tbuckley/cabot-search huggingface dataset:
RAP80 mRNA expression impact on sporadic high-grade serous ovarian cancer survival.
Authors: Margarita Romeo, Niki Karachaliou, Imane Chaib, Cristina Queralt, Itziar de Aguirre, Maria Carmen Gomez, Maria Sanchez-Ronco, Joaquim Radua, Jose Luis Ramirez, Rafael Rosell
Journal: Journal of Clinical Oncology (2015)

e16571 Background: Genome instability is a major feature of high-grade serous ovarian carcinomas (HGSOC), partially driven by defects in homologous recombination (HR). BRCA1 promoter hypermethylation is the leading cause of HR defects in sporadic HGSOC (5-31%). The prognostic impact of low BRCA1 expression in sporadic HGSOC after first-line chemotherapy remains unclear. RAP80 and PIAS1 modulate HR through the RAP80/Abraxas/BRCA1 complex and, RAP80 deficiency is associated to excessive HR that also generates genome instability. Methods: In order to examine the potential effect of RAP80 and PIAS1 on outcome in patients with sporadic HGSOC, we retrospectively analyzed mRNA expression of BRCA1, RAP80 and PIAS1 in tumor samples from 35 surgical patients who received standard adjuvant or first-line chemotherapy. The effects of the expression of these gens on progression-free survival (PFS) and overall survival (OS) were examined . Results: Median OS for all patients was 62.79 months. Carboplatin and paclitaxel combination was used in 88.57% of cases. In the univariate analyses of clinical factors, advanced FIGO stage, residual disease at surgery > 1 cm and absence of systematic staging and/or debulking surgeryemerged as prognostic markers of poorer outcome. Gene expression analysis was successful in 71.4% of cases for BRCA1, 91.4% of cases for RAP80 and 100% of cases for PIAS1. The association between each gene expression level and outcome was assessed by means of Cox regression analyses adjusted for the three meaningful clinical prognostic factors. We found that high RAP80 expression levels were associated with longer PFS (HR = 0.690, 95%CI 0.526-0.903, p= 0.007) and OS (HR = 0.751, 95%CI 0.566-0.997, p= 0.047). No significant association was observed between outcome and high PIAS expression or BRCA1 expression. Conclusions: Our study is the first to highlight a prognostic role for RAP80 in HGSOC, indicating that low RAP80 expression may confer a poorer survival in sporadic HGSOC patients treated with the standard first-line chemotherapy. These findings can help to understand HR alterations in sporadic HGSOC.
Associations of cell cycle genetic variants with aggressive prostate cancer in the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial.
Authors: Melissa Huynh, Chirag Vyas, Kathryn L. Penney, Adam S. Kibel
Journal: Journal of Clinical Oncology (2019)

175 Background: The need to differentiate patients at risk for developing aggressive prostate cancer (CaP) from those at risk for less aggressive disease has led to efforts to identify genetic markers to predict disease course and personalize treatment. A study with participants from Johns Hopkins Medical Institutions (JHMI) and Washington University (WU) found single nucleotide polymorphisms (SNPs) in cell cycle genes were associated with risk of aggressive CaP. We sought to replicate those results in the European-American population of the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. Methods: We focused on variants associated with aggressive CaP in the JHMI and WU cohorts, which included 13 SNPs in 12 genes ( CCNC, CCND3, CCNG1, CCNT2, CDK2, CDK6, MDM2, SKP2, TERF2, WEE1, YWHAB, YWHAH). Variants were genotyped using the Pyrosequencing assay. Patients were classified into high risk (Gleason≥8, pT3b, N+, M+), low risk (Gleason≤7, ≤pT3a, N0, M0) or non-cancer control groups based on clinicopathologic characteristics. Logistic regression analysis was used to compare genotype frequencies of each variant between groups using the dominant model. Results: There were 108 aggressive and 1080 non-aggressive CaP patients, and 1155 controls . CDK6 ( rs8) was associated with increased risk of any CaP (OR 1.2, 95% CI 1.02-1.42; p = 0.032) and high risk disease (OR 1.63, 95% CI 1.09-2.42; p = 0.017) vs. controls. In contrast, the JHMI and WU cohort found CDK6 variants to be protective against aggressive CaP. CCNG1 ( rs11541970) approached significance (p = 0.052) between high risk and control groups, and CCNC conferred a protective effect consistent with the prior study, but did not reach significance (p = 0.101). No associations with any cell cycle gene variants were detected when comparing high and low risk patients. Conclusions: Our study did not replicate the results from the JHMI and WU cohorts. CDK6 predicted an increased risk of developing any CaP and high risk CaP. However, directionality was opposite to the prior study, indicating that this variant is unlikely to be a true predictor of increased risk of or protection from aggressive CaP.
Timing of docetaxel chemotherapy and impact on outcomes in metastatic castrate-resistant prostate cancer (MCRPC).
Authors: Alastair Thomson, Adam Pollard, Frances May Mark
Journal: Journal of Clinical Oncology (2019)

298 Background: Docetaxel use has led to a significant prolongation in overall survival (OS) in metastatic prostate cancer after castrate resistance, with a more substantial OS gain when used in combination with initial androgen deprivation therapy (ADT). There is however limited information on outcomes in patients who initially do not receive chemotherapy, perhaps through patient choice or impaired performance status, who become suitable for docetaxel, comparing earlier with later docetaxel treatment. Methods: We retrospectively reviewed patients’ electronic clinical and prescribing records diagnosed with MCRPC and treated with docetaxel from 01/01/2006 to 24/11/2016 in a single centre in the UK. Data was reviewed for number of individual treatments received pre and post chemotherapy, including initial ADT, enzalutamide, abiraterone, docetaxel, cabazitaxel, mitoxantrone, radium 223, single agent steroids and diethylstilboestrol. Prostate specific antigen (PSA) response, number of cycles and dosing of docetaxel and OS were also reviewed. Results: 168 consecutive patients with MCRPC receiving docetaxel were reviewed. Median Gleason grade across the three groups was 8. 48 patients (29%) received docetaxel after 1 or 2 previous treatments, 105 (63%) after 3 or 4 previous treatments and 15 (9%) after 5 or 6. PSA response rates were superior in the earlier treated group (61%, p=0.003), compared with 30% and 31% respectively in the later groups. Median number of cycles was 5.5 overall, with a mean weighted dose received of 396mg/m2, 373mg/m2 and 301mg/m2 in the after 1 or 2 treatments, after 3 or 4 treatments and after 5 or 6 treatment groups. Median OS from castrate resistance for the earlier group was 29 months, not significantly less (p=0.1) than the 35 months for an intermediate number of prior treatments and 42 months for the later treated group. Conclusions: In this group of patients in routine clinical practice who do not receive docetaxel with initial ADT, PSA response rates are significantly improved and overall dose received is higher with subsequent earlier use. However, overall survival is not significantly different between the early and later docetaxel treated patients.
Abstract P067: A Co-Design Approach to Validate a Text Message Bank for Use With Older Adults at Risk of Cardiovascular Disease
Authors: Jessica C Ardo, Jung-Ah Lee, Janet Hildebrand, Diana Guijarro, Hassan G Ghasemzadeh, Lorraine S Evangelista
Journal: Circulation (2019)

Purpose/Aims: To describe the design and validation of a text message bank that will be used for an mHealth behavioral change intervention -- Fitness Intensive Therapy ( Get FIT+ ) in order to improve healthy eating and enhance physical activity in a sample of older adults (≥ 60 years) at risk for cardiovascular disease. Background: Short message service (SMS) has been widely used in patient follow-up and disease management, showing improvements in medication adherence, symptom monitoring, appointment attendance and satisfaction with health services. However, most studies usually focus on the effectiveness of SMS and lack information regarding the development and validation of their content to guarantee adequate understanding and appeal of SMS strategies by end users. Methods: An initial bank of 68 SMS text messages was developed to focus on healthy eating, physical activity and provide motivational feedback through an extant literature review for promoting behavior change to engage in healthy lifestyles. The messages were organized into three subsets [e.g., healthy eating (24 messages), physical activity (24 messages), other goals and compliance (20 messages)] for field validation. An expert panel (N = 5) evaluated each subset of SMS text messages. Consistent with the Get FIT+ project that will utilize the text messages, additional validation was conducted with 5 older adults (≥ 60 years old) from diverse ethnic backgrounds representative of the population in Orange County. Two to three people evaluated each of the three SMS text message subsets (N = 5, 40% male). User demographics, phone literacy, understanding and appeal of each SMS text message was assessed using a 27-item questionnaire. Results: The text message content included educational, motivational and goal progress feedback on the topics of nutrition, physical activity and compliance/other goals. Overall, the three SMS datasets received a total of 10 evaluations each. All evaluations—10 out of 10 (100%) valid responses—revealed an adequate understanding of the key idea contained in the SMS text message. The older adults’ average appeal score of the three datasets was 9.0 (SD±0.2) of 10 points. Participants did not make significant suggestions to change the wording of the messages, but provided excellent and useful feedback to optimize the messaging. Implications: The final set of SMS text messages produced had very high rates of understanding and appeal among an expert panel and older adults who represented the potential recipient. This study highlights the importance of developing and validating a database of simple, feedback-oriented SMS text messages, grounded in evidence and theory, with an expert panel and active engagement of potential end users.
Efficacy and safety of chronomodulated hepatic arterial infusion (chronoHAI) of irinotecan (I), oxaliplatin (0) and fluorouracil (F) as salvage treatment for patients (pts) with heavily pretreated liver-predominant metastatic colorectal cancer (MCC).
Authors: Ablavi Ahoefa Adani-Ife, Mohamed Bouchahda, Pasquale F. Innominato, Abdoulaye Karaboué, Ayhan Ulusakarya, Mazen Haydar, Sameh Awad, Hassan Errihani, Rene Adam, Francis Levi, Jean Francois Morere
Journal: Journal of Clinical Oncology (2015)

e14582 Background: Effective treatment options are limited for MCC pts after failure on systemic chemotherapy. The combination of I, O and F as, chronoHAI could revert prior resistance through exploiting circadian differences between healthy liver and metastases. This study aimed at defining the efficacy and safety of this schedule in heavily pretreated pts with liver-predominant MCC. Methods: Data from all consecutive pts with unresectable liver-predominant MCC treated with chronoHAI after failure on standard systemic chemotherapy were reviewed. Pts received I (180mg/m² on day 1 from 2AM to 8AM), O (85mg/m² from day 2 to day 4 from 10 AM to 10 PM) and F (2800mg/m² from day 2 to day 4 from 10PM to 10 AM) via a programmable multichannel pump connected to a hepatic arterial catheter every 3 weeks. Toxicities were graded according to NCI-CTC-AEv3.Tumor responses were evaluated according to RECIST criteria. Survival data were referred to chronoHAI onset. Results: Sixty-one pts were treated between March 2000 and October 2014.The majority had progressive disease (79%), and had received ≥ 3 prior chemotherapy lines (62%). Estimated liver involvement ≥ 50% was observed in 43% of pts. Median number of cycles was 5 (1-22). The most frequent Grade 3-4 toxicities per pt consisted in neutropenia (26.2%), diarrhea (20%), peripheral neuropathy (8.2%) and abdominal pain (6%).Catheter-related complications were thrombosis (32.7%), infection (4.9%) and extravasation (4.9%). No severe hepatic toxicities were reported. Of 58 pts assessed for response, 26 (44.8%) had an objective response (1 CR, 25PR) and 10 had stable disease resulting in a disease control rate of 62%. Median time to treatment failure and median overall survival for all pts were 3.5 [95%CL, 2.9-4.1] and 19.3 [12.1-26.5] months, respectively. Metastases downsizing enabled hepatic resection in 12 pts (20%) resulting in median OS of 56.3months [31-81.5] in these pts. Conclusions: Chronomodulated triplet HAI chemotherapy is a promising safe and active rescue treatment for heavily pretreated pts with liver-predominant MCC.
Clinical trial update on bispecific antibodies, antibody-drug conjugates, and antibody-containing regimens for acute lymphoblastic leukemia
Authors: Delong Liu, Juanjuan Zhao, Yongping Song, Xiaofeng Luo, Ting Yang
Journal: Journal of Hematology & Oncology (2019)

The relapse rate remains high after chemotherapy for adult patients with acute lymphoblastic leukemia (ALL). With better molecular diagnosis and classification as well as better assessment for minimal residual disease, major progress in the treatment for refractory and/or relapsed ALL is being made. In addition to the tyrosine kinase inhibitors (TKIs) for Philadelphia chromosome-positive ALL, immunotherapeutic agents, blinatumomab, inotuzumab ozogamicin (INO), and chimeric antigen receptor (CAR) T cells, are changing the treatment paradigm for ALL. Blinatumomab and INO are being incorporated into induction chemotherapy regimens and combined with TKIs for ALL therapy. A novel low-intensity regimen, miniHCVD-INO-blinatumomab, appears to be less toxic and more effective than conventional intensive chemotherapy regimens. This review summarized new therapeutic researches of ALL and updated latest progress in clinical trials on bispecific antibodies, antibody-drug conjugates, and new regimens incorporating these novel antibodies.
Transbronchial cryobiopsy in fibrosing interstitial lung disease: modifications of the procedure lead to risk reduction
Authors: Lars Hagmeyer, Dirk Theegarten, Jeremias Wohlschläger, Thomas Hager, Marcel Treml, Simon Dominik Herkenrath, Khosro Hekmat, Matthias Heldwein, Winfried J Randerath
Journal: Thorax (2019)

Sixty-one subjects with fibrosing interstitial lung disease were prospectively analysed to determine the efficacy of transbronchial cryobiopsy (CryoTBB) and the effect of procedural modifications which were introduced after an interim analysis of the first 19 subjects. The modifications significantly reduced complication rates from 84% to 14% (p<0.001). 30-day-mortality was 2%. The algorithm with initial CryoTBB and surgical lung biopsy (SLB) as optional step-up procedure was feasible. CryoTBB led to a confident diagnosis in 46/61 subjects (75%). Only 21% out of all subjects were forwarded for SLB. As the modified CryoTBB reduced but not eliminated the risk of severe complications, tissue sampling should be limited to patients where confident diagnosis enables life prolonging therapy. Trial registration number: NCT01714518.
Can oncology readmissions be reduced? The Cleveland Clinic experience.
Authors: Alberto J. Montero, James Stevenson, Amy E. Guthrie, Carolyn Best, Lindsey Martin Goodman, Armida Parala, Ruth Lagman, Brian James Bolwell, Matt E. Kalaycio, Alok A. Khorana
Journal: Journal of Clinical Oncology (2015)

6573 Background: Reducing 30-day readmissions is a national policy priority. Readmissions in medical oncology patients have not been extensively evaluated, and may not be reasonably preventable. We examined the impact of interventions focused on reducing oncology readmissions in the palliative medicine (PM) and general medical oncology (GMO) units. Methods: Baseline rates of readmissions were gathered in the period January 2013 to March 2014. Interventions were initiated in the period leading to April 1, 2014 including: (i) provider education, (ii) within 48 hours post-discharge nursing phone calls, and (iii) within-5-day post-discharge provider follow-up appointments. Calling nurses performed symptom management, education and encouraged prescription/appointment compliance. Results: There were a total of 3,729 combined admissions and 1,003 readmissions in the baseline period, for a readmission rate of 26% for PM and 27% for GMO units. In the 8-month intervention period (May-Dec 2014), there were 1,694 admissions, and 396 readmissions. Callbacks and 5-day appointments were monitored with a mean compliance of 77% and 70%, respectively, improving during the study period. PM readmission rates declined by 5% to 21% (p = 0.01, relative risk reduction 19%). GMO readmissions also decreased by 3% to 24% (p = 0.02, relative risk reduction 11%). The mean total cost of one readmission was $18,365, suggesting an annual potential cost savings of $2.91 million with the observed reduction in readmissions. Conclusions: Readmission reductions in both units were achieved through better systematic transitions to outpatient care, including follow-up calls and early provider visits; thereby leading to a reduction in utilization of inpatient resources. These data suggest that efforts focused on improving outpatient care transition are effective in reducing oncology readmissions. This is particularly relevant in the transition towards novel bundled payment models in oncology. The observed feasibility and patient/provider acceptance of these interventions suggests sustainability, and will be validated over longer time periods.
Abstract 11315: Ideal Cardiovascular Health, Cardiometabolic Remodeling, and Heart Failure in African-Americans: The Jackson Heart Study
Authors: Aferdita Spahillari, Sameera Talegawkar, Adolfo Correa, J. J Carr, James G Terry, Joao Lima, Jane E Freedman, Saumya Das, Robb Kociol, Sarah de Ferranti, Donya Mohebali, Stanford Mwasongwe, Katherine L Tucker, Venkatesh L Murthy, Ravi V Shah
Journal: Circulation (2016)

Background: Though African-Americans are at disproportionately high risk for heart failure (HF) and cardiometabolic disease, few studies have evaluated the association between ideal cardiovascular health metrics and cardiometabolic diseases or incident HF in African-Americans. Hypothesis: Ideal cardiovascular health is associated with adverse cardiometabolic phenotypes and incident HF. Methods: A total of 4195 African-American participants without prevalent coronary heart disease with 7 ideal cardiovascular health (ICVH) metrics measured at baseline (2000-2004) underwent evaluation by cardiac magnetic resonance (CMR; n=1188) and/or abdominal computed tomography (CT; n=2352). 3661 (87%) participants were followed for incident HF. Results: Mean age at baseline was 54.4 years (65% women). A lower composite score of ICVH at baseline was associated with greater LV hypertrophy, greater LV concentric remodeling, worse LV strain, and greater visceral and subcutaneous adipose tissue in follow-up (all P &lt;0.0001). Ideal BMI, absence of smoking, controlled blood pressure and normoglycemia were associated with improved cardiac and adiposity phenotypes. Relative to individuals with 0-2 ideal ICVH factors, African-Americans with 3 factors had 48% lower incident HF risk (HR 0.52, 95% CI 0.35-0.75, P=0.0006) and those with ≥ 4 factors had 58% lower HF risk (HR 0.42, 95% CI 0.24-0.76, P=0.004). Of the 7 components of ICVH, non-ideal physical activity, smoking, and impaired glucose control were associated with incident HF risk. Conclusions: In African-Americans, lower ideal cardiovascular health in mid-life is associated with later adverse cardiometabolic remodeling and incident HF. Lack of physical activity, smoking and impaired glucose control are associated with incident HF risk and represent potential targets for prevention of cardiometabolic disease and HF in African-Americans.
High-Dose Vitamin D Supplementation During Pregnancy and Asthma in Offspring at the Age of 6 Years
Authors: Nicklas Brustad, Anders U. Eliasen, Jakob Stokholm, Klaus Bønnelykke, Hans Bisgaard, Bo L. Chawes
Journal: JAMA (2019)

This long-term follow-up of a randomized trial reporting no apparent effect of high-dose vs standard-dose prenatal vitamin D supplementation on wheezing in children at the age of 3 years extends the findings an additional 3 years and describes asthma risk at the age of 6 years.
Identifying molecular determinants of response to apalutamide (APA) in patients (pts) with nonmetastatic castration-resistant prostate cancer (nmCRPC) in the SPARTAN trial.
Authors: Felix Y Feng, Shibu Thomas, Michael Gormley, Angela Lopez-Gitlitz, Margaret K. Yu, Shinta Cheng, Deborah S. Ricci, Oliver Brendan Rooney, Paul N. Mainwaring, David Olmos, Fred Saad, Simon Chowdhury, Boris A. Hadaschik, Nicholas Fishbane, Elai Davicioni, Yang Liu, Eric Jay Small, Matthew Raymond Smith
Journal: Journal of Clinical Oncology (2019)

42 Background: The SPARTAN trial recently demonstrated that addition of APA to androgen deprivation therapy (ADT) improved metastasis-free survival (MFS) and second progression-free survival (PFS2) in nmCRPC pts. We performed transcriptome-wide profiling of available primary tumor samples from pts in SPARTAN to evaluate potential biomarkers of response or resistance to APA+ADT. Methods: Pts included in SPARTAN were at high risk of developing metastasis.We used a commercially available genomic assay (DECIPHER prostate test, GenomeDx Biosciences, Inc., San Diego, CA) to assess gene expression in 233 archived primary tumors from SPARTAN pts. Using a Cox proportional hazard model, we assessed the association between scores and subtypes from previously derived prognostic and predictive gene signatures, such as DECIPHER and basal (BA) vs luminal (LU) subtyping. Results: Pts with high DECIPHER scores had greater treatment effect with APA+ADT than those with low scores. Pts with LU, a subtype known to be sensitive to ADT, greatly benefited from APA+ADT. Pts with BA, typically resistant to ADT, also benefited from APA+ADT. Conclusions: DECIPHER score and BA or LU subtype may be biomarkers of response to APA+ADT. DECIPHER may be useful for identifying pts for early treatment intensification with APA or other agents, and molecular subtyping may be an effective approach for pt selection in trials combining novel therapies with APA. Clinical trial information: NCT01946204. [Table: see text]