bluuebunny/crossref_metadata_2025_split huggingface dataset:
Real-World Assessment of Clinical Outcomes Among First-Line Sunitinib Patients with Clear Cell Metastatic Renal Cell Carcinoma (mRCC) by the International mRCC Database Consortium Risk Group
Authors: Savard Marie-France , Wells J. Connor , Graham Jeffrey , Dudani Shaan , Steinharter John A. , McGregor Bradley A. , Donskov Frede , Bjarnason Georg A. , Vaishampayan Ulka N. , Hansen Aaron R. , Iafolla Marco A.J. , Zanotti Giovanni , Huynh Lynn , Chang Rose , Duh Mei S. , Heng Daniel Y.C. 
Published: February 2020

Abstract

Background
International Metastatic Renal Cell Carcinoma (mRCC) Database Consortium (IMDC) risk groups are important when considering therapeutic options for first-line treatment.

Materials and Methods
Adult patients with clear cell mRCC initiating first-line sunitinib between 2010 and 2018 were included in this retrospective database study. Median time to treatment discontinuation (TTD) and overall survival (OS) were estimated using Kaplan-Meier analysis. Outcomes were stratified by IMDC risk groups and evaluated for those in the combined intermediate and poor risk group and separately for those in the intermediate risk group with one versus two risk factors.

Results
Among 1,769 patients treated with first-line sunitinib, 318 (18%) had favorable, 1,031 (58%) had intermediate, and 420 (24%) had poor IMDC risk. Across the three risk groups, patients had similar age, gender, and sunitinib initiation year. Median TTD was 15.0, 8.5, and 4.2 months in the favorable, intermediate, and poor risk groups, respectively, and 7.1 months in the combined intermediate and poor risk group. Median OS was 52.1, 31.5, and 9.8 months in the favorable, intermediate, and poor risk groups, respectively, and 23.2 months in the combined intermediate and poor risk group. Median OS (35.1 vs. 21.9 months) and TTD (10.3 vs. 6.6 months) were significantly different between intermediate risk patients with one versus two risk factors.

Conclusion
This real-world study found a median OS of 52 months for patients with favorable IMDC risk treated with first-line sunitinib, setting a new benchmark on clinical outcomes of clear cell mRCC. Analysis of intermediate risk group by one or two risk factors demonstrated distinct clinical outcomes.

Implications for Practice
This analysis offers a contemporary benchmark for overall survival (median, 52.1 months; 95% confidence interval, 43.4–61.2) among patients with clear cell metastatic renal cell carcinoma who were treated with sunitinib as first-line therapy in a real-world setting and classified as favorable risk according to International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk group classification. This study demonstrates that clinical outcomes differ between IMDC risk groups as well as within the intermediate risk group based on the number of risk factors, thus warranting further consideration of risk group when counseling patients about therapeutic options and designing clinical trials.
Combined Expression of Plasma Thrombospondin-2 and CA19-9 for Diagnosis of Pancreatic Cancer and Distal Cholangiocarcinoma: A Proteome Approach
Authors: Le Large Tessa Y.S. , Meijer Laura L. , Paleckyte Rosita , Boyd Lenka N.C. , Kok Bart , Wurdinger Thomas , Schelfhorst Tim , Piersma Sander R. , Pham Thang V. , van Grieken Nicole C.T. , Zonderhuis Barbara M. , Daams Freek , van Laarhoven Hanneke W.M. , Bijlsma Maarten F. , Jimenez Connie R. , Giovannetti Elisa , Kazemier Geert 
Published: February 2020

Abstract

Background
Minimally invasive diagnostic biomarkers for patients with pancreatic ductal adenocarcinoma (PDAC) and distal cholangiocarcinoma (dCCA) are warranted to facilitate accurate diagnosis. This study identified diagnostic plasma proteins based on proteomics of tumor secretome.

Materials and Methods
Secretome of tumor and normal tissue was collected after resection of PDAC and dCCA. Differentially expressed proteins were measured by mass spectrometry. Selected candidate biomarkers and carbohydrate antigen 19-9 (CA19-9) were validated by enzyme-linked immunosorbent assay in plasma from patients with PDAC (n = 82), dCCA (n = 29), benign disease (BD; n = 30), and healthy donors (HDs; n = 50). Areas under the curve (AUCs) of receiver operator characteristic curves were calculated to determine the discriminative power.

Results
In tumor secretome, 696 discriminatory proteins were identified, including 21 candidate biomarkers. Thrombospondin-2 (THBS2) emerged as promising biomarker. Abundance of THBS2 in plasma from patients with cancer was significantly higher compared to HDs (p &lt; .001, AUC = 0.844). Combined expression of THBS2 and CA19-9 yielded the optimal discriminatory capacity (AUC = 0.952), similarly for early- and late-stage disease (AUC = 0.971 and AUC = 0.911). Remarkably, this combination demonstrated a power similar to CA19-9 to discriminate cancer from BD (AUC = 0.764), and THBS2 provided an additive value in patients with high expression levels of bilirubin.

Conclusion
Our proteome approach identified a promising set of candidate biomarkers. The combined plasma expression of THBS2/CA19-9 is able to accurately distinguish patients with PDAC or dCCA from HD and BD.

Implications for Practice
The combined plasma expression of thrombospondin-2 and carbohydrate antigen 19-9 is able to accurately diagnose patients with pancreatic cancer and distal cholangiocarcinoma. This will facilitate minimally invasive diagnosis for these patients by distinguishing them from healthy individuals and benign diseases.
Comparative Effectiveness of Palliative Chemotherapy in Metastatic Breast Cancer: A Real-World Evidence Analysis
Authors: Feinberg Bruce , Kish Jonathan , Dokubo Igoni , Wojtynek Jeff , Gajra Ajeet , Lord Kevin 
Published: February 2020

Abstract

Background
In the absence of randomized controlled trials, real-world evidence may aid practitioners in optimizing the selection of therapy for patients with cancer. The study's aim was to determine real-word use, as well as compare effectiveness, of single-agent and combination chemotherapy as palliative treatment for female patients with metastatic breast cancer (mBC).

Materials and Methods
Using administrative claims data from the Symphony Health's Integrated Oncology Dataverse, female patients with mBC treated with at least one chemotherapy-only treatment (COT) between January 1, 2013, and December 31, 2017 were selected. The frequency of use of single-agent versus combination chemotherapy overall and by line of therapy (LOT) was calculated whereas effectiveness was measured using time to next treatment (TNT).

Results
A total of 12,381 patients with mBC were identified, and 3,777 (31%) received at least one line of COT. Of the 5,586 observed LOTs among the 3,777 patients, 66.5% were single-agent and 33.5% combination chemotherapy. Combination chemotherapy was most frequently used in first-line (45%) and least frequently in fifth-line (16%). Across all LOTs, median TNT was significantly longer for single-agent versus combination chemotherapy (5.3 months vs. 4.1 months, p &lt; .0001). Comparison of median TNT by LOT showed significance in third-line and greater but not in first-line or second-line. Among single agents, the median TNT for patients receiving capecitabine was longest in comparison to all other single agents.

Conclusions
The frequency of combination COT use, particularly in first-line, warrants further research given published guideline recommendations. The observed TNT difference favoring single-agent treatment in later lines supports guideline recommendations. Variance between single-agent preference and observed TNT was noteworthy.
Inverse Association of Age with Risk of Lymph Node Metastasis in Superficial Colorectal Cancer: A Large Population-Based Study
Authors: Zhang Qing-Wei , Sun Long-Ci , Tang Chao-Tao , Liang Qian , Zhou Yang-Yang , Chen Hui-Min , Gao Yun-Jie , Ge Zhi-Zheng 
Published: February 2020

AbstractBackgroundSuperficial colorectal cancer (SCRC) is defined as colorectal cancer (CRC) confined to the mucosa or submucosa. Endoscopic resection (ER) is widely used to resect differentiated SCRC from patients without lymph node metastasis (LNM). However, it is unclear whether ER is suitable for use with patients with differentiated early-onset SCRC because early-onset CRC is more aggressive. Therefore, we aimed to investigate the association between age of CRC onset and LNM.Materials and MethodsWe retrieved data for patients with surgically resected differentiated-type SCRCs from the Surveillance, Epidemiology, and End Results (SEER) database. Rate of LNM was compared among patients aged 18–39, 40–49, 50–59, 60–69, and ≥70 years. The association between age and LNM was further examined using multivariate logistic regression.ResultsWe retrieved 34,506 records of differentiated SCRCs from the SEER database, including 667 patients aged 18–39 years, 2,385 aged 40–49, 8,075 aged 50–59 years, 9,577 aged 60–69 years, and 13,802 aged ≥70 years. Rates of LNM were 15.74%, 14.13%, 10.67%, 8.07%, and 6.76% for patients aged 18–39, 40–49, 50–59, 60–69, and ≥70 years, respectively. We found an inverse correlation between age at diagnosis and risk of LNM from the univariate analysis (p &lt; .001). Compared with patients aged 18–39, the odds ratios with 95% confidence interval (CI) for patients aged 40–49, 50–59, 60–69, and ≥70 years were 0.90 (0.71–1.15, p = .376), 0.69 (0.56–0.87, p = .001), 0.54 (0.43–0.68, p &lt; .001), and 0.47 (0.38–0.60, p &lt; .001), respectively.ConclusionIn differentiated SCRCs, younger age at diagnosis was associated with higher risk of LNM.Implications for PracticeEndoscopic resection (ER) is widely used to resect differentiated superficial colorectal cancer (SCRC) without lymph node metastasis (LNM). However, no study has ever investigated risk of LNM of early-onset SCRC compared with average onset SCRC to explore whether ER is suitable for early-onset SCRC. To the authors' knowledge, this population-based study is the first study to find inverse correlation between age at diagnosis and risk of LNM in differentiated SCRCs. This finding indicates that ER may not be suitable for young patients with differentiated SCRC. Because the 30-day operative mortality after surgery is higher but the risk of LNM is lower in older patients compared with younger patients, ER for differentiated SCRCs may be advantageous over surgery for older patients.
Rhabdomyosarcoma: An Overview
Authors: Dagher Ramzi , Helman Lee 
Published: February 2020

Abstract
Rhabdomyosarcoma (RMS) is a malignant tumor of mesenchymal origin thought to arise from cells committed to a skeletal muscle lineage. With approximately 250 cases diagnosed yearly in the United States, it is the third most common extracranial solid tumor of childhood after Wilms' tumor and neuroblastoma. Important epidemiologic, biologic, and therapeutic differences have been elucidated within the RMS family. Common sites of primary disease include the head and neck region, genitourinary tract, and extremities. A site-based tumor-nodes-metastasis staging system is being incorporated into use for assessing prognosis and assigning therapy in conjunction with the traditional surgicopathologic clinical grouping system. The development of intensive multimodality treatment protocols tested in large-scale international trials has resulted in significant improvements in outcome, especially for patients with local or locally extensive disease for whom a 60%-70% disease-free survival can be expected. Despite aggressive approaches incorporating surgery, dose-intensive combination chemotherapy, and radiation therapy, the outcome for patients with metastatic disease remains poor. Future challenges include the development of less toxic therapy for patients with localized disease and new approaches for patients with metastatic disease.
Surgical Management of Esophageal Carcinoma
Authors: Reed Carolyn E. 
Published: February 2020

Abstract
Surgical management of esophageal carcinoma is reviewed. The anatomy and biology are briefly mentioned, since these factors mitigate against the success of surgery. Staging, the key to proper treatment allocation and prognosis, is discussed, including the use of endoscopic ultrasonography, positron emission tomography, and thoracoscopy/laparoscopy. Patient selection and preparation for surgery are important considerations. Surgical techniques are then discussed, as are the advantages and disadvantages of various approaches, the morbidity of surgical resection, survival, and quality-of-life issues. Adjuvant treatment strategies (preoperative radiation, induction chemotherapy, induction chemoradiotherapy, and postoperative treatment) are summarized.
Defining the Emetogenicity of Cancer Chemotherapy Regimens: Relevance to Clinical Practice
Authors: Hesketh Paul J. 
Published: February 2020

Abstract
Significant progress has been made in recent years in developing more effective and better tolerated means to prevent nausea and vomiting induced by cancer chemotherapy. The most significant development has been the introduction of a new class of antiemetic agents, the selective antagonists of the type 3 serotonin receptor. With the new antiemetic therapeutic options and their attendant higher costs has come a need to define evidence-based guidelines to assist in their judicious and cost-effective use. A number of predictive factors for antiemetic risk have been defined. Some of these factors relate to the patient population (age, gender, history of ethanol consumption, and prior experience with chemotherapy), and some relate to the treatments administered. Clearly, the most important of all these factors in predicting risk of emesis is the intrinsic emetogenicity of the chemotherapy. Although an “ideal” emetogenic classification schema for chemotherapy has yet to be realized, recent developments in this area have allowed a more precise estimation of emetogenic risks and have provided antiemetic guideline groups with a useful foundation on which to base their treatment recommendations.
Surgical Treatment and Other Regional Treatments for Colorectal Cancer Liver Metastases
Authors: Yoon Sam S. , Tanabe Kenneth K. 
Published: February 2020

Abstract
The liver is the most common site of distant metastasis from colorectal cancer. About one-fourth of patients with liver metastases from colorectal cancer have no other sites of metastasis and can be treated with regional therapies directed toward their liver tumors. Surgical resection of colorectal cancer liver metastases can result in a 24%-38% five-year survival, but only a minority of patients are candidates for resection. Other regional therapies such as cryosurgery, radiofrequency ablation, and hepatic intra-arterial chemotherapy may be offered to patients with unresectable but isolated liver metastases. The efficacy of these treatments is still being determined. For most patients with spread of metastatic colorectal cancer beyond the liver, systemic chemotherapy rather than regional therapy is a more appropriate option.
Leukemia in Infants
Authors: Felix Carolyn A. , Lange Beverly J. 
Published: February 2020

Abstract
Acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) in infants have in common a high incidence of translocations of the MLL gene at chromosome band 11q23. Similar translocations occur in leukemias associated with chemotherapies that target DNA topoisomerase II. MLL has numerous different partner genes. The role of the many MLL fusion proteins in leukemogenesis is not yet understood. The t(4;11) translocation, the most common translocation in infant ALL, adversely affects the outcome. Additional genetic changes, especially Ikaros alterations, are found in infant ALL. Other forms of myeloid leukemia in infants present as myelodysplastic and myeloproliferative syndromes, which may be associated with constitutional disorders. This review will consider all leukemia in infants, but will focus on leukemias with MLL gene translocations.
A Retrospective Review of Blood Transfusions in Cancer Patients with Anemia
Authors: Estrin Jason Todd , Schocket Lisa , Kregenow Robert , Henry David H. 
Published: February 2020

Abstract
Background: The factors contributing to blood transfusions in patients with anemia of chronic disease are not well documented in the literature. We analyzed all blood transfusion events within a single oncology practice to determine if certain chemotherapy drugs, cancer types, or other factors necessitated more frequent transfusions.
Patients and Methods: Out of 331 patients receiving chemotherapy, 103 (31%) patients received a blood transfusion in 1995. Each of these charts was reviewed and sorted by diagnosis, treatment medications, and past transfusion and/or treatment history. Hemoglobin levels were obtained for each transfusion received in 1995.
Results: The average hemoglobin at time of transfusion was 7.9 g/dl. Higher hemoglobin levels at transfusion were observed for patients over the age of 60 and patients who received prior chemotherapy. Lower hemoglobin levels at transfusion were observed for patients receiving Epoetin Alfa and sarcoma patients. The average number of red blood cell (RBC) units transfused in 1995 was 5.1 per patient. More units were given to patients receiving etoposide, while fewer units were given to those receiving ifosfamide. We created a transfusion severity index (TSI) to jointly measure these two variables.
Conclusion: The results of this study identify transfusion needs associated with certain groups of cancer patients and with certain types of chemotherapy drugs.
The Use of Thymidylate Synthase Inhibitors in the Treatment of Advanced Colorectal Cancer: Current Status
Authors: Papamichael D. 
Published: February 2020

Abstract
The combination of 5-fluorouracil (5-FU) and leucovorin has been the unofficial “standard” therapy for patients with colorectal cancer for over a decade. Recently, however, a number of new agents targeted against the enzyme thymidylate synthase have been synthesized and are in various stages of development. The currently available thymidylate synthase inhibitors are discussed.
Enormous efforts have been made over the years to improve the efficacy of 5-FU, the most popular of these agents. Biochemical modulation by leucovorin has been the most successful so far. Continuous infusion schedules also appear to be advantageous over bolus administration. However, marked intra- and interpatient variability, combined with nonlinear elimination kinetics and erratic oral bioavailability are relative limitations to further development of 5-FU. New oral 5-FU prodrugs such as UFT, S-1, and Capecitabine may help to overcome some of these difficulties. Eniluracil, a potent inhibitor of the enzyme dihydropyrimidine dehydrogenase, may also help by overcoming potential 5- FU resistance mechanisms, in addition to increasing its bioavailability. Of the antifolate-based inhibitors, Tomudex is in the most advanced stage of development. Similar efficacy with 5-FU and a convenient schedule may suggest a role in future combination regimens.
It is quite likely that even the most optimal thymidylate synthase inhibition will have limitations in terms of clinical efficacy. Novel combinations of 5-FU or its analogs with agents that have different mechanisms of action (e.g., oxaliplatin, irinotecan) could provide important new opportunities for improving the outlook of patients with colorectal cancer.
Influence of grading on the compressibility of saturated loess soils
Authors: Xu L. , Gao C. , Lan T. , Lei J. , Zuo L. 
Published: February 2020

A series of oedometer tests was carried out on natural loess and artificial soils. The loess soils were retrieved from sandy loess, silty loess and clayey loess zones within the Chinese Loess Plateau, as well as Yili area, Xinjiang Province outside the Chinese Loess Plateau. The results show clear influences of grading on soil compressibility. With the finer particle content increasing in loess, the compression paths turn from slightly upwards concave to upwards convex. The collapse index Ic defined in this study increases with the increasing Cu and decreases with the increasing D60. Locations of the soil normal consolidation lines in v–log σ′v plane are also influenced by soil grading characterised by the D60 and Cu. The intact clayey loess has more significant structure effect than the intact silty loess. Compared with the silty and clayey loess, the intact sandy loess has negligible structure effect on soil compressibility. For a given sampling site, deep loess has a higher yielding stress point and is more difficult to compress to the intrinsic compression line than shallow loess, revealing the effect of stress history on the soil compressibility.
Object and Subject of Legal Regulation as Components of the Structural Organization of Law and Order
Authors: Svinin E. V. 
Published: February 2020

The relationship of the legal order with the categories "object of legal regulation" and "subject of legal regulation" has not been studied comprehensively enough. The legal literature has developed an approach to defining the structure of law and order as a set of public relations regulated by law. This approach seems limited, since it inevitably leads to the identification of the structure of the rule of law and the subject of legal regulation. Other aspects of the interaction of law and order with the categories "object of legal regulation" and "subject of legal regulation" are yet to be studied.The multi-aspect nature of the "law and order" category necessitates an integrated approach to its structure, for the analysis of the categories "object of legal regulation" and "subject of legal regulation" are of great methodological importance. The peculiarities of the manifestation of order in the legal sphere allow us to distinguish three relatively independent sides of a single concept: law and order as a "norm", "process" and "result" of legal life.The study of static and dynamic structures of law and order is impossible without analyzing the categories "object of legal regulation" and "subject of legal regulation". These categories are considered as the most important components of the structural organization of law and order. In this capacity, they allow you to see the internal logic and regularities of the manifestation of order in the system of legal phenomena such as sources of law, the system of law, the system of legislation, legal relations and legal activity.The application of the categories "object of legal regulation" and "subject of legal regulation" allows you to create a comprehensive and complete picture of the structure of law and order. However, it seems that legal science should pay more attention to these categories. The established traditional and dogmatic views need a new system update. The development of a private theory of the object of legal regulation and the subject of legal regulation will make it possible to achieve significant results in understanding other fundamental categories, in particular the legal order.