tbuckley/cabot-search huggingface dataset:
Health risks and quality of life of female heart transplant recipients
Authors: LS Evangelista, K Dracup, L Doering, J Kobashigawa
Journal: Circulation (2002)

Health Risks and Quality of Life of Female Heart Transplant Recipients Lorraine S Evangelista, Univ of CA, Los Angeles, Los Angeles, CA; Kathleen Dracup, Univ·: Of CA, San Francisco, San Francisco, CA; Lynn Doering, Jon Kobashigawa, Univ of CA, Los · Angeles, Los Angeles, CA Several studies suggest that female heart transplant recipients (HTR) are at an increased risk for rejection and death after surgery, but few studies have evaluated the potential reasons :tor this compromised outcome. The purpoo~ of this study was to describe health risk behaviOfS (smoking, exposure to second hand smoke ( ESHS ) and alcohol use) and health risk indicators (obesity, hypertension, hyperlipidemia, and diabetes mellitus ( OM )) of female HTR and examine relationships between these health risks and indicators, demographic and clinical characteristics, and quality of life (QOL). Methods: Fifty-nine female HRT (age, 54.3 ± 12. 7; tirne since transplant, 5.5±4.5 years; predominantly Whites ( 59%), married ( 56%), unemployed ( 80°/o)), were enrolled from a single heart transplant center. Demographic and clinical data, risk. behaviors and QOL were obtained through self-report and chart reviews. Urine cotinine, .height and weight were measured to verify smoking and obesity. Results: Although one-thirrl of women stopped smoking and drinking prior to transplant, some continued or resumed these high-risk behaviors after surgery (9% and 28°/o, respectively). Thirty-nine percent reported ESHS; 29°/o were being treated for OM; 40o/o were obese and hypertensive; and 53% had hypertipldemia. Approximately half of the women reported their QOL as poor-fair; the remainiflD half reported good, very good, or excellent QOL. Race, marital status and employment status were associated with greater health risks; non-whites, married and unemployed women were more likely to have OM, obesity, and hyperlipidemia, respectively (p < .05). Years since transplant was associated with increased risk for hypertension and hyperlipidemia (p<.05). Smoking, drinking, and ESHS were all associated with lower QOL (p < .001). CONCLUSION: Although a majority of female HTR has made healthy lifestyle changes, a substantial proportion has not. Health-risks related to immunosuppressive therapy increase with · time since transplant. Our findings suggest the need for multiple risk factor interventions to decrease health risks and improve OOL; female HTR who have had their transplant bey<l'nd 5 years warrant increased scrutiny.
Evolution of overall survival according to year of diagnosis (2008-2014) and subtypes, among 16703 metastatic breast cancer (MBC) patients included in the real-life "ESME" cohort.
Authors: Suzette Delaloge, Monia Ezzalfani, Veronique Dieras, Thomas Denis Bachelot, Marc Debled, William Jacot, Etienne Brain, Marie-Ange Mouret-Reynier, Anthony Goncalves, Florence Dalenc, Anne Patsouris, Jean-Marc Ferrero, Christelle Levy, Laurence Vanlemmens, Claudia Lefeuvre, Simone Mathoulin-Pélissier, Thierry Petit, Coralie Courtinard, Christian Cailliot, David Pérol
Journal: Journal of Clinical Oncology (2017)

1078 Background: Real-life data may help checking that public investments match closely medical needs. During the last decade, several drugs have been released on the market for MBC on the basis of a potential impact on overall survival (OS). Based on the large real-life ESME cohort, we aimed to describe the time evolution of MBC OS according to main phenotypes. Methods: ESME is a unique MBC national cohort including all consecutive patients (pts) who initiated treatment for MBC between 1/01/08 and 31/12/14 in the 18 French comprehensive cancer centres. ESME collects retrospective data using clinical trial-like methodology including quality assessments. Database lock was 8/12/2016. Primary objective was the impact of year of MBC diagnosis on OS. Multivariate Cox regressions were used with adjustment for main prognostic covariates. Results: 15170 out of 16703 pts in ESME had full IHC data allowing their classification as HR+HER2- (N=9922), HER2+ (N=2863), or HR-HER2- (N=2321) cases. Median FU and OS for the whole cohort are 4.05 yrs [95 CI: 3.98-4.12], and 3.1 yrs [95 CI: 3.03-3.18] respectively. In the adjusted multivariate analysis, year of MBC diagnosis, age at MBC, subtype (using HER2+ as reference), disease-free interval (DFI), visceral involvement, and number (nbr) of metastatic sites are significant OS predictors (table) although with low effect for the first item. Age at MBC, DFI, visceral involvement, and nbr of metastatic sites remained significant prognostic variables in subtypes. Year of diagnosis was no longer significant in HR+HER2- nor HR-HER2- cases (HR=0.997, p=0.71 and HR=0.997, p=0.84), while it was highly significant in HER2+ cases (HR=0.91, p&lt;0.0001). Conclusions: Although OS of MBC has slightly improved over the past decade, this remains mostly confined to HER2+ cases, highlighting the need for new strategies for the luminal and triple negative populations. [Table: see text]
Prophylaxis drug monitoring of itraconazole and voriconazole in the paediatric onco-haematological setting
Authors: F.G. De Rosa, L. Baietto, A. D’Avolio, G. Ventimiglia, M. Siccardi, E. Biasin, F. Carraro, F. Nesi, M. Simiele, M. Sciandra, G. Di Perri
Journal: Clinical Microbiology and Infection (2010)
FOXAI: a phase II trial evaluating the efficacy and safety of hepatic arterial infusion of oxaliplatin plus fluorouracil/leucovorin for advanced hepatocellular carcinoma
Authors: Ning Lyu, Youen Lin, Yanan Kong, Zhenfeng Zhang, Longzhong Liu, Lie Zheng, Luwen Mu, Jianpeng Wang, Xishan Li, Tao Pan, Qiankun Xie, Yaru Liu, Aihua Lin, Peihong Wu, Ming Zhao
Journal: Gut (2017)

We read with interest the article of recent advances in clinical practice of hepatocellular carcinoma (HCC) treatment by Bruix et al in Gut. 1 In this review, the Barcelona Clinic Liver Cancer (BCLC) Group recommended sorafenib as the standard treatment for BCLC-C stage (advanced stage) HCC. However, application of sorafenib as first treatment for advanced HCC worldwide was low according to a multiregional, large-scale, longitudinal cohort study.2 This may be attributed to some limitations of sorafenib: low response rate, modest survival advantage, complex mechanism underlying acquired resistance and high-level heterogeneity of individual response.3 4 Recently, evidence from an individual patient data meta-analysis of phase III randomised controlled trial showed no improvement in overall survival attributable to sorafenib for HBV-related HCC.5 Therefore, more alternative strategies are highly required.6 

Hepatic arterial infusion (HAI) chemotherapy (HAIC) attracted more attentions in recent years due to high response rates and …
RISK FACTORS FOR INJURIES IN ELITE YOUTH TENNIS PLAYERS
Authors: Joost van Mechelen, Joske Nauta, Babette Pluim, Evert Verhagen
Journal: British Journal of Sports Medicine (2017)

Background The number of elite junior tennis players is growing. However, very little is known about the risk factors for injuries in this specific population. Objective To identify risk factors for musculoskeletal injuries in elite youth tennis players. Design A prospective cohort study during the 2012–2013 Dutch tennis season. Setting Elite youth players. Participants Players were recruited from the Dutch national high-performance program during the pre-season intake. Seventy-three players agreed to participate (age range 11–14 years, 29 girls and 44 boys). All 73 players completed the entire follow-up period. Assessment of Risk Factors At baseline all players underwent a basic screening. Potential risk factors recorded included: (1) anthropometric data, (2) joint range of motion(ankle, hip, and shoulder), (3) pubertal stage, (4) current physical complaints. Main Outcome Measurements During the season, players reported physical complains on a weekly basis through the OSTRC injury questionnaire. The outcome of interest were the musculoskeletal injuries, subdivided into acute and overuse injuries. Results During the season, 113 musculoskeletal injuries were reported (78% overuse injuries). For acute injuries, no significant risk factors could be identified. Only pre-season complaints showed a borderline association with all acute injuries (HR 0.36 [95% CI 0.12–1.06], yes=1). When only considering lower extremities, a significant association between preseason complaints and injury at the lower extremity could be reported (HR 0.29 [95% CI 0.10–0.88], yes=1). Overuse injuries were significantly associated with total hours of sports participation (OR 7.15 [95% CI 1.32–38.98]) and wearing supportive insoles (OR 0.13 [95% CI 0.02–0.79], yes=1). Conclusions Preseason complaints, total hours of sports participation and the use of supportive soles were the factors associated of injuries in elite youth tennis players. Gender, pubertal stage and range of motion were not found to be risk factors for tennis injuries.
Genomic profiling of metaplastic breast cancer: A single center experience.
Authors: Michelle Afkhami, Idoroenyi Usua Amanam, Patricia A. Aoun, Dan Schmolze, Susan Yost, Paul Henry Frankel, Kim Nguyen, Wai (Kim) Wai Yu, Thehang H. Luu, Yuan Yuan
Journal: Journal of Clinical Oncology (2017)

e12041 Background: Metaplastic breast cancer (MpBC) is a rare malignancy with aggressive clinical presentation and poor prognosis. The goal of this study is to characterize MpBC at the genomic level with targeted exome sequencing and correlate with clinical-pathological characteristics. Methods: We have Identified 23 patients (pts) with a diagnosis of MpBC through the COH Cancer Registry from 1995 to 2013. A next generation sequencing based panel (Onco48) was performed on 21 pts on using the Ion AmpliSeq™ Kit. Molecular testing for two pts was performed at FoundationOne®. Patient’s clinical-pathological characteristics were also captured (age, race, stage, chemotherapy, radiation therapy history, and 5-year relapse free survival (RFS)). Results: Of the 21 specimens tested with COH Onco48, 3 failed to yield results. Of the 20 pts included in the analysis, 1 pt did not have survival information available. The median age at time of diagnosis was 68 years (range 35-93). All of the tumors were TNBC. The subtypes of MpBC were: squamous (35%), spindle (30%), mixed squamous and spindle (15%) and chondroid (20%). A total of 70% of pts received (neo)adjuvant chemotherapy, and 65% received radiation therapy. Median follow-up of alive pts is 63 months. Median RFS and OS have not been reached for entire cohort with a lower 95% of PFS of 22.2 months. The most commonly mutated genes included TP53 (65%), PIK3CA (45%), PTEN (15%).In a univariate analysis, the association of p53, PTEN, PIK3CA mutations and breast cancer specific survival. RFS at 2 years was 33% (0.03-0.64) for those with PIK3CA mutations, and 100% for those without (p&lt;0.01, log-rank). Overall survival was 56% at 2 years in pts with PIK3CA mutations (95% CI 0.23-0.88) compared with 100% in pts without PIK3CA mutations (p&lt;0.02). There are no statistically significant association between P53, PTEN mutation and survival. Conclusions: PIK3CA mutation confers poor prognosis in this small cohort of patients with MpBC. A larger cohort of pts is needed to verify these findings.
The utilization of pre-treatment neutrophil to lymphocyte ratio as a predictive marker for response to nivolumab therapy in non small cell lung cancer.
Authors: Isabel Ruth Preeshagul, Kevin M. Sullivan, Doru Paul, Nagashree Seetharamu
Journal: Journal of Clinical Oncology (2017)

e20634 Background:The tumor immune environment is integral in lung cancer progression. Cancer cells attract neutrophils through chemokine signaling pathyways into the tumor stroma. Neutrophils promote angiogenesis, metastasis and inhibit apoptosis whereas lymphocytes assist with tumor defense. Increased peritumoral neutrophil-to-lymphocyte ratio (NLR) has been shown to mediate T cell anergy and tumor immune evasion. In solid tumor pre-clinical models, elevated blood NLR correlates with increased tumor neutrophil infiltration and decreased CD3(+) T-cell infiltration. Immunotherapy is a promising anticancer strategy in Non-Small Cell Lung Cancer (NSCLC). We hypothesized that peripheral blood NLR could serve as a predictive marker for clinical benefit (CB) from this intervention. Methods:A single institution retrospective analysis of 81 patients with NSCLC treated with Nivolumab from July 2015 to November 2016. Each patient’s NLR was calculated prior to starting Nivolumab. A cut-off of 5 categorized NLR as high or low based on prior studies. The presence or absence of CB (objective response or stable disease per RECIST 1.1) after at least 3 months of therapy was determined. Descriptive statistics were utilized to summarize the data. Fischer exact test was used to compare proportions and student t test to compare means. Results:79 patients were included. 54 (68%) had low NLR and 25 (31.6%) had high NLR. 44 patients (81.48%) in the low NLR group and 7 (28%) in the high NLR group experienced CB (28%) at 3 months. This difference was statistically significant (P = 0.0001). The mean time to progression(TTP) for the low NLR population was 5.53 months, as compared to 2.39 months in the high NLR group( p = 0.0001) (95% confidence interval 1.59 to 4.55).The mean TTP in the CB cohort was 6.42 months in the low NLR group and 4.43 months in the high NLR group (p = 0.0052 ) (95% CI 0.61 to 3.39). Conclusions:The immune response to cancer is lymphocyte dependent. In our study, the majority of patients with low NLR experienced CB from Nivolumab whereas most of the patients with elevated NLR did not. NLR as a predictive biomarker should be further investigated in large prospective studies.
Abstract TMEM-042: MALIGNANT EXTRACELLULAR VESICLES CAUSE MESOTHELIAL CELL DAMAGE TOWARD PERITONEAL DISSEMINATION IN OVARIAN CANCER
Authors: Akira Yokoi, Takahiro Ochiya
Journal: Clinical Cancer Research (2017)

Abstract PURPOSE: To elucidate novel mechanisms of peritoneal dissemination by focusing on extracellular vesicles BACKGROUNDS AND SUMMARY: Metastasis to the abdominal cavity is frequently observed in ovarian cancer patients and is one of the reasons for the unfavorable outcomes. Extracellular vesicles (EVs), including exosomes and microvesicles, are small membrane vesicles that contain various bioactive molecules, such as microRNAs, mRNAs and proteins, and they are released from all cell types and play key physiological roles in intercellular communication. Recent evidence has demonstrated that cancer cells secrete EVs to both proximal surrounding cells and distal sites, thereby enabling the development of a cancer microenvironment that in turn promotes cancer metastasis. We established orthotopic mouse models by using 4 ovarian carcinoma cell lines with different metastatic traits and investigated the functions of cancer-derived EVs. The EVs from highly metastatic cells strongly induced metastatic behavior in moderately metastatic tumors. Notably, the metastatic cancer EVs efficiently induced apoptotic cell death in mesothelial cells in vitro and in vivo, thus resulting in the destruction of the peritoneal mesothelium barrier. Whole transcriptome analysis showed that MMP1 was significantly elevated in mesothelial cells treated with highly metastatic cancer EVs, and intact MMP1 mRNAs were selectively packaged in the EVs. Importantly, MMP1 expression in ovarian cancer is tightly correlated with a poor prognosis, particularly in stage I patients. Moreover, we found MMP1 mRNA-carrying EVs in the ascites of cancer patients, and these EVs also induced apoptosis in mesothelial cells. CONCLUSIONS: Our findings provide a promise for the understanding of a previously unknown mechanism for peritoneal dissemination that is associated with cancer-derived EVs, and which may be novel biomarkers for prognosis and can provide a new therapeutic strategy for inhibiting metastasis by disrupting the EVs. Citation Format: Akira Yokoi and Takahiro Ochiya. MALIGNANT EXTRACELLULAR VESICLES CAUSE MESOTHELIAL CELL DAMAGE TOWARD PERITONEAL DISSEMINATION IN OVARIAN CANCER [abstract]. In: Proceedings of the 11th Biennial Ovarian Cancer Research Symposium; Sep 12-13, 2016; Seattle, WA. Philadelphia (PA): AACR; Clin Cancer Res 2017;23(11 Suppl):Abstract nr TMEM-042.
Thrombophilia Testing in Provoked Venous Thromboembolism
Authors: Arjun Gupta, Ravi Sarode, Srikanth Nagalla
Journal: JAMA Internal Medicine (2017)

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Pharmacogenetics revisits bevacizumab in breast cancer patients: An ancillary analysis of the UCBG trial COMET—A French multicentric prospective study from R&amp;D UNICANCER.
Authors: Gerard A. Milano, Jean-Yves Pierga, Jocelyn Gal, Laurence Llorca, Coraline Dubot, Gilles Romieu, Isabelle Desmoulins, Etienne Brain, Anthony Goncalves, Jean-Marc Ferrero, Paul H. Cottu, Marc Debled, Olivier Tredan, Emmanuel Chamorey, Marco Carlo Merlano, Jérôme Lemonnier, Marie-Christine Etienne-Grimaldi
Journal: Journal of Clinical Oncology (2017)

1079 Background: Bevacizumab (Beva) is no longer unanimously recommended in the management of breast cancer (BC). Given the absence of faithful predictors of Beva treatment outcome, we made the hypothesis that constitutional gene polymorphisms could play a role in this context. We report the pharmacogenetic ancillary study of the prospective COMET trial conducted in advanced BC patients (pts) receiving first-line Beva associated with paclitaxel. Methods: Relevant targeted gene polymorphisms were analyzed (blood) in 203 prospective pts (mean age 55.3, median follow-up 24 months). VEGFA at positions -2578C &gt; A (rs699947), -1498T &gt; C (rs833061), -634G &gt; C (rs2010963), and 936C &gt; T (rs3025039) were analyzed by PCR-RFLP. VEGFR1 319A &gt; C (rs9582036), VEGFR2 at positions 604C &gt; T (rs2071559), 1192C &gt; T (rs2305948), 1416T &gt; A (rs1870377), IL8 251T &gt; A (rs4073), CYP2C8 139C &gt; T (rs1572080), 399T &gt; C (rs10509681) and ABCB1 at positions 1199 C &gt; TA (rs2229109), 2677G &gt; TAC (rs2032582) were analyzed by Mass-Array Agena. ABCB1 1236C &gt; T (rs1128503) and 3435T &gt; C (rs1045642) were analyzed by pyrosequencing. All fitted HWE. Results: Median progression-free survival (PFS) was 10.8 months. VEGFR1 319A allele was associated with longer PFS (p = 0.03). The VEGFA-1498T allele was significantly associated with both longer overall survival (OS) (p = 0.005) and PFS (p = 0.065). The VEGFA -2578C allele was associated with greater OS (p = 0.002) and PFS (p = 0.071). These two VEGFA polymorphisms were in linkage disequilibrium (p &lt; 0.0001). Multivariate Cox analysis showed that VEGFA -2578 (p = 0.001) and VEGFR2 1416 (p = 0.025) were significant predictors of OS: the score of favorable alleles (VEGFA -2575C and VEGFR2 1416T) was highly associated with OS (p = 0.0003), with median survival at 24 months being 30% for score 0 (95%CI 15-61), 65% for score 1 (95%CI 55-75) and 90% for score 2 (95%CI 67-90). Conclusions: Application of an easy-to-perform low-cost genotyping test may identify strong predictors of Beva outcome in metastatic BC pts. In the current era of precision medicine, a pharmacogenetic-based personalized Beva therapy deserves to be prospectively validated in BC pts. Clinical trial information: 2012-A00244-39.
Concurrent Chemoradiotherapy with or without Anti-EGFR-Targeted Treatment for Stage II-IVb Nasopharyngeal Carcinoma: Retrospective Analysis with a Large Cohort and Long Follow-up
Authors: Rui You, Yi-Jun Hua, You-Ping Liu, Qi Yang, Yi-Nuan Zhang, Ji-Bin Li, Chao-Feng Li, Xiong Zou, Tao Yu, Jing-Yu Cao, Meng-Xia Zhang, Rou Jiang, Rui Sun, Hao-Yuan Mo, Ling Guo, Ka-Jia Cao, Ai-Hua Lin, Ying Sun, Chao-Nan Qian, Jun Ma, Ming-Yuan Chen
Journal: Theranostics (2017)

We examined the benefits of the combination of anti-EGFR targeted treatment, cetuximab (CTX) or nimotuzumab (NTZ) and concurrent platinum-based chemoradiotherapy (CCRT) compared with CCRT alone in patients with stage II - IVb nasopharyngeal carcinoma (NPC). A total of 1,628 eligible patients with stage II - IVb NPC, who received CCRT (three cycles of 100 mg/m2 cisplatin every 3 weeks with intensity-modulated radiotherapy) with or without CTX or NTZ between June 2009 and December 2013 were included in the analysis. Using propensity scores to adjust for potential prognostic factors, a well-balanced cohort of 878 patients was created by matching each patient who received CTX or NTZ plus CCRT with no more than four patients who received CCRT alone (1:4). Efficacy and safety were compared between CTX/NTZ plus CCRT and CCRT alone arms. Compared with CCRT alone, treatment with CTX/NTZ plus CCRT was associated with a significantly increased overall survival (3-year OS, 96.6% vs. 92.9%, P = 0.015), improved disease-free survival (3-year DFS, 93.5% vs 86.9%, P = 0.028), and improved distant metastasis-free survival (3-year DMFS, 94.6% vs 89.3%, P = 0.030). Increased rate of CTX related-skin reaction and mucositis was observed in the CTX plus CCRT arm. Multivariate analysis demonstrated the combination of CTX/NTZ was a significant protective factor for OS, DFS, and DMFS in patients treated with CCRT. Our analysis suggests that the addition of CTX/NTZ to CCRT is more effective for maximizing survival in patients with stage II-IVb NPC compared with CCRT alone.
Enasidenib induces acute myeloid leukemia cell differentiation to promote clinical response
Authors: Michael D. Amatangelo, Lynn Quek, Alan Shih, Eytan M. Stein, Mikhail Roshal, Muriel D. David, Benoit Marteyn, Noushin Rahnamay Farnoud, Stephane de Botton, Olivier A. Bernard, Bin Wu, Katharine E. Yen, Martin S. Tallman, Elli Papaemmanuil, Virginie Penard-Lacronique, Anjan Thakurta, Paresh Vyas, Ross L. Levine
Journal: Blood (2017)