tbuckley/cabot-search huggingface dataset:
Progression-free survival (PFS) as a surrogate end point for overall survival (OS) in first-line treatment of advanced epithelial ovarian cancer (EOC).
Authors: Katrin Marie Sjoquist, Chee Lee, Sally Lord, Mark D. Chatfield, Michael Friedlander, John Simes, Ian Marschner
Journal: Journal of Clinical Oncology (2012)

5081 Background: The duration and cost of clinical trials of first-line chemotherapy in advanced EOC could be reduced if a surrogate endpoint were used in place of OS. The consensus of the Gynecological Cancer Intergroup was that PFS is the preferred primary end point for these trials due to potential confounding of post-progression therapy on OS. We performed a systematic review to assess the extent to which treatment effect on PFS is predictive of OS in this patient population. Methods: Randomised trials of first-line chemotherapy comparing platinum containing regimens in advanced EOC were identified; trials with non-platinum backbone, maintenance strategies or biological containing therapies were excluded. Summary data (hazard ratios (HR), median PFS and OS and the ratios of medians between treatment arms) were extracted. Weighted least-square (WLS) R 2 by trial sample size derived using linear regression was used to report correlation. Results: 15 eligible trials with 19 treatment comparisons were identified comprising a total of 16,598 patients. There was a good correlation between treatment effect on PFS and OS (correlation of HR: r, 0.88, WLS R 2 , 0.71; correlation of ratios of medians: r, 0.84, WLS R 2 , 0.72). Good correlation between treatment effect on PFS and OS was also observed in various prognostic subgroups (Table). Conclusions: In clinical trials of first-line platinum based chemotherapy without biological agents in advanced EOC, treatment effect on PFS and OS is highly correlated. PFS could be considered as a primary end point when evaluating future first line strategies in advanced EOC. [Table: see text]
A pooled safety and efficacy analysis of the FOLFOX4 regimen (bi-monthly oxaliplatin plus fluorouracil/leucovorin) in elderly compared to younger patients with colorectal cancer
Authors: D. J. Sargent, R. M. Goldberg, H. Bleiberg, A. De Gramont, C. Tournigand, T. Andre, M. L. Rothenberg, I. M. Tabah-Fisch
Journal: Journal of Clinical Oncology (2006)

3517 Background: The combination of oxaliplatin, fluorouracil, and leucovorin is effective in many patients with colon cancer treated in either the advanced or adjuvant disease setting. To better identify the risks &amp; benefits of this regimen for elderly patients we compared safety &amp; efficacy data for the FOLFOX4 regimen (oxaliplatin plus fluorouracil/leucovorin administered bimonthly) in patients over &amp; under 70 years of age. Methods: We conducted a retrospective analysis of 3742 patients (614 aged ≥ 70) with colorectal cancer enrolled in four clinical trials using the same FOLFOX4 regimen as adjuvant therapy, or as first- or second-line therapy in advanced disease. Endpoints included grade ≥ 3 adverse events, response rate (RR) (in studies of advanced disease), progression (metastatic)/relapse free (adjuvant) survival (P/RFS), overall survival (OS), and dose intensity. Results: Age ≥ 70 was associated with slightly higher rates of neutropenia and thrombocytopenia but no other grade ≥ 3 adverse events (see table). There was no difference in 60-day mortality (1.1% vs 2.3%, p=0.20). We observed no significant difference in any measure of therapeutic impact of FOLFOX based on age, including P/RFS, OS, response rate, or dose intensity (see table). Conclusions: The FOLFOX4 regimen maintains its efficacy/safety ratio in elderly patients with colorectal cancer, and was administered per protocol at similar drug doses compared to the younger patients enrolled on these trials. Age alone should not be a factor limiting the use of FOLFOX4 provided patients are carefully evaluated and monitored. This analysis was supported by Sanofi-Aventis [Table: see text] [Table: see text]
Gender affects survival from medulloblastoma only as a function of age: A SEER registry study
Authors: E. K. Curran, G. M. Le, J. M. Propp, K. L. Cobb, P. G. Fisher
Journal: Journal of Clinical Oncology (2006)

9005 Background: Males have a higher incidence of medulloblastoma (MB) than females, but studies examining whether gender affects survival are conflicting and limited. We aimed to determine the effect of gender on outcome in MB, via rigorous analysis of a large data set, comprised solely of MB patients. Methods: 1,226 subjects–763 males and 463 females–were identified from 1973 to 2002, using the Surveillance Epidemiology End Results (SEER-9) registry. MB was strictly defined, using histology and site codes, to exclude non-cerebellar embryonal tumors (primitive neuro-ectodermal tumors [PNETs]). Kaplan-Meier analysis and logrank tests were performed using SPSS 12.0. Because children &lt;3 years (yr) of age are known to have worse survival, patients were stratified by age &lt;3 yr at diagnosis (95 male, 82 female) and ≥3 yr (668 male, 381 female). Results: There was no significant difference in overall survival between males and females (logrank p= 0.22; median survival: males 90 months [mo], females 152 mo). Among subjects ≥3 yr, females had significantly greater survival than males (logrank p=.02; median survival: males 93 mo, females 211 mo). In children &lt;3 yr, there was a trend toward worse survival in females (median survival: males 27 mo, females 13 mo), although this was not significant (logrank p=0.24). Females &lt;3 yr comprised a significantly greater proportion of patients with medulloblastoma, compared to individuals ≥3 yr (chi-squared test p=.01). Conclusions: Females with MB have a survival advantage only in subjects ≥3 yr. In children &lt;3 yr, females no longer possess this survival advantage and possibly have a worse outcome. The effect of gender on survival and incidence in MB warrants additional biologic investigation, and may differ in very young children with MB. No significant financial relationships to disclose.
Offline: COVID-19—a reckoning
Authors: Richard Horton
Journal: The Lancet (2020)

"To be clear we have one strategic aim: save lives." So stated a UK Government health adviser in an email sent to me last weekend. It was an email filled with frustration. "Part of the considerable difficulty in managing this epidemic", he wrote, "where we know a number of things but have some major gaps in knowledge (especially around asymptomatic transmission by age, which has major implications), is to do this in a way where we minimise the negative health impact of interventions on other aspects of health, both physical and mental…And try to think through the endgame from the start, where the endgame is quite some time off." The UK Government at last announced this week a series of emergency—Prime Minister Boris Johnson called them "drastic"—powers to address the escalating public health emergency that is coronavirus disease 2019 (COVID-19).
Global Regulation of the Histone Mark H3K36me2 Underlies Epithelial Plasticity and Metastatic Progression
Authors: Salina Yuan, Ramakrishnan Natesan, Francisco J. Sanchez-Rivera, Jinyang Li, Natarajan V. Bhanu, Taiji Yamazoe, Jeffrey H. Lin, Allyson J. Merrell, Yogev Sela, Stacy K. Thomas, Yanqing Jiang, Jacqueline B. Plesset, Emma M. Miller, Junwei Shi, Benjamin A. Garcia, Scott W. Lowe, Irfan A. Asangani, Ben Z. Stanger
Journal: Cancer Discovery (2020)

Abstract Epithelial plasticity, reversible modulation of a cell's epithelial and mesenchymal features, is associated with tumor metastasis and chemoresistance, leading causes of cancer mortality. Although different master transcription factors and epigenetic modifiers have been implicated in this process in various contexts, the extent to which a unifying, generalized mechanism of transcriptional regulation underlies epithelial plasticity remains largely unknown. Here, through targeted CRISPR/Cas9 screening, we discovered two histone-modifying enzymes involved in the writing and erasing of H3K36me2 that act reciprocally to regulate epithelial-to-mesenchymal identity, tumor differentiation, and metastasis. Using a lysine-to-methionine histone mutant to directly inhibit H3K36me2, we found that global modulation of the mark is a conserved mechanism underlying the mesenchymal state in various contexts. Mechanistically, regulation of H3K36me2 reprograms enhancers associated with master regulators of epithelial-to-mesenchymal state. Our results thus outline a unifying epigenome-scale mechanism by which a specific histone modification regulates cellular plasticity and metastasis in cancer. Significance: Although epithelial plasticity contributes to cancer metastasis and chemoresistance, no strategies exist for pharmacologically inhibiting the process. Here, we show that global regulation of a specific histone mark, H3K36me2, is a universal epigenome-wide mechanism that underlies epithelial-to-mesenchymal transition and mesenchymal-to-epithelial transition in carcinoma cells. These results offer a new strategy for targeting epithelial plasticity in cancer. This article is highlighted in the In This Issue feature, p. 747
CARDIOTOXICITY DURING CANCER TREATMENT CAUSES MORE REGIONAL THAN GLOBAL DYSFUNCTION: THE PREFECT STUDY
Authors: Henning Steen, Moritz Montenbruck, Blaz Gerzak, Arne Kristian Schwarz, Sebastian Kelle, Sorin Giusca, Grigorios Korosoglou, Susan Dent, Daniel Lenihan
Journal: Journal of the American College of Cardiology (2020)
Racial differences in prostate cancer incidence and mortality.
Authors: Marc Bjurlin, Patrick Guinan, Kevin Christensen, Marvin Rubenstein
Journal: Journal of Clinical Oncology (2012)

e15119 Background: Prostate cancer is the second leading cause of male cancer deaths in the U.S. There are significant racial differences in prostate cancer incidence and mortality. Methods: The SEER Database for 2008 was analysed for designated areas: Connecticut, Detroit, and Hawaii, assuming that these areas are surrogates for whites, blacks, and Asians, respectively. Results: Incidence and mortality (see Table). Conclusions: Assuming that the geographic SEER areas (Conn, Det, Ha) are surrogates for whites, blacks, and Oriental populations, we conclude that the incidence and mortality rates for blacks are higher than those for whites and Orientals. [Table: see text]
Effect of zeb1 and zeb2 on pancreatic fibrobast-induced epithelial-to-mesenchymal transition (EMT) in pancreatic cancer.
Authors: Laura Visa, Esther Samper, Mariana Rickmann, Antonio Postigo, Esther Sanchez-Tillo, Laureano Fernandez-cruz, Josep Balsells, Joan Maurel, Xavier Molero, Eva Cristina Vaquero
Journal: Journal of Clinical Oncology (2012)

e21035 Background: EMT renders neoplastic cancer cells the ability to migrate and to invade distant organs. The hallmark of EMT is the loss of E-cadherin, which is a prerequisite for epithelial tumor cell invasion. In pancreatic cancer, loss of tumor E-cadherin is an independent predictor of poor outcome. Aims: To analyze the effect of pancreatic fibroblasts (PF) on inducing EMT in pancreatic cancer cells and to identify the transcription factors (Snail, Slug, ZEB1, ZEB2) that mediate EMT process. Methods: Human PFs were isolated from human pancreatic specimens obtained from chronic pancreatitis and from unaffected margins of pancreatic adenocarcinoma and serous cistoadenoma. PF were cultured until complete cellular activation, as assessed by expression of α-smooth muscle actin, vimentin and fibronectin. Human pancreatic cancer cells Panc-1 were exposed to PF conditioned medium (PF-CM) and EMT analyzed by cell morphology, migration, and E-cadherin expression (quantitative RT-PCR and immunoblot). Gene expression of Snail, Slug, ZEB1, and ZEB2 was analyzed by quantitative RT-PCR, and their activity modulated by siRNA Results: Conditioned media from all types of activated PFs induced EMT changes in Panc-1 cells, as shown by 1) morphological transition from cobblestone shaped to fibroblast-like cells, 2) stimulation of cell migration, and 3) E-cadherin down–regulation; mRNA expression of Snail transiently increased at 30 min after exposure to PF returning to basal levels afterwards; mRNA levels of ZEB1 were not up-regulated upon exposure to PF-CM. However, ZEB1 protein greatly accumulated after 48h incubation with PF-CM, suggesting that PF prevent ZEB1 degradation in Panc-1 cells. Combined RNA downregulation of ZEB1 and ZEB2, but not of Snail and/or Slug, suppressed E-cadherin repression induced by PF. Conclusions: Activated PFs promote the invasive phenotype of pancreatic cancer cells through ZEB1 and ZEB2 activation.
Chemotherapy-associated thrombosis in cancer outpatients: Risk factors and decision making of a prophylactic approach.
Authors: Martina Torchio, Benvenuto Franceschetti, Carla Cavali, Sonia Zanirato, Angelo Olgiati, Valerio Gristina, Marco Danova
Journal: Journal of Clinical Oncology (2013)

e20647 Background: Venous thromboembolism (VTE), is a negative predictor of survival in pts with advanced cancer. International guidelines don’t recommend routine prophlaxis but suggest to consider pts, undergoing chemotherapy (CT), with high risk of VTE. Many clinical risk factors for cancer-associated VTE have been evaluated in a 5 parameter-based (body mass index, platelet and leucocyte counts, hemoglobin value and tumor site) scoring system, the Khorana score, utilized to indicate a prophylactic approach. We prospectively applied this score in cancer outpts beginning CT and an implementation based on 6 addictional factors analysis (sex, age, central venous catheter, CT-agents, antiangiogenetic drugs, erithropoiesis stimulating agent) to evaluate their impact in pts assignment into risk groups. Methods: We studied adult pts, followed at our Department from August 2011 to December 2012, with advanced cancers (breast, NSCLC, colorectal, pancreatic/gastric, urogenital, LNH, Hodgkin's disease, HD, and MM), receiving a first or second line standard CT. We stratified pts into three risk groups (score 0= low; score 1-2=intermediate; score 3-4-5=high) considering both the Khorana scoring system and its implementation. Results: We analyzed 169 pts (103F/66M, median age 62.3, range 35-80 yrs), pt population included: 38 breast, 32 colorectal, 31 LNH, HD and MM, 27 urogenital, 22 NSCLC and 19 pancreatic/gastric. With the Khorana score 49 pts were assigned to the low risk, 87 pts to the intermediate risk (57 with score=1, 28 with score=2), 16 pts (9.4%) to the high risk group (9 with score=3, 4 with score=4, 3 with score=5). When we considered 11 parameters 37 pts (21.8%) were assigned to the high risk group. Conclusions: A more comprehensive quantification of VTE risk, also considering new independent factors, is mandatory for a correct decision making of an antithrombotic-prophylactic approach.
Assessment of coronary heart disease risk in testicular cancer survivors
Authors: S. C. Palmer, J. Carver, L. Jacobs, K. H. Schmitz, C. Fung, E. Mohler, D. J. Vaughn
Journal: Journal of Clinical Oncology (2006)

4592 Background: Testicular cancer survivors (TCS) who receive cisplatin-based chemotherapy (CBCT) are reported to have an increased risk of coronary heart disease (CHD) compared to chemo-naive TCS (J Clin Oncol 21:1513–1523, 2003). We hypothesized that TCS treated with CBCT would demonstrate abnormal objective measures of future CHD risk compared to chemo-naive TCS. Methods: TCS ≥ 2 years from diagnosis underwent evaluation using established objective measures predictive of future CHD risk: body mass index (BMI), Framingham relative risk (RR), flow-mediated endothelium-dependent vasodilation of the brachial artery (FMD), carotid artery intima-media thickness (IMT), serum intercellular adhesion molecule-1 (ICAM-1), and high sensitivity C-reactive protein (hs-CRP). Data were analyzed using parametric and non-parametric statistics as appropriate. Results: 30 TCS who received CBCT and 20 chemo-naive TCS were recruited. The mean age and time from diagnosis were similar between the 2 groups. Both groups demonstrated elevated BMI, increased Framingham RR, and impaired FMD, consistent with an increased risk of CHD. However, there were no statistically significant differences in these measures between the two groups. Carotid IMT, ICAM-1, and hs-CRP were not significantly abnormal and these measures also did not differ between the two groups. Conclusions: TCS demonstrate abnormal objective measures of CHD risk in both CBCT-treated and chemo-naive groups. These data suggest that behavioral interventions to modify CHD risk should target all TCS independent of chemotherapy status. All values reported are mean ± standard deviation [Table: see text] No significant financial relationships to disclose.
EFFECT OF A SINGLE DOSE OF THE INTERLEUKIN-6 RECEPTOR ANTAGONIST TOCILIZUMAB ON MARKERS OF NEUTROPHIL EXTRACELLULAR TRAPS IN PATIENTS WITH NON-ST ELEVATION MYOCARDIAL INFARCTION
Authors: Ragnhild Helseth, Ola Kleveland, Thor Ueland, Rune Wiseth, Jan Kristian Damaas, Kaspar Broch, Annika Elisabet Michelsen, Bjørn Bendz, Lars Gullestad, Paal Aukrust, Ingebjoerg Seljeflot
Journal: Journal of the American College of Cardiology (2020)
EVALUATION OF THE INCLUSION OF WOMEN AND DEFINITIONS OF ANGINA IN LITERATURE THAT INFORMS CURRENT ACCF/AHA GUIDELINES ON UNSTABLE ANGINA AND NSTEMI
Authors: Catherine Kreatsoulas, Frank F. Zhou, Sravya B. Shankara, Kaitlyn E. Stanislawzyk, Anirudh Dwarakanath
Journal: Journal of the American College of Cardiology (2020)
Retrospective analysis of nanoparticle albumin-bound paclitaxel (<i>nab</i>P) administered as a single agent in the treatment of recurrent stage IV (st4) non-small cell lung cancer (NSCLC).
Authors: Ashish Saxena, Paul J. Christos, Jennifer M. Cagney, Ronald J. Scheff
Journal: Journal of Clinical Oncology (2012)

e18029 Background: NabP is a formulation of P designed to reduce toxicity of therapy and increase drug delivery to tumor cells. An established therapy for st4 breast cancer, single-agent nabP has also been shown to produce responses in frontline therapy of st4 NSCLC. Its role in relapsed NSCLC has not been well reported. Methods: We analyzed the records of st4 NSCLC patients (pts) treated with single-agent nabP at our institution. Cases were assessed with regard to age, sex, KPS, histology, line of systemic therapy, prior taxane exposure, # of cycles administered, dose attenuation, and progression-free survival (PFS) estimated by Kaplan-Meier analysis. Standard dosing of nabP was considered to be 260 mg/m2 IV Q 21 days. Disease was considered to have progressed on the date of any clinical assessment (typically CT scan) that led the treating oncologist to conclude that disease had progressed. All pts completed nabP therapy except 1, who was assessed at 427 days of follow up. Results: From Oct 2008 to Jan 2012, 15 st4 NSCLC pts (median age 67, range 48 to 82; 8 F, 7 M; KPS 60-80%; 12 adenocarcinoma, 2 squamous cell, 1 unspecified) received a median of 3 cycles (range 1-17) of single-agent nabP. All pts received at least 1 prior line of systemic therapy in the st4 setting: 6 received nabP as 2 nd line therapy, 4 as 3 rd line, and 5 as 4 th line. 5 pts had also received prior chemotherapy for early stage NSCLC. 9 pts were taxane-naïve; 6 had received prior taxane therapy. 10 pts began nabP at standard dose; 5 began on an attenuated dose or schedule. Subsequent dose reduction occurred in 3 pts due to toxicity (fatigue, myelosuppression). Only 1 patient discontinued treatment due to toxicity (myalgias, arthralgias). Median PFS for all pts was 82 days (95% CI 35 to 205 days). Older age reduced risk of progression [hazard ratio 0.93 per 1-year age increase (95% CI 0.86 to 0.99), P=0.04]. Prior taxane exposure decreased PFS (median 39 vs. 113 days, P=0.07 by log-rank test). PFS did not vary by KPS, histology, or line of therapy. Conclusions: Single-agent nabP administered in relapsed St4 NSCLC is well tolerated and associated with extension of PFS, particularly in older and taxane-naïve pts.
RADIOTHERAPY AND CARDIAC IMPLANTABLE DEVICES: A MULTI-CENTER, PROSPECTIVE, IN-VITRO EVALUATION
Authors: Enrico Di Girolamo, Massimiliano Marini, Paolo De Filippo, Marianna Appignani, Nanda Furia, Fabrizio Di Girolamo, Cristina Leidi, Anna Delana, Agnese Barbareschi, Stefano Andreoli, Domenico Genovesi, Maria Daniela Falco
Journal: Journal of the American College of Cardiology (2020)
EVALUATING THE RELATIONSHIP BETWEEN QUANTITATIVE MEASURES OF MYOCARDIAL PERFUSION AND BIOMARKERS OF MYONECROSIS, INFLAMMATION AND VASOCONSTRICTION
Authors: Elizabeth R. P Anderson, Vaiibhav N. Patel, Justin A. Pieper, Richard L. Weinberg, Edward P. Ficaro, Salim Hayek, Ravi V. Shah, Matthew C. Konerman, Venkatesh L. Murthy
Journal: Journal of the American College of Cardiology (2020)
MULTIMODAL CARDIAC IMAGING APPROACH IN ATYPICAL CHEST PAIN RESULTING IN PRIMARY RIGHT ATRIAL CARDIAC SPINDLE CELL SARCOMA
Authors: Hector Lopez de la Garza, José Gildardo Paredes-Vázquez, Jaime Alberto Guajardo Lozano, Hector Guillermo Betancourt Del Campo, Vicente Jimenez Franco, Hernan Azpiri, Carlos Jerjes-Sánchez, Juan Alberto Quintanilla Gutierrez, Felipe Valdes, David Rodriguez, Jathniel Panneflek
Journal: Journal of the American College of Cardiology (2020)
EPICARDIAL ADIPOSE TISSUE EVALUATED BY CARDIAC MAGNETIC RESONANCE PREDICTS ADVERSE OUTCOMES IN HEART FAILURE PATIENTS
Authors: Reza Mohebi, Carlos Santos-Gallego, Darian de Luna, Kenny Daici, Juan Antonio Requena Ibanez, Ariana Patricia Vargas, Valentin Fuster, Angel Sanz Salvo, Juan J. Badimon
Journal: Journal of the American College of Cardiology (2020)
VASCULAR RESPONSE OF A POLYMER-FREE, PACLITAXEL-COATED STENT (ZILVER PTX) VERSUS A POLYMER-COATED, PACLITAXEL-ELUTING STENT (ELUVIA) IN HEALTHY SWINE ILIOFEMORAL ARTERIES
Authors: Atsushi Sakamoto, Hiroyuki Jinnouchi, Anne Cornelissen, Yu Sato, Masayuki Mori, Rika Kawakami, Daniela Fuller, Neel Gadhoke, Raquel Fernandez, Liang Guo, Frank D. Kolodgie, Renu Virmani, Aloke V. Finn
Journal: Journal of the American College of Cardiology (2020)