tbuckley/cabot-search huggingface dataset:
Sequencing of Androgen-Deprivation Therapy With External-Beam Radiotherapy in Localized Prostate Cancer: A Phase III Randomized Controlled Trial
Authors: Shawn Malone, Soumyajit Roy, Libni Eapen, Choan E, Robert MacRae, Gad Perry, Julie Bowen, Rajiv Samant, Scott Morgan, Julia Craig, Kyle Malone, Scott Grimes
Journal: Journal of Clinical Oncology (2019)

Dose-escalated radiotherapy (RT) with androgen-deprivation therapy (ADT) is a standard definitive treatment of localized prostate cancer (LPCa). The optimal sequencing of these therapies is unclear. Our phase III trial compared neoadjuvant versus concurrent initiation of ADT in combination with dose-escalated prostate RT (PRT).Patients with newly diagnosed LPCa with Gleason score ≤ 7, clinical stage T1b to T3a, and prostate-specific antigen < 30 ng/mL were randomly allocated to neoadjuvant and concurrent ADT for 6 months starting 4 months before RT (neoadjuvant group) or concurrent and adjuvant ADT for 6 months starting simultaneously with RT (concurrent group). The primary end point was biochemical relapse-free survival (bRFS). Stratified log-rank test was used to compare bRFS and overall survival (OS). Incidence of grade ≥ 3 late RT-related toxicities was compared by log-rank test.Overall, 432 patients were randomly assigned to the neoadjuvant (n = 215) or concurrent group (n = 217). At 10 years, bRFS rates for the two groups were 80.5% and 87.4%, respectively. Ten-year OS rates were 76.4% and 73.7%, respectively. There was no significant difference in bRFS (P = .10) or OS (P = .70) between the two groups. Relative to the neoadjuvant group, the hazard ratio for the concurrent group was 0.66 (95% CI, 0.41 to 1.07) for bRFS and 0.94 (95% CI, 0.68 to 1.30) for OS. No significant difference was observed in the 3-year incidence of late RT-related grade ≥ 3 GI (2.5% v 3.9%) or genitourinary toxicity (2.9% v 2.9%).In our study, there was no statistically significant difference in bRFS between the two treatment groups. Similarly, no difference was seen in OS or late RT-related toxicities. On the basis of these results, both neoadjuvant and concurrent initiations of short-term ADT with dose-escalated PRT are reasonable standards of care for LPCa.
Abstract I12: CD40 immunotherapy for pancreatic cancer
Authors: Robert H. Vonderheide
Journal: Cancer Research (2019)

Abstract CD40 is a cell-surface member of the TNF receptor superfamily that upon activation can license dendritic cells (DC) to promote antitumor T-cell activation and re-educate macrophages to destroy tumor stroma. Mechanistically, the combination of chemotherapy followed by CD40 mAb functions as an “in situ” vaccine; in addition, destruction of stroma by CD40-activated macrophages may enhance chemotherapy delivery. In a recent study sponsored by the Parker Institute of Cancer Immunotherapy of gemcitabine and nab-paclitaxel chemotherapy plus CD40 mAb APX005M, with or without PD-1 nivolumab mAb, we found the objective response rate among 30 patients with untreated, metastatic pancreatic cancer was more than 50% in the DLT-evaluable population. 13 patients experienced an AE leading to discontinuation, and 10 patients experienced a treatment-related serious AE. Two DLTs were observed, grade 3 and 4 febrile neutropenia, respectively. A three-arm randomized study of gemcitabine, nab-paclitaxel with APX005M, or with nivolumab, or with both APX005M and nivolumab has completed enrollment. Evidence to date suggests that CD40 activation is a critical and nonredundant mechanism to convert “cold” tumors to “hot” (with prominent tumor infiltration of T cells), sensitizing them to checkpoint inhibition. Citation Format: Robert H. Vonderheide. CD40 immunotherapy for pancreatic cancer [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Advances in Science and Clinical Care; 2019 Sept 6-9; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2019;79(24 Suppl):Abstract nr I12.
Decline in the incidence of colorectal cancer and the associated mortality in young Italian adults
Authors: Manuel Zorzi, Giulia Martina Cavestro, Stefano Guzzinati, Luigino Dal Maso, Massimo Rugge
Journal: Gut (2019)

BACKGROUND Recent evidence has shown that although the incidence rate (IR) of colorectal cancer (CRC) is decreasing among older adults in several high-income countries, rates have increased in adults younger than 50 years.AIM To determine recent incidence trends of CRC in Italy up to 2014 by sex, age, and area.DESIGN, SETTING, AND PARTICIPANTS This study estimated the incidence of CRC using data from 48 Cancer Registry (2003-2014), including 60% of Italian population.MAIN OUTCOMES Annualized percentage changes and incidence rate ratios of CRC.RESULTS From 2003 to 2014, the incidence of CRC decreased both for men (Annual Percent Change -1.6, 95%CI -2.1 to -1.0) and for women (APC -1.2, 95%CI -1.8 to -0.6).Notably, menfemale ratio is 1 below age 50 years while it is approximately 1.5 over 50 years of age.A significant decrease of incidence emerged in Northern Italy (from 11.1 per 100,000 in 2003 to 8.5 in 2014, APC -2.4), while stable rates were observed in Southern Italy (from 8.6 in 2003 to 8.8 in 2014; APC 0.05).CONCLUSIONS Leveling of CRC incidence in young adults among Italian areas strongly supports the need to reinforce research on specific risk factors and lifestyles possibly affecting these younger cohorts.
Effect of obstructive sleep apnoea and its treatment with continuous positive airway pressure on the prevalence of cardiovascular events in patients with acute coronary syndrome (ISAACC study): a randomised controlled trial
Authors: Manuel Sánchez-de-la-Torre, Alicia Sánchez-de-la-Torre, Sandra Bertran, Jorge Abad, Joaquín Duran-Cantolla, Valentín Cabriada, Olga Mediano, María José Masdeu, Mari Luz Alonso, Juan Fernando Masa, Antonia Barceló, Mónica de la Peña, Mercè Mayos, Ramón Coloma, Josep M Montserrat, Eusebi Chiner, Salvador Perelló, Gemma Rubinós, Olga Mínguez, Lydia Pascual, Anunciación Cortijo, Dolores Martínez, Albina Aldomà, Mireia Dalmases, R Doug McEvoy, Ferran Barbé, Laura Abad, Aida Muñoz, Elisabet Zamora, Ignacio Vicente, Sandra Inglés, Carlos Egea, Jaime Marcos, Almudena Fernández, Jorge Ullate, Joaquín Durán Carro, Jose L Rodríguez, María J Mendoza, Raul Labeaga, David Diez, Berenice Muria, Chechu Amibilia, Amaia Urrutia, Sonia Castro, Leyre Serrano, Idoia Salinas, Ruth Diez, Ana Martínez, Marina Florés, Estefanía Galera, Anna Mas, Montserrat Martínez, Maricel Arbonés, Silvia Ortega, Alicia Martín, Jose M Román-Sánchez, Ma Isabel Valiente-Diaz, Ma Esther Viejo-Ayuso, Concepción Rodríguez-García, Noelia Sánchez-Rodríguez, Nieves Mayoral, Francisco J Rubio, Yunelsy Anta-Mejias, Sofía Romera-Peralta, Pilar Resano, Ramón Arroyo-Espilguero, María Bienvenido-Villalba, Laura Vigil, Enriqueta Ramírez, María Piñar, Elisabet Martínez, Carmen Múñoz, Estrella Ordax, Name Surname, Jaime Corral, Francisco J Gómez de Terreros Caro, Estefanía García-Ledesma, Rocío Gallego, Jose L Cabrero, Ricardo Pereira, Paloma Giménez, Miguel Carrera, Javier Pierola, Cristina Villena, Magdalena Campaner, Ana M Fortuna, Patricia Peñacoba, Abel J Martínez García, Sergio García Castillo, Lara Navas, Onintza Garmendia, Monique Suárez, José Sancho, Nuria Farre, Gil Bonet, Alfredo Bardaji, Anna Villares, Ma José Vázquez
Journal: The Lancet Respiratory Medicine (2019)
Bone Turnover Markers in Osteoporosis
Authors: Jennifer J. Kelly
Journal: JAMA (2019)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Sustained Coevolution in a Stochastic Model of Cancer–Immune Interaction
Authors: Jason T. George, Herbert Levine
Journal: Cancer Research (2019)

The dynamic interactions between an evolving malignancy and the adaptive immune system generate diverse evolutionary trajectories that ultimately result in tumor clearance or immune escape. Here, we create a simple mathematical model coupling T-cell recognition with an evolving cancer population that may randomly produce evasive subclones, imparting transient protection against the effector T cells. T-cell turnover declines and evasion rates together explained differences in early incidence data across almost all cancer types. Fitting the model to TRACERx evolutionary data argued in favor of substantial and sustained immune pressure exerted upon a developing tumor, suggesting that clinically observed incidence is a small proportion of all cancer initiation events. This dynamical model promises to increase our quantitative understanding of many immune escape contexts, including cancer progression and intracellular pathogenic infections. SIGNIFICANCE: The early cancer-immune interaction sculpts intratumor heterogeneity through the selection of immune-evasive clones. This study provides a mathematical framework for investigating the coevolution between an immune-evasive cancer population and the adaptive immune system.
Gene Expression and Genomic Markers Identify a Subpopulation of Poor Prognosis t(4;14) Patients in Newly Diagnosed Multiple Myeloma
Authors: Maria Ortiz, Fadi Towfic, Erin Flynt, Nicholas Stong, Sneh Lata, Dharanya Sampath, Dan Rozelle, Matthew Trotter, Jill Corre, Hervé Avet-Loiseau, Anjan Thakurta
Journal: Blood (2019)
Abstract A41: Cancer-associated fibroblast (CAF) specific biomarkers in pancreatic ductal adenocarcinoma (PDAC): Transcriptomic and molecular insight
Authors: Jayarani F. Putri, Yutaro Kumagai, Yoshihiro Miyazaki, T. Oda, Yasuyuki S. Kida
Journal: Cancer Research (2019)

Abstract Pancreatic ductal adenocarcinoma (PDAC) is one of malignancy-related death with poor prognosis. The late diagnosis due to nonspecific symptoms, highly aggressive nature, intrinsic resistance to chemotherapeutic, and the lack of effective therapeutic are the main causes of poor prognosis in PDAC. This cancer type comprises up to 90% cellular component of desmoplastic stroma that holds a major role in drug resistance and malignancy. The complexity of the genome is another leading cause of molecular alteration in PDAC. Hence, the urge to find the prognosis marker for PDAC is extremely needed for the new therapeutic regimens. In this study we performed RNA-seq analysis from MSC in single and co-cultured conditions (in vitro), MSC and Xeno-MSC (in vivo), and patient-derived CAF. Read alignment and junction mapping was accomplished using HISAT2 and cufflinks respectively and followed by map reads using UCSC hg38 reference genome annotation. Data were expressed as fragments per kilobase of exon per million fragments mapped (FPKM). Three out of eight clusters on heatmap were selected based on their expression pattern across all the samples. Approximately 900 transcripts from selected clusters were classified into three major protein classes: transcription factors, kinases, and membrane proteins. Remarkably, several genes on selected clusters have been studied in CAF, giving proof of the fidelity of our data analysis. Prompted to get more specific CAF-related genes, we put more parameters such us: unexpressed in normal pancreatic, relatively low expression in pancreatic cancer, ≥2 folds increase of CAF mRNA expression to normal or pancreatic cancer, and have not studied in PDAC. We found 16 transmembrane protein-coding genes that are potentially involved in CAF remodeling. To gain a better understanding of tumor-CAF interaction from these candidate genes, immunostaining using paraffin sections from tumor-bearing mice model together with αSMA/IL6 and protein analysis was carried out. We sought the downstream pathways as well to discover novel regulatory networks and causal relationship between CAF and pancreatic cancer. Our study addresses the extent to which factor(s) can reset stromal alteration and elucidate the role of transmembrane protein during CAF reprogramming. Citation Format: Jayarani F. Putri, Yutaro Kumagai, Yoshihiro Miyazaki, T. Oda, Yasuyuki S. Kida. Cancer-associated fibroblast (CAF) specific biomarkers in pancreatic ductal adenocarcinoma (PDAC): Transcriptomic and molecular insight [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Advances in Science and Clinical Care; 2019 Sept 6-9; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2019;79(24 Suppl):Abstract nr A41.
Abstract O.54: Alteration of Left Ventricular Performance and Aortic Elastic Properties in Patients After Kawasaki Disease With Coronary Artery Aneurysm Even Without Cardiac Ischemia
Authors: Jun Oyamada, Shunsuke Shimada, Mieko Okazaki, Manatomo Toyono
Journal: Circulation (2015)

Introduction: Recent studies have suggested that patients after Kawasaki disease (KD) have altered arterial stiffness. However, there is little evidence of the relationship between arterial stiffness and left ventricular (LV) global function of KD patients without cardiac ischemic region. Hypothesis: We hypothesized that the alteration in the elastic properties of the ascending aorta may influence both LV function. Methods: Sixty one patients after KD (age, 6.1±4.0 years) were studied, comprising 15patients with CAAs and 46 patients without CAA. All the patients with CAAs showed no cardiac ischemic region confirmed by myocardial perfusion SPECT. Using pulsed Doppler echocardiography combined with Doppler tissue imaging, mitral peak velocities during early diastole (E) and LV peak myocardial velocities during early diastole (e’) and systole (s’) were measured. The ratio of E/e’ was used as an index of filling pressure of the LV. From Doppler tissue imaging, Doppler-derived index of combined systolic/diastolic myocardial performance (Tei index) was calculated as a surrogate for LV global function. We also obtained aortic stiffness index (ASI), and aortic distensibility (AD) from the measurements of the ascending aorta with noninvasive evaluation of blood pressure. Results: In all the patients, febrile periods of acute stage of KD showed significantly positive correlation with ASI, and showed significantly negative correlation with AD (both p &lt;0.05). E/e’ showed significantly positive correlations with ASI, pulse pressure and showed significantly negative correlations with s’, and AD (both p &lt;0.05). The patients with CAAs showed significantly greater pulse pressure, LV Tei index and ASI than those without CAAs (all p &lt;0.05). Conclusions: KD especially with CAAs showed subclinical abnormal LV performance that is related to altered central aortic elastic properties.
Biomarkers of response and resistance to PI3K inhibitors in estrogen receptor-positive breast cancer patients and combination therapies involving PI3K inhibitors
Authors: M. Brandão, R. Caparica, D. Eiger, E. de Azambuja
Journal: Annals of Oncology (2019)

In this review, we discuss biomarkers of response and resistance to PI3K inhibitors (PI3Ki) in estrogen receptor-positive breast cancer, both in the early and advanced settings. We analyse data regarding PIK3CA mutations, PI3K pathway activation, PTEN expression loss, Akt signalling, insulin levels, 18FFDG-PET/CT imaging, FGFR1/2 amplification, KRAS and TP53 mutations. Most of the discussed data comprise retrospective and exploratory studies, hence many results are not conclusive. Therefore, among all of these biomarkers, only PIK3CA mutations have proved to have a predictive value for treatment with the α-selective PI3Ki alpelisib (SOLAR-1 trial) and the β-sparing PI3Ki taselisib (SANDPIPER trial) in the advanced setting. Since the accuracy of current individual biomarkers is not optimal, a composite biomarker, including DNA, RNA and protein expression data, to more precisely assess the PI3K/AKT/mTOR pathway activation status, may arise as a promising approach. Finally, we describe the rational for new combination therapies involving PI3Ki and anti-HER2 agents, chemotherapy, CDK4/6 inhibitors, mTOR inhibitors or new endocrine treatments and discuss the ongoing trials in this field.
Oral Leukoplakia and Risk of Progression to Oral Cancer: A Population-Based Cohort Study
Authors: Anil K Chaturvedi, Natalia Udaltsova, Eric A Engels, Jed A Katzel, Elizabeth L Yanik, Hormuzd A Katki, Mark W Lingen, Michael J Silverberg
Journal: JNCI Journal of the National Cancer Institute (2019)

Abstract Background The optimal clinical management of oral precancer remains uncertain. We investigated the natural history of oral leukoplakia, the most common oral precancerous lesion, to estimate the relative and absolute risks of progression to cancer, the predictive accuracy of a clinician’s decision to biopsy a leukoplakia vis-à-vis progression, and histopathologic predictors of progression. Methods We conducted a retrospective cohort study (1996–2012) of patients with oral leukoplakia (n = 4886), identified using electronic medical records within Kaiser Permanente Northern California. Among patients with leukoplakia who received a biopsy (n = 1888), we conducted a case-cohort study to investigate histopathologic predictors of progression. Analyses included indirect standardization and unweighted or weighted Cox regression. Results Compared with the overall Kaiser Permanente Northern California population, oral cancer incidence was substantially elevated in oral leukoplakia patients (standardized incidence ratio = 40.8, 95% confidence interval [CI] = 34.8 to 47.6; n = 161 cancers over 22 582 person-years). Biopsied leukoplakias had a higher oral cancer risk compared with those that were not biopsied (adjusted hazard ratio = 2.38, 95% CI = 1.73 to 3.28). However, to identify a prevalent or incident oral cancer, the biopsy decision had low sensitivity (59.6%), low specificity (62.1%), and moderate positive–predictive value (5.1%). Risk of progression to oral cancer statistically significantly increased with the grade of dysplasia; 5-year competing risk-adjusted absolute risks were: leukoplakia overall = 3.3%, 95% CI = 2.7% to 3.9%; no dysplasia = 2.2%, 95% CI = 1.5% to 3.1%; mild-dysplasia = 11.9%, 95% CI = 7.1% to 18.1%; moderate-dysplasia = 8.7%, 95% CI = 3.2% to 17.9%; and severe dysplasia = 32.2%, 95% CI = 8.1%–60.0%. Yet 39.6% of cancers arose from biopsied leukoplakias without dysplasia. Conclusions The modest accuracy of the decision to biopsy a leukoplakia vis-à-vis presence or eventual development of oral cancer highlights the need for routine biopsy of all leukoplakias regardless of visual or clinical impression. Leukoplakia patients, particularly those with dysplasia, need to be closely monitored for signs of early cancer.
The effect of ageing on the resolution of inflammation
Authors: Wezi Sendama
Journal: Ageing Research Reviews (2019)

Ageing is associated with the development of a low-level, systemic, chronic inflammation known as "inflammaging". This chronic inflammatory state can contribute to diseases of ageing such as sarcopenia and frailty. The presence of inflammaging suggests a failure of the cell clearance mechanisms that ordinarily aid in the resolution of inflammation after pathogen infiltration or tissue injury. This review aims to explore what is known of how the processes involved in the resolution of inflammation might become defective with age.
Private Equity Investment in Behavioral Health Treatment Centers
Authors: Benjamin Brown, Eloise O’Donnell, Lawrence P. Casalino
Journal: JAMA Psychiatry (2019)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Psychiatry HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Psychiatry journal
The effect of different treatment modalities on survival in elderly patients with locally advanced non-small cell lung cancer
Authors: A. Sakin, S. Sahin, M.M. atci, A. Sakin, N. Yasar, C. Geredeli, F. Aksaray, S. Cihan
Journal: Pulmonology (2019)

The aim of this study is to investigate the effect of treatment modalities on survival among unoperat ed and locally-advanced non-small cell lung cancer (NSCLC) patients aged 70 years and older, representing real-life data. From 2005 through 2017, medical records of 2259 patients with lung cancer from Okmeydani Training and Research Hospital-Istanbul/Turkey were reviewed retrospectively. Patients with locally advanced NSCLC ≥ 70 years of age who did not undergo surgery for lung cancer were reviewed. In total, 130 patients were eligible for the final analysis. Patients were stratified into four groups as: chemotherapy (CT), concurrent chemoradiotherapy (cCRT), sequential chemoradiotherapy (sCRT), and radiotherapy (RT) only. Of the 130 patients included in the analysis; CT, cCRT, sCRT, and RT only were applied to 25(19.2%), 30(23.1%), 31(23.8%), and 44(33.8%) patients, retrospectively. Twelve (9.2%) patients were female. Median age was 72 years (range, 70–88). Sixty (46.2%) patients had stage IIIA disease and 70(53.8%) patients had stage IIIB disease. Median progression-free survival(mPFS) in patients treated with CT, cCRT, sCRT, and RT were 8.0, 15, 10, and 9.0 months, respectively(p = 0.07). Corresponding median overall survival (mOS) were 10, 33, 20, and 15 months (p = 0.04). In multivariate analysis, stage IIIB disease [hazard ratio (HR), 2.8], ECOG-PS 2(HR, 2.10), and ECOG-PS 3–4(HR, 5.13) were found to be the negative factors affecting survival, while cCRT (HR, 0.45) and sCRT (HR, 0.50) were the independent factors associated with better survival. This study showed that the use of combined treatment modality was associated with better survival in elderly patients with locally advanced NSCLC, with the greatest survival observed in patients treated with cCRT. We therefore suggest that cCRT, when feasible, should be strongly considered in locally advanced NSCLC patients 70 years and over.