tbuckley/cabot-search huggingface dataset:
The 2010 National Comprehensive Cancer Network (NCCN) risk assessment and genetic counseling (RA/GC) study: Operational aspects of RA/GC programs at academic medical centers.
Authors: Stephen L. Sherman, Beth Crawford, Karen Giammicchio, Lisa Kimbro, Agnes Masny, Kristen Mahoney Shannon
Journal: Journal of Clinical Oncology (2012)

e16510 Background: In 2010 NCCN conducted a Risk Assessment and Genetic Counseling (RA/GC) study focused on the operational aspects of RA/GC programs and services at NCCN Member Institutions (MIs). The primary aims were benchmarking of RA/GC operations and practice patterns. Methods: A survey instrument was developed by NCCN staff in consultation with RA/GC leaders at NCCN MIs. The survey collected quantitative and descriptive data on RA/GC program organization, staffing, and patient volume and also included questions on patient referral, test disclosure, and program funding. Results: 19/21 (90%) NCCN MIs participated. The mean number of patients seen annually for 17 MIs reporting data was 872 (range 130 – 2,200). The mean number of patients seen annually per 1.0 genetic counseling full-time equivalent was 272 (range 152 – 422). RA/GC services are made available to patients by scheduled appointment only at 5 MIs (26%) versus by appointment or with on-call genetic counselors at 14 MIs (74%). However, 11/19 (58%) MIs reported the time between initial patient contact and appointment was greater than 2 weeks. Self-sufficient RA/GC program funding was consistently cited by survey respondents as one of the greatest challenges, with 18 MIs indicating that they require institutional support, whereas only 11 indicated that reimbursement from third-party payors contributed to funding. Pertaining to disclosure, respondents estimated that 48% of test results were disclosed to patients via telephone and 39% in-person. The remaining disclosures were made based on patient preference. Conclusions: The availability of on-call RA/GC resources at most NCCN MIs likely indicates an effort to increase the number of patients that receive RA/GC services, but based on times to first appointment, access remains an issue. The 2011 recommendations of the National Society of Genetic Counselors state that the disclosure of test results in-person is often very helpful. However, the percentage given by telephone remains substantial. Dissemination of RA/GC benchmark data and identification of best practices will promote enhanced operations and patient access at NCCN MIs.
CETUXICOL, a phase II trial randomizing standard treatment with or without cetuximab in primary cervical cancer treatment.
Authors: Suzy Marie Elisabeth Scholl, Anne De la Rochefordiere, Peter Petrow, Anne Floquet, Thierry Petit, Severine Alran, Dominique Berton-Rigaud, Maura Campitelli, Claire Chiara-Bruneaud, Michel Fabbro, Virginie Fourchotte, Frederic Guyon, Florence Joly, Christine Kerr, Sophie Maillard, Mathieu Minsat, Corine Plancher, Marius Pop, Xavier Sastre, Philippe Beuzeboc
Journal: Journal of Clinical Oncology (2012)

e15535 Background: Advanced stage cervical cancer (CC) remains a public health issue despite preventive vaccines and screening. EGFR is over-expressed in 50 to 85% of CC and activated in 20%, suggesting that EGFR blockage may be a promising treatment approach. Methods: A randomized phase 2 trial on 78 stage IB2–III patients from 11 French Cancer Centres evaluated the tolerance and early response to cetuximab, an anti EGFR antibody. 40 patients received cetuximab + standard RT and Cisplatinum based chemotherapy (arm A) and 38 patients received standard treatment (B). Primary endpoint is DFS at 2 years and presently not reached. MRI imaging revealed no difference in median (44 vs 40) tumour sizes between arms; there was no difference in age, menopausal status, PI and smoking habits. Parametrial involvement was clinically diagnosed in 19 and 20 cases respectively. Presence of lumbar or para-aortic lymph nodes was an exclusion criterion. Three patients withdrew consent in the cetuximab arm, one accepted standard treatment. Treatment schedules were incomplete in 13 (A) and 14 (B) patients for reasons of haematological or renal toxicity. Results: Surgical resection was feasible in 24 (65%) and 26 (70%) patients in arms A and B respectively.Tolerance was satisfactory in both arms, with significantly more acne form reactions in the cetuximab arm of grade 2 (n= 19) and 3 (n=4). More patients had diarrhea (n=8 vs 4: ns) associated with nausea and vomiting of grade 3 (n=4) and 4 (n=1) in the cetuximab arm (ns).Early results show a complete response at 6 weeks by MRI in 18% and 8% for arms A and B respectively. A central blinded review of the imaging and pathology slides is presently ongoing. Conclusions: The prediction of a response to EGFR targeted therapy in cervical cancer remains a matter of debate since no precise molecular studies are available. Consequently, no decisive results have been achieved in early trials of non selected patients with late stage disease (GOG 76-DD). Biopsy samples are available for the majority of our patients and analyses of EGFR expression, cellular sub-localization and main mutations in the PI3K pathway are ongoing. Molecular studies to allow hierarchical decision making are warranted in future studies.
Early Relapse of Follicular Lymphoma after Rituximab-Based Biologic Doublet Upfront Therapy Is Associated with Increased Risk of Death: A Combined Analysis from CALGB Studies 50402, 50701 and 50803 (Alliance)
Authors: Frederick Lansigan, Ian Barak, Brandelyn Nicole Pitcher, Sin-Ho Jung, Bruce Cheson, Myron S. Czuczman, Barbara W. Grant, Peter Martin, Eric D. Hsi, Heiko Schoder, Scott E. Smith, Nancy L Bartlett, John P. Leonard, Kristie Blum
Journal: Blood (2016)
LATE COMPLICATIONS AND CARDIOPULMONARY PERFORMANCE IN ADULTS WITH FONTAN PHYSIOLOGY: RV-DOMINANT VERSUS THOSE WITH LV-DOMINANT OR UNSEPTATED VENTRICLES
Authors: Christoph Haller, Susan L. Roche, Rachel Wald, Simone Bartelse, Eric Pham-Hung, Candice Silversides, Erwin Oechslin, Jack Colman, Edward Hickey
Journal: Journal of the American College of Cardiology (2017)
총회구연 : Guggulsterone이 간성상세포의 활성 및 생존에 미치는 영향
Authors: 김보현, 양종인, 이정훈, 정고은, 김휘영, 명선정, 김윤준, 윤정환, 이효석, 김정룡
Journal: Clinical and Molecular Hepatology (2009)
The FAM-GEM-1 study: Frequency and characteristics of familial melanoma in Spain.
Authors: Ivan Marquez Rodas, Manuel Martin-Gonzalez, Eduardo Nagore, Cristina Gomez Fernandez, Jose Antonio Aviles Izquierdo, Cayetana Maldonado-Seral, Virtudes Soriano, Margarita Majem, Virginia Palomar Coloma, Rocio Maseda, Alfonso Martin-Carnicero, Teresa Puértolas, Elena Godoy Gijon, Pablo Cerezuela, Maria Ochoa de Olza, Begona Campos Balea, Elisabeth Perez Ruiz, Ainara Soria Rivas, Irene Gil-Arnaiz, Salvador Martin-Algarra
Journal: Journal of Clinical Oncology (2014)

9039 Background: Melanoma risk is determined by environmental, phenotypical and familial background. Literature describes a 5-10% of melanoma cases in a familial setting. Familial melanoma (FM) is classically defined as >2 first degree relatives with melanoma in a family. Multiple melanomas (MM), pancreatic cancer (PC) in family and multiple nevi are also risk criteria. In Spain, there are several local studies about epidemiology and characteristics of FM, but there are no studies exploring all the territory Methods: FAM-GEM-1 is a national, observational, 2 years-registry study (2011-2013), conducted by the Spanish Multidisciplinary Melanoma Group (GEM), whose principal objective was to assess the rate of patients with FM in Spain. Secondary objectives were to analyze if FM patients are different in terms of clinical, pathological and/or molecular features; and to create a registry of FM for further studies. We present the final results of the 1,049 patients registered. Results: In Spanish population, according to this representative sample, 7%patients meet FM criteria. In the univariate analysis, FM patients have more frequently MM, and less Breslow index, positive mitosis and positive nodes. No differences in other prognosis factors or characteristics were found (Table). Conclusions: Although FM seem to have better prognosis characteristics, it is not clear if these differences are due to a bias (more concern that leads these patients to earlier diagnosis) or to real molecular differences. Further studies are needed to elucidate it. * Fisher or t student p< 0.05 vs non-FM (%): for valid data FM N (%) 73 (7) Non-FM N (%) 976 (93) Age, mean, (SD) 53.1 (15.5) 55.2 (16.3) Age < 50 y 30 (41) 356 (36.5) Male 43 (58.9) 487 (49.9) Phototype I-II 34 (46.6) 482 (49.4) Freckles 18 (25) 308 (31.6) Multiple nevi 18 (25.4) 195 (20.5) Previous nevus 23 (43.4) 265 (36.9) MM 7 (9.6)* 35 (3.6) Breslow (mm), mean, (SD) 1.5 (1.7)* 2.3 (2.7) Breslow>1 mm 21 (38.2)* 458 (60.2) Ulceration 11 (16.7) 184 (22.9) Mitosis 20 (37.7)* 355 (55) Positive Nodes 14 (19.4)* 278 (29.5) Metastases 7 (9.6) 148 (15.2) BRAF mutant 5 (71) 59 (51.8) Other tumor (non-skin) 8 (11) 85 (8.7) PC in family (first and second degree) 4 (5.5) 37 (3.8) Other tumors in family (first degree) 32 (43.8) 439 (44.9)
ASSOCIATION OF REMNANT-LIKE PARTICLE CHOLESTEROL AND LOW-DENSITY LIPOPROTEIN TRIGLYCERIDE WITH INCIDENCE OF CARDIOVASCULAR EVENTS: THE ARIC STUDY
Authors: Anum Saeed, Christie Ballantyne, Wensheng Sun, Gerardo Heiss, Thomas Mosley, Cameron Guild, Eric Boerwinkle, Elena Feofanova, Yu Bing, Salim Virani, Josef Coresh, Vijay Nambi, Ron Hoogeveen
Journal: Journal of the American College of Cardiology (2017)
LOW URINARY CGMP/BNP RATIO IS ASSOCIATED WITH WORSE OUTCOMES IN HEART FAILURE BUT IS INCREASED BY TREATMENT WITH SACUBITRIL/VALSARTAN: AN ANALYSIS OF PARADIGM-HF
Authors: Pardeep Jhund, Jean Rouleau, Karl Swedberg, Michael Zile, Martin Lefkowitz, Margaret Prescott, Victor Shi, Scott Solomon, Milton Packer, John McMurray
Journal: Journal of the American College of Cardiology (2017)
Melanoma Guidelines
Authors: Alan N Houghton, Daniel G Coit, Adil Daud, Raza A Dilawari, Dominick Dimaio, Jared A Gollob, Naomi B Haas, Allan Halpern, Timothy M Johnson, Mohammed Kashani-Sabet, William G Kraybill, Julie R Lange, Mary Martini, Merrick I Ross, Wolfram E Samlowski, Stephen F Sener, Kenneth K Tanabe, John A Thompson, Vijay Trisal, Marshall M Urist, Michael J Walker
Journal: Journal of the National Comprehensive Cancer Network (2006)

In 2006, an estimated 62,190 new cases of melanoma will be diagnosed, and approximately 7910 patients will die of the disease in the United States. The incidence of melanoma continues to increase dramatically. Risk factors for melanoma include family history, dysplastic nevi, and fair skin that sunburns easily; however, melanoma can occur in any ethnic group and in people who have not had substantial sun exposure. The NCCN Melanoma guidelines attempt to distill and simplify an enormous body of knowledge and experience into fairly simple management algorithms. For the most recent version of the guidelines, please visit NCCN.org
Genomic and Epigenomic Heterogeneity of Hepatocellular Carcinoma
Authors: De-Chen Lin, Anand Mayakonda, Huy Q. Dinh, Pinbo Huang, Lehang Lin, Xiaoping Liu, Ling-wen Ding, Jie Wang, Benjamin P. Berman, Er-Wei Song, Dong Yin, H. Phillip Koeffler
Journal: Cancer Research (2017)

Abstract Understanding the intratumoral heterogeneity of hepatocellular carcinoma is instructive for developing personalized therapy and identifying molecular biomarkers. Here we applied whole-exome sequencing to 69 samples from 11 patients to resolve the genetic architecture of subclonal diversification. Spatial genomic diversity was found in all 11 hepatocellular carcinoma cases, with 29% of driver mutations being heterogeneous, including TERT, ARID1A, NOTCH2, and STAG2. Similar with other cancer types, TP53 mutations were always shared between all tumor regions, that is, located on the “trunk” of the evolutionary tree. In addition, we found that variants within several drug targets such as KIT, SYK, and PIK3CA were mutated in a fully clonal manner, indicating their therapeutic potentials for hepatocellular carcinoma. Temporal dissection of mutational signatures suggested that mutagenic processes associated with exposure to aristolochic acid and aflatoxin might play a more important role in early, as opposed to late, stages of hepatocellular carcinoma development. Moreover, we observed extensive intratumoral epigenetic heterogeneity in hepatocellular carcinoma based on multiple independent analytical methods and showed that intratumoral methylation heterogeneity might play important roles in the biology of hepatocellular carcinoma cells. Our results also demonstrated prominent heterogeneity of intratumoral methylation even in a stable hepatocellular carcinoma genome. Together, these findings highlight widespread intratumoral heterogeneity at both the genomic and epigenomic levels in hepatocellular carcinoma and provide an important molecular foundation for better understanding the pathogenesis of this malignancy. Cancer Res; 77(9); 2255–65. ©2017 AACR.
Contemporary Conditioning Regimen before Allogeneic Stem Cell Transplantation for Children with Non-Malignant Diseases
Authors: Christina Peters, Mary Slatter, Paul Veys, Franco Locatelli, Adriana Balduzzi, M. Akif Yesilipek, Jean-Hugues Dalle, Marina Cavazzana, Jaap Jan Boelens, Isaac Yaniv, Ansgar S Schulz, Jacek Wachowiak, Manfred Hoenig, Arjan C Lankester, Benedicte Neven, Eric Beohou, Arnaud Dallisier, Peter Bader, Andrew Gennery
Journal: Blood (2016)
SEMI-QUANTITATIVE EVALUATION OF CORONARY ARTERIAL PATENCY AFTER IMPLANTATION OF A METALLIC STENT: A COMPARISON BETWEEN 320 SLICE CT AND INVASIVE CORONARY ANGIOGRAM WITH CONSIDERATION OF STENT SIZE, LENGTH, AND TYPE, AS WELL AS THE SPECIFIC CORONARY ARTERY IMPLANTED
Authors: Nobusada Funabashi, Hiroyuki Takaoka, Yoshihide Fujimoto, Yoshio Kobayashi
Journal: Journal of the American College of Cardiology (2017)
Fractional Flow Reserve–Guided Multivessel Angioplasty in Myocardial Infarction
Authors: Pieter C. Smits, Mohamed Abdel-Wahab, Franz-Josef Neumann, Bianca M. Boxma-de Klerk, Ketil Lunde, Carl E. Schotborgh, Zsolt Piroth, David Horak, Adrian Wlodarczak, Paul J. Ong, Rainer Hambrecht, Oskar Angerås, Gert Richardt, Elmir Omerovic
Journal: New England Journal of Medicine (2017)

In patients with ST-segment elevation myocardial infarction (STEMI), the use of percutaneous coronary intervention (PCI) to restore blood flow in an infarct-related coronary artery improves outcomes. The use of PCI in non-infarct-related coronary arteries remains controversial.We randomly assigned 885 patients with STEMI and multivessel disease who had undergone primary PCI of an infarct-related coronary artery in a 1:2 ratio to undergo complete revascularization of non-infarct-related coronary arteries guided by fractional flow reserve (FFR) (295 patients) or to undergo no revascularization of non-infarct-related coronary arteries (590 patients). The FFR procedure was performed in both groups, but in the latter group, both the patients and their cardiologist were unaware of the findings on FFR. The primary end point was a composite of death from any cause, nonfatal myocardial infarction, revascularization, and cerebrovascular events at 12 months. Clinically indicated elective revascularizations performed within 45 days after primary PCI were not counted as events in the group receiving PCI for an infarct-related coronary artery only.The primary outcome occurred in 23 patients in the complete-revascularization group and in 121 patients in the infarct-artery-only group that did not receive complete revascularization, a finding that translates to 8 and 21 events per 100 patients, respectively (hazard ratio, 0.35; 95% confidence interval [CI], 0.22 to 0.55; P<0.001). Death occurred in 4 patients in the complete-revascularization group and in 10 patients in the infarct-artery-only group (1.4% vs. 1.7%) (hazard ratio, 0.80; 95% CI, 0.25 to 2.56), myocardial infarction in 7 and 28 patients, respectively (2.4% vs. 4.7%) (hazard ratio, 0.50; 95% CI, 0.22 to 1.13), revascularization in 18 and 103 patients (6.1% vs. 17.5%) (hazard ratio, 0.32; 95% CI, 0.20 to 0.54), and cerebrovascular events in 0 and 4 patients (0 vs. 0.7%). An FFR-related serious adverse event occurred in 2 patients (both in the group receiving infarct-related treatment only).In patients with STEMI and multivessel disease who underwent primary PCI of an infarct-related artery, the addition of FFR-guided complete revascularization of non-infarct-related arteries in the acute setting resulted in a risk of a composite cardiovascular outcome that was lower than the risk among those who were treated for the infarct-related artery only. This finding was mainly supported by a reduction in subsequent revascularizations. (Funded by Maasstad Cardiovascular Research and others; Compare-Acute ClinicalTrials.gov number, NCT01399736 .).
RELATIONSHIP BETWEEN PROXIMAL AORTA MORPHOLOGY AND PROGRESSION RATE OF AORTIC STENOSIS
Authors: Romain Capoulade, Jonathan G. Teoh, Philipp E. Bartko, Eliza Teo, Jan-Erik Scholtz, Lionel Tastet, Mylène Shen, Christos Mihos, Yong H. Park, Garcia Julio, Eric Larose, Eric Isselbacher, Thoralf Sundt, Thomas MacGillivray, Serguei Melnitchouk, Brian Ghoshhajra, Philippe Pibarot, Judy Hung
Journal: Journal of the American College of Cardiology (2017)
Changing Landscape of Congenital Heart Disease
Authors: Berto J. Bouma, Barbara J.M. Mulder
Journal: Circulation Research (2017)

Congenital heart disease is the most frequently occurring congenital disorder affecting ≈0.8% of live births. Thanks to great efforts and technical improvements, including the development of cardiopulmonary bypass in the 1950s, large-scale repair in these patients became possible, with subsequent dramatic reduction in morbidity and mortality. The ongoing search for progress and the growing understanding of the cardiovascular system and its pathophysiology refined all aspects of care for these patients. As a consequence, survival further increased over the past decades, and a new group of patients, those who survived congenital heart disease into adulthood, emerged. However, a large range of complications raised at the horizon as arrhythmias, endocarditis, pulmonary hypertension, and heart failure, and the need for additional treatment became clear. Technical solutions were sought in perfection and creation of new surgical techniques by developing catheter-based interventions, with elimination of open heart surgery and new electronic devices enabling, for example, multisite pacing and implantation of internal cardiac defibrillators to prevent sudden death. Over time, many pharmaceutical studies were conducted, changing clinical treatment slowly toward evidence-based care, although results were often limited by low numbers and clinical heterogeneity. More attention has been given to secondary issues like sports participation, pregnancy, work, and social-related difficulties. The relevance of these issues was already recognized in the 1970s when the need for specialized centers with multidisciplinary teams was proclaimed. Finally, research has become incorporated in care. Results of intervention studies and registries increased the knowledge on epidemiology of adults with congenital heart disease and their complications during life, and at the end, several guidelines became easily accessible, guiding physicians to deliver care appropriately. Over the past decades, the landscape of adult congenital heart disease has changed dramatically, which has to be continued in the future.
Preliminary results of a randomized phase II study comparing two schedules of temozolomide in combination with sorafenib in patients with advanced melanoma
Authors: R. K. Amaravadi, L. M. Schuchter, A. Kramer, S. F. Barth, J. Villanueva, A. B. Troxel, D. A. Tuveson, K. L. Nathanson, P. J. O’Dwyer, K. T. Flaherty
Journal: Journal of Clinical Oncology (2006)

8009 Background: Sorafenib (SO) is an oral Raf kinase/VEGFR-2 inhibitor that has anti-melanoma activity when given with carboplatin/paclitaxel. The primary objective of this study is to estimate the duration of progression-free survival (PFS) for patients with metastatic melanoma (MM) taking SO + temozolomide (TEM). Secondary objectives are to determine the optimal dosing of TEM when given with SO, response, and toxicity rates. Correlative studies include BRAF genotyping and assessment of intratumoral Raf inhibition. Methods: Patients with MM and ECOG PS&lt;2 are eligible. Prior therapy is allowed. Accrual is designed for 167 patients in one stage. All patients receive SO 400 mg po bid continuously. After one week of SO alone, patients without brain metastasis and no prior TEM are randomized to receive either extended daily dosing (EDD): TEM 75 mg/m 2 po qd for 6 /8 weeks (Arm A), or standard dosing (STD): TEM 150 mg/m 2 po qd for days1–5/28 (Arm B). Patients with prior TEM use are treated with EDD (Arm C) and patients with brain metastasis without prior TEM are treated with STD (Arm D). Responses are assessed using RECIST criteria. Results: 65 patients were evaluated for toxicity. Of these, 58 received SO + TEM and were evaluable for response (Table). SO + TEM resulted in a 24% overall response rate (ORR) [95% CI 11–41%] in patients without brain metastasis or prior TEM and 20% ORR [95% CI 3–56%] in patients with brain metastasis and no prior TEM. Observed grade 3 toxicities attributable to study medication were: hand-foot syndrome (12%), rash (8%), nausea (5%), anorexia (8%), and hypertension (3%). Nausea and anorexia were more prevalent with STD. Tumor blocks and 8 paired biopsy samples have been collected for correlative studies. Conclusions: Initial phase II results demonstrate encouraging antitumor activity and safety profile for SO + TEM in MM. Updated PFS data, response and toxicity rates, and correlative results will be presented. [Table: see text] [Table: see text]
Trastuzumab treatment and the risk of central nervous system (CNS) metastases
Authors: M. C. Pinder, H. Chang, K. R. Broglio, L. B. Michaud, R. L. Theriault, A. Sahin, T. Buchholz, G. N. Hortobagyi, F. J. Esteva
Journal: Journal of Clinical Oncology (2007)

1018 Background: In the era of trastuzumab, HER2-positive breast cancer confers an increased risk of central nervous system (CNS) metastases. While several studies have examined CNS metastases in trastuzumab-treated patients, data are sparse regarding CNS metastases in trastuzumab-naïve HER2-positive patients. We evaluated time to CNS metastasis, death, and death subsequent to brain metastasis in relation to trastuzumab treatment. Methods: The study population included 750 patients diagnosed with HER2-positive metastatic breast cancer (HER2+ MBC) between June 1977 and January 2006. The association between trastuzumab treatment and the outcomes of time to CNS metastasis and time to death following CNS metastasis were determined using Cox proportional hazards models that included trastuzumab treatment as a time-dependent covariate. Multivariable Cox proportional hazards models were fit to determine the association between trastuzumab treatment and outcomes after adjustment for known prognostic factors. Patients with HER2+ MBC treated at our institution before trastuzumab was available served as our control group. Results: Of the 750 patients included, 689 patients received trastuzumab during the follow-up period while 61 patients were not treated with trastuzumab. Median follow-up was 32 months. A total of 251 patients developed CNS metastases. After adjusting for other prognostic variables including age, ER status, PR status, pathological stage, and site of initial metastasis, patients who received trastuzumab had 2.84 times the risk of CNS metastases (95 % CI = 1.87, 4.30, p &lt; 0.0001) compared to patients who did not receive trastuzumab. Time to death following brain metastasis did not differ significantly between trastuzumab- treated and -untreated patients. Conclusions: In our large series, patients with HER2+ MBC treated with trastuzumab were at significantly increased risk of developing CNS metastases compared to patients who did not receive trastuzumab. This finding warrants further investigation into biological mechanisms that may account for this difference. No significant financial relationships to disclose.