difference between groups for blood transfusion, overall complications, pancreatic fistula, length of stay, reoperation, readmission or mortality. R0 rate was 100% for resected patients. Post-operative 90-day mortality was 1.1%. Median overall survival of resected patients was longer than in non-resected patients (25.9 vs. 14.8 months, p = 0.01), while AR had comparable overall survival to SR (19.7 vs. 28.4 months, p = 0.41). Conclusions: Patients with non-progressive stage 3 PDAC after NAT should be considered for pancreas resection. AR had comparable clinical and oncologic outcomes to SR. Resection may offer a survival advantage over non-surgical therapy alone, and AR should be considered if required to obtain a negative resection margin.
First line gemcitabine and nab-paclitaxel chemotherapy for localized pancreatic ductal adenocarcinoma.
Authors: Gulhati Pat , Prakash Laura , Katz Matthew H. G. , Wang Xuemei , Javle Milind M. , Shroff Rachna T. , Fogelman David R. , Lee Jeffrey Edwin , Tzeng Ching-Wei David , Lee Jeffrey H , Weston Brian , Tamm Eric P. , Bhosale Priya , Koay Eugene Jon , Maitra Anirban , Wang Huamin , Wolff Robert A. , Varadhachary Gauri R. 
Published: January 2019

369 Background: Chemotherapy is widely used as a component of treatment of localized pancreatic ductal adenocarcinoma (PDAC). Pre-operative chemotherapy is associated with early treatment of micro-metastases and guaranteed delivery of all components of multimodality therapy. For locally advanced (LA) PDAC, induction chemotherapy is standard of care. We evaluated the use of gemcitabine and nab-paclitaxel (Gem/nab-P) as first-line therapy in localized PDAC. Methods: Records of pts with localized PDAC who initiated Gem/nab-P at a single institution from 2013-2015 were retrospectively reviewed. Clinicopathologic features, dose and outcomes were evaluated. Pts were staged using our previously published criteria: potentially resectable (PR), borderline type A (BR-A) (anatomy amenable to vascular resection), BR-B (biology suspicious for metastatic disease including high CA19-9), BR-C (co-morbidities requiring medical optimization), and LA. Co-morbidities were classified using adult comorbidity evaluation-27 score. Overall survival (OS) was analyzed using Kaplan Meier method. Results:99 pts [M/F: 50/49; median age: 70 yrs (range 30-85); PR/BR/LA: 45/14/40] were treated with Gem/nab-P. Clinical staging showed PR+BR-A/BR-B+C: 20/39. BR-B+C included one or more of the following factors: age ≥80 yrs [13%], ECOG PS ≥2 [13%], moderate/severe co-morbidities [55%], CA19-9≥1000 [28%], suspicion for metastatic disease [21%]. Majority of pts received biweekly Gem/nab-P dosing [standard/biweekly/other: 10/80/9] with minimal grade 4 toxicity. 45/99 pts received chemoradiation after Gem/nab-P [30Gy/50.4Gy: 15/30]. 12/20 (60%) PR+BR-A, 2/39 (5%) BR-B+C and 1/40 (3%) LA pts underwent pancreatectomy. 13/15 resected pts received adjuvant chemotherapy. At median follow-up of 26 mo, median OS was 18 (95% CI: 15.6-20.5) mo for all, 17 (95% CI: 14.6-19.5) mo for unresected and not reached for resected pts (p = 0.03). Conclusions: A significant number of pts with resectable PDAC albeit aggressive biology (BR-B) and/or medically inoperable disease (BR-C) received first-line Gem/nab-P; resection rates were lower compared to PR/BR-A pts. Biweekly dosing is being used in localized PDAC and is well tolerated.
Effect of adjuvant radiation on survival for extra-hepatic cholangiocarcinoma.
Authors: Takahashi Caitlin , Shridhar Ravi , Huston Jamie , Patel Anjan Jayantilal , Brown Richard H. , Koehler Kevin , Briceno Pedro , Meredith Ken Lee 
Published: January 2019

377 Background: Extra-hepatic cholangiocarcinomas (EHC) are low-incidence cancers that are difficult to diagnose and associated with a dismal prognosis. Surgery remains the only option for durable survival however R1 resections are high. We sought to examine the impact of adjuvant therapies on survival in patients with EHC. Methods: Utilizing the National Cancer Database we identified patients who underwent resection for EHC. We then stratified by adjuvant therapy (chemo(AC) or chemoradiation(CRT). Baseline comparisons of patient characteristics were made using Mann-Whitney U, Kruskal Wallis and Pearson’s Chi-square test as appropriate. Survival analyses were performed using the Kaplan-Meier method. Multivariable cox proportional models (MVA) were developed to identify predictors of survival. All statistical tests were two-sided and α < 0.05 was considered significant. Results: We identified 4334 patients who underwent EHC resection: AC = 775, CRT = 1254, no adjuvant (NA) therapy = 2305 and a median age of 67 (18-90) years. R0 resections was performed in 71.6% of patients and the median LN harvest was 9 (3-18). R0 resections and lymph node negative patients demonstrate improved survival p < 0.001 and p < 0.001. Adjuvant therapy did not improve survival in R0 resections, p = 0.2. However survival was benefited in R1 patients, with those receiving CRT demonstrating the most significant improvement: median and overall 5-year survival AC = 16.7 months 8%, CRT = 23.1 months, 20.4%, and NA = 16.1 months and 11.6% p < 0.001. In LN- patients CRT (47.3 months, 47%) but not AC (45 months, 44.5%) demonstrated benefit in survival compared to NA (37.8 months, 40.1) p = 0.04 and p = 0.7. Additionally, patients with LN+ and R1 resection had survival benefit when treated with (CRT 24.9 months and 24.3%), compared to NA (20.2 and 21.1%), p = 0.02. AC (24 months and 24%) did not demonstrate survival in these patients, p = 0.21. MVA demonstrated that age, T-stage, LN+, R0 resection and CRT were predictors of survival. Conclusions: Adjuvant CRT improves survival for patients with EHC who underwent R1 resections, and in LN- and LN+ patients. However, AC only benefited node positive patients with R0 resections. Patients with resected EHC should be referred for adjuvant CRT.
Phase 2 study of carfilzomib for the treatment of patients with advanced neuroendocrine cancers.
Authors: Singh Jaswinder , Shipley Dianna , Cultrera Jennifer , Chua Cynthia , Cohn Allen Lee , Soriano Andres O. , Bendell Johanna C. 
Published: January 2019

382 Background: Carfilzomib (CFZ) is an irreversible proteasome inhibitor (PI) that exhibits anti-proliferative and pro-apoptotic activity in solid and hematologic tumor cells i n vitro, and is US FDA approved for multiple myeloma. Proteasomes degrade cell cycle inhibitor proteins and inhibition of these proteins offers a novel therapy for the treatment of patients with neuroendocrine tumors (NET). This phase 2 study evaluated the efficacy of CFZ for patients with advance NETs. Methods: Pts with biopsy-proven, advanced, well-to-moderately differentiated NETs, including typical carcinoid and pancreatic islet cell tumors, were treated with CFZ 20 mg/m2 IV Days (D) 1 and 2, then 56 mg/m2 IV D 8, 9, 15, and 16 of Cycle (C) 1, followed by CZF 56 mg/m2 IV D 1, 2, 8, 9, 15, and 16 of C 2 and beyond. Pts continued study treatment (tx) until intolerable toxicity, disease progression, or withdrawal of consent. Restaging occurred every 3 cycles. The primary endpoint was overall response rate (ORR); secondary endpoints were disease control rate (DCR), progression free survival (PFS), and toxicity. Results: 62 pts were enrolled: median age 63 yrs, 61% female, 50% ECOG 0/50% ECOG 1. 65% of pts had carcinoid tumors and 35% of pts had pancreatic NET. The most common primary sites of disease were the pancreas (34%) and the small intestines (21%). 74% of pts had prior systemic therapy, 42% had prior surgery and 16% had prior radiotherapy. Median tx duration was 11 wks. At the time of data cutoff, 31% of pts remained on tx. 32% of pts discontinued due to progressive disease, 16% due AE, and 21% due to pt or physician decision. Two pts (3%) had a confirmed partial response (PR) and 1 pt (2%) had an unconfirmed PR; 4 ongoing patients have not yet been evaluated for response. The ORR was 3.23% (95% CI 0.4%, 11.2%), the DCR was 53.23% (CI 95% 40.1%, 66.0%), and median PFS was 8.1 months. The most frequently reported tx-related AEs were nausea (52%; Grade 3/4 [G3/4], 2%), fatigue (42%; G3/4, 3%), vomiting (36%; G3/4, 2%), and diarrhea (27%; G3/4, 5%). Conclusions: CFZ tx was well-tolerated in this pt population. Future plans will be determined once response data are available on all patients. Updated results will be presented. Clinical trial information: NCT02318784.
Prognosis of hepatic failure with the albumin-bilirubin model for hepatocellular carcinoma after stereotactic body radiotherapy with and without transplant.
Authors: Hasan Shaakir , Kirichenko Alexander V. , Renz Paul , Kudithipudi Vijay , Vincent Molly , Machado Lorenzo , Uemura Tadahiro , Thai Ngoc 
Published: January 2019

384 Background: The Albumin-Bilirubin (ALBI) model is a validated prognostic assessment of cirrhosis in hepatocellular carcinoma (HCC), stratifying patients to grades 1(ALBI-1), 2(ALBI-2), or 3(ALBI-3). We reported that ALBI distinguishes patients at higher risk for hepatic failure(HF) after stereotactic body radiotherapy (SBRT) within the Child Pugh(CP) A population. We now apply the ALBI model to both CP-A and CP-B patients after SBRT with or without orthotropic liver transplant (OLT), and assess its prognostic capability of overall survival (OS) and HF relative to the CP model. Methods: From 2009-2017, 68 patients with 81 HCC lesions and CP-A (45) or CP-B (23) cirrhosis completed SBRT in this IRB approved study. The median dose was 45 Gy (35 - 57 Gy) in 4-7 fractions. Initial ALBI and CP scores were measured against OS and progression of CP class, which was recorded every 3-4 months. Median follow-up = 18 months. Results: The median age = 62 and tumor size = 3.5 cm (1.1 Ð 11 cm). 26 patients were ALBI-1, 31 ALBI-2, and 11 ALBI-3 prior to SBRT. For all patients, 2-year local control was 96%. 1 and 2 year OS was 77% and 54%, disease free survival was 71% and 40%, and freedom from CP progression was 71% and 56%, respectively. OS was significantly different between ALBI-1, ALBI-2, and ALBI-3 patients (P = 0.01), as was progression of CP class (P<0.001). When stratified by initial CP class, there were no significant differences in survival or CP progression [Table 1]. In a subset of 37 CP-A and 15 CP-B without OLT, rates of progressive cirrhosis were better predicted by ALBI (P<0.001) than CP class (P=0.09). Conclusions: Compared to the CP model, the ALBI index more precisely predicted HF and OS in HCC patients for both early and intermediate cirrhosis. Its application may help better select candidates for OLT after SBRT, who may be at higher risk for HF than initially predicted. [Table: see text]