tbuckley/cabot-search huggingface dataset:
Work status after treatment for breast cancer: A controlled, prospective, longitudinal study of an ethnically diverse cohort.
Authors: Victoria Susana Blinder, Sujata Patil, Carolyn E. Eberle, Gabriel Jung, Lewis J. Kampel, Caroline Hwang, Ting Bao, Mark E. Robson, Manmeet Malik, Francesca Gany
Journal: Journal of Clinical Oncology (2018)

6583 Background: Cancer-associated job loss is associated with financial strain, debt, and bankruptcy. The identification of workers at highest risk is critical to the development of interventions. Methods: We surveyed employed women aged 18-64 with stage I-III breast cancer who spoke Chinese, English, Korean, or Spanish. Baseline surveys were during adjuvant tx; follow-up surveys were 4 months post-tx. Our primary outcome was post-tx work status (working full- or part-time vs. any other work status). We used healthy peers to control for disparities in non-cancer unemployment and multivariable analyses to identify predictors of work status in pts. Results: Our sample (n = 440) was 23% black, 18% Chinese, 8% Korean, 30% Latina, and 21% non-Latina white (NLW). 31% had household income < 200% of the Federal Poverty Level (FPL), 26% were under-/uninsured, 33% worked in service/manufacturing, 84% had chemotx. Overall, 72% were working post-tx. The proportion of working pts vs. controls was 0.78 for blacks, 0.71 for Chinese, 0.73 for Korean, 0.77 for Latinas, and 0.96 for NLW. Among pts, independent predictors of not working were older age, Chinese ethnicity, low income, service/manufacturing job, lack of employer accommodations, and stage III cancer (Table 1). Conclusions: Breast cancer exerts a disparate negative impact on employment in minority women, which persists after controlling for disparities in background unemployment. Chinese pts were observed to have triple the odds of job loss (vs. whites). Interventions are needed to promote job retention in minority and low-income women, particularly those who lack work accommodations or are in high-risk jobs. Odds of not working 4 months post-treatment. OR 95% CI Age* 1.07 1.04 1.11 Race/ethnicity Black† 2.41 0.95 6.08 Chinese† 3.04 1.16 8.00 Korean† 3.40 0.97 11.8 Latina† 2.31 0.93 5.74 Job type Service/manufacturing† 2.62 1.35 5.09 Sales/administrative† 1.35 0.63 2.92 Household income < 200% FPL 3.12 1.65 5.88 Employer was accommodating 0.33 0.20 0.57 Cancer stage II† 1.47 0.82 2.61 III† 2.65 1.21 5.81 *OR for 1-yr increase in age†Reference values: white race, manager/professional, stage INot significant: employer size, self-employed
GEINO 1402: A phase Ib dose-escalation study followed by an extension phase to evaluate safety and efficacy of crizotonib in combination with temozolomide (TMZ) and radiotherapy (RT) in patients with newly diagnosed glioblastoma (GB): Results of the dose-escalation phase.
Authors: Maria Martinez Garcia, Miguel J. Gil Gil, Estela Pineda Losada, Guillermo Velasco, Francesc Alameda, Alvaro Taus, Jaume Capellades, Ana Márquez-Martín, Beatriz Sarmiento, Carlos Mesia Barroso, Jordi Bruna Escuer, Eugenia Verger, Aurelio Hernandez-Lain, Manuel Guzman, Juan Manuel Sepúlveda
Journal: Journal of Clinical Oncology (2018)

2054 Background: Crizotinib is an ALK, ROS-1 and c-MET inhibitor with an interesting rationale to be tested in NDGB due to the role of MET signaling in gliomagenesis and stem cell maintenance and capability of midkine, a recently discovered ALK ligand, to promote resistance of glioma cells to anticancer therapies such as RT and TMZ. Primary objective of this trial was to determine maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of crizotinib in combination with RT and TMZ. Methods: Eligible patients received crizotinib with standard RT and TMZ and afterwards continued crizotinib daily with sequential adjuvant TMZ. Additional treatment with crizotinib beyond 6 TMZ cycles was allowed at the discretion of physician. Crizotinib MTD was determined using a standard “3+3” dose escalation design. Dose-limiting toxicities were observed during the first 12 weeks of therapy. Results: 12 patients (median age: 53,5 (33-60 y)) were enrolled in 3 crizotinib cohorts (200 mg/QD, 250 mg/QD and 200 mg/BID). Most common related adverse events (all grades) were: nausea (66.7%), asthenia (58.3%), transaminitis (50%), neutropenia (50%), constipation (41.7%) and diarrhea (41.7%). Thirteen drug-related AEs ≥ G3 were reported, 5 neutropenia, 2 thrombopenia, 2 transaminitis, 1 asthenia, 1 lymphopenia, 1 constipation and 1 hypophosphatemia. 3 DLTs were observed (transaminitis G3, neutropenia G4 and constipation G3): 0/3 in cohort 1 (200 mg/QD); 1/6 in cohort 2 (250 mg/QD) and 2/3 in cohort 3 (200 mg/BID). Median follow-up of 18.3 m(months) (5.4-34.5) and 8 events, median PFS was 16.8 m (95% IC: 8,2-25,3). Three patients died and median OS has not been reached. OS at 6m was 92%, at 12m 80% and 60% at 24m. Conclusions: On the basis of observed DLTs, the safety profile and MTDs, a dose regimen of crizotinib 250 mg/QD in association to standard RT and TMZ has been selected for further investigation in the expansion phase. At this point, efficacy results, especially PFS, seem very encouraging. Funding for this study was provided by Pfizer, Inc, New York, USA Clinical trial information: NCT02270034.
Influence of acute graft-versus-host disease (aGVHD) during allogeneic hematopoietic stem cell transplantation (HSCT) engraftment admission on hospital length of stay (LOS), charges, and costs.
Authors: Jingbo Yu, Shreekant Parasuraman, Anshul Shah, Siva Narayanan
Journal: Journal of Clinical Oncology (2017)

e18544 Background: aGVHD is a common complication of allogeneic HSCT and a significant cause of transplant-related morbidity and mortality. Limited data exist on healthcare resource use and costs of aGVHD during HSCT engraftment admission. This study estimated LOS, charges, and costs of aGVHD during HSCT engraftment admission in the US. Methods: Inpatient discharges between 2009-2013 using the Nationwide In-patient Sample (NIS) database were analyzed. NIS is a representative (20% stratified) sample of all discharges from US community hospitals included in the Healthcare Cost and Utilization Project (HCUP). Discharges for allogeneic HSCT engraftment admissions with aGVHD (ICD-9 279.51) were compared with those without GVHD. Costs were calculated from hospital charges using a standard HCUP Charge-to-Cost Ratio. LOS, charges, and costs were compared using Wilcoxon rank sum test. Correlation between LOS and charges or costs was calculated using Pearsons coefficient. Results: 729 discharges with aGVHD and 5958 discharges without GVHD were analyzed. Demographic characteristics were similar for both groups except age: female (40% vs 42%), Caucasian (67% vs 68%), private insurance (60% vs 63%); mean age was 39 and 45 years for patients with and without aGVHD respectively (p &lt; 0.001). In-hospital mortality rate was 16% for patients with aGVHD vs 5% without GVHD (p &lt; 0.001). Despite younger age of the aGVHD group, mean unadjusted LOS was significantly longer, and mean unadjusted charges and costs were significantly higher with aGVHD vs without GVHD (54.2 days vs 29.8 days, $690,244 vs $366,213, $218,425 vs $122,387, respectively). Charges and costs were directly proportional to LOS (r = 0.711, p &lt; 0.001). Conclusions: Overall, occurrence of aGVHD during HSCT engraftment admission resulted in almost doubling of LOS, charges, and costs. Mitigating aGVHD may reduce LOS and subsequent inpatient resource use for HSCT. [Table: see text]
Clonal evolution of uveal melanoma metastases.
Authors: Jessica Yang, Heather M. Geiger, Junfei Zhao, James C. Chen, Kanika Arora, Minita Shah, Armida Fabius, Magali Cavatore, Cyriac Kandoth, Taha Merghoub, Jacob Lowell Glass, Grazia Ambrosini, Kimberly Mayumi Komatsubara, Gary K. Schwartz, Raul Rabadan, Nicolas Robine, Alexander Noor Shoushtari, Richard D. Carvajal
Journal: Journal of Clinical Oncology (2018)

e21534 Background: Uveal melanoma (UM) is characterized by a long latency period between the time of initial diagnosis and the development of metastatic disease, with a limited understanding of genomic and transcriptomic changes that occur with tumor evolution and metastasis. Methods: We performed rapid autopsy on a single patient with widely metastatic UM. Whole-exome sequencing (WES), RNA sequencing (RNA-Seq), and DNA methylation profiling were performed on 11 tumor samples from 7 anatomic sites (3 liver; 2 nodal; 2 soft tissue; 1 each of lung, bone, perisplenic, and perioptic). Phylogeny was inferred from DNA single-nucleotide variants and copy number aberrations. Differentially expressed (DE) genes between the phylogenetic clusters were identified by DESeq2 and analyzed for enrichment of biological themes using DAVID 6.8. Results: Phylogeny derived from WES data mapped tumor evolution from “early” (n = 5) to “late” (n = 6) lesions, which was consistent with clustering based on methylation profiling. Phylogeny based on RNA-Seq analysis did not demonstrate similar evolutionary grouping likely due to variable sample purity. While monosomy 3, amplification of 8q, and loss of 6q were observed in all 11 lesions, additional cytogenetic changes including gains in 6p and loss of 8p occurred in “late” lesions. 32 recurrent mutations (seen in > 1 site) including BAP1 and GNA11 were detected in all lesions, whereas “late” lesions contained additional mutations in ATM, WWOX, INCA1, and CDH26. Several low-impact mutations located on chromosomes 9 and 11 found in “early” lesions were no longer present in “late” lesions, corresponding to chromosomal loss. A total of 1359 DE genes (FDR 1%) were identified between the two groups, with enrichment for terms related to inflammatory response, defense response, and catabolic metabolism. Conclusions: We identify two distinct genetic and epigenetic subsets of UM metastases which reflect an evolutionary pattern of development. Characterization of functional differences between subsets is being pursued to elucidate mechanisms of UM tumor dissemination.
TCT-609 Choosing Between Transcatheter, Surgical, and Medical Management in Cancer Patients With Severe Aortic Stenosis
Authors: Dinu Balanescu, Teodora Donisan, Michael Schechter, Tariq Dayah, Daryl Sudasena, Biswajit Kar, Igor Gregoric, Dana Giza, James Stone, Danielle Stone, David Boone, Juan Lopez-Mattei, Peter Kim, Syed Yusuf, Mehmet Cilingiroglu, Konstantinos Toutouzas, Fernando Boccalandro, Richard Smalling, Konstantinos Marmagkiolis, Cezar Iliescu
Journal: Journal of the American College of Cardiology (2018)
TCT-118 The impact of bifurcation stenting techniques on the clinical events: the stratified analysis of 2,510 bifurcated lesions according to MADS classification in the Global LEADERS trial
Authors: Norihiro Kogame, Taku Asano, Ply Chichareon, Rodrigo Modolo, Kuniaki Takahashi, Chun-Chin Chang, Yuki Katagiri, None luc janssens, Pedro A. Lemos, Carlos Macaya, Pawel Jasionowicz, Neville Kukreja, Mohamed Abdellaoui, Yoshinobu Onuma, Pascal Vranckx, Marco Valgimigli, Stephan Windecker, Patrick Serruys
Journal: Journal of the American College of Cardiology (2018)
Defending evidence informed policy making from ideological attack
Authors: Chris Bonell, Rebecca Meiksin, Nicholas Mays, Mark Petticrew, Martin McKee
Journal: BMJ (2018)

The world faces a new era of greater hostility to experts and evidence, argue <b>Chris Bonell and colleagues</b>. The antidote, they say, is to remind the public how evidence based policy making evolved—and of its advantages and limitations
Predicting risk for non-adherence to oral 6-mercaptopurine (6MP) in children with acute lymphoblastic leukemia (ALL) results from the Children's Oncology Group AALL03N1 study.
Authors: Smita Bhatia, Yanjun Chen, Wendy Landier, Lindsey Hageman, Yutaka Yasui, Mary V. Relling, F. Lennie Wong
Journal: Journal of Clinical Oncology (2016)

10531 Background: Poor adherence to oral 6MP (measured electronically [MEMS]) increases relapse risk in children with ALL (JAMA Oncol 2015); non-adherers are significantly more likely to over-report 6MP intake (Blood 2015). However, use of MEMS to assess adherence is logistically impractical in the clinic, creating a need for alternative options to identify non-adherers and institute interventions in real-time. Methods: We have developed a prediction model for 6MP non-adherence (MEMS-based adherence rate < 90%) using receiver operating characteristic (ROC) analyses in 407 children with ALL receiving oral 6MP for maintenance (mean age at study 7.7±4.4y; 67.8% males; 35% Caucasians, 34% Hispanics, 16% African Americans, 15% Asians). The cohort was divided into a training set (n = 257) and a test set (n = 150) using stratified random sampling (stratified by race/ethnicity, gender, age at study and 6MP non-adherence). We used logistic regression with backward variable elimination, guided by change in area under ROC (AUC), to create a prediction model in the training set, retaining a parsimonious set of demographic/ clinical variables. We validated this model using the test set. Finally, we created a binary risk classifier to identify individuals at high risk (predicted probability ≥ 0.3) for non-adherence. Results: Predictors retained in the final training set model included race/ethnicity, age at study, household income, parental education, family structure, ALL blast cytogenetics, absolute neutrophil count, 6MP dose-intensity and same vs. varied time of daily 6MP intake. AUC of the final training set model was 0.79 (95%CI, 0.73-0.85), indicating good discrimination. Validation in the test set yielded an AUC of 0.75 (95%CI, 0.64-0.86). The risk classifier had an accuracy of 85% and performed well (sensitivity: 68.4%, specificity: 77.2%, positive and negative predictive values: 54.5% and 86%, respectively). Conclusions: We derived and validated a risk prediction model with readily available clinical and demographic data that could be useful for identifying children at high risk for 6MP non-adherence during maintenance therapy for ALL.
Breast Cancer in nonagenarians: Single institutional experience in development country.
Authors: Daniele Neves, Juliana Souza, Sabrina Chagas
Journal: Journal of Clinical Oncology (2018)

e22032 Background: Elderly patients are often excluded from clinical trials and their management is controversial, especially nonagenarians. Treatment goals in elderly patients should be symptoms relief and enhance quality of life. Methods: We identified all patients with 90 years or more treated with breast cancer between 2013 and 2017 in our oncology clinic, ONCOCLINICA. We retrospectively reviewed their records. Geriatric assessment was not reported for our patients. Results: Of 104 nonagenarians patients evaluated at ONCOCLINICA, we identified 30 breast cancer patients, all women. Nineteen patients (63%) received palliative care, but only 3 patients (10%) had documented metastatic disease. Twenty-seven (90%) patients received hormone therapy, 16 (59%) as palliative treatment. Of 11 patients in adjuvant scenario, 4 patients (36%) were submitted to surgery after 90 years old and 6 patients (54%) between 85 and 90 years old. Four patients (13%) received palliative chemotherapy, one had manageable toxicity and 1 had to stop the treatment. Of three patients who received Trastuzumab, 2 had cardiotoxicity. Patient’s benefit was reported in 28 pts (93.3%). 71.2% and 53.4% were still using hormone therapy in 5y and 10y. Median time receiving chemotherapy was 2.36 months. Conclusions: Nonagenarians patients are frequently undertreated. Fit elderly should be properly treated with surgery and hormonal therapy when indicated. The majority of patients had have HR-positive tumors at diagnosis, and received hormonal therapy (adjuvant or palliative) with a very high clinical benefit reported. Median time receiving chemotherapy was low. Geriatric assessment should be used to detect fit patients to benefit with treatment.
Acid-triggered echogenic nanoparticles for contrast-enhanced ultrasound imaging and therapy of acute liver failure
Authors: Yebin Go, Hanui Lee, Lipjeong Jeong, Semi Sun, Eunmi Hong, Eunkyeong Jung, Changgon Ko, Joungyoun Noh, Sanghun Park, Moungyoung Lee, Chulgyu Song, Dongwon Lee
Journal: Biomaterials (2018)
Impact of electronic decision support and targeted educational intervention to increase adherence with ASCO Choosing Wisely breast cancer staging guideline.
Authors: Dedeepya Konuthula, Maureen Canavan, Scott F. Huntington, Michael Strait, Teresita Vega, Kim Framski, Kerin B. Adelson
Journal: Journal of Clinical Oncology (2018)

e18826 Background: ASCO Choosing Wisely recommends against ordering PET, CT, or bone scan as part of the initial staging workup for patients with early stage breast cancer. We implemented a two-step quality improvement intervention to increase adherence with this guideline. Methods: During a 4-month educational run-in period (from 07/2015 to 10/2015), we visited each of our medical oncology care centers and academic breast oncology team to discuss the ASCO Choosing Wisely breast cancer imaging recommendations. On 1/1/16, we turned on an electronic decision support reminder (best practice advisory or BPA) in our electronic health record (EHR). To assess impact, we compared imaging ordered for stage I/II breast cancer patients who did not receive neoadjuvant therapy and were treated in the Smilow Cancer Hospital/Yale Cancer Center health system during a pre-intervention (diagnosed 7/1/14-6/30/15) and post-intervention period (diagnosed 1/1/16-12/31/16). Cancer stage was obtained through the Yale Tumor Registry, and imaging utilization was measured for each patient during the 90-day period following diagnostic biopsy. Results: We identified 748 women in the pre- and 764 women in the post-intervention period with stage I/II breast cancer. After the intervention, the average number of scans ordered per patient among patients for whom imaging was ordered decreased from 1.92 (SD 0.97) to 1.70 (SD 0.71), p = 0.049. The average number of CTs ordered for patients for whom at least one CT was ordered decreased from 1.24 (SD 0.61) to 1.05 (0.22), p = 0.005. The percentage of patients for whom at least one advanced imaging test was ordered decreased from 17.2% to 13.7%. This decrease approached but did not achieve statistical significance, p = 0.060. Conclusions: We implemented a health system wide intervention using provider education and an electronic decision support tool to reduce advanced imaging during evaluation of early stage breast cancer. The intervention was acceptable to providers, and the post-intervention period had a trend towards less imaging utilization. Future work will aim to identify and address the main barriers to adopting Choosing Wisely guidelines.
Abstract 18015: “Apical Sparing” Longitudinal Strain Pattern With Cardiac MRI Correlates With LGE Distribution in Cardiac Amyloidosis
Authors: Lynne K Williams, Julian Forero, Anna Calleja, Diego Delgado, Andrew M Crean, Harry Rakowski, Paaladinesh Thavendiranathan
Journal: Circulation (2015)

Introduction: Regional variations in longitudinal strain (LS) have been demonstrated on echocardiography in patients with cardiac amyloidosis (CA). Hypothesis: We aimed to describe regional patterns in LS using feature-tracking software applied to cardiac MRI images (CMR) in CA, hypertrophic cardiomyopathy (HCM), and Anderson-Fabry’s disease (AFD) and to relate these patterns to late gadolinium enhancement (LGE). Methods: Patients with CA (n=51) were compared to left ventricular mass index balanced patients with HCM (n=20) and AFD (n=20). LS analysis was performed using Velocity Vector Imaging (VVI) on steady state free precession cine images (4, 3, and 2-chamber views). Values were recorded for each of 18 myocardial segments. A regional LS ratio representing “apical sparing” was calculated as the ratio of the sum of the apical segmental LS values divided by the sum of the basal and mid-segmental LS values. LGE was quantified for the basal, mid, and apical myocardial segments using a threshold of 5SD above remote myocardium. A regional LGE ratio was calculated similar to the “apical sparing” ratio. Results: The regional LS ratio was significantly higher in patients with CA (1.05±0.49) than in patients with AFD (0.79±0.24; p=0.025) and HCM (0.84±0.32; p=0.025). In patients with CA there was a regional difference in LGE burden, with lower LGE in the apex (31.9±20%) compared to the basal (52.7±22%) and mid-segments (37.9±19%). The regional LGE ratio was significantly lower in patients with CA (0.34±0.14) than in patients with AFD (0.54±0.64; p&lt;0.001) and HCM (0.73±0.41; p&lt;0.001). Conclusions: Cardiac amyloidosis is characterized by regional variations in LS from base to apex. “Apical sparing” in LS is seen with CMR images and can be an additional tool to differentiate CA from other causes of LVH. The concomitant presence of a base to apex gradient in LGE burden by CMR suggests that the regional strain gradient may be associated with burden of amyloid deposition.
Abstract 13316: Statin Therapy Prevents the Development of Contrast-induced Nephropathy in Patients Undergoing Percutaneous Coronary Intervention for Acute Coronary Syndromes
Authors: Theodoros Zografos, Gerasimos Siasos, Evangelos Oikonomou, Konstantinos Mourouzis, Stathis Dimitropoulos, Miriam Anastasiou, Alexis Antonopoulos, Manolis Vavuranakis, Sotiris Tsalamandris, Marina Zaromitidou, Vicky Tsigkou, Dimitris Tousoulis
Journal: Circulation (2015)

Introduction: Contrast-induced nephropathy (CIN) is often encountered following percutaneous coronary intervention (PCI) in patients with acute coronary syndromes (ACS) and is associated with high in- hospital morbidity and mortality. Statins may prevent the development of CIN, however their efficacy in patients with ACS has not been evaluated. Hypothesis: We conducted a meta-analysis of randomized controlled trials (RCTs) to assess statin efficacy in the prevention of CIN in patients undergoing PCI for ACS. Methods: PubMed, EMBASE, MEDLINE and the Cochrane Central Register were searched for RCTs from inception to September 2014 to compare high-dose statins (rosuvastatin 40mg/day, atorvastatin 80mg/day or simvastatin 80mg/day) with low-dose (atorvastatin 10mg/day, simvastatin 10mg/day) o placebo treatment in patients with ACS, undergoing PCI. Study-specific odds ratios (ORs) were calculated, and between-study heterogeneity was assessed using the I2 statistic. We used a random effects model meta-analysis to pool the OR. Results: Seven RCTs, including 5174 patients were included in the analysis. CIN occurred in 126 (4.9 patients in the high dose statin group and in 232 (8.9%) patients in the low dose or placebo group (OR: 0.50, 95% confidence interval: 0.38- 0.66, p&lt;0.001). The observed heterogeneity between the included studies was low (I2=19%, p=0.28). Conclusions: High-dose statin therapy is effective at preventing the development of CIN in the high-risk population of patients undergoing PCI for ACS.