bluuebunny/crossref_metadata_2025_split huggingface dataset:
Does a common vascular origin confer similar prognosis to malignant tumors of the liver?
Authors: Groeschl Ryan T. , Pappas Sam G , Christians Kathleen K. , Tsai Susan , Quebbeman Edward J , Gamblin T. Clark , Turaga Kiran 
Published: February 2017

186 Background: Unlike the ubiquitous hepatic hemangioma, malignant vascular tumors (MVT) of the liver are uncommon and poorly understood. We hypothesized that tumor histology is a predominant factor associated with survival in these tumors. Methods: Patients with hepatic angiosarcoma (AS), hemangioendothelioma (HE) and its epithelioid variant (EHE), or hemangiopericytoma (HP) were identified using the SEER database (1973-2007). Standardized incidence rates were calculated based on the 2000 U.S. population. Prognostic factors were studied with Cox regression modeling. Results: We included 297 patients with MVT (207 AS, 28 HE, 56 EHE, 6 HP) with an annual standardized incidence of 3 per million. Patients with AS were likely to be older at diagnosis (median 63 yrs, p = 0.001) and less likely to be female (38%, p < 0.001). All tumors demonstrated metastatic potential, although EHE and AS had the highest rate of regional or distant metastases (75% each, p = 0.05, Table 1). Patients with EHE had the overall longest median survival of 75 (30-183) months (p < 0.001). Surgical resection and transplant did not improve the overall survival of patients with EHE in multivariate models (p = 0.2, 0.9). Conclusions: Histology is an important factor in determining survival for patients with hepatic MVT. Patients with EHE have the longest OS even in the absence of surgical intervention, whereas patients with AS have shorter survival but appear to benefit from surgery. [Table: see text]
Clinical significance of circulating tumor cells in blood from patients with advanced or recurrent esophageal cancer.
Authors: Tanaka Motomu , Takeuchi Hiroya , Hiraiwa Kunihiko , Nakamura Rieko , Takahashi Tsunehiro , Wada Norihito , Kawakubo Hirofumi , Saikawa Yoshiro , Omori Tai , Kitagawa Yuko 
Published: February 2017

19 Background: Circulating tumor cells (CTCs) measured by the CellSearch system in metastatic breast cancer have been reported to correlate with the response to chemotherapy. The purpose of this study was to clarify the clinicopathologic characteristics of CTCs in patients with advanced or recurrent esophageal cancer. Methods: CTCs from 35 patients with advanced or recurrent esophageal cancer were measured by this system before initiation of a new line of therapy and more than 3 weeks after initiation of therapy. Correlation between CTC counts and clinicopathologic variables was examined. Results: Of the 35 patients, 14 patients (40%) had recurrent esophageal cancer and 21 patients (60%) had primary advanced esophageal cancer. Their mean age was 65 years (range, 43 to 89 ). Of the 14 patients with recurrent esophageal cancer, measurable lesions included metastasis to lymph nodes, kidney metastasis, liver metastasis, and lung metastasis. With regard to their therapeutic effect, 1 patient (3%) obtained a complete response, 14 (40%) had a partial response, 9 (26%) had stable disease, 11 (31%) had progressive disease. Of the 15 patients with complete response and partial response, the number of CTCs diminished in 8 patients (53%). Of the 20 patients with stable disease and progressive disease, the number of CTCs increased in 16 patients (80%). The change in CTCs tended to correlate with disease progression and chemotherapeutic effect (P=0.07). The survival of patients with >3 CTCs was shorter than that of patients with <3 CTCs both before initiation of a new line of therapy (P=0.026) and more than 3 weeks after initiation of therapy (P=0.003). Conclusions: This study suggests that measurement of CTCs in advanced or recurrent esophageal cancer patients could be useful as a tool for predicting patients’ survival and monitoring response to cancer therapy.
Patients with liver cancer suitable for sorafenib evaluation registry (LIVER) in Poland.
Authors: Krzemieniecki Krzysztof , Simon Krzysztof , Zieniewicz Krzysztof , Pecilo Pawel 
Published: February 2017

194 Background: Due to chronic hepatitis and cirrhosis as main risk factors of HCC – patients in Poland can be treated either by oncologists or by gastroenterologists. As no data exist on HCC patient flow between these specialities, this registry was set up. We also wanted to know the differences in both specialities’ approach to targeted therapies. Methods: Data of patients treated by oncologists (LIVER 2) and gastroenterologists (LIVER 1) were recorded. Descriptive statistical methods and U-Mann-Whitney and Fisher tests were used. Results: 478 patients were included into registry from 2009 until the end of 2010. 70% of patients were male. In 42% cases HCC was caused by HCV and in 24% by HBV. LIVER 2 recorded more patients with unknown HCC aetiology than LIVER 1 (35% vs 15%). The HCC diagnosis was made based on CT scan (80%, ns), US scan (74% in LIVER 1 vs 47% in LIVER 2, p<0,0001) or biopsy (72% LIVER 2 vs 48% LIVER 1, p<0,0001). Patients with advanced stage of HCC according to BCLC scale and poor performance status were more frequently seen by oncologists (LIVER 2), similar prevalence in Child Pugh status was observed in both groups (p<0,05 for all). Registry showed differences in frequency of extrahepatic lesions (10% LIVER 1 42% in LIVER 2, p<0,05). Most common co morbidities were diabetes (32%), liver disorders (39%), hypertension (61%), coronary disease (24%). Median AFP level was 100 ng/ml in LIVER 1 and 219 in LIVER 2 (p=0,057). Registry showed that for gastroenterologists reasons to consider sorafenib as next step in therapy was in 47% cases HCC progression, in 51% good performance status and in 55% sorafenib was found as the only one therapy suitable due to contraindications for other treatments. Oncologists consider sorafenib therapy in 56% cases due to HCC progression and in 72% cases due to good performance status. Among patients considered for targeted therapy, approximately 20% presented Child Pugh B status. Conclusions: This is the first detailed HCC registry in Poland covering the different therapeutic area specialists. Patients with more advanced HCC and worse performance status are more frequently treated by oncologists (p<0,05). The data shows need of early HCC detection interdisciplinary system referring patients to the oncologist.
Cost-effectiveness of FOLFIRINOX for first-line treatment of metastatic pancreatic cancer.
Authors: Attard Cheryl L. , Brown Stephen , Alloul Karine , Moore Malcolm J 
Published: February 2017

199 Background: The ACCORD 11/0402 trial demonstrates that FOLFIRINOX (5-fluorouracil, leucovorin, irinotecan, and oxaliplatin) is significantly more efficacious than the current standard of gemcitabine (G) monotherapy in the first line treatment of metastatic pancreatic cancer (mPC). This study assesses for public payers the cost-effectiveness of first-line FOLFIRINOX compared to first-line G in Canadian mPC patients. Methods: A Markov model was used to estimate how patients progress through the following states: ‘stable’, ‘progressed’, ‘dead’. OS and PFS data were derived from the trial data. Published utility data and Canadian cost data were applied based on time in each state and treatment related adverse event (AE) rates. Costs included first and second-line therapy, monitoring, AE and end of life costs. Costs and outcomes are discounted at 5%. Two separate analyses were made. Analysis 1: Based on trial data (First-line FOLFIRINOX → second-line G versus First-line G → second-line platin-based chemo, G-CSF usage allowed). Analysis 2: Current Ontario Treatment Patterns (first-line FOLFIRINOX → second-line G vs first-line G → best supportive care, no G-CSF usage). Results: All analyses found that using first-line FOLFIRINOX produced more life years and QALY than treatment strategies that used first-line G. The probabilistic sensitivity analysis results for both analyses support the use of FOLFIRINOX for first-line treatment of mPC. FOLFIRINOX has a greater than 95% and 90% probability of being cost effective at an $80,000 threshold for Analysis 1 and Analysis 2 respectively. Conclusions: First-line FOLFIRINOX significantly prolongs median OS by more than 4 months over G (11.3 vs 6.8 months, HR=0.57). Given the favorable costs per QALYs, the improvement in clinical efficacy and the limited available treatment options, FOLFIRINOX represents an attractive cost-effective treatment for mPC. [Table: see text]
MicroRNA analysis of fine-needle aspirates from pancreatic cancer.
Authors: Philip Philip Agop , Saleh Husain , Ali Shadan , Chen Wei , Palazzolo Paulette , Sethi Seema , Sarkar Fazlul H. 
Published: February 2017

200 Background: Tissue-based research is a major challenge in localized pancreatic cancer (PC) especially those with locally advanced unresectable or borderline resectable disease. Approximately half of the patients are diagnosed by a fine needle aspirate (FNA) /biopsy of the pancreatic primary tumor with limited tissue available for correlative assays. Micro-RNAs (miRNAs) are biomarkers with the potential to be developed for prognostic and predictive purposes. Moreover, these molecules can facilitate the development of targeted therapies in PC. Methods: miRNA expression profiling and quantitative real-time PCR (qRT-PCR) were performed from RNA (25-100 ng per patient) extracted from formalin-embedded cell blocks (FFPE) obtained from diagnostic FNA of the pancreas. Expression profiles of miRNAs were compared to those from patients undergoing pancreatic biopsy for non-malignant conditions. Results: Cell blocks from FNAs from twenty-nine and 15 patients with pancreatic adenocarcinoma and non-malignant conditions were studied, respectively. miRNA profiling demonstrated deregulation of over 228 miRNA. The top 7 were validated by qRT-PCR. The expression of let-7c, let-7f, and miR-200c were significantly reduced in most patients. Conversely, the expression levels of miR-486-5p and miR-451 were significantly elevated. Significant interindividual variations were also noted in expression of certain miRNAs. Conclusions: FFPE obtained from diagnostic FNA of pancreatic tumor can be a valuable resource to study miRNA expression profiles of multiple miRNAs and undertake qRT-PCR in patients with localized PC and further supports the use of diagnostic FNA in RNA-based translational research. miRNA expression can be developed for use as prognostic and predictive biomarkers in future clinical trials in patients with PC.
Comparative analysis of treatments, utilization, and survival benefit in HCC patients: A real-world analysis of SEER Medicare.
Authors: Shaya Fadia T. , Breunig Ian Michael , Mullins C. Daniel , Pandya Naimish B. , Chirikov Viktor , Seal Brian S. , Hanna Nader 
Published: February 2017

214 Background: We explore various treatments at all stages of Hepatocellular Carcinoma (HCC), in a SEER (Surveillance, Epidemiology and End-Results Program) Medicare population and assess their impact on HCC-specific and overall survival. Methods: Medicare enrollees, older than 65, with an initial diagnosis of a primary HCC between 2000-07 were followed up through end of 2009. Data are from the SEER and linked Medicare databases, with claims generated from Medicare parts A and B. Using multivariate Cox-proportional hazards models, we assessed overall and HCC-related mortality in relation to receipt of treatment/no treatment, adjusting for demographics, general health status (CCI), cancer stage and liver conditions. Results: Out of the 9054 HCC patients, older than 65, who did not get a liver transplant, 76% were Caucasian, 8% African American (AA), 63% male, and 37% got treatment [12% transarterial chemoembolization (TACE), 12% systemic chemotherapy, 1.5% selective internal radiation therapy (SIRT), 9% external beam radiation therapy (EBRT), 8% surgical resection and 9% ablative therapy]. Treatment was associated with a reduction of overall (HR=0.35, P= <0.001) and HCC-related (0.33, <0.001) mortality. HCC-related mortality was significantly reduced in those getting resection (0.38, <0.001), ablation (0.59, <0.001), TACE (0.76, <0.001), EBRT (0.85, 0.017), or chemotherapy (0.85, 0.013). Significant reduction in overall mortality was seen with resection, ablation and TACE but not with chemotherapy, EBRT or SIRT. No particular treatment was associated with greater mortality reduction in early vs advanced stages. Patients with poor underlying health status (CCI>1) had higher mortality (1.27, <0.001). Alcohol related disease, Hep C, and moderate/severe liver dysfunction were not significantly associated with overall or HCC related mortality. Caucasians and non-African Americans had lower overall mortality (0.87, <0.001). Conclusions: In HCC SEER Medicare patients, all treatments except SIRT were associated with a significant reduction in HCC related mortality. A limitation of this study is that, through the data, we cannot accurately depict the severity of the disease.
Can we identify patients with cancer at high risk for cachexia? A prospective study in pancreatic cancer (PC).
Authors: Fogelman David R. , Wang Xin Shelley , Hassan Manal , Li Donghui , Javle Milind M. , Katz Matthew H.G. , Overman Michael J. , Varadhachary Gauri R. , Shroff Rachna T. , Wolff Robert A. , Abbruzzese James L. 
Published: February 2017

219 Background: Identifying PC patients at high risk for cachexia may allow for early intervention to prevent it. Symptoms such as pain, nausea and anorexia may predict weight loss. Inflammatory cytokines are also associated with cachexia. We evaluated the ability of each to predict weight loss in newly diagnosed PC patients. Methods: Using the M. D. Anderson Symptom Inventory (MDASI), we assessed baseline symptoms in untreated advanced or metastatic PC patients. The survey assesses severity of symptoms on a 0-10 scale. Baseline serum levels of IL-1a, IL-1b, IGF-1, CXCL-12, CXCL-16, CRP, IL-6, IL-8, VEGF, CEA, and CA 19-9 were measured via ELISA. Using STATA (version 12), we generated multivariable logistic regression models with a backward selection procedure. This allowed us to evaluate all potential univariate correlates with 5% and 10% weight loss at P<.1 to create a multivariate model containing variables of p<.05. Student t-test was used to compare the mean values of cytokines across different strata. Results: We evaluated 72 patients (33M/39F). Weight loss of >5% or death was observed in 44 patients (62%) and >10% or death in 24 (34%). 61 pts (30M/31F) survived sixty days after the start of treatment with 5% and 10% weight loss seen in 33 (54%) and 13 (21%), respectively. Baseline severe loss of appetite was most strongly associated with weight loss (OR 15.3, p=.005), compared to those with a moderate loss of appetite (OR 4.7, p=.058), nausea (OR 9.4, p=.048), or shortness of breath (OR 7.4, p=.063). Neither diarrhea nor vomiting correlated with weight loss, nor did age, tumor markers, or treatment with platinum drugs, opiates, or erlotinib. Baseline cytokine levels were available for 23 patients. Mean CXCL-16 (p=.05) and IL-6 (p=.045) levels were greater in patients with weight loss. Serum erythropoietin levels may be negatively associated with weight loss (p=0.06). An analysis of the remaining patients’ samples will be available at the meeting. Conclusions: Both alterations in serum cytokines and specific symptoms may predict the development of cachexia. A more robust analysis of circulating cytokines may allow us to design interventions which prevent or delay cachexia in patients with advanced pancreatic cancer.
Cost-effectiveness of treating patients with advanced progressive pancreatic neuroendocrine tumor with everolimus versus sunitinib in the United States.
Authors: Casciano Roman , Chulikavit Maruit , Perrin Allison , Liu Zhimei , Wang Xufang , Babigumira Joseph , Garrison Louis P 
Published: February 2017

226 Background: Everolimus and sunitinib were recently approved to treat patients with advanced, progressive pancreatic neuroendocrine tumors (pNETs). This analysis examines the projected cost-effectiveness of everolimus versus sunitinib in this setting from a US payer perspective. Methods: A lifetime Markov model was developed to simulate a cohort of advanced, progressive pNET patients and to estimate the cost per incremental life-years gained (LYG) and quality-adjusted life years (QALYs) gained when treating with everolimus as compared to sunitinib. Absent head-to-head trials, efficacy data were based on a weight-adjusted indirect comparison of the two agents using the respective phase 3 trial data. Disease or health states considered in the model included: stable disease without adverse events, stable disease with adverse events, disease progression, and death. Costs of anti-tumor therapies, symptomatic care drugs, and post-progression therapy were based on wholesale acquisition cost. Other costs including physician visits, tests, infusions, hospitalizations, adverse event costs, and end-of-life care costs were obtained from literature and/or standard sources such as the Healthcare Cost and Utilization Project and Medicare reimbursement rates. Utility inputs were based on a UK time trade-off study. Sensitivity analyses were conducted to test the model’s robustness. Results: In the base case analysis, the estimated gain of everolimus over sunitinib was 0.448 LYs (0.304 QALYs) at an incremental cost of $12,673, resulting in an incremental cost-effectiveness ratio (ICER) of $28,281/LYG ($41,702/QALY gained), which fell within the cost per QALY range for many other widely used oncology drugs. The analysis was sensitive to the uncertainty of the sunitinib trial results; however, a probabilistic sensitivity analysis showed the results were consistent across simulations. Conclusions: While the analysis is limited by its reliance on an indirect comparison of two phase 3 studies rather than a single head-to-head trial, everolimus is expected to be cost-effective relative to sunitinib in advanced pNET.
Health plan budget impact of introducing everolimus for treatment of advanced progressive pancreatic neuroendocrine tumors in the United States.
Authors: Casciano Roman , Chulikavit Maruit , Sriprasert Michelle , Liu Zhimei , Wang Xufang , Garrison Louis P 
Published: February 2017

229 Background: Everolimus was recently approved for treatment of patients with advanced progressive pancreatic neuroendocrine tumors (pNET) based on a clinically meaningful and statistically significant increase in progression-free survival. To understand the financial impact of introducing everolimus into the market, a model was developed to simulate a typical health plan in the United States (US). Methods: A cross-sectional budget impact model with a one-year time horizon was developed. Disease prevalence and drug usage data were derived from a real-world data source. Costs for anti-tumor therapy and underlying care included concomitant medications, physician visits, treatment infusion, surgical procedures, tests, hospitalizations, and adverse event (AE) management. Resource utilization rates were derived from a physician survey-based resource utilization study; treatment-related AE rates were taken from secondary literature. Drug costs were Wholesale Acquisition Costs (2011). Medical procedure and hospitalization costs were based on Medicare fee schedules for current procedure terminology and diagnosis-related group codes. AE costs were obtained from the literature. The model assessed the initial annual budget impact, under the assumption that everolimus and sunitinib, another recently approved targeted therapy, replace most currently available chemotherapy treatments. Results: Based on published prevalence rates, for a health plan with 1,000,000 members, an annual count of 12 advanced pNET patients was projected. The model estimated a $22,657 budget increase ($0.0019 per member per month or $0.0227 per member per year [PMPY]). The largest percent increase in budget was associated with anti-tumor treatments; infusions and surgical procedures represented the largest percent decrease in costs. Scenario analyses indicated that increasing the percentage of everolimus use (by reducing that of sunitinib) resulted in a decrease in the overall budget compared to baseline. Conclusions: Our model predicts that treating pNET patients with everolimus will have a minimal budget impact on US health plans, amounting to about $0.027 PMPY.
Phase I trial of gene-mediated cytotoxic immunotherapy combined with resection for pancreatic adenocarcinoma.
Authors: Shirley Lawrence Andrew , Marsh Christopher , Walker Jon , Coyle Walter , Tahiri Sanaa , Manzanera Andrea G , Aguilar Laura K. , Aguilar-Cordova Estuardo , Chung Vincent M. , Bloomston Mark 
Published: February 2017

241 Background: While surgical resection of pancreatic adenocarcinoma provides the only chance of cure, long-term survival is still poor. Immunotherapy approaches may improve outcomes. Gene Mediated Cytotoxic Immunotherapy (GMCI) generates a systemic anti-tumor vaccine effect through intra-tumoral delivery of an adenoviral vector expressing the HSV-thymidine kinase gene (AdV-tk) followed by anti-herpetic prodrug administration. This is the first application of GMCI in pancreatic cancer. Methods: This study evaluated 4 dose levels of AdV-tk (3x1010 to 1x1012 vector particles) injected into pancreatic tumors via EUS 2 weeks before resection. Patients then underwent attempt at resection. If resection was undertaken, AdV-tk was injected into the resection bed. If resection was not possible, AdV-tk was injected into the primary tumor. The prodrug, Valacyclovir, was given for 14 days after each injection. Postoperative therapy was not protocol-driven. Results: The study accrued 14 patients with 12 completing therapy: 3 at each of the 4 planned dose levels. One patient died of an unrelated myocardial infarction 2 days after initial injection and one patient dropped out mid-treatment after metastases were found at surgery. Median age was 67 years (range 40-81). Of 12 patients explored, 4 were not resected due to distant metastases (N=3) or locally advanced disease (N=1). Three patients had Grade 3 possibly-related adverse events: 2 abdominal pain and one dehydration with renal insufficiency. There were no dose limiting toxicities and no grade 4 clinical adverse events. Grade 3-4 laboratory abnormalities were AST/ALT, bilirubin, alkaline phosphatase and lipase, all in patients with obstructive jaundice. Post-operative complications included 2 patients who developed abscesses requiring drainage. Six of 12 patients are alive 5-34 months after start of treatment including 5 resected patients and one unresected. Conclusions: AdV-tk can be safely injected into potentially resectable pancreatic tumors prior to planned resection. Early results are encouraging and justify further evaluation in a Phase 2 study.