tbuckley/cabot-search huggingface dataset:
Patterns of chemotherapy (CT) use in a U.S.-wide cohort of patients (pts) with metastatic gastric cancer (MGC).
Authors: Thomas Adam Abrams, Gary Meyer, Lisa M. Hess, Yajun Zhu, Sui Zhang, Astra M. Liepa, Jeffrey A. Meyerhardt, Deborah Schrag, Peter C. Enzinger, Charles S. Fuchs
Journal: Journal of Clinical Oncology (2018)

112 Background: MGC is associated with poor survival outcomes. Despite multiple therapeutic options, there is no clearly defined standard-of-care (SOC) CT algorithm. Assessing MGC treatment trends of CT utilization is of critical import. Few population studies have examined the frequencies and temporal trends of MGC CT regimens. This study was designed to address this knowledge deficit. Methods: Eligible pts had biopsy-proven MGC diagnoses and received CT between Jan 2005 and Dec 2016 at academic, private or community hospital practices using IntrinsiQ, a US-wide CT order entry system that captures pt, provider and CT data. Temporal trends were analyzed in the context of SOC changes during the study’s observational period. Results: Among 4,333 MGC pts, median age was 64; 74% were male. In 1 st -line CT, 26% received fluoropyrimidine [FU] + oxaliplatin (FOLFOX), 15% received epirubicin + platinum + FU [ECF/EOX], 15% received docetaxel (D) + cis/carboplatin (C) + FU [DCF], 13% received C + paclitaxel, 10% received C + FU [CF], 5% received taxane [TAX] monotherapy. FOLFOX use has increased steadily to 41% in 2015 while DCF use dropped from 29% in 2007 to below 10% by 2015. Biologics were used in 11% of all 1 st -line starts and 24% of all 2 nd -line starts. Trastuzumab represented 72% of 1 st line biologic use (with or without CT backbones), overall use increased from 0% in 2008 to 16% of 1 st line in 2015 In 2 nd line, no single treatment regimen was used in more than 7% of patients in 2005, but the use of newer treatments has increased over time: trastuzumab use increased from 0% in 2008 to a peak of 22% in 2016 and ramucirumab use increased from 0% in 2012 to its peak in 2015 of 26%. Conclusions: This population-based study provides insight into US MGC treatment patterns and recent trends with the availability of novel agents. [Table: see text]
Optimal surrogate endpoint of survival for gastric cancer patients undergoing neoadjuvant chemotherapy.
Authors: Takaomi Hagi, Yukinori Kurokawa, Yasuhiro Miyazaki, Tsuyoshi Takahashi, Koji Tanaka, Tomoki Makino, Makoto Yamasaki, Kiyokazu Nakajima, Masaki Mori, Yuichiro Doki
Journal: Journal of Clinical Oncology (2018)

141 Background: Surrogate endpoint of survival for gastric cancer patients undergoing neoadjuvant chemotherapy (NAC) has not been established yet. To determine the most optimal surrogate endpoint, we compared the validity of outcomes according to the endoscopic or histological response criteria and other histological factors in gastric cancer patients who underwent NAC. Methods: The target population in this study was 77 gastric cancer patients who underwent NAC followed by curative gastrectomy between January 2010 and December 2016. In histological response criteria, if necrosis or disappearance of the tumor was present in more than 2/3 of the primary lesion, the case was diagnosed as a histological responder. Hazard ratio (HR) for RFS in responders according to each factor was estimated, and survival curves were compared between responders and non-responders using log-rank test. Results: The number of patients in each regimen was as follows: docetaxel/cisplatin/S-1, 40; docetaxel/oxaliplatin/S-1, 16; cisplatin/S-1, 15; S-1/oxaliplatin, 4; docetaxel/S-1, 2. The endoscopic and histological response rates were 73% (56/77) and 16% (12/77), respectively. The proportions of patients with ypT0-1 and ypN0 were 17% (13/77) and 23% (18/77), respectively. HRs were 0.761 (log-rank p = 0.43) in the endoscopic response criteria, 0.879 (log-rank p = 0.77) in the histological response criteria, 0.703 (log-rank p = 0.46) in ypT0-1, and 0.121 (log-rank p = 0.001) in ypN0, respectively. Three-year RFS rates in ypN status were ypN0/1/2/3 = 93%/48%/43%/14%. Conclusions: Pathological ypN status was the most optimal surrogate endpoint of RFS for gastric cancer patients undergoing NAC. Patients with ypN0 would be expected for long relapse-free survival.
Influence of cardiovascular (CV) comorbidities on the selection of hormone deprivation therapy (HDT) in the treatment of metastatic prostate cancer (mPCa).
Authors: Jan Lehmann, Markus Flesch, Sebastian Vosgerau, Michael Gedamke
Journal: Journal of Clinical Oncology (2018)

TPS392 Background: HDT with LHRH agonists (LHRH) or LHRH-antagonists (degarelix, D) is the standard of care in advanced mPCa. A correlation between leuprolide/goserelin and an increased risk of CV events as compared to D has been shown in a pooled analysis of 6 RCTs in 2013, therefore we aimed to evaluate potential changes in selection of HDTs in Germany. Methods: To evaluate changes in selection of HDT, we compared data from a retrospective (2013 - 2014) and prospective (FPFV in 09/2014) study on CV disease and selection of ADT that were collected from the same pool of study sites. In the ProComD, a two-arm, prospective non-interventional study (NIS), potential comorbidity dependent differences in the selection of D vs LHRH treatment were investigated. Preceding the ProComD we conducted the retrospective randomised analysis to determine baseline CV disease frequencies in ADT treated patients. Results: In the retrospective part, frequencies of CV-disease were skewed towards LHRH compared to D (59.8 vs. 49.0 %). In the prospective ProComD data on patients with a minimum follow-up period of one year (visit 5, n = 238, D = 149, LHRH = 89) up to two years (visit 7, n = 84, D = 51, LHRH = 33) were documented. Baseline criteria were generally similar except for disease T-stage (p = 0.0038). The average age of patients was 74.4 years. Stage distribution: D vs. LHRH, pT2 26.8/28.1 %, pT3 23.5/38.2 %, pT4 5.4/1.1 %, unkown. 44.3/32.6 %, cNX 51.0/44.9 %, cN0 32.2/42.7 %, cN+ 16.8/12.4 %, cMX 26.8/23.3 %, cM0 34.9/47.2 %, cM1 38.2/29.2 %. Comorbidities were reported in 184 patients (77.3 %). Most frequent comorb. were vascular and metabolic diseases (hypertension and diabetes mellitus; (n = 139/57; 75.5/31.0 %) followed by cardiac diseases (n = 74; 40.2 %). More patients with peripheral arterial disease (PAD) (17.9 vs 3.0 %) and cardiac diseases (41.9 vs 37.3 %) received D as compared to LHRH. Conclusions: Our results indicate that selection of ADT seems to have shifted following new data on CV-risk differences between leuprolide/goserelin and degarelix. Patients with cardiac and PAD comorbidities have received more often degarelix treatment as compared to LHRH treatment.
COMPARISON OF EFFECTIVENESS, SAFETY, AND THE NET CLINICAL OUTCOME BETWEEN DIFFERENT DIRECT ORAL ANTICOAGULANTS IN 162,707 NON-VALVULAR ATRIAL FIBRILLATION PATIENTS TREATED IN US CLINICAL PRACTICE
Authors: Steve Deitelzweig, Allison Keshishian, Xiaoyan Li, Melissa Hamilton, Cristina Masseria, Kiran Gupta, Xuemei Luo, Jack Mardekian, Keith Friend, Anagha Nadkarni, Xianying Pan, Onur Baser, Gregory Y.H. Lip
Journal: Journal of the American College of Cardiology (2018)
The effect of adjuvant chemotherapy in patients without local nodal metastases following neoadjuvant chemoradiotherapy and esophagectomy for locally advanced esophageal cancer.
Authors: Christopher Duane Nevala-Plagemann, Samual Francis, Courtney Christine Cavalieri, Shane Lloyd, Ignacio Garrido-Laguna
Journal: Journal of Clinical Oncology (2018)

111 Background: Neoadjuvant chemoradiation therapy (CRT) followed by esophagectomy is the current standard of care for patients with locally advanced esophageal cancer. The potential benefit of additional postoperative chemotherapy is still under investigation. In this study, we utilized the National Cancer Database to assess the effect of adjuvant chemotherapy in patients who were found to have node negative disease (pN0) following surgery. Methods: Patients with locally advanced esophageal cancer who received neoadjuvant CRT followed by esophagectomy from 2004 to 2014 were retrospectively identified using the National Cancer Database. Patients who were postoperatively staged as pN0 were then separated based on whether or not they received adjuvant chemotherapy. Using Kaplan-Meier estimation and a multivariate cox regression analysis, the overall survival of those who received adjuvant therapy was then compared to those who received neoadjuvant CRT alone. Results: 3,159 patients with locally advanced esophageal cancer underwent neoadjuvant CRT and were found to be pN0 following surgery. 119 of these patients received postoperative chemotherapy. The 1, 5, and 8-year overall survival in those receiving adjuvant therapy was 95.9%, 49.9%, and 47.7% compared to 85.8%, 44.6%, and 33.0% in those receiving neoadjuvant CRT alone, respectively (p = 0.019). Based on multivariate analysis, receiving adjuvant chemotherapy was independently associated with increased overall survival (p = 0.011; HR 0.658; 95% CI, 0.476 to 0.908). Conclusions: Adjuvant chemotherapy may improve survival in patients with locally advance esophageal cancer who have no evidence of local nodal metastases following surgery. Additional clinical trials are needed to further confirm which patients may benefit from adjuvant therapy and to determine the optimal postoperative therapeutic regimen.
Patients perspectives on adjuvant therapy in renal cell carcinoma.
Authors: Dena Battle, Eric Jonasch, Hans J. Hammers, Ithaar Derweesh, Daniel J. George, Axel Bex, Borje Ljungberg, Michael D. Staehler
Journal: Journal of Clinical Oncology (2018)

644 Background: At this point in time, there is no approved adjuvant therapy (AT) for renal cell carcinoma (RCC) . The discussion on AT is driven by the pending maturation of overall survival (OS) data for sunitinib in patients at high risk for recurrence. Data on patient´s perception of AT are missing. The purpose of this study was to assess the value of specific adjuvant outcome measures to patients with RCC. Methods: We conducted a survey-monkey survey in n=450 patients with RCC on the perspective on AT. The survey was promoted via kccure.org, facebook and smartpatients.com. Question were not related to specific results of adjuvant trials but asking only about the attitude towards AT as an intervention. Results: Median age was 55.6 years (17-82 years) and 56.4% of the patients were female. 73.6% of the patients underwent nephrectomy as primary therapy, while 22.0% had a partial nephrectomy. 76.4% of the patients had clear cell RCC. 39.1% had recurrence of RCC and 35.3% were receiving systemic therapy for metastatic RCC. 63.1% of patients would use AT if it prolonged OS, followed by 60.1% if AT prolonged disease free survival (DFS), 42.7% if AT demonstrated acceptable toxicity, and 36.7% if guaranteed insurance coverage and efficacy. Experience with systemic therapy was correlated with a wish for a prolonged OS (p&lt;0.0001). Patients with a history of systemic therapy rely on the physician’s recommendation in contrast to patients without a history of systemic therapy (p&lt;0.0001). The recurrence status, age, initial stage and type of surgery had no influence on the patients´ decisions. 28.0% of the patients would need more information prior to their decision, 24.2% would only take AT with a proven OS benefit, 16.9% would use AT if there was moderate toxicity, 13.6% would use AT independent of the associated toxicity level, 8.2% would only use AT without any toxicity. 3.8% of the patients would not use AT. Patients on systemic therapy had a significant higher acceptance of toxicity (p&lt;0.0001). Conclusions: Patients are willing to use AT to achieve OS and DFS benefits, and place lower emphasis on toxicity. These data provide an important perspective on patient perceptions of AT, and emphasize the need for patient education on harms and benefits of AT.
Differences in survival among non-urothelial bladder cancers: Analyses of SEER 1988-2008.
Authors: Jeanny B. Aragon-Ching, Donald Henson
Journal: Journal of Clinical Oncology (2018)

425 Background: Non-urothelial cancers of the urinary bladder are rare, and typically &lt; 5% incidence. They are generally considered more aggressive without clear guidelines for treatment. Methods: Incident cases of non-urothelial bladder cancers that included squamous cell carcinoma, adenocarcinoma, small cell carcinoma and sarcomas were identified in the SEER (Surveillance, Epidemiology, and End Results) Database. Demographic information, pathologic characteristics and 5-year disease-specific survival were calculated and compared using multivariate Cox regression and Kaplan-Meier curves. Results: A total of 235,537 incident cases of bladder carcinomas were identified in the years 1998 – 2008, of which 3096 cases were squamous cell carcinoma, 1175 were neuroendocrine carcinoma where small cell carcinomas made up the majority with 859 patients, 671 was comprised of adenocarcinomas, representing 0.28%, and sarcomas were 88 cases, making up 0.03% of all cases combined. The majority of patients were White (90%) although more African-Americans (15%) were seen with adenocarcinoma. The table shows the number of cases and 5-year survival according to stage. Median survival was greatest for adenocarcinoma at 179 months with a 5–year survival rate of 58%, followed by sarcomas with a median survival of 23 months, with a 5-year survival rate of 47%, followed by squamous cell carcinomas with a median survival time of 15 months and a 5-yr survival rate of 37% and the least favorable survival was for small cell carcinoma, 17 months median time, with a 5-yr survival rate of 31%. Conclusions: Non-urothelial cancers have a uniformly less favorable survival compared to urothelial cancers, highlighting the need for improved therapeutic strategies in these cohorts of patients. [Table: see text]
Doctors will need an understanding of genomics, says HEE
Authors: Abi Rimmer
Journal: BMJ (2014)

Doctors will, in the future, need an understanding of genomics, Health Education England (HEE) has said.

HEE’s strategic framework for 2014-29 looks ahead at changes that are likely to influence the health and social care workforce.1 It said that one trend for the future would be the ability to use patients’ genetic profile to develop …
A third of GPs in Wales are considering changing career, says BMA
Authors: Abi Rimmer
Journal: BMJ (2016)

Almost a third of GPs in Wales are considering changing their career, and half would not recommend a career in general practice, a survey conducted by the BMA has found.

An online survey of 244 GPs in Wales, carried out in August 2016, found that 27% of respondents were considering a career change and 14% were considering moving abroad.1

The survey also found that …
Transcriptomic heterogeneity of androgen receptor activity in primary prostate cancer: Identification and characterization of a low AR-active subclass.
Authors: Daniel Eidelberg Spratt, Mohammed Alshalalfa, Adam Weiner, Nick Fishbane, Rohit Mehra, Rayford Walter, Nicholas Erho, Adam Dicker, Stephen J. Freedland, Jeffrey Karnes, Andrew Glass, Sheila Weinmann, Elai Davicioni, Ashley Ross, Robert Benjamin Den, Felix Y Feng, Edward M. Schaeffer
Journal: Journal of Clinical Oncology (2018)

2 Background: Significant genomic diversity exists in the androgen receptor ( AR) and its activity (AR-A) in mCRPC. In localized prostate cancer, the biologic, prognostic, and therapeutic clinical implications of AR-A heterogeneity have yet to be interrogated Methods: Genome-wide expression profiles of FFPE RP or biopsy tumor samples were evaluated from a prospective registry cohort (n = 5,239, NCT02609269) and six retrospective institutional cohorts (n = 1,170). AR-A was calculated based on expression of 9 targets of AR.. Results: Utilizing 6,409 localized prostate adenocarcinomas with full transcriptomic data, we found there was marked inter-individual transcriptomic diversity in AR and AR-A expression, and weak correlation between them (r = 0.08 to 0.36 based on cohort), in contrast to mCRPC that has a strong correlation between AR and AR-A expression (r = 0.76). Additionally, serum PSA had no correlation to intratumoral AR-A (r = 0.06). Unsupervised hierarchical clustering identified a distinct subclass of low AR-A prostate tumors, which had increased markers of immunogenicity (decreased T-regs and MDSCs, and increased CD3 effector T-cells), increased neuroendocrine marker expression ( NCAM1, ENO2, and SCG2), and decreased DNA repair pathway expression (all p &lt; 0.001). Clinically, low AR-A tumors had more rapid development of metastatic disease in three independent cohorts, were more prone to develop resistance to hormonal therapy and develop CRPC, and were found at an increased frequency in African-American men. Interrogating in vitro drug sensitivity analyses utilizing the NCI-60 panel, low AR-A tumors appear more sensitive to platinum chemotherapy and PARP inhibition, and less sensitive to hormone therapy and taxanes. Conclusions: The diversity in AR-signaling in localized prostate cancer represents important biological heterogeneity that is both prognostic and predictive of treatment response. These findings are provocative in that low AR-A tumors may be more susceptible to immunotherapy, PARP inhibition, platinum chemotherapy, and/or radiotherapy. Patients with low AR-A tumors warrant dedicated biomarker enhanced clinical trials.
Disadvantaged pupils less likely to apply or be accepted for career in medicine
Authors: Caroline White
Journal: BMJ (2016)

Pupils from disadvantaged backgrounds in the United Kingdom are less likely than other pupils to apply to study medicine and are less likely to be accepted when they do, researchers have found.

A study of applications to UK medical schools between 2009 and 2012 shows that between a fifth and a third, depending on UK country, of all medical school applicants live in the most affluent areas.1

Researchers from the University of Dundee reviewed applications to 22 UK medical schools between 2009 and 2012 from 32 964 UK residents aged 19 and under, using United Kingdom clinical aptitude test (UKCAT) data. They assessed applicants’ home postcode, type of school, and parents’ jobs and whether they were …
IMPLEMENTING MACHINE LEARNING ALGORITHM TO IDENTIFY PATIENTS AT RISK OF DEVELOPING ELEVATED LEFT SIDED CARDIAC FILLING PRESSURES
Authors: Kinjan Patel, Marton Tokodi, Partho P. Sengupta, Ashok Runkana, Sirish Shrestha, George Sokos, Marco Caccamo, James Mills
Journal: Journal of the American College of Cardiology (2018)
A multifaceted coating on titanium dictates osteoimmunomodulation and osteo/angio-genesis towards ameliorative osseointegration
Authors: Long Bai, Zhibin Du, Jingjing Du, Wei Yao, Jiaming Zhang, Zeming Weng, Si Liu, Ya Zhao, Yanlian Liu, Xiangyu Zhang, Xiaobo Huang, Xiaohong Yao, Ross Crawford, Ruiqiang Hang, Di Huang, Bin Tang, Yin Xiao
Journal: Biomaterials (2018)
INTERLEUKIN-1 BLOCKADE REDUCES NT-PROBNP SERUM LEVELS IN PATIENTS WITH STABLE HEART FAILURE WITH PRESERVED EJECTION FRACTION
Authors: Cory Trankle, Justin Canada, Salvatore Carbone, Leo Buckley, Marco Giuseppe Del Buono, Sanah Christopher, Dinesh Kadariya, Chau Vo, Nayef Abouzaki, Ross Arena, Benjamin Van Tassell, Antonio Abbate
Journal: Journal of the American College of Cardiology (2018)
Vascular targeted photodynamic therapy for pancreatic ductal adenocarcinoma: A pre-clinical success
Authors: R. Goldschmidt, N. Koudinova, K. Sasson, D. Preise, L. Agemy, V. Mohan, F. Bochner, I. Sagi, M. Neeman, A. Scherz
Journal: Annals of Oncology (2018)
CARDIAC SARCOIDOSIS PRESENTING WITH ACUTE MYOCARDIAL INFARCTION AND VENTRICULAR FIBRILLATION
Authors: Amrita Mukhopadhyay, Amanda Klinger, Kamil Faridi, Anuradha Godishala, Duane Pinto, Peter Zimetbaum, Loryn Feinberg
Journal: Journal of the American College of Cardiology (2018)
Abstract P1-15-04: Outcome of small (≤1 cm), node-negative breast cancer
Authors: M Muzaffar, P Namireddy, R Naqash, J Wong, N Vohra
Journal: Cancer Research (2018)

Abstract Background: Screening mammogram has resulted in increased diagnosis of very small breast cancers, especially less than 1 cm node negative. These small tumors have excellent prognosis with cancer-specific survival rates as high as 90% to 95%. This study evaluates outcome in different subtypes of very early breast cancer in a national population database. Method: Patients with stage I breast cancer, tumor ≤ 1cm with negative nodes (T1aN0 (&amp;lt;0.5cm), T1bN0 (≥ 0.5cm to ≤ 1cm) diagnosed between 2006 and 2011 were identified in the SEER database. We excluded patients with missing biomarker information. Treatment outcome and prognostic factors for disease-specific survival (DSS) and overall survival (OS) were evaluated. Results: We identified 70,543 cases and included 54,796 patients with stage T1aN0M0 and T1bN0M0 in the final analysis. The mean age was 62.09 yrs. (CI 95% 62.2-61.99), 84% are white, 7% black and 7% others.89% had ER positive tumor, 11% ER negative and 3% had Her 2 positive tumors.71% of patients had T1b (≤ 1cm). The 5-year disease specific survival (DSS) and overall survival (OS) for patients with stage T1aN0, T1bN0 was 98.7% and 93.7%, respectively. Estrogen receptor (ER) positive tumors were associated with improved 5-yr DSS 99% vs. 96% in ER negative (p&amp;lt;0.0001) and OS in ER positive 94% vs. 92%( p&amp;lt;0.0001). Among white patients 5-yr DSS was 98.8% and OS was 93.7% while 5yr-DSS was 94%, OS 91.5% among black vs. 5-yr DSS 99% and OS 96.3% in others (Asian or Pacific Islanders, AI), (p&amp;lt;0.0001). Tumor subtype was not associated with significant difference in outcome but T1a tumor was associated with OS 94.5% vs. 93.4% with T1b tumors (p&amp;lt;0.0001) On cox model analysis factors which correlated with prolonged DSS and OS are race (p&amp;lt;0.0001), older age (p&amp;lt;0.0001), ER positivity (p&amp;lt;0.0001) and tumor less than 5mm (p=0.0006). Conclusions: Very early breast cancer is associated with excellent outcome but has some heterogeneity. Nonwhite/Non Black race was associated with better survival compared to white and black patients. ER positive tumors, and older age were also associated with better outcome. This data while reassuring also brings into question the overtreatment of this disease subset. One of the limitations of this dataset is lack of details of systemic therapy administered. Conventional prognostic factors are not sufficient to risk stratify very early breast cancer and molecular profiling may help identify patients who will need adjuvant treatment. Citation Format: Muzaffar M, Namireddy P, Naqash R, Wong J, Vohra N. Outcome of small (≤1 cm), node-negative breast cancer [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P1-15-04.
Pevonedistat, a first-in-class NEDD8-activating enzyme inhibitor, combined with azacitidine in patients with AML
Authors: Ronan T. Swords, Steven Coutre, Michael B. Maris, Joshua F. Zeidner, James M. Foran, Jose Cruz, Harry P. Erba, Jesus G. Berdeja, Wayne Tam, Saran Vardhanabhuti, Iwona Pawlikowska-Dobler, Hélène M. Faessel, Ajeeta B. Dash, Farhad Sedarati, Bruce J. Dezube, Douglas V. Faller, Michael R. Savona
Journal: Blood (2018)
CLINICAL USEFULNESS OF PRECISE DAPT SCORE TO PREDICT CARDIOVASCULAR OUTCOMES IN PATIENTS WITH ATRIAL FIBRILLATION UNDERGOING PERCUTANEOUS CORONARY INTERVENTION WITH STENTING
Authors: Yusuke Iwasaki, Takahisa Yamada, Takashi Morita, Yoshio Furukawa, Shunsuke Tamaki, Masato Kawasaki, Atsushi Kikuchi, Masahiro Seo, Iyo Ikeda, Eiji Fukuhara, Tsutomu Kawai, Jun Nakamura, Abe Makoto, Masatake Fukunami
Journal: Journal of the American College of Cardiology (2018)