tbuckley/cabot-search huggingface dataset:
Clinicopathological prognostic and predictive factors of malignant peripheral nerve sheath tumors (MPNST) survival and treatment efficacy.
Authors: Pawel Sobczuk, Pawel Teterycz, Marcin Zdzienicki, Marcin Napierala, Tadeusz Morysinski, Tomasz Switaj, Piotr Rutkowski, Anna Malgorzata Czarnecka
Journal: Journal of Clinical Oncology (2019)

e22537 Background: MPNST accounts for about 5% of soft tissue sarcomas. It is known to have high metastatic potential and poor prognosis, but reported long-term outcomes vary widely across published series. Our study aimed to determine factors affecting clinical outcome in a large cohort of patients (pts) with MPNSTs treated at reference sarcoma center. Methods: 289 consecutive pts (144 woman and 145 man) referred, diagnosed and treated between 03/1998 and 04/2018 were analyzed. Kaplan-Meier estimator and the log-rank test were used in survival analysis and multivariate Cox proportional hazards model was used to confirm the correlation. Results: Mean age at diagnosis was 50y (15-86). 39 (13.5%) pts were NF1 positive, 12 were primary diagnosed with metastatic disease. After median follow-up of 66.5 months (m) (95% confidence interval, CI 58.1 – 85.2) 151 pts continue treatment or follow-up. Median OS was 55.7m (39.3 - 148.9) in the whole group while 5y survival rate was 48.8% (CI: 42.8-55.7%). 37/167 pts with radical resection in reference center developed local recurrence, and 75/92 pts operated first in regional hospitals. Median DFS was 29.7m (CI: 16.1-58.3) in case of treatment in reference center and 4.1m (CI: 2.4-9.2) in case of regional hospital (p &lt; 0.001).72 pts developed metastatic disease and were treated with chemotherapy. Median PFS on 1st line was 5.6m (CI: 3.3 - 8.1), There were no statistically significant differences in survival rates nor in response rates between doxorubicin- and ifosfamid-based regiments. Tumor size at diagnosis (HR:2.33, CI: 1.50-3.62), high grade (HR:3.31, CI:2.14-5.12) and R0 resection (HR:0.47, CI:0.30-0.72) were the strongest independent predictors of DFS and OS. (neo)adjuvant radiotherapy did not influenced LRFS in case of R0 resection but improved LRFS when complete resection was not feasible (HR: 0.22 CI: 0.08-0.58 p = 0.002). Conclusions: MPSNT is a highly aggressive tumor with poor prognosis. High quality surgery remains the mainstay of management for these patients, but multimodal treatment should be considered in majority of cases in MDT units. There is unmet need for new therapies in advanced/metastatic cases.
Integrating concept maps into a medical student oncology curriculum.
Authors: Sam Brondfield, Allen Seol, Katherine Hyland, Arianne Teherani, Gerald Hsu
Journal: Journal of Clinical Oncology (2019)

10506 Background: Proliferating knowledge domains have prompted medical schools to reconsider how best to facilitate multidisciplinary learning. Concept maps promote knowledge retention and integration; however, the feasibility and utility of integrating concept maps into a medical student oncology curriculum as a learning and assessment tool have not previously been described. Methods: In 2015-2016, all 152 second-year University of California, San Francisco (UCSF) medical students in a hematology/oncology course produced a concept map about a single cancer type over four weeks. Two of three graders independently scored each map using a standard rubric. We used linear regression to calculate the Pearson correlation coefficient between graders and between concept map scores and preclinical examination scores, USMLE Step 1 scores, and clerkship grades. We sent course evaluations to 50 randomly selected students (as is typical in the UCSF curriculum) and performed an inductive content analysis of open-ended comments about concept mapping. Results: We graded all 152 concept maps. Inter-rater reliability was excellent ( r = 0.95 or greater between the graders). Concept map scores did not correlate with preclinical or clinical performance. 43 of 50 students (86%) rated the helpfulness of concept mapping on a 5-point agreement scale (1=strongly disagree; 5=strongly agree). The median rating was 3, and the mean (SD) rating was 2.81 (1.44). 22 of 50 (44%) students submitted comments about concept mapping. Some (9 of 22) found concept mapping useful, expressing themes such as “learning the material better” and delving into the “details.” Others (7 of 22) did not, expressing themes such as preferring “other study methods” and feeling that concept mapping was “busy work” or “stressful.” Conclusions: Integrating concept maps into a medical student oncology curriculum was feasible, and we demonstrated reliability evidence as an assessment tool. Future studies should explore whether integrating concept maps earlier in medical school, producing multiple concept maps over time with training and feedback, or developing concept maps collaboratively may increase utility as a learning and assessment tool.
Cost-utility of adjuvant trastuzumab in Her-2/neu positive breast cancer: A Canadian perspective
Authors: C. Skedgel, D. Rayson, T. Younis
Journal: Journal of Clinical Oncology (2007)

6574 Background: Recent RCTs have demonstrated a significant disease-free and overall survival advantage with adjuvant trastuzumab (aTZ) compared to chemotherapy alone in women with Her2/neu positive breast cancer. However, as aTZ is also associated with considerable costs and an increased risk of cardiotoxicity, an economic evaluation was undertaken to estimate the cost-utility (CU) of aTZ in terms of cost per quality-adjusted life year (QALY) gained relative to chemotherapy alone. Methods: A Markov model was developed to calculate the incremental costs and outcomes of 12 months of aTZ following chemotherapy in a hypothetical cohort of 1,000 women with Her2/neu positive breast cancer over a lifetime horizon. The model consisted of four broad health states: 1) disease-free, 2) local recurrence, 3) distant recurrence and 4) death. Each survival state was stratified as experienced with or without cardiotoxicity. The baseline rate of recurrence, the hazard ratio (HR) of recurrence with aTZ and the rate of adverse cardiac events were taken from recent RCTs. Age-sex specific background mortality, based on Statistics Canada life tables, was also incorporated. The cost of aTZ was based on our previous cost study (Drucker et al, ASCO 2006). Costs of local and distant cancer recurrence were derived from the literature, with an adjustment for the cost of palliative TZ (Potvin et al, ASCO 2005). Utility weights were taken from the literature. The model took a direct payer perspective, with costs reported in 2006 Canadian dollars (CDN$). Costs and QALYs were both discounted by 3% annually. The primary analysis assumed 5 years of benefit with aTZ therapy and an HR=1.0 over the remainder of the horizon. Results: Per 1,000 treated patients, aTZ was associated with a lifetime gain of 1,267 QALYs and an incremental cost of CDN$38.8 million. Lifetime CU was CDN$30,630 per QALY gained. aTZ met a CDN$50,000/QALY threshold at year 17. CU results were particularly sensitive to changes in the analysis horizon and assumptions regarding the long-term HR of aTZ. Conclusions: The lifetime CU of aTZ appears reasonable. However, further clinical follow-up is required to clarify the long-term outcomes of aTZ and confirm these CU estimates. No significant financial relationships to disclose.
A Novel HER3-Targeting Antibody–Drug Conjugate, U3-1402, Exhibits Potent Therapeutic Efficacy through the Delivery of Cytotoxic Payload by Efficient Internalization
Authors: Yuuri Hashimoto, Kumiko Koyama, Yasuki Kamai, Kenji Hirotani, Yusuke Ogitani, Akiko Zembutsu, Manabu Abe, Yuki Kaneda, Naoyuki Maeda, Yoshinobu Shiose, Takuma Iguchi, Tomomichi Ishizaka, Tsuyoshi Karibe, Ichiro Hayakawa, Koji Morita, Takashi Nakada, Taisei Nomura, Kenichi Wakita, Takashi Kagari, Yuki Abe, Masato Murakami, Suguru Ueno, Toshinori Agatsuma
Journal: Clinical Cancer Research (2019)

Abstract Purpose: HER3 is a compelling target for cancer treatment; however, no HER3-targeted therapy is currently clinically available. Here, we produced U3-1402, an anti-HER3 antibody–drug conjugate with a topoisomerase I inhibitor exatecan derivative (DXd), and systematically investigated its targeted drug delivery potential and antitumor activity in preclinical models. Experimental Design: In vitro pharmacologic activities and the mechanisms of action of U3-1402 were assessed in several human cancer cell lines. Antitumor activity of U3-1402 was evaluated in xenograft mouse models, including patient-derived xenograft (PDX) models. Safety assessments were also conducted in rats and monkeys. Results: U3-1402 showed HER3-specific binding followed by highly efficient cancer cell internalization. Subsequently, U3-1402 was translocated to the lysosome and released its payload DXd. While U3-1402 was able to inhibit HER3-activated signaling similar to its naked antibody patritumab, the cytotoxic activity of U3-1402 in HER3-expressing cells was predominantly mediated by released DXd through DNA damage and apoptosis induction. In xenograft mouse models, U3-1402 exhibited dose-dependent and HER3-dependent antitumor activity. Furthermore, U3-1402 exerted potent antitumor activity against PDX tumors with HER3 expression. Acceptable toxicity was noted in both rats and monkeys. Conclusions: U3-1402 demonstrated promising antitumor activity against HER3-expressing tumors with tolerable safety profiles. The activity of U3-1402 was driven by HER3-mediated payload delivery via high internalization into tumor cells.
Integrative analysis of prognostic biomarkers derived from multiomics panels helps discrimination of chronic kidney disease trajectories in people with type 2 diabetes
Authors: Michael Kammer, Andreas Heinzel, Jill A. Willency, Kevin L. Duffin, Gert Mayer, Kai Simons, Mathias J. Gerl, Christian Klose, Georg Heinze, Roman Reindl-Schwaighofer, Karin Hu, Paul Perco, Susanne Eder, Laszlo Rosivall, Patrick B. Mark, Wenjun Ju, Matthias Kretzler, Mark I. McCarthy, Hiddo L. Heerspink, Andrzej Wiecek, Maria F. Gomez, Rainer Oberbauer
Journal: Kidney International (2019)
Psychiatry in General Practice
Journal: JAMA (1952)

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
Relationship among ETV1 genetic polymorphisms, PFS, and microRNA in gastrointestinal stromal tumors.
Authors: Haibo Qiu, Wei Zhuang, Xiaojun Zhou, Xueding Wang, Zhiwei Zhou, Min Huang
Journal: Journal of Clinical Oncology (2019)

e22513 Background: In order to evaluate the pharmacokinetic and pharmacogenomic determinants for prognosis of gastrointestinal stromal tumor (GIST). It is necessary to explore a biological predictors to predict and optimal therapeutic strategy. But there were few studied conducted to explore the germline mutation and its mechanisms. Methods: A total of 75 GIST patients treated with Imatinib were enrolled. 35 SNPs (single nucleotide polymorphisms) in KIT/ PDGFRA/ PDGFRB/ ETV1/ FLT1/ MAPK1 et. al were detected using Agena Massarray matrix-assisted laser desorption / ionization-time of flight (MALDI-TOF) platform. COX regression analyses were performed to evaluate the key factors of PFS. The luciferase reporter system of rs3735343 wild type and mutation were established. The GIST-T1 cell line was used to evaluate the biology effect of rs3735343. This study was approved by the ethical committee of Sun Yat-Sen University Cancer Center. Results: Several factors influence the PFS, including KIT somatic mutation, tumor size and germline mutation ABCC4 rs4148551, ETV1 rs3735343, FLT1 rs3751397, KIT rs3822214. And COX regression showed that rs3735343 and tumor size are associated with PFS (P = 0.009 and 0.032, Risk Ratio = 8.995 and 4.173). And we found that rs3735343 mutation type can regulate ETV1 3’UTR and protein expression level through miR-4311 in vitro. Conclusions: The primary determinants of PFS in this somatic and germline mutation model suggested new biomarkers and different mechanisms involved in prognosis. This is the first report showed that ETV1 genetic polymorphisms may influence the prognosis through miRNA-4311. Targeting ETV1, miRNA-4311 or their relative pathway might be a new therapy strategy.
P048 Predictive value of the different capillaroscopic patterns in early raynaud phenomenon
Authors: J Uceda, R Hernandez, JL Marenco
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Career situation of first and presenting author</h3> Assistant. <h3>Introduction</h3> The Raynaud phenomenon (RP) affects 3%–5% of the population. Most RPs are primary. The risk of the onset of autoimmune disease associated with RP (ADRP) is arround 12%, and the diagnosis is usually made within 2 years of its onset. Capillaroscopy is a innocuous and inexpensive technique that is very useful in the study of RP. <h3>Objectives</h3> The primary goal was to evaluate the capillaroscopic findings and theirs different patterns in patients with RF as the only symptom and establish their relationship between the subsequent development of ADRF. We have evaluated the relationship between the presence of the antinuclear antibodies (ANA) and the association with ADRF. <h3>Methods</h3> We conducted an observational, descriptive, cross-sectional study of 98 patients with RP as the main manifestation. Periungual capillaroscopy was performed from the 3rd to the 5th finger of both hands. Sociodemographic variables, and results of ANA were described. To assess the validity of capillaroscopy as a diagnostic test, we determined the sensitivity, specificity, and positive and negative predictive value (PPV, NPV). <h3>Results</h3> 73.5% were women. The median time of evolution of the RP was 2.5 years. 76% were ANA negative. The evaluation of the predictive capacity of capillaroscopy for the development of EARP yields the following Results. sensibility: 83,3% (62,6–95,2), specificity: 78% (66,8–86,9), PPV 34,1% (24,5–45,3), PNV 97,1% (93,3–98,8). The capillaroscopic findings were: 62% no alterations, 21.4% no specific capyllaroscopy changes, 14.3% 'scleroderma' type capillaroscopic pattern, and 2% characteristic pattern of mixed connective tissue disease (MCDT). None of the patients who did not present alterations developed autoimmune disease. Of the 21 patients who presented nonspecific changes, 5 developed limited systemic sclerosis (SSc), 3 MCTD, and 1 diffuse SSc. Of the 14 patients who presented 'scleroderma' type capillaroscopic pattern, 5 develop limited SSc, 3 diffuse SSc, 2 MCTD and 1 did not present autoimmune disease. Of the two patients with characteristic alterations of MCDT, 1 developed this disease. When analyzing the relationship between the presence of ANA and the association with ADRF we found that it was independent (p: 0.002) of the result of capillaroscopy, being the risk of developing the disease in a patient with positive ANA 8.5 times higher than in an ANA negative patient. <h3>Conclusions</h3> Capillaroscopy in patients with RP has a high PNV, which allows us to estimated, with high reliability, the association of this phenomenon with autoimmune disease in patients with normal capillaroscopic patterns. <h3>Disclosure of Interest</h3> None declared.
Secondary genomic alterations in Ewing sarcoma.
Authors: An Uche, Warren Allen Chow, Sherri Z. Millis
Journal: Journal of Clinical Oncology (2019)

11024 Background: Ewing sarcoma (ES) is the second most common bone cancer in children and young adults. The prognosis of recurrent or metastatic ES is poor, with a 5-year overall survival &lt;30%. ES is characterized by translocations involving ETS transcription factors ( EWS– FLI and EWS– ERG translocations are the most common). Secondary somatic alterations in ES are infrequently described. Aberrations in fibroblast growth factor receptor 4 ( FGFR4), a receptor tyrosine kinase protein that plays an important role in cellular processes,have been shown to contribute to carcinogenesis in different types of cancer.More recently, the FGFR4-Gly388Arg (G388R) single nucleotide polymorphism (SNP), with the substitution of arginine instead of glycine in the transmembrane domain of the receptor, is found to significantly increase the risk of breast and prostate cancer. Mouse embryonic fibroblasts derived from knock-in strain of homologous FGFR4-G388R mice display a transformed phenotype, and TGFα-induced mammary carcinogenesis in this strain is significantly enhanced. The association between FGFR4 G338R SNP and ES has not been evaluated. We evaluated the frequency of FGFR4 G338R and whether comprehensive genomic profiling (CGP) might uncover additional, potentially targetable, genomic alterations (GA) in ES. Methods: Tissue from 253 patients with ES was assayed by hybrid-capture based CGP (FoundationOne Heme, next generation sequencing (NGS), analysis which includes both DNA sequencing of 406 genes and RNA sequencing of 265 genes), performed in the course of clinical care to evaluate GAs, including base substitutions, indels, amplifications, copy number alterations and gene fusions/rearrangements. Tumor mutational burden (TMB) was calculated from a minimum of 1.4 Mb sequenced DNA and reported as mutations/Mb. Microsatellite instability (MSI) status was determined by a novel algorithm analyzing 114 specific loci. Results: CGP identified several GAs in ES: TP53 (n= 50, 20%), MLL3 (n=15, 6%), MSH3 (n=14, 5%), ARID1A (n=11, 4%) and FGFR4 (n=3, 1%). FGFR4 G338R SNP was found in almost half of the patients (n=123, 49%). Conclusions: Secondary GAs in TP53, MLL3, MSH3, ARID1A and FGFR4 were found in more than one third of patients with ES (n=93, 37%). FGFR4 G388R SNP was detected in nearly half of patients, and may represent an alternative method of sarcomagenesis. Overall, the frequency of these GAs is significantly greater than previously reported. These GAs may inform the potential for targeted therapies.
Improved outcome and selection bias in primary breast surgery for patients with metastatic breast cancer.
Authors: Lejla Hadzikadic Gusic, John Falcone, Kandace P. McGuire, Atilla Soran, Emilia Diego, Christine R. Thomas, Priscilla F. McAuliffe, Marguerite Bonaventura, Ronald Johnson, Gretchen M. Ahrendt
Journal: Journal of Clinical Oncology (2013)

1098 Background: Retrospective studies showing improved survival in patients with metastatic breast cancer (MBC) who undergo surgical treatment of the primary tumor have been criticized for bias in favor of younger, healthier women with lower disease burden. We attempted to identify these biases in our population. Methods: Our institutional cancer registry was queried for patients with MBC from 1994-2010. Demographics, clinical, radiologic and pathologic staging, as well as treatments and outcomes were recorded. Surgical and non-surgical groups were compared for differences in overall survival (OS) and clinicopathologic variables, including comorbidities, using uni- and multivariate analysis. Results: Ninety-one patients with metastatic disease identified within 3 months of initial diagnosis were eligible. 53% (48 pts) had primary breast surgery and 47% (43 pts) did not undergo surgery. Patients in the surgery group were younger on univariate analysis (mean age 53 vs. 62, p&lt;0.01). Neither BMI (mean 30 vs. 29 kg/m²) nor Charlson comorbidity score (mean 6 in both groups) were significantly different, p=NS. Bone metastases were more common in the surgery group (48 vs. 26%) and multiple metastases in the non-surgery group (35 vs. 17%), p&lt;0.05. Patients in the non-surgery group had ≥ 1 visceral metastasis when compared to the surgery group (62 vs. 35%), p&lt;0.05. Higher OS was demonstrated in the surgery group both with Kaplan Meier curves (p&lt;0.05) and univariate analysis (mean 3 vs. 2 yrs, 95% CI 2.6, 3.7), p&lt;0.05. Survival was higher in the surgery group (p&lt;0.01), at 1 year, but this difference did not persist at 3 and 5 years. On multivariate analysis, only difference in age remained significant (p&lt;0.01). Conclusions: Our study supports existing data that women with MBC who have surgical treatment of the primary tumor have an improved survivorship. However, it also suggests a bias towards increased use of surgery in patients who are younger with smaller burden of metastatic disease. We did not find a bias in favor of healthier patients. Further study to determine the mechanism and magnitude of benefit of primary tumor extirpation is still needed.
Natriuretic Peptide Response and Outcomes in Chronic Heart Failure With Reduced Ejection Fraction
Authors: James L. Januzzi, Tariq Ahmad, Hillary Mulder, Adrian Coles, Kevin J. Anstrom, Kirkwood F. Adams, Justin A. Ezekowitz, Mona Fiuzat, Nancy Houston-Miller, Daniel B. Mark, Ileana L. Piña, Gayle Passmore, David J. Whellan, Lawton S. Cooper, Eric S. Leifer, Patrice Desvigne-Nickens, G. Michael Felker, Christopher M. O'Connor
Journal: Journal of the American College of Cardiology (2019)
Johnson and Johnson ordered to pay $572m in landmark opioid liability case
Authors: Owen Dyer
Journal: BMJ (2019)

An Oklahoma judge has ruled that Johnson and Johnson helped to fuel the state’s opioid crisis, in the first case where a US court has found an opioid maker liable in America’s addiction epidemic.

Thad Balkman, Cleveland County district judge, ordered the company to pay Oklahoma $572m (£467m; €516m) to fund treatment programmes, law enforcement, and other costs associated with the epidemic.

“The opioid crisis has ravaged the state of Oklahoma and must be abated immediately,” Balkman said, reading his decision. “As a matter of law, I find that defendants’ actions caused harm.”

The ruling comes as Purdue Pharma, the maker of OxyContin and a company frequently accused of promoting excessive opioid use by physicians, is mulling a global settlement of over 2000 consolidated lawsuits that could see its owners, the Sackler family, relinquish control of the company.

Purdue was originally one of …
A Rare Mutation of β1-Adrenergic Receptor Affects Sleep/Wake Behaviors
Authors: Guangsen Shi, Lijuan Xing, David Wu, Bula J. Bhattacharyya, Christopher R. Jones, Thomas McMahon, S.Y. Christin Chong, Jason A. Chen, Giovanni Coppola, Daniel Geschwind, Andrew Krystal, Louis J. Ptáček, Ying-Hui Fu
Journal: Neuron (2019)