tbuckley/cabot-search huggingface dataset:
Abstract 11142: Association of Age, Race, and HIV Disease Severity with Incident Atrial Fibrillation in HIV-Infected Persons
Authors: Jonathan C Hsu, Yongmei Li, Gregory M Marcus, Priscilla Y Hsue, Rebecca Scherzer, Carl Grunfeld, Michael G Shlipak
Journal: Circulation (2012)

Background- Cardiovascular disease is common in HIV-infected persons; however, the most common cardiac arrhythmia, atrial fibrillation (AF), has not been well-studied in this population. We investigated the associations of traditional demographic risk factors and longitudinal measures of HIV disease severity with risk of incident AF in a contemporary cohort of HIV-infected individuals. Methods and Results- We studied a national sample of 30,533 HIV-infected veterans followed in the Veterans Affairs HIV Clinical Case Registry from 1996-2011. Using proportional-hazards regression for multivariable analysis, we examined the independent associations of age, race, CD4+ cell count, and viral load with the outcome of incident AF. Over a median follow-up of 6.75 years, 780 (2.55%) patients developed AF. After multivariable adjustment for potential confounders, patients ≥65 years of age had an 8-fold greater risk of AF compared to patients <35 years of age (hazard ratio [HR], 7.9; 95% confidence interval [CI], 5.1...
The impact of body weight status on health care utilization and costs among long-term cancer survivors.
Authors: Xuesong Han, Zhiyuan Zheng, Ahmedin Jemal
Journal: Journal of Clinical Oncology (2016)

6612 Background: Obesity is associated with substantial health and economic burden in the general population. Little is known about the impact of body weight status on health care utilization and related costs among cancer survivors. This study examines the health care utilization and medical expenditures associated with underweight, overweight and obesity among long-term cancer survivors. Methods: Long-term cancer survivors (defined as 2 or more years post diagnosis) aged ≥ 18 years (N = 8,143) were identified from the 2008-2012 nationally representative Medical Expenditure Panel Survey. We calculated average annual health care utilization (office-based visit, emergency room visit, number of prescribed medicines) and total medical expenditures by body weight status (underweight, normal weight, overweight, obese), using a 2-part modeling approach controlling for age, race/ethnicity, sex, education, marital status, poverty status, region, urban/rural status, health insurance and smoking status. The additional health care utilization and medical expenditures associated with underweight, overweight and obesity compared to normal weight were estimated from the models. Results: Compared to normal weight cancer survivors, underweight survivors had significantly higher emergency room visits (0.26 [95%CI = 0.09-0.43]) and higher medical expenditures ($5938 [95%CI = $1999-9877]) per person per year; obese survivors had an additional 1.4 (95%CI = 0.5-2.3) office-based visits, 0.05 (95%CI = 0.003-0.10) emergency room visits, 13.5 (95%CI = 11.3-15.8) prescribed medicines, and $3005 (95%CI = 1602-4408) medical expenditures per person annually. The excess annual medical expenditures associated with underweight and obesity among long-term cancer survivors translates to about US$ 1.2 billion and US$ 12 billion, respectively, nationally. Conclusions: For long-term cancer survivors, being underweight or obese was associated with increased healthcare utilization and substantial medical expenditures. Policies and practices promoting a healthy lifestyle and achieving and maintaining a normal body weight for obese cancer survivors may reduce healthcare utilization and economic burden.
TCT-344 Comparison of tissue prolapse after stent deployment at culprit lesion and non-culprit lesion in acute myocardial infarction
Authors: Hyuck Jun Yoon, Yun-Kyeong Cho, Cheol Hyun Lee, Seung-Ho Hur, Chang-Wook Nam, Sang-Woong Choi, Hyungseop Kim
Journal: Journal of the American College of Cardiology (2018)
Variation from guidelines-based cancer treatment and disparity in patient outcomes throughout the United States.
Authors: Vincent W. Li, Diana Saville, William W. Li
Journal: Journal of Clinical Oncology (2016)

e18077 Background: Antiangiogenic cancer therapy was first FDA approved in 2004 and is now an integral part of cancer treatment guidelines. We sought to quantify whether guideline-based usage of antiangiogenesis agents varied in the U.S., and whether cancer patient outcomes also varied. We focused on 7 tumor types for which antiangiogenic agents are indicated. Methods: >100 U.S. metropolitan statistical areas (MSAs) were queried from a CDC database. Mortality-to-Incidence Ratio (MIR) was used a proxy measure of survival and overall outcome. For each cancer, mean national MIR was compared to local MIRs to assess geographic variations of outcomes. MSAs were mapped to counties, and morality and incident rates obtained based on age, gender, and race. To assess whether poor local outcomes relative to the rest of the country was associated with local deviations from treatment guidelines, actual treatment usage was quantified by examining ICD, CPT, HCPCS, and NDC codes using Decision Resources Group claims data analytics. Results: Significant geographic disparity was found in patient outcomes, as shown by variations in mortality (MIR) for each cancer type by MSA location. For colorectal cancer (CRC) as an example, the national mean MIR was 0.376 but many metropolitan areas had higher mortality rates >2 standard deviations from the national mean. For the cancers examined, guideline-based utilization of antiangiogenic agents was less than expected. Whereas optimal guideline-based treatment utilization could approximate 100% for mut-K-ras metastatic CRC (mCRC), actual usage of bevacizumab for mCRC was only 36.6% across all MSAs. In MSAs with poorest CRC outcomes, bevacizumab use was lower than that of the national mean. Conclusions: Substantial variations in guideline-based care exist for antiangiogenic therapies, which may contribute to the local disparities observed in cancer survival. Traditional medical education and evidence-based guideline-directed practices may be insufficient to promote optimal treatment adoption. Areas where cancer survival rates are exceptionally poor may be targets for innovative education interventions to improve guideline-based cancer care using antiangiogenic agents.
Noninvasive molecular subtyping and risk stratification of DLBCL.
Authors: Florian Scherer, David Matthew Kurtz, Aaron M. Newman, Henning Stehr, Alexander F.M. Craig, Mohammad S Esfahani, Alexander F. Lovejoy, Jacob J. Chabon, Daniel M. Klass, Chih Long Liu, Li Zhou, Cynthia Glover, Ranjana H. Advani, Lauren Shizue Maeda, Neel K. Gupta, Ronald Levy, Robert S. Ohgami, Christian Kunder, Maximilian Diehn, Ash A. Alizadeh
Journal: Journal of Clinical Oncology (2016)

7554 Background: Clinically distinct DLBCL subsets can be stratified using gene expression profiles (GEP), allowing prognostic classification based on cell-of-origin (COO) with potential therapeutic implications. Current methods for COO assessment either rely on adequate tumor tissue or are limited by low accuracy and reproducibility. Circulating tumor DNA (ctDNA) is a noninvasive biomarker for tumor detection with potential for DLBCL disease monitoring. Here, we explored the utility of ctDNA for tumor subtyping and risk stratification. Methods: Using a training cohort originally classified by mRNA GEP (n = 142), webuilt a novel COO classifier based on somatic variants detected by tumor DNA genotyping. COO classifier performance was then assessed on 76 tumor and 41 plasma samples using CAPP-Seq, a highly sensitive method for ctDNA detection and noninvasive plasma genotyping for all major somatic mutation classes (Newman et al., Nat. Med. 2014). COO classifier results were compared against the Hans algorithm. Additionally, associations between ctDNA and clinical indices for noninvasive risk stratification were assessed by Pearson correlation, Mann-Whitney test and Cox regression. Results: CAPP-Seq genotyping allowed COO assessment in 100% of patients using tumor tissue. Tumor COO classification with CAPP-Seq (GCB = 45 / Non-GCB = 31) was highly concordant with plasma-based COO classification (88% - 93% depending on ctDNA levels) and showed 84% concordance with the Hans algorithm. COO classification by CAPP-Seq from either tissue or plasma samples significantly predicted PFS (P = 0.008 and 0.02, respectively), while classification by Hans criteria showed no significant difference (P = 0.29). Pretreatment ctDNA levels were significantly correlated with LDH (r = 0.94), PET/CT metabolic tumor volume (r = 0.67), stage (P = 0.0003) and IPI (P < 0.0001). High ctDNA concentrations at diagnosis were strongly associated with PFS (P < 0.0001), with assessment of independent prognostic value ongoing in a larger validation cohort. Conclusions: CAPP-Seq ctDNA profiling allows accurate noninvasive DLBCL COO subtyping and clinical risk stratification. Further investigation is required to characterize its potential role in guiding therapy decisions.
Outcomes of patients with gene fusion driven cancers treated on early phase clinical trials.
Authors: Roman Groisberg, Kenneth R. Hess, David S. Hong, John Heymach, Aung Naing, Sarina Anne Piha-Paul, Filip Janku, Milind M. Javle, Mimi I-Nan Hu, Anthony Paul Conley, Funda Meric-Bernstam, Vivek Subbiah
Journal: Journal of Clinical Oncology (2018)

2590 Background: Gene fusions result in a constitutively activated tyrosine kinase that causes uncontrolled cell proliferation. Some fusions are actionable with multi-kinase inhibitors that are FDA approved or in development. We reviewed patients with gene fusions treated with a targeted agent in a large Phase 1 program. Methods: We reviewed charts of patients treated on trials with targeted therapies in our phase 1 clinic between 2009 and 2017. Targeted was defined as affecting either the fusion gene itself or a downstream pathway. Demographic information including diagnosis, age, sex, date of first dose on trial, date of progression, best response by RECIST, and date of death. Information on fusions was obtained from next generation sequencing or FISH performed as part of oncologic management. Results: A total 85 patients (M:F, 46:39) with gene fusions were identified and 59 (68.6%) were treated with a targeted agent. Tumors included sarcomas (N = 49, 57.6%), NSCLC (N = 17, 20%), cholangiocarcinoma (N = 7, 8.2%), salivary gland (N = 4, 4.7%), thyroid (N = 3, 3.5%), GBM (N = 2, 2.3%), HG neuroendocrine tumors (N = 2, 2.3%), colon and lymphoma (N = 1 each, 1.1%). Most common fusions were RET (KIF5B = 15, CCDC6 = 2, Other: 1) and EWS-FLI1 (N = 12, 20%). Other fusion partners in our dataset included FGFR2/3 (N = 9, 15.3%), NTRK1/3 (N = 7, 11.9%), ALK (N = 3, 5.1%), ROS1 (N = 2, 3.4%), and BRAF (N = 1, 1.7%). Most therapies targeted the fusion itself except in sarcomas where downstream pathways (c-MET, IGF1R, nuclear redistribution) were targeted. Best response was CR in three patients (5%), PR in 12 patients (20%), and SD in 21 patients (35.6%) for a clinical benefit rate of 61%. Median PFS was 7.1 months, 95% CI [4.8,15.4] and OS was 19.6 months, 95% CI [10.8, 29.4]. This compares favorably with historical unmatched (PFS = 2.2, OS = 9 mo) and matched therapy for mutations (PFS = 5.2, OS = 13.4 mo) in phase 1 trials (PMID: 22966018). Conclusions: Gene fusion driven cancers are actionable. Patients with fusions have comparable response rates to historical molecularly matched targeted therapy data in our phase 1 group, but have longer PFS and OS. Further study is needed for molecular mechanisms of response and resistance to fusion targeted therapies.
Concurrent chemotherapy and radiation versus chemotherapy alone for N3 stage IIIb NSCLC in elderly patients.
Authors: Angel Qin, Elizabeth Lusk, Stephanie Daignault-Newton, Bryan J. Schneider
Journal: Journal of Clinical Oncology (2018)

8536 Background: The NCCN guidelines recommend treating stage IIIB NSCLC (non-small cell lung cancer) with concurrent chemotherapy and radiation (chemo-RT). There is data to suggest that N3 stage IIIB disease conveys worse prognosis, but this has not been explicitly interrogated. There is also concern regarding the safety of chemo-RT in patients ≥70 years old as they are under-represented in clinical trials, have worse overall survival, and experience increased toxicities. We therefore sought to interrogate the survival of N3 Stage IIIB NSCLC using the NCDB (National Cancer Database) with a focus on patients ≥70 years old. Methods: We conducted a retrospective analysis on data from the 2014 NCDB PUF (participant user file) of patients diagnosed with N3 stage IIIB NSCLC between 2010 and 2013. Kaplan-Meier method was used for median overall survival (OS) with log-rank tests. Multivariable Cox models were used for multivariable and subgroup analyses. Results: 9,769 patients were included in our analysis, 7,770 who received chemo-RT and 1,999 who received chemotherapy alone. A higher proportion of patients in the chemotherapy group were ≥70 years old compared to the chemo-RT group (46.6% and 34.5% respectively, p < 0.0001). The median OS for the chemo-RT group was 16.4 months compared to 12.7 months for the chemotherapy group (p < 0.0001). For patients ≥70 years old, the median OS was 15.0 months for those who received chemo-RT compared to 12.4 months for chemotherapy alone (p < 0.0001). In multivariable analyses, the benefit of chemo-RT was similar regardless of age. For age < 70, the hazards ratio (HR) was 0.73 with a 95% confidence interval (CI) of 0.67-0.79 and for age ≥70, HR = 0.77, 95% CI = 0.71-0.83 (p = 0.43). Subgroup analyses in patients ≥70 indicated a benefit to chemo-RT (HR < 1.0) across all patient and disease strata, including Charlson Comorbidity Index (p < 0.05 irrespective of score). Conclusions: There is a survival benefit to chemo-RT versus chemotherapy alone in N3 stage IIIB NSCLC in patients ≥70 years old, who represented 37% of all patients. Our findings suggest that age and comorbidity index alone should not preclude clinicians from recommending aggressive therapy to these patients.
Abstract 15417: Hospital Mortality of Adults After Congenital Heart Surgery Can be Predicted by a Version of the Aristotle Comprehensive Complexity Score
Authors: Jürgen Hörer, Manfred Vogt, Michael Wottke, Julie Cleuziou, Zsolt Prodàn, Jelena Kasnar-Samprec, Christian Schreiber, Rüdiger Lange
Journal: Circulation (2010)

Objective: The predictive power of the Aristotle Basic Complexity (ABC), and the Aristotle Comprehensive Complexity (ACC) score for hospital mortality after congenital heart surgery has been demonstrated for children, but not for adults. We sought to evaluate the ABC, and the ACC score for adults, and to improve the discriminative power of the ACC score by adding risk factors, specifically present in adults, and not considered in the ACC score. Methods: Data of all consecutive patients aged 16 or more who underwent surgery for congenital heart disease between 2005 and 2008 were collected. ABC and ACC scoring was performed according to the Aristotle Institute guidelines (Denver, USA). The impact of 5 potential risk factors for hospital mortality, not considered in the ACC score, was analyzed by logistic regression modelling. The odds ratios of significant risk factors, were added to the ACC score to compile the modified ACC score. The discriminatory power of the scores was assessed using the area under the...
Immune-related expression profiles and sunitinib response in metastatic clear cell renal cell carcinoma (ccRCC).
Authors: Òscar Reig, Mercedes Marin, Natalia Jimenez, Laia Pare, Patricia Galvan, Carmen Mallofre, Aleix Prat, Begona Mellado
Journal: Journal of Clinical Oncology (2018)

e16579 Background: Antiangiogenic drugs, such as sunitinib (SU), can modulate the immune system through the inhibition of VEGFA decreasing the MDSC and Treg infiltration and preventing T cell anergy. We investigated if immune-related gene expression predicts sunitinib activity in ccRCC. Methods: 42 metastatic ccRCC patients treated with SU were included in this retrospective biomarker study. The expression of 730 immune-related genes (PanCancer Immune Profiling Panel, Nanostring) was evaluated in FFPE tumor samples form nephrectomy specimens. Results: Patients with high expression of T cell (CD8 T cell, Tgd, Th1 and Th2), NKCD56dim, aDC and B cells signatures had an overall response rate (ORR) of 60% compared to those with low expression (ORR 20%; p < 0.05). Several signatures were independently associated with PFS after adjustment with IMDC classification and line of treatment (Table 1). An unsupervised clustering analyses using the 730 genes revealed two groups of samples with high (C1) and low (C2) expression of most immune genes. C1 cluster had higher ORR (70% vs 18.2%, p = 0.0014) and better PFS (HR 0.45 (95% CI, 0.22 - 0.92), p = 0.028) than C2. Conclusions: Our results suggest that high expression of immune-related cell-type signatures identified before treatment identify patients likely to benefit from sunitinib in ccRCC. Progression-Free Survival Signatures Univariate Multivariate HR (95% CI) P HR (95% CI) P NK cell 0.44 (0.25 – 0.77) 0.0035 0.39 (0.22 – 0.72) 0.0024 Eosinophil 0.46 (0.24 – 0.87) 0.0177 0.52 (0.28 – 0.97) 0.0399 Th1 cell 0.62 (0.40 – 0.96) 0.0323 0.59 (0.37 – 0.94) 0.0273 CD8T cell 0.63 (0.42 – 0.93) 0.0217 0.61 (0.39 – 0.94) 0.0239 Treg 0.67 (0.45 – 0.98) 0.0413 0.63 (0.42 – 0.94) 0.0249 T cell 0.68 (0.47 – 0.99) 0.0429 0.64 (0.43 – 0.93) 0.0203
The CCTG CO.26 trial: A phase II randomized study of durvalumab plustremelimumab and best supportive care (BSC) vs BSC alone in patients with advanced colorectal carcinoma (CRC) refractory to standard therapies.
Authors: Eric Xueyu Chen, Derek J. Jonker, Hagen F. Kennecke, Sheryl L. Koski, Alice Chia-chi Wei, Nadine M Magoski, Dongsheng Tu, Christopher J. O'Callaghan
Journal: Journal of Clinical Oncology (2017)

TPS3621 Background: Durvalumab (D) is a human monoclonal antibody (mAb) that inhibits binding of programmed cell death ligand 1 (PD-L1) to its receptor (PD-1) thereby preventing reduction in the number and efficacy of activated T-cells. Tremelimumab is a mAb directed against the cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) thereby resulting in enhanced T-cell activation and anti-tumour activity. Monotherapy with the anti-PD-1 agent pembrolizumab has demonstrated significant activity in CRC pts with tumours demonstrating microsatellite instability (MSI-H). Inhibiting PD-1/PD-L1 alone is likely of limited benefit in advanced CRC as only 5% of pts are MSI-H. Targeting both PD-L1 and CTLA-4 may have additive or synergistic activity as the mechanisms of action of CTLA-4 and PD-L1 inhibition are non-redundant. This study is designed to evaluate whether combining PD-L1 and CTLA-4 inhibition will lead to improved patient survival vs BSC alone in advanced CRC, regardless of MSI status. Methods: This randomized phase II study (ClinicalTrials.gov NCT02870920) will assess the efficacy and safety of D+T vs BSC in pts with metastatic or advanced, unresectable, refractory CRC (n = 180). Pts have failed standard chemotherapy based regimens containing a fluoropyrimidine, irinotecan and oxaliplatin (and an EGFR inhibitor, if Ras wild type) and no other therapeutic options. Pts are randomized in a 2:1 ratio to receive D (1500 mg) D1 q 28 days and T (75 mg) D1 for first 4 cycles. Treatment will continue until disease progression, death, intolerable toxicity, or patient/investigator decision to stop. Primary endpoint is overall survival; secondary endpoints include progression free survival, safety, overall response rate and quality of life. Analysis will be according to randomized group stratified by ECOG PS (0 vs 1) and site of tumour (right vs transverse vs left vs rectum). In addition, blood, plasma, and archival tissue will be collected and assessed for potential prognostic and predictive biomarkers, including tumour MSI status. As of February 1 2017, 20 pts have been randomized and recruitment is ongoing. Clinical trial information: NCT02870920.
Clinical features of breast cancer patients with bone marrow metastasis.
Authors: Jing Sun, Guangyu Yao, Mengdi Yang, Yiyi Zhou, Hui Zhao
Journal: Journal of Clinical Oncology (2018)

e13028 Background: Bone marrow metastasis from breast cancer (BC) is relatively rare, and the prognosis is poor. This study was to investigate breast cancer patients with bone or bone marrow metastasis in order to find out the clinical features to guide clinical treatment and improve prognosis. Methods: A retrospective analysis was conducted in BC patients with bone or bone marrow metastasis in Shanghai Sixth People's Hospital from January 2010 to January 2017. Clinical materials were collected such as age, skeletal-related events (SREs), histological subtype and survival. Patients were followed up by telephone every six months after the last time they leave hospital. Kaplan-Meier analysis was used to calculate survival. Cox Regression was used to analyze the influence of the age at diagnosis, SREs, visceral metastasis, combination therapy, type of bone metastasis and pain degree. IBM SPSS statistics 24 was used to do analyses. Results: 19 patients were breast cancer with bone marrow metastasis confirmed by bone marrow biopsy and 12 cases had pathological reports of BM lesions and the subtype is estrogen receptor (ER) + of each case (100%). 219 patients were breast cancer with bone metastasis (BM) diagnosed by pathological examinations or radiographic evidence and 125 cases had pathological reports of BM lesions and 90 cases were ER+ (72%). The incidence of SREs in bone marrow metastasis group (89.5%) was significantly higher than BM group (67.1%) (p< 0.05). The median survival of patients with bone marrow metastasis group (10.00 ± 4.55 months) was significantly shorter than BM group (25.00 ± 3.24 months) (p< 0.01). In bone marrow metastasis group, survival was associated with combination therapy and pain degree. The median survival of patients with combination therapy (21.00 ± 5.24 months) was significantly longer than patients with single chemotherapy (5.00 ± 2.72 months) (p< 0.05). Conclusions: Bone marrow metastasis was associated with decreased overall survival and high incidence of SREs. ER+ of BM lesion was related to bone or bone marrow metastasis. Combination therapy prolonged the survival of patients with bone marrow metastasis.
TCT-223 Efficacy and Safety of Transfemoral Transcatheter Aortic Valve Replacement under General Anesthesia versus Local Anesthesia. Insights from TRYTOM Registry (International, Multicenter, Latin-American Registry)
Authors: Marcelo Abud, Henrique Ribeiro, Antonio Dager, Matias Sztejfman, Rogerio Sarmento-Leite, Pablo Lamelas, Fernando Cura
Journal: Journal of the American College of Cardiology (2018)