tbuckley/cabot-search huggingface dataset:
eMouvoir: Randomized study estimating the impact of a personalized and remote support centered on physical activity (PA) for patients (pts) after breast cancer (BC).
Authors: Laurence Vanlemmens, Amelie Anota, Emilie Bogart, Virginie Nerich, Didier Cauchois, Alain Dewitte, Etienne Dormeuil, Eric Lartigau, Flora Le Gall, Hervé Mocaer, Aurelie Thenot, Marc-Antoine Brochard, Marie-Cecile Le Deley
Journal: Journal of Clinical Oncology (2019)

TPS11631 Background: BC pts can reduce their health-related quality of life (HRQoL) encompassing physical, psychological and social components due to cancer and treatments (trts). Despite the strong evidence of the beneficial effects of EPA for BC pts on HRQoL, the cancer pts’ EPA levels most often decline after diagnosis and trts due to physical and psychological components, accessibility to exercise programs, time constraints. Connected watches can now contribute to pts’ deeper commitment to their program by providing reliable trends of their EPA metrics. Notwithstanding this recent progress, cancer pts keep facing challenges to maintain a regular EPA. We aim at evaluating a holistic intervention including a physical activity educator, coaching pts remotely for 4 months (mo), to improve HRQoL after BC. Methods: eMouvoir is a multicenter randomized, controlled phase 3 trial started 4-6 mo after the end of trt among non-metastatic BC pts. It assesses the benefit of a personalized remote EPA coaching, including a connected watch, access to a digital platform, personalized objectives, ≥2 messages per week, weekly lessons, for a 4-mo duration, compared to the standard supportive approach (recommendations for EPA made during visits with the oncologist) in terms of HRQoL. The randomization is balanced 1:1 and controlled for HRQoL at inclusion, trts, exercise practice, age, access to the Internet and center. Main eligibility criteria are: age ≥18; adjuvant or neoadjuvant trt for non-metastatic BC; medical certificate for sports practice. Patients without a connected device are eligible. HRQoL is evaluated using the SF-36 questionnaire, at 4, 8 and 12 mo. Both components (physical and mental summary) at 12 mo are used as co-primary endpoints. The study includes a health-economics evaluation, using EQ-5D and EQ VAS, to estimate the incremental cost-utility ratio. Based on the following assumptions: expected mean difference for each SF-36 component at 12 mo =3 points, standard deviation=15, power=90%, 2-sided alpha=2.5%, 10% drop-outs, 1242 evaluable pts are required, leading to 1380 pts. The trial is funded by the French ministry of health and should open enrollment soon.
Delays in diagnosis in young patients with leukemia and lymphoma.
Authors: Lena Winestone, Jeffrey McPheeters, Diane Puccetti, Jennifer Jill Wilkes, Lori S. Muffly, Justine Kahn, Henry J. Henk, Jill P. Ginsberg, Theresa Keegan, Brad H. Pollock, Elysia Marie Alvarez
Journal: Journal of Clinical Oncology (2019)

e18138 Background: Patients diagnosed with leukemia and lymphoma typically present with nonspecific symptoms, making a timely diagnosis difficult. Little is known about factors associated with delays in diagnosis. We hypothesized that age, minority race/ethnicity, and low income are associated with greater time to diagnosis. Methods: Using the OptumLabs Data Warehouse, which includes claims data for privately insured enrollees in a large US health plan, we identified 17,536 pediatric (0-14 y), adolescent (15-21 y), and young adult (22-39 y) patients diagnosed with acute leukemia or lymphoma between 2001-17. Using this retrospective cohort, potential cancer-related symptoms occurring up to 6 months pre-diagnosis were identified. Delay was defined as &gt; 3 months from symptom onset to diagnosis. Contingency table analysis with chi-squared tests and unconditional logistic regression were used to estimate the association between sociodemographic factors and delays in diagnosis. Results: Seventy-eight percent of patients had a diagnosis of a cancer-related symptom in the 6 months prior to diagnosis. The most common presenting symptoms were lymphadenopathy, fever, and cytopenias. The median days to diagnosis was longer in young adults (93) than children (86) or adolescents (81) (p = &lt; 0.0001). For pediatric v. AYA patients, median days to diagnosis differed for those with constitutional symptoms (18 v. 37, p = &lt; 0.001), infectious symptoms (93 v. 74, p = &lt; 0.001), and cytopenias (11 v. 22, p = &lt; 0.001). Multivariable analysis identified younger age, female sex, and low household income to be significantly associated with delays in diagnosis (table below). Conclusions: In this large cohort of privately insured patients, adolescents had the shortest time to diagnosis. We saw no disparities by race/ethnicity or education but observed that low income ( &lt; $40K) and female patients had greater odds of delays in diagnosis. [Table: see text]
Association between smoking status and lymph node metastasis in Chinese patients with T1 non-small cell lung cancer: A real-world observational study.
Authors: Feng Jiang, Heng Zhao, Xiaofei Li, Lunxu Liu, Yang Liu, Jian Hu, Xiangning Fu, Yin Li, Yijun Xu, Deruo Liu, Haiying Yang, Lin Xu
Journal: Journal of Clinical Oncology (2019)

e20012 Background: Smoking and lymph node metastasis (LNM) are widely known to be the important risk factor for the induction and poor prognosis of non-small cell lung cancer (NSCLC) , respectively. However, the association between smoking status and LNM in Chinese patients with NSCLC is largely unknown. Methods: The patients with pathologically diagnosed T1 NSCLC undergoing surgical resection during 2014 to 2017 were retrospectively reviewed based on LinkDoc database. Patients without smoking status in the case records were excluded. Chi-square test was used for comparison between groups. Results: Of the 10,622 patients enrolled, 1,760 patients had LNM (16.6%). For smoking status, 3,260 (30.7%) patients were recorded with smoking history, with an average smoking index (SI) of 221.2. The incidence of LNM especially N2 station LNM in patients who ever smoked was significantly higher than those of never smokers in the enrolled population (22.8% vs. 13.6%, p &lt; 0.001; N2: 14.3% vs. 9.1%, p &lt; 0.001). Similarly, a larger proportion of current smokers than never smokers had LNM (24.0% vs. 13.6%, p &lt; 0.001), and also more current smokers in only N2 station LNM (14.1% vs. 9.1%, p &lt; 0.001). However, no statistically difference was observed in the proportion of patients with LNM particularly with N2 LNM between former and current smokers (24.0% vs. 22.8%, p = 0.401; N2: 14.1% vs. 14.3%, p = 0.887). Compared with non to light smoking (SI &lt; = 400), patients with middle to heavy smoking ( &gt; 400) were found to be more likely to develop LNM (N1/N2: 24.8% vs. 14.6%, p &lt; 0.001; N2: 14.3% vs. 9.8%, p &lt; 0.001). Conclusions: These findings from the real-world study indicated a close association between smoking both former and current and LNM especially N2 station LNM in patients with T1 NSCLC. [Table: see text]
Tailored dose-dense chemotherapy in combination with trastuzumab as adjuvant therapy for HER2-positive breast cancer: A secondary analysis of the phase III PANTHER trial.
Authors: Theodoros Foukakis, Antroula Papakonstantinou, Alexios Matikas, Nils-Olof Bengtsson, Per Malmström, Elham Hedayati, Guenther G. Steger, Michael Untch, Laila Hübbert, Hemming Johansson, Mats Hellstrom, Michael Gnant, Sibylle Loibl, Richard Greil, Volker Moebus, Jonas C. S. Bergh
Journal: Journal of Clinical Oncology (2019)

553 Background: Dose-dense (DD) adjuvant chemotherapy improves outcomes in early breast cancer (BC). However, there are no data to inform on the combination of DD chemotherapy with trastuzumab for patients with HER2-positive disease. Methods: This is a protocol predefined secondary analysis of the randomized phase 3 PANTER trial. Women 65 years old or younger with node-positive or high-risk node negative BC were randomized 1:1 to either tailored according to hematologic nadirs and DD epirubicin/cyclophosphamide (4 cycles) followed by 4 cycles of docetaxel (tDD EC/D) or standard 3-weekly 5-fluorouracil/E/C (3 cycles) and D (3 cycles); Patients with HER2-positive disease received 1 year of adjuvant trastuzumab. In addition, HER2-positive and an equal number of matched for age, treatment group and institution, HER2-negative patients that were enrolled in Swedish sites were enrolled in a predefined study of cardiac safety and underwent echocardiography or MUGA and electrocardiography at baseline and at four and six years of follow-up. The primary endpoint was BC relapse-free survival (BCRFS). Results: There were 342 HER2-positive patients; 335 received at least one dose of trastuzumab, while 29 patients discontinued trastuzumab prematurely. BCRFS was not statistically significantly in favor of tDD EC/D (HR = 0.68, 95% CI 0.37 – 1.27, P= 0.231). Cardiac outcomes after four and six years of follow-up did not differ significantly between HER2-positive and HER2-negative patients, nor between tDD and standard treatment. Conclusions: To our knowledge, these are the only data on combining DD adjuvant chemotherapy and trastuzumab in BC. The combination decreased the risk for BC relapse by 32% compared to standard treatment, a statistically non-significant difference. Its efficacy and safety merit further evaluation as part of both escalation and de-escalation strategies. Clinical trial information: NCT00798070.
Population-based cancer predisposition testing as a component of newborn screening: A cost-effectiveness analysis.
Authors: Jennifer Yeh, Natasha K. Stout, Aeysha Chaudhry, Michael Gooch, Pamela McMahon, Kurt D. Christensen, Lisa Diller, Ann C. Wu
Journal: Journal of Clinical Oncology (2019)

10021 Background: The role of population-based newborn genetic testing to identify infants at high risk of childhood-onset cancers has not been studied, despite the availability of cancer surveillance guidelines for early detection in high-risk infants and children. Methods: We developed the Precision Medicine Prevention and Treatment (PreEMPT) Model to estimate the value of targeted population-based newborn genomic sequencing (tNBS) for a select panel of genes associated with early onset pediatric malignancy. Cohorts of US newborns were simulated under tNBS screening vs. usual care, from birth to death. Six pediatric cancer predisposition syndromes were included in the model with mutations in RET, RB1, TP53, DICER1, SUFU or SMARCB1 assigned at birth, using mutation prevalence and disease risks drawn from the published literature, as well as SEER, ClinVar and gnoMAD databases. Newborns with mutations underwent cancer surveillance based on established guidelines for each gene-related pediatric malignancy. Survival benefit was modeled as a reduction in proportion of advanced disease, cancer deaths, and treatment-related late mortality risks. Costs were based on published literature and national databases. Results: In a typical US birth cohort of 4 million newborns, we estimated 1280 cancer cases in the malignancies associated with this gene panel would be detected before age 20 under usual care, resulting in 451 cancer deaths and 490 living with radiation exposure risks. tNBS would prevent 8 cancers (in RET mutation carriers), avert 34 deaths through surveillance, result in 3190 life-years (LY) gained and a 13% relative reduction in proportion of adult survivors at risk for radiation-associated late mortality. Given a sequencing cost of $30 (e.g., $5/gene), the incremental cost-effectiveness ratio (ICER) for tNBS was $230,500 per LY saved; if no additional cost was incurred beyond standard newborn screening, the ICER decreased to $101,100/LY. Conclusions: Population-based genetic testing of newborns can reduce mortality associated with pediatric cancers and could potentially be cost-effective as sequencing costs decline. Further work will include modeling a broader panel of predisposition genes.
AB0300 LIVER DISORDERS DURING RHEUMATOID ARTHRITIS
Authors: Aicha Ben Tekaya, Khaoula Zouaoui, Ines Mahmoud, Olfa Saidane, Mohamed Ben Hammamia, Rawdha Tekaya, Leila Abdelmoula
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Hepatic disease in rheumatoid arthritis (RA) are rare, but can be impactful for patients. Though some hepatic manifestations are directly related to RA, whereas others may be sequelae of treatment or caused by concomitant autoimmune diseases. <h3>Objectives</h3> We have tried through this study to focus on the liver disorders during the monitoring of rheumatoid arthritis and to identify the different etiologies. <h3>Methods</h3> This is a retrospective descriptive study of patients with rheumatoid arthritis (ACR-EULAR 2010 criteria) followed a rheumatology department between 2012 and 2018 with liver function disorder. We have specified the epidemiological, clinical, biological and therapeutic characteristics and the different explorations carried out for these patients. <h3>Results</h3> We included 61 patients in our study (3 men and 58 women). Mean age was 52.13 years [26-82]. Average duration of RA was 9.2 years [0.5-30]. Mean DAS28 was 5.95 [3-8.33]. RA was immunopositive in 88,5% of the cases and erosive in 93,44% of the cases. Most of patients received symptomatic treatment (98% paracetamol, 87% non-steroidal anti-inflammatory drugs, 84% corticosteroids).As for conventional csDMARD, 72% of patients were treated with methotrexate, 8.2% with anti-malarial, 22.95% with salazopyrine and 11.47% with leflunomide. Three patients received biologic DMARDs (1 rituximab and 2 TNF-Blockers). Hepatic disorders were:cholestasis (95%), cytolysis (33%) and concomitant cytolysis and cholestasis (28%). The etiological investigation undertaken linked these disorders of the liver function disorders to the RA treatment in 50% of the cases.Methotrexate was incriminated in the genesis of this liver enzyme abnormalities in 14 cases, the salazopyrine in 2 cases, the leflunomide in 1 case, paracetamol and nonsteroidal anti-inflammatory drugs in 11 cases and rituximab in 1 case. Hepatic immunological investigation was negative in all cases. We have not noted any hepatitis B seroconversion. Two patients had hepatitis C. One patient presented active hepatitis C serology with signs of fibrosis (A2F2) at the liver biopsy puncture. Abdominal ultrasound showed signs of non-alcoholic fatty liver disease in 34.42% of cases. The biopsy puncture of the liver was performed in 9 patients showing chronic hepatitis lesions (n=1), hepatic atrophy (n=1), steatosis with portal and peri-sinus fibrosis (n=1). The etiological investigation was negative in 10% of cases. <h3>Conclusion</h3> In our study, the liver function disorders during RA are in half of the cases of iatrogenic origin. This requires rigorous monitoring of patients followed for RA in order to improve their management. <h3>Disclosure of Interests</h3> None declared
FIRST REPORT OF ERC-1671 (GLIOVAC) VACCINE USE IN GLIOBLASTOMA PATIENTS WITH RECURRENT DISEASE
Authors: Daniela A Bota, Chrystel Pretto, Peter Hantos, Florence M Hofman, Thomas C Chen, Jose A Carrillo, Virgil E Schijns, Apostolos Apostolos Stathopoulos
Journal: Neuro-Oncology (2012)

Author(s): Bota, Daniela A; Pretto, Chrystel; Hantos, Peter; Hofman, Florence M; Chen, Thomas C; Carrillo, Jose A; Schijns, Virgil E; Stathopoulos, Apostolos Apostolos
Abstract 17070: Impact of Cardiac Beta-adrenergic Receptor Density Evaluated by Cardiac PET on Chronotropic Incompetence
Authors: Toshihiko Goto, Shohei Kikuchi, Kent Mori, Kosuke Nakasuka, Marina Kato, Kazuaki Wakami, Hidekatsu Fukuta, Hitomi Narita, Iida Akihiko, Nobuyuki Ohte
Journal: Circulation (2017)

Introduction: Chronotropic incompetence (CI), defined as the inability of the heart to increase its rate commensurate with increased activity, produces exercise intolerance, and is an independent p...
Designing circulating tumor DNA-based interventional clinical trials in oncology
Authors: Daniel V. Araujo, Scott V. Bratman, Lillian L. Siu
Journal: Genome Medicine (2019)

Circulating tumor (ct) DNA is a powerful tool that can be used to track cancer beyond a single snapshot in space and time. It has potential applications in detecting minimal residual disease and predicting relapse, in selecting patients for tailored treatments, and in revealing mechanisms of response or resistance. Here, we discuss the incorporation of ctDNA into clinical trials.
Prevalence of asymptomatic Leishmania infection and associated risk factors, after an outbreak in the south-western Madrid region, Spain, 2015
Authors: Ana Victoria Ibarra-Meneses, Eugenia Carrillo, Javier Nieto, Carmen Sánchez, Sheila Ortega, Alicia Estirado, Pello Latasa Zamalloa, Juan Carlos Sanz, Luis García-Comas, María Ordobás, Javier Moreno
Journal: Eurosurveillance (2019)

Background A large outbreak of leishmaniasis with 758 cutaneous and visceral leishmaniasis cases occurred in 2009 in Fuenlabrada, in the south-west of the Madrid region of Spain. Aim We aimed to determine the prevalence of asymptomatic Leishmania infection after this outbreak, and its associated risk factors. Methods A cross-sectional study of 804 healthy individuals living in Fuenlabrada who had no history of leishmaniasis, was conducted between January and July 2015. Asymptomatic infections were sought by either a combination of PCR, immunofluorescent antibody titre, and direct agglutination tests, or by whole blood stimulation assay (WBA) with interleukin-2 (IL-2) quantification. Results Using the first approach, prevalence of asymptomatic individuals was 1.1% (9/804), while the second returned a value of 20.7% (143/804). Older age, being male, proximity to the park where the focus of infection was identified, and living in a detached house, were all strongly associated with the prevalence of asymptomatic infection. Conclusions The true number of infected individuals may be underestimated if only serological methods are used. The combination of WBA with IL-2 quantification may allow to better determine the prevalence of asymptomatic Leishmania infection, which would be useful in establishing control measures and in quantifying their impact. In our study, the use of WBA with IL-2 quantification also helped establish the risk factors that influence exposure to and infection by Leishmania .
AB0842 POTENTIAL RISKS FOR OSTEOPOROSIS AND SARCOPENIA IN ALCOHOLIC WOMEN
Authors: Kayo Masuko, Chie Iwahara, Seiji Sakate, Yumiko Tanaka, Shigemi Kamiya, Yuki Mizukami
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Recent statistics indicated an accumulating number of patients with alcohol dependency in Japan. In particular, there had been a considerable increase in the number of alcoholic women, reaching up to 130,000 patients. Because alcoholic women often have insufficient dietary intake and physical inactivity, they may be at risk for low bone mineral density and decreased muscle power. However, these points may not be widely recognized, and the current program for the rehabilitation of alcoholism may not be sufficient to address this issue. <h3>Objectives</h3> To assess the risk for osteoporosis and sarcopenia in alcoholic women from a nutritional viewpoint <h3>Methods</h3> Thirty-two women (mean age: 42.9 ± 7.49 years) who were admitted to the Alcoholics Rehabilitation Program (ARP) for alcoholism, which was diagnosed according to International Classification of Diseases (ICD)-10, were enrolled in the study. The patients were subjected to self-answered questionnaire, nutritional assessment by expert dietitians, and measurement of body composition and grip strength. <h3>Results</h3> Of the 32 patients, 14 (44.0%) had a history of eating disorder, mostly anorexia. All 32 patients had elevated levels of transaminases at the time of admission. History of bone fracture was present in eight of the 32 (25.0%) patients; among them, at least three (9.4%) cases were considered to be due to a fragility fracture. The mean body mass index (BMI) was 20.4 kg/m2; 10 (31.3%) patients had BMI &lt; 18. The average energy intake was low at 1,474.5 ± 324.3 kcal. Twenty-one (65.6%) patients were taking dietary calcium of &lt;650 mg/day, which is the level recommended for adult women. The mean grip strength was 23.8 ± 6.5 kg, and 8 (25%) patients had grip strength of only &lt;18 kg, which is the definition of sarcopenia in the Asian elderly. <h3>Conclusion</h3> Young to middle-aged alcoholic women should be treated as having high risks for osteoporosis and sarcopenia. ARP should include multidisciplinary assessment and interventions to prevent future locomotive disabilities. <h3>Disclosure of Interests</h3> None declared
Integrative analyses of signaling and DNA damage repair pathways in patient-derived xenograft (PDX) models from NCI’s patient-derived models repository (PDMR).
Authors: Biswajit Das, Yvonne A. Evrard, Li Chen, Rajesh Patidar, Tomas Vilimas, Justine N. McCutcheon, Amanda Peach, Nikitha Nair, Shahanawaz Jiwani, Susanne Borgel, John Carter, Raymond Divelbiss, Marianne Radzyminski, Jesse Stottlemyer, Zhenlin Ju, Rehan Akbani, Chris Alan Karlovich, Paul M. Williams, Melinda G. Hollingshead, James H. Doroshow
Journal: Journal of Clinical Oncology (2019)

3111 Background: Patient-derived xenografts (PDXs) are increasingly being used in translational cancer research for preclinical drug efficacy studies. The National Cancer Institute (NCI) has developed a Patient-Derived Models Repository (NCI PDMR; pdmr.cancer.gov ) of PDXs with clinical annotation, proteomics, and comprehensive genomic datasets to facilitate these studies. Here, we present an integrative genomic, transcriptomic, and proteomic analysis of critical signaling and DNA damage repair pathways in these PDX models, which represent 9 common and multiple rare tumor histologies. Methods: 304 PDX models from 294 patients were established from various solid tumor histologies from patients with primary or metastatic cancer. Whole Exome Sequencing, RNA-Seq and Reverse Phase Protein Array (RPPA) were performed on 2-9 PDXs per model across multiple passages. An integrative workflow was applied on multiple data sets to detect pathway activation. Results: We profiled 10 signaling and 5 DNA repair pathways in the PDMR dataset. We observed that: (i) a large fraction (40%) of PDX models have at least 1 targetable mutation in the RTK/RAS and/or PIK3CA pathways; (ii) 131 models (45%) have putative driver and oncogenic mutations and copy number variants (CNVs) in the WNT, TGFRb , NRF2 and NOTCH pathways. In addition, 17% of PDX models have targetable mutations in DNA damage repair pathways and 20 PDMR models have a DNA mismatch repair defect (MSI-H). We confirmed activation of the signaling pathways in a subset of PDX models by pathway enrichment analysis on gene expression data from RNASeq and phosphoprotein-specific antibody binding data from RPPA. Activation of DNA repair processes was confirmed by enrichment of relevant mutational signatures and loss of heterozygosity in these PDX models. Conclusions: Genomic analysis of NCI PDMR models revealed that a large fraction have clinically relevant somatic alterations in key signaling and DNA damage repair pathways. Further integrative analyses with matched transcriptomic and proteomic profiles confirmed pathway activation in a subset of these models, which may prioritize them for preclinical drug studies.