bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neutrophil/lymphocyte ratio (NLR) may predict prognostic factor with gemcitabine/cisplatin/S-1 (GCS) for patients with advanced biliary tract cancer (MITSUBA /KHBO1401-1B).
Authors: Otsuru Toru , Ioka Tatsuya , Nagano Hiroaki , Hatano Etsuro , Eguchi Hidetoshi , Kanai Masashi , Kobayashi Shogo , Seo Satoru , Baba Hideo , Taketomi Akinobu , Yoshimura Kenichi 
Published: May 2019

e15656 Background: There is little information available about prognostic markers of gemcitabine, cisplatin, and S-1 (GCS) in patients with advanced biliary tract cancer (aBTC). Neutrophil/lymphocyte ratio (NLR) in several cancers including aBTC was reported to be a prognostic and/or predictive factor associated with clinical outcomes. There are no data about relation between NLR and clinical outcome in patient with aBTC who underwent GCS. Methods: Baseline demographics and NLR at enrollment were retrospectively evaluated in 119 patients who received GCS treatment in MITSUBA / KHBO1401 randomized phase III trial, which showed significant superiority of GCS to GC. The clinical utility of the NLR was evaluated by receiver operating characteristic (ROC) curves, and the cutoff values for NLR were 3.7. We divided these patients based on estimated NLR, and evaluated the clinicopathological factors and survival in the two groups (NLR ≧ 3.7 or < 3.7). Results: 32 patients were in NLR ≧ 3.7group and 87 patients were in NLR < 3.7 group. The progression-free survival between two groups was not significantly different (p = 0.45). Although, the median overall survival (OS) of NLR ≧ 3.7 group was 10.4 months, while OS of NLR < 3.7 group was 18.5 months (HR 0.55, 95% confidential interval [CI] 0.36-0.87; p = 0.01).The ratio that was able to continue chemotherapy from initial administration six months later was 83.4%of NLR < 3.7 group, and 65.6% of NLR ≧ 3.7 group (p = 0.04). Conclusions: Our study confirmed that high NLR is associated with worse OS, and suggested it may be a predictive marker for GCS chemotherapy in patients with aBTC.
Postsurgical multiple-sites sampling procedure for the precise detection of microvascular invasion of hepatocellular carcinoma.
Authors: Zhou Qian , Chen Lili , Chen Shuling , Cao Qinghua , Peng Sui , Liao Bing , Kuang Ming 
Published: May 2019

e15657 Background: Microvascular invasion (MVI) is an important risk factor of recurrence for hepatocellular carcinoma (HCC). We aimed to explore the relationship of the number of sampling sites (NuSS) and sampling location with positive rate of MVI, and investigate cut-off values for NuSS. Methods: From May 2010 to Feb 2017, 910 HCC patients undergone hepatectomy with well-preserved tissue blocks were retrospectively enrolled. Associations between NuSS and positive rates of MVI were investigated. The thresholds of NuSS according to different factors were determined by Chow test and Breakpoints function, and validated prospectively in 118 patients. In validation cohort, MVI positive rates in different sampling locations were estimated. Results: The positive rates of MVI increased as NuSS increased ( P < 0.001). Tumor size and number were two factors influencing NuSS. A minimum of four, six, eight and eight sampling sites were required for detecting MVI in solitary tumors measuring 1.0-3.0 cm, 3.1-4.9 cm and ≥ 5.0 cm and multiple tumors. The positive rates of MVI as per developed thresholds were significantly higher in all the tumor subgroups of validation cohort than those in routine clinical practice in training cohort (46.7% vs. 20.6%, P= 0.048; 44.4% vs. 24.4%, P= 0.025; 73.3% vs. 50.3%, P= 0.004; 67.7% vs. 45.4%, P= 0.026). The positive rates of MVI in tumor interface were higher than those in proximal and distal paracancerous and normal liver parenchyma. Conclusions: The different thresholds of NuSS according to tumor size and number, and sampling distribution according to location provided evidences of standardized sample collection of liver cancer specimen for accurate MVI diagnosis.
Functional personalized oncology to determine drug sensitivity in cholangiocarcinoma.
Authors: Zarrinpar Ali , Kim Un Bi , Grandori Carla , Schaub Franz , Rosati Rachele 
Published: May 2019

e15672 Background: Rare tumors, such as cholangiocarcinoma (CC), have no established treatment protocols, forcing clinicians to select therapies based on educated guesses or small case series. Genomic tumor analyses fail to identify options for most patients. Here, we show the feasibility of using a high-throughput functional assay to test targeted drug libraries on individual patient-derived tumor organoids from CC to yield experimentally-validated therapeutic options. Methods: Three consecutive patients with CC who were undergoing a standard of care biopsy or resection were enrolled in an IRB-approved study. Patient characteristics, demographics, tumor pathology, including Next Generation Sequencing (NGS) data and organoid-derived drug recommendations are shown in the Table. Specimen (~ 200 mg of tumor) was shipped on ice overnight to SEngine Precision Medicine for tumor-derived organoid culture and sensitivity analysis. Organoids were evaluated using a multi-dose response to each drug in a library of 120 FDA-approved and investigational drugs and compared those responses to all prior patients. This established both functional sensitivity and the uniqueness of each patient’s response. Results: We tested operational logistics, tumor growth rates, and chemosensitivity reporting timelines. This has allowed us to: 1) operationalize the expansion process, 2) quantify turn-around time, and 3) identify any technical or logistic barriers. All specimens resulted in adequate growth for sensitivity characterization. None of the NGS studies resulted in recommendations for sensitivity to targeted chemotherapy. Conversely, tumor organoid assays rapidly identified selective, personalized drugs. Conclusions: We have shown the feasibility of this approach in CC. Our preliminary results will inform the design of a future prospective clinical trial to establish and validate this method to select personalized cancer treatments for rare malignancies.[Table: see text]
Retrospective analysis of outcomes with different adjuvant treatments in cholangiocarcinoma: An NCDB review.
Authors: Mamadgi Jyothika , Babar Laila , Lundeen Kristina , Abel Stephen , Verma Vivek , Wegner Rodney E , Raj Moses S. 
Published: May 2019

e15677 Background: Annually approximately 5000 cases of cholangiocarcinoma are reported in the US. Of these, less than 40% are treated surgically with a curative intent. Post resection, local and distant recurrence rates are as high as 35% within two years. Positive surgical margins, with either Microscopic (R1) or Macroscopic (R2) disease, confer a higher risk of recurrence. We aim to analyze survival outcomes for different adjuvant treatment strategies in patients with R1/R2 resection. Methods: We queried the NCDB from 2004-2015 for patients with non-metastatic cholangiocarcinoma, who had an R1/R2 resection status post surgery. We then stratified these patients into three arms based on the adjuvant treatment they received: combined chemotherapy and radiation (CRT) vs chemotherapy (CTH) vs observation (OBS). Mean overall survival (OS) was compared for these three groups. OS was calculated from the date of diagnosis to the date of last contact or death using Kaplan Meier curves to present the cumulative probability of survival, with log-rank statistics to assess significance. Results: We identified 522 patients who met our inclusion criteria. Of these, 178 received CRT adjuvantly, 171 CTH, and 173 were observed. The OS in these arms was 42 vs 32 vs 30 months respectively (pooled p < 0.04). As compared to CRT, the hazard ratio was 1.4 (95% CI 1.07-1.72) for CTH and 1.6 (95% CI of 1.2-2.1) for OBS arm. At one year, 83% vs 41% vs 20% of the patients were alive in the respective cohorts and at 5 years, the OS rates were 56% vs 25% vs 13% respectively. Conclusions: Our data demonstrates that combined chemotherapy and radiation is superior to either chemotherapy increase in overall survival for CRT when compared to CHT and observation alone.
Chronotherapeutic regimen with liposomal cisplatin for systemic treatment of primary liver cancer.
Authors: Tavartkiladze Levan , Tavartkiladze Alexandre , Sordia Teimuraz , Gvajaia Ani 
Published: May 2019

e15678 Background: Primary liver cancer (HCC) treatment is one of the priority issues of clinical oncology due to inefficiency and quantitative lack of medicines. The goal of our research was to perform treatment of Primary Liver Cancer, based on chronobiological mechanisms, assessment of treatment efficiency and advantage over the standard regimen. Methods: A total of 21 patients with HCC participated in the study. The treatment was performed by Liposomal Cisplatin. Assessment of cancer cells sensitivity to platinum group medicines was performed using RT-PCR method by expression of DNA methyltransferase I gene. During 24 hours, with 2-hour intervals, circulating tumor cells (CTC) were taken from peripheral venous blood. At the end, in all samples circadian regimens of DNA methyltransferase I gene expression were studied. According to obtained results, the circadian peak of gene expression was registered at 02:00-04:30 am time interval. Results: According to the study design of the 21 patients 12 ones received treatment based on chronotherapy regimens (investigated group, infusions were made at 02:00-04:30 am), 9 patients received treatment with standard regimen (control group, infusion was performed at 10:00-12:00 am). Infusions were performed according to the protocol with 1 week intervals for 9 weeks (a single infusion dose 150mg/m2). The treatment efficiency was evaluated 9 weeks later by the following parameters: AFP serum level and computer tomography of the liver. Results of the study demonstrated significant differences in treatment efficacy. During chemotherapy performed in chronotherapy regimen in patient's blood plasma, the AFP concentration decreased on average by 36.5% compared to the initial value, however in the control group the AFP concentration decreased on average by 13.7%. By CT positive dynamics was detected in both groups, but with significant advantage in case of chronotherapy regimen, size reduction of tumor growth by 27.1% on average was associated with fibrous transformation and prominent decrease of vascularization was found. In the control group, size reduction of the tumour growth was seen, however only by 6.3% on average. Patients clinical condition as well as CBC data differed with significant prevailing in case of chronotherapy. Conclusions: Obtained results confirm high clinical significance of chronobiological features of gene expression in antitumour therapy as well as importance of the development of new, up-to-date protocols for HCC – highly aggressive tumour therapy based on chronotherapy principles.
The impact of sorafenib on the treatment and survival of advanced hepatocellular carcinoma (HCC): Analysis of the National Cancer Database (NCDB) from 2004 to 2014.
Authors: Opneja Aman , Cioffi Gino , Alahmadi Asrar , Patil Nirav , Bajor David Lawrence , Saltzman Joel N. , Barnholtz-Sloan Jill , Lee Richard T. 
Published: May 2019

e15682 Background: HCC is a common cause of mortality in the U.S. among men and women (5thand 7th, respectively) with overall five-year survival of ~18%. Sorafenib was the only FDA approved therapy for advanced HCC from 2007 until 2018. This study analyzes trends in the treatment and survival of advanced HCC before and after sorafenib approval. Methods: Adult patients ( > 18 years) with diagnosis of HCC treated with only chemotherapy from 2004 – 2014 were identified in NCDB database. Comparisons were made between 3 time frames: 2004 – 2007 (pre-sorafenib), 2008 – 2011 (early sorafenib) and 2012 – 2014 (late sorafenib). Patients treated with single or multi-agent chemotherapy were analyzed. Cox proportional hazards models were used for univariate and multivariable analyses. Kaplan-Meier method was used for survival analysis. Results: The NCDB contained 33,136 patients with HCC diagnosed between 2004 – 2014 and treated with chemotherapy alone. Patients were generally men (77.4%), over the age of 50 years (92.4%), with an elevated AFP at diagnosis (64.4%), and had limited co-morbidities (76.0%, Charlson/Deyo score of 0-1). The T-stages were T1 (26.3%), T2 (20.5%), T3 (25.6%), and T4 (16.2%). The number and proportion of patients treated with single agent chemotherapy increased significantly during the study period: 2,733 (45.3%) pre-sorafenib, 9,723 (72.7%) early sorafenib, and 13,502 (86.1%) late sorafenib. The proportion of all HCC patients in the NCDB receiving only chemotherapy increased from 17.2% to 26.4% to 28.3% across the 3 time frames. The survival of patients with advanced HCC treated only with chemotherapy improved significantly in the early and late sorafenib cohorts compared to the pre-sorafenib cohort (10.3 months (95% CI: 9.8-10.6) vs. 12.3 months (12.0-12.7) vs. 15.5 months (15.1-15.9), p-value < 0.001). Age > 70 years, male sex, higher Charlson/Deyo score ( > 1), elevated AFP at diagnosis, and higher T-stage were associated with worse survival (p value < 0.001). Conclusions: The approval of sorafenib has dramatically increased the use of chemotherapy for the treatment of advanced HCC and has resulted in a significant survival advantage.
Combinational strategies of immunotherapy for hepatocellular carcinoma: One institutional experience in Taiwan.
Authors: Chen Jo-Pai , Hsueh Fu-Jen , Lu Wei-Chen , Ma Wei-li , Wu Hsu , Kuo Sung Hsin 
Published: May 2019

e15684 Background: Nivolumab in CheckMate40 study for advanced HCC has brought ORR 15 to 20% and DCR 55%. Our goup found lymph node or lung metastasis responded better and increased PDL1 expression in tumor-infiltrating immune cells after sorafenib (by Lu in AACR & Liver Cancer 2018), suggesting sequential or combination use of sorafenib and immunotherapy. In the 1st line setting, bevacizumab and atezolizumab has brought encouraging response, even with extrahepatic spread and/or macrovascular invasion. Methods: From early 2016 till now, 28 advanced HCC patients had received immunotherapy-containing regimens in Yun-Lin Branch of National Taiwan University Hospital. We have reviewed basic characteristics and regimens to find out their outcomes and responders characters. Results: In 28 patients (1 sorafenib-naive); 14 hepatitis B & 10 hepatitis C; intrahepatic lesions only 25%, lymph node and/or lung metastasis 11%, fulminant spread 64%. The ORR was 25% and DCR was 53.6%. In 5 pembrolizumab users, 1 stable disease; 2 with 200 mg & 3 with 2 mg/kg triweekly; 1(hepatitis B with fulminant metastasis) to fatal liver rupture after bevacizumab and pembrolizumab. In 23 nivolumab users, ORR was 30%; dosage ranging from 0.3 to 3 mg/kg (56.5%) biweekly; 16 combined with metronomic chemotherapy, 10 with bevacizumab, 10 with chemotherap, 7 with bevacizumab and chemotherapy; 1 (failing sorafenib, TACE, & regorafenib) experienced liver necrosis to fatal liver failure after bevacizumab and nivolumab. 7 patients with partial response. Conclusions: In our institution, nivolumab combined with metronomic chemotherapy, low dose bevacizumab or sorafenib, or chemotherapy and even several combination regimens could produce favorable benefits and toxicity profiles in advanced HCCs regardless of viral etiology, even in heavily-treated and fulminant status. Possible combinational strategies of immunotherapy need to be developed with more rationales and biomarkers investigation.[Table: see text]
Predictors of mortality following cardiac surgery for carcinoid heart disease.
Authors: Iliescu Cezar , Balanescu Dinu Valentin , Hassan Saamir , Lopez-Mattei Juan , Palaskas Nicolas , Dasari Arvind , Halperin Daniel M. , Yao James C. , Kar Biswajit , Gregoric Igor , Nathan Sriram , Durand Jean-Bernard , Karimzad Kaveh , Kim Peter Y. , Iliescu Gloria , Balanescu Serban Mihai , Marmagkiolis Konstantinos , Donisan Teodora 
Published: May 2019

e15692 Background: Carcinoid Heart Disease (CHD) complicates 50% of carcinoid syndrome cases and represents a major cause of mortality in these patients. Surgery continues to be the only strategy to improve survival in CHD. We aimed to evaluate predictors of mortality following surgery for CHD. Methods: We retrospectively analyzed patients with CHD and a history of valve surgery presenting at a tertiary cancer center between November 2005 and March 2018. Data regarding symptoms, clinical findings, and CHD treatment were collected. Overall survival (OS, time interval from heart surgery to death) was calculated. Univariate Cox proportional hazards regression analyses were conducted to identify variables that were associated with OS. Results: We identified 25 patients with CHD who underwent surgical replacement with bioprosthetic valves: 10 (40%) the tricuspid valve (TV), 11 (44%) TV and pulmonary valve (PV), 3 (12%) TV, PV, and aortic valve, and 1 (4%) all 4 valves. Among them, 19 (76%) survived at least 12 months after the surgery. Clinical factors associated with decreased OS are presented in Table 1. Conclusions: OS following surgery is dictated by the severity of CHD at the time of surgery. Worse outcomes are predicted by a history of congestive heart failure, the number of symptoms, and ascites. Better selection criteria are needed in order to choose the candidates for surgery who will benefit the most. [Table: see text]
Circulating tumor DNA analysis of neuroendocrine tumors.
Authors: Starr Jason Scott , Mody Kabir , Roberts Ali , Kasi Pashtoon Murtaza 
Published: May 2019

e15698 Background: Neuroendocrine tumors (NETs) and carcinomas (NECs) are a diverse group of tumors with an equally diverse biology and clinical behavior. Data on tissue-based genomic profiling of NETs exists, however, there is limited data using circulating tumor DNA (ctDNA) technology. We sought out to characterize NETs via ctDNA to identify genomic alterations. Methods: 27 patients with metastatic NET/NEC with 32 total plasma samples were analyzed using Guardant360 ctDNA assay. Breakdown of NET/NEC by location: 14 pancreatic NET (pNET), 11 NEC, 1 small bowel NET, 1 lung NET. The ctDNA test detects single nucleotide variants in 54-73 genes, copy number amplifications, fusions, and indels in selected genes. Results: Of the 27 patients, 19 (70%) had a detectable genomic alteration. The detectable (non-synonymous) alterations are as follows: TP53 (n = 14, 70%), NF1 (n = 8, 40%), EGFR (n = 5, 25%), BRCA2 (n = 4, 20%), KRAS (n = 4, 20%), ARID1A (n = 3, 15%), CDK6 (n = 3, 15%), ALK (n = 3, 15%), MET (n = 2, 10%), PTEN (n = 2, 10%), BRAF (n = 2, 10%), MTOR (n = 2, 10%) AKT1 (n = 1), BRCA1 (n = 1), CCND2 (n = 1), CCNE1 (n = 1), CTNNB1 (n = 1), ESR1 (n = 1), FGFR2 (n = 1), HRAS (n = 1), IDH1 (n = 1), KIT (n = 1), MYC (n = 1), NOTCH1 (n = 1), NRAS (n = 1), PDGFRA (n = 1), RAF1 (n = 1), RB1 (n = 1), SMAD4 (n = 1), STK11 (n = 1), TSC1 (n = 1), ERBB2 (n = 1), PIK3CA (n = 1). Conclusions: This experience highlights the feasibility of ctDNA to help identify genomic alterations in this patient population. Further studies incorporating ctDNA testing in this patient population are warranted.
Predictors of post-operative mortality following pancreatectomy: A contemporary nationwide analysis.
Authors: Hasan Shaakir , Abel Stephen , Verma Vivek , Schiffman Suzanne , Thakkar Shyam , Kulkarni Abhijit , Williams Harry Kenneth , Monga Dulabh , Finley Gene Grant , Kirichenko Alexander , Horne Zachary D. , Wegner Rodney E 
Published: May 2019

e15706 Background: To date, the only curative option for pancreatic cancer is surgical resection, which only 15-20% of patients are eligible for at diagnosis. The conventional operation is a pancreaticoduodenectomy which carries a mortality risk of 3-7%. We used the National Cancer Database (NCDB) to examine surgical outcomes following pancreatectomy. Methods: We queried the NCDB from 2004-2015 for patients with stage I-III adenocarcinoma of the pancreas treated surgically. Outcomes reported were 30 and 90 day mortality, readmission within 30 days, and prolonged hospital stay. Prolonged hospital stay was defined as 17 days and 8 cases per year was used to define high volume centers. Multivariable logistic regression was used to identify predictors of all outcomes. Propensity matching was conducted to account for indication bias. Results: We identified 24,798 patients meeting eligibility criteria. The median patient age was 66 (40-90). The majority of patients were stage T3 (47%) N0 (65%) with pancreatic head lesions (83%). Fifty-seven percent of patients were treated with a Whipple procedure. Most patients (83%) were treated with surgery up front. Overall unadjusted risk of 30 day and 90 mortality ranged from 1.32-2.54% and 4.1-7.12%, respectively, depending on extent of surgery. On multivariable analysis predictors of 30 day mortality included preoperative therapy, increased age, higher comorbidity score, lower income, type of surgery, and treatment at a low volume center. Ninety day mortality was associated with preoperative therapy, increased age, increased comorbidity score, higher T stage, more extensive surgery, and treatment at a low volume center. Multivariable analysis revealed increased comorbidity score, treatment at an academic facility, and non-partial pancreatectomy as predictive of readmission. Prolonged hospital stay was associated with increasing age, decreased education, lower income, non-Caucasian race, more extensive surgery, and more remote year of treatment. Propensity matched Kaplan-Meier analysis showed improved survival with treatment at high volume centers, median survival of 23 months compared to 21 months (p = 0.0026). Conclusions: In the largest population based series to date, the 30 day mortality rates remain acceptably low with an increase seen at 90 days. The predictors of post-operative mortality seen here (age, comorbidity score, extent of surgery, and center volume) highlight the need for appropriate patient selection and physician experience to help achieve the best possible perioperative outcomes.