tbuckley/cabot-search huggingface dataset:
Predictive value of ATP7b, BRCA1, BRCA2, PARP1, RAP80, HOXA9, DAXX, ERCC1, thioredoxin-1, TSP1, and TXR1 genes in patients with epithelial ovarian cancer (EOC) WHO received platinum-taxane first line therapy.
Authors: Ioannis Sougklakos
Journal: Journal of Clinical Oncology (2016)

e17086 Background: Τo evaluate the predictive value of genes involved in resistance to platinum-taxane chemotherapy in patients with epithelial ovarian cancer (EOC). Material and Methods: Microdissected formalin-fixed tumoral samples from 187 EOC patients’ primary tumors were analyzed. Ninety samples correspond to the experimental and ninety seven to the validation set, and patients were matched in clinical characteristics and pathological features. All specimens were analyzed for ATP7b, BRCA1, BRCA2, PARP1, RAP80, HOXA9, DAXX, THIOREDOXIN-1, TSP1, TXR1 mRNA expression by quantitative real-time PCR. Most of the patients (172 out of 187) received carboplatin-paclitaxel regimen. Expression levels were correlated with overall survival (OS) and progression free survival (PFS) by multivariate analysis. Results: Patients with high THIOREDOXIN-1 and TSP1 expression presented longer PFS (p = 0.001 and p < 0.001, respectively) and OS (p = 0.024 and p < 0.001, respectively). High TXR1 expression was associated with decreased PFS (p < 0.001) and OS (p < 0.001). Multivariate analysis demonstrated that high TXR1/low TSP1 expression was an independent factor for decreased PFS (HR 1.94; 95% CI 1.48–2.92; p = 0.008) and OS (HR 3.89; 95% CI 2.16–6.87; p < 0.001), whereas low THIOREDOXIN-1 expression was correlated with decreased PFS (HR 1.44; 95% CI 1.05–2.84; p = 0.043) and OS (HR 2.38; 95% CI 1.78–2.77; p = 0.009). Conclusions: These findings indicate that TXR1/TSP1 and THIOREDOXIN-1 expression could be used for the prediction of resistance to treatment of EOC patients and, therefore merit to be further evaluated.
Acalabrutinib monotherapy in patients (pts) with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL).
Authors: Martin JS Dyer, Sven De Vos, Jia Ruan, Christopher Flowers, Kami J. Maddocks, Simon Rule, Ahmed M. Hamdy, Raquel Izumi, J. Greg Slatter, Jean Cheung, Melanie M. Frigualt, Helen Wei, Sanchita Mourya, Naomi N. H. Hunder, Nathan Hale Fowler
Journal: Journal of Clinical Oncology (2018)

7547 Background: Acalabrutinib, a highly selective, potent, covalent BTK inhibitor, was assessed as monotherapy in pts with R/R de novo DLBCL. Methods: Eligible pts aged ≥18 y, with ECOG PS ≤2 and confirmed R/R non-germinal center (GCB) type DLBCL assessed by local IHC received oral acalabrutinib 100 mg bid until progressive disease (PD) or unacceptable toxicity. The primary endpoint was safety. Secondary endpoints included pharmacokinetics (PK), pharmacodynamics and investigator-assessed overall response rate (ORR; per Lugano criteria), duration of response (DOR) and progression-free survival (PFS). Results: 21 pts enrolled. To most recent prior therapy, 11 were relapsed (rel; partial response or better [≥PR], then PD), 10 were refractory (ref; no response/stable disease). Median age was 64 y (range 32-84); 86% had ECOG PS ≤1; 57% had extranodal disease; 81% had Ann Arbor stage III/IV; median no. of prior therapies was 3 (range 1-5). Median time on study was 3.9 mo (range 0.8-22.5); 1 pt continues therapy. Pts discontinued treatment primarily for PD (81%); 2 pts discontinued due to AEs (considered unrelated). PK was similar to prior studies, with rapid absorption and clearance; median steady-state BTK target occupancy was 97%-99% (n=5). ORR (≥PR) for all pts was 24% (5/21; 19% complete response [CR]). NanoString subtyping conducted on 15 pts revealed 5 GCB, 9 activated B-cell (ABC), and 1 unclassified DLBCL. The Table lists characteristics of the 5 responders. Common AEs (any grade) were diarrhea (43%), fatigue (43%), anemia (29%), cough (29%) and dizziness (29%); common Grade 3/4 AEs were anemia (24%), fatigue (10%) and abdominal pain (10%). Three pts had Grade 5 AEs (respiratory failure, meningeal progression, and sepsis); none were drug related. No atrial fibrillation, hypertension, TLS or Grade ≥3 bleeding AEs occurred. Conclusions: Acalabrutinib monotherapy was tolerable and had activity in difficult-to-treat DLBCL pts, including ref pts, supporting further studies in DLBCL. Clinical trial information: NCT02112526.Pt Subtype by Nanostring Rel/ref Prior therapies, # Best response DOR, mo PFS, mo 1 ABC Ref 3 CR 0.7+ 2.6+ 2 ABC Rel 2 CR 13.7+ 15.5+ 3 ABC Rel 2 PR 1.8 3.7 4 (ongoing) GCB Ref 3 CR 15.9+ 20.3+ 5 Missing Rel 4 CR 1.9 3.8 +Censored.
Older adults' perspectives on incorporating life expectancy in cancer screening.
Authors: Kimberley Lee, Antonio C. Wolff, Craig Evan Pollack, Cynthia Boyd, Sydney Morss Dy, Nancy Schoenborn
Journal: Journal of Clinical Oncology (2016)

6588 Background: Professional societies recommend that a patient’s life expectancy be incorporated in cancer screening as the benefits of screening may take years to accrue but the harms may be more immediate. Older adults’ perspectives regarding incorporating life expectancy into cancer screening recommendations remain largely unknown. Methods: We conducted individual interviews with 30 community dwelling adults 65+ years of age. We explored their perspectives on the role of life expectancy in cancer screening and preferences for related discussions; we also explored reactions to a recommendation to not perform cancer screening in patients not likely to live 10 years. Two investigators independently coded audio recordings of the interviews using qualitative content analysis and results are summarized as major themes rather than numerical representations. Results: The participants’ mean age was 76, 57% were female, and 80% were white. We identified five major themes: Most participants believe that factors such as health and functional status should be considered along with age in cancer screening decisions; Despite these beliefs, most participants reacted negatively to the wording of the recommendation not to perform cancer screening in patients not likely to live 10 years; Participants reported skepticism for physicians’ abilities to estimate life expectancy; Many participants did not want their provider to explicitly discuss life expectancy with them as a reason for stopping cancer screening but an offer to discuss life expectancy with option to decline was acceptable to participants; Patients who endorsed high levels of trust in their physician were more receptive to the life expectancy-related discussions. Conclusions: Despite increasing recommendations that advocate for life expectancy to be incorporated in cancer screening decisions, older adults report being skeptical of physicians’ ability to estimate life expectancy and reluctant to discuss life expectancy in the context of cancer screening. Physicians should ask for permission to discuss life expectancy, then provide detail according to the patients’ comfort level, so they may make informed, individualized decisions regarding cancer screening.
Abstract 20471: Local Induction of miR21 Increases Fibrous Cap Stability in Vulnerable Atherosclerotic Lesions
Authors: Hong Jin, Yuhuang Li, Alexandra Bäcklund, Ekaterina Chernogubova, Albert Busch, Suzanne Eken, Peter Gustafsson, Ljubica Perisic, Ulf Hedin, Lars Maegdefessel
Journal: Circulation (2017)

Purpose of the current study was to assess the role of miRNAs in fibrous cap stability of advanced atherosclerotic lesions. We used a miRNA-array to analyze laser captured micro-dissected tissue sp...
Management of patients with head and neck cancer (HNC) and synchronic stage I or II lung cancer. SYNCHRON GFPC 15-01 study.
Authors: Laurie Saramon, Nicolas Paleiron, Gilles Robinet, Radj Gervais, Pierre Fournel, Hervé Le Caer, Henri Berard, Olivier Bylicki, Jean Rousset, Gerald Valette, Christos Chouaid
Journal: Journal of Clinical Oncology (2017)

e20048 Background: There is few published data’s of the management of patients with a HNC and a synchronic lung cancer. The aim of this observational study was to describe in a multicentric setting the management of these patients. Methods: The study included, consecutively all patients diagnosed between January 2011 and December 2015 in 19 French centers with a HNC and a synchronic lung cancer. Patients were described per the clinical characteristics, management and outcomes. Patient characteristics and treatment information was analyzed descriptively. Kaplan-Meier estimation was used to assess median overall survival. Results: The study included 62 patients: men : 84%; 62 ± 1.3 years old, current smokers: 68%, asbestos exposure: 11%; performans status: 0 and 1 for 22.5% and 66% of the patients respectively; hight rate of comorbidities, cardiovascular: 68%, COPD: 32%. Main histology for HNC was squamous: 98%, in oral cavity: 32%, oropharyngeal: 21%, hypo-pharyngeal: 22.5% and laryngeal: 24%. T classification was T1, T2, T3 and T4 in 18%, 29%, 29% and 16% of cases respectively, and N classification was N0, N1, N2, N3, for 40%, 24%, 21% and 6% of cases respectively. The main treatment was surgery, 47%, and chemo-radiotherapy, 52%. The diagnosis of lung cancer impacts the HNC management in 21% of the cases. Median delay between HNC and first day treatment was 54 ± 6 days. HNC progressive free survival rate was 68% at 2 years. Lung cancers were localized (stages I: 81%, stages II: 19%), squamous: 32%, adeno-carcinomas: 47%, larges cells or sarcomatosis: 7%. Main treatments were surgery: 56%, mainly lobectomy, radiotherapy: 15%, radio-chemotherapy: 10% and chemotherapy alone: 26%. Six patients didn’t receive active treatment. Median delay of treatment was 150 ± 16 days. Lung cancer progressive free survival rate was 28% at 2 years. OS was 55% at 2 years, better for stage I than stage II lung cancers. Conclusions: Synchronic lung cancer at HCN diagnosis impact management and outcomes of HNC with a delay in the management of lung cancer. Specific recommendations should be elaborate to improve the management of these patients.
Survival analysis of patients carrying different FLT3 mutations (internal tandem duplication (ITD) and tyrosine kinase domain (TKD) mutations) in 459 consecutive non M3 newly diagnosed acute myeloid leukemia (AML).
Authors: Eugenia Franchini, Cristina Papayannidis, Giovanni Marconi, Andrea Ghelli Luserna di Rorà, Giorgia Simonetti, Viviana Guadagnuolo, Antonella Padella, Valentina Robustelli, Elisa Zuffa, Maria Chiara Abbenante, Claudia Venturi, Marco Manfrini, Sarah Parisi, Stefania Paolini, Chiara Sartor, Silvia Lo Monaco, Elena Tenti, Maria Chiara Fontana, Emanuela Ottaviani, Giovanni Martinelli
Journal: Journal of Clinical Oncology (2016)

e18521 Background: AML is a disease with a high number of various mutations and genomic abnormalities; most of them have a proved prognostic value. We focused on FLT3 gene, which shows a high heterogeneity of mutations, to assess how difference in mutations affect prognosis. Methods: In a cohort of 459 consecutive patients, we analyzed at the diagnosis FLT3 gene with qualitative PCR, Denaturing High Pressure Liquid Chromatography, and Sanger sequencing in positive patients. Survival analysis was performed with Kaplan-Meier method using Mantel-Cox test. Results: At diagnosis, 55 out of 459 patients (12.0%) harbor ITD mutation, 22/459 (4.8%) TKD mutation; 4/459 (.9%) ITD mutated patients had concomitant TKD mutation. Median survival was 13.2 months in ITD group, 6.5 months in TKD group, and 27.2 months in ITD/TKD group. There were no statistical difference between these groups. In 3 TKD patients, ITD mutation was detected after first course of therapy; we cannot define if it is due to detection limit, or to a de novo mutation in a sub-clone. In 1 patient a TKD mutation emerged after several week of treatment with a FLT3 inhibitor, with concomitant loss of therapy response. This finding can underline a mechanism of resistance to FLT3 inhibitors drugs. In ITD mutant patients, we considered the number of nucleotide duplicated. Fifteen out of 55 patients harboring ITD involving a low number of nucleotides (ITD < 30 nucleotides) showed a better outcome in term of overall survival compared with 40/50 patients harboring ITD involving high number of nucleotides (ITD ≥30 nucleotides)(p = 0.009). Median OS was 33.8 and 12.6 months in the 2 groups, respectively. Conclusions: In AML, FLT3 mutation defines a poor prognosis. Particularly in the ITD group, we proved that patients with worst prognosis is identified by ITD major or equal to 30 nucleotides. In the era of personalized medicine, we should check biological impact of every peculiar mutation to better define treatment strategy tailored on single patients. Acknowledgments: founded by ELN, AIL, AIRC, Progetto Regione-Università 2010-12 (L.Bolondi), FP7 NGS-PTL project
Inhaled corticosteroids in COPD: friend or foe?
Authors: Alvar Agusti, Leonardo M. Fabbri, Dave Singh, Jørgen Vestbo, Bartolome Celli, Frits M.E. Franssen, Klaus F. Rabe, Alberto Papi
Journal: European Respiratory Journal (2018)

The efficacy, safety and positioning of inhaled corticosteroids (ICS) in the treatment of patients with chronic obstructive pulmonary disease (COPD) is much debated, since it can result in clear clinical benefits in some patients (“friend”) but can be ineffective or even associated with undesired side effects, e.g. pneumonia, in others (“foe”). After critically reviewing the evidence for and against ICS treatment in patients with COPD, we propose that: 1) ICS should not be used as a single, stand-alone therapy in COPD; 2) patients most likely to benefit from the addition of ICS to long-acting bronchodilators include those with history of multiple or severe exacerbations despite appropriate maintenance bronchodilator use, particularly if blood eosinophils are &gt;300 cells·µL −1 , and those with a history of and/or concomitant asthma; and 3) the risk of pneumonia in COPD patients using ICS is higher in those with older age, lower body mass index (BMI), greater overall fragility, receiving higher ICS doses and those with blood eosinophils &lt;100 cells·µL −1 . All these factors must be carefully considered and balanced in any individual COPD patient before adding ICS to her/his maintenance bronchodilator treatment. Further research is needed to clarify some of these issues and firmly establish these recommendations.
EORTC1527/JCOG1609INT: Diffusion-weighted MRI (DW-MRI) assessment of liver metastasis to improve surgical planning (DREAM).
Authors: Kozo Kataoka, Carmela Aves Caballero, Laurence Collette, Kenichi Nakamura, Yoji Kishi, Patrick Starlinger, Hiroaki Onaya, Takeshi Suto, Michel Ducreux, Yasuhiro Shimada, Sabine Tejpar, Laura Rubbia-brandt, Gina Brown, Manabu Shiozawa, Serge Evrard
Journal: Journal of Clinical Oncology (2017)

TPS3633 Background: For patients with initially unresectable colorectal liver metastases (CRLM) with good clinical response to chemotherapy, the presence of disappearing liver metastases (DLMs) diagnosed by CT is a major independent prognostic factor. DW-MRI as well as contrast enhanced (CE)-MRI is recommended to detect and characterize CRLM. However, the correlation between radiological and pathological complete response has not been fully investigated using these latest imaging and pathology techniques. Our main aim is to demonstrate the added value of DW-MRI, CE-MRI to that of CT alone to provide precise assessment of the viability of DLMs. In addition, we aim to optimize the therapeutic management of CRLM patients. No prospective study has been conducted to determine the predictive value of DW-MRI combined with CE-MRI in confirming sites of DLMs and assessing their true status. Methods: This is the first collaborative study between EORTC, ESSO and JCOG with an integrated quality assurance program for imaging, surgery and pathology. Patients with unresectable CRLM will receive standard systemic chemotherapy and liver resection if resectable. Both CT and MRI (DW-MRI, CE-MRI and T1/T2) will be used to identify confirmed DLMs (cDLMs). cDLMs will be either resected or, if resection is not possible, followed-up without resection until 2 years after surgery to evaluate the true status of the cDLMs. The primary endpoint is negative predictive value (NPV) of DW-MRI, CE-MRI, T1/T2 and CT in confirming the status of cDLMs using as reference either the histopathological complete response or the absence of a local recurrence at the site of cDLMs during the follow up period of 2 years. The study aims at excluding a NPV≤0.85 and is powered under the alternative that the NPV≥0.95. The planned sample size is 92 evaluable (resected or left behind) cDLMs, with a 1-sided alpha of 5% and a power of 90% adjusting for within-patient correlation between cDLMs of 0.2 and an average number of 2 cDLMs per patient. Approximately 400 patients will be registered from European, Japanese and US sites over 3 years. As of February 2017, 2 patients have been enrolled. Clinical trial information: NCT02781935.
A phase I trial of pomalidomide for children with recurrent, progressive/refractory central nervous system (CNS) tumors: A Pediatric Brain Tumor Consortium (PBTC) study.
Authors: Jason R. Fangusaro, Duane Anthony Mitchell, Mehmet Kocak, Arzu Onar-Thomas, Zsila Sousan Sadighi, Patricia Ann Baxter, Eugene I. Hwang, Jianping Huang, Ira J. Dunkel, Maryam Fouladi, Katherine E. Warren
Journal: Journal of Clinical Oncology (2017)

10543 Background: CNS malignancies are the most common solid tumors among children. Novel therapies are needed to help improve the survival outcomes in children with recurrent disease. Pomalidomide is an immunomodulatory agent thought to also function through a combination of anti-angiogenic, anti-inflammatory and cytotoixic activity making it a good candidate to explore in pediatric CNS tumors. Methods: A Phase I trial of pomalidomide was conducted among children ≥ 3 to &lt; 21 years old with recurrent, progressive/refractory CNS tumors using the “rolling 6” dose escalation design. The primary objective was to determine the maximum tolerated dose (MTD) and/or recommended Phase II dose (RP2D) when given orally once daily for 21 consecutive days of a 28-day course. Once the MTD was established, 12 additional patients were enrolled on expansion cohorts based on age and steroid use. Results: 29 children were enrolled and 25 were evaluable for dose limiting toxicity (DLT) evaluation. The MTD was 2.6 mg/m 2 (Dose level 2). DLTs observed at dose level 3 (3.4 mg/m 2 ) included diarrhea (n = 1), thrombocytopenia (n = 1) and lung infection (n = 1), all grade 3. The most common toxicities were grade 1 lymphopenia (55%), leukopenia (62%) and thrombocytopenia (38%). There were no obvious differences in tolerability based on age or steroid use. Pharmacokinetics were similar to those observed in adults and increased in a dose-dependent manner. At the RP2D of 2.6 mg/m 2 , the C max was 97.4 ng/mL and the t½ was 4.1 hours. The median number of treatment cycles was 1.6 (0.2-12.3). Two patients, one with an oligodendroglioma and one with anaplastic pleomorphic xanthoastrocytoma, had long term stable disease for 9 and 18+ cycles. No objective responses were observed. Twelve month progression-free and overall-survivals were 5.2+/-3.6% and 12.8+/-8.5%, respectively. Immunologic correlate analyses are ongoing. Conclusions: The RP2D of pomalidomide is 2.6 mg/m 2 in children with recurrent brain tumors. Further prospective evaluation of this agent alone or in combination will be necessary to better understand its efficacy in specific pediatric CNS tumor populations. Clinical trial information: NCT02415153.
Abstract 12134: Gut Microbiota Play a Role in Calcific Aortic Valve Stenosis
Authors: Duygu Kocyigit, Kadri M Gurses, Marcus Stahlman, Jan Boren, Mehmet F Soyal, Hande Canpinar, Dicle Guc, Arzu Ayhan, Tuncay Hazirolan, Kudret Aytemir, Necla Ozer, Lale Tokgozoglu
Journal: Circulation (2017)

Introduction: Degenerative aortic valve disease is the most prevalent valvular heart disease. Its pathogenesis has not been elucidated clearly. Hypothesis: In this study, we aimed to investigate th...
Parents’ understanding of the risk of late effects of pediatric cancer therapy.
Authors: Katie Greenzang, Angel Cronin, Tammy I Kang, Jennifer W. Mack
Journal: Journal of Clinical Oncology (2016)

10522 Background: Over 80% of children with cancer will become long-term survivors, yet the majority of survivors experience late effects of cancer or its treatment. Previous work demonstrated that parents are more pessimistic than physicians about their child’s risk of late effects. We evaluated how parental understanding of the likelihood of late effects differs by physician-estimated risk. Methods: We surveyed 352 parents of children with cancer within 12 weeks of diagnosis, and the children’s oncologists, at Dana-Farber/Boston Children’s Cancer and Blood Disorders Center and Children’s Hospital of Philadelphia. We assessed parent and physician perceptions of the likelihood of the child having future limitations in physical abilities, intelligence or quality of life (QOL) as a result of cancer treatment. Children with a physician-estimated risk of limitations of 50% or greater were defined as high risk. Results: Physicians considered 22% of children at high risk of physical impairments, 9% high risk for impairments in intelligence, and 6% high risk for impaired QOL (Table). Among high-risk children, 38% of parents recognized this risk in physical abilities, 21% in intelligence, and 5% in QOL. Accuracy, defined as concordant parent and physician estimates, was higher among parents of children at lower risk of future limitations in intelligence (p = 0.001) and QOL (p < 0.001) than in those with high risk. Regardless of the child’s risk of future impairment, the majority of parents considered it extremely or very important to receive information about the impact of cancer treatment on their child’s future (92%), and preferred a high level of detail (86%). Conclusions: Although most parents want detailed information about life after cancer, most parents of children at high risk of future impairment do not recognize this risk. Strategies to improve communication about late effects may better meet information needs, and improve parent understanding of risk of future impairment. Physician estimated risk of impairment. High Risk ( ≥ 50%) Moderate Risk (10-49%) Low Risk ( < 10%) Limitations in Physical Abilities 76 (22) 153 (43) 123 (35) Limitations in Intelligence 33 (9) 142 (40) 177 (50) Limitations in Quality of Life 22 (6) 161 (46) 169 (48)
Abstract 19608: Electrical Signature of Heart Failure With Preserved Ejection Fraction
Authors: Kyndaron Reinier, Aapo Aro, Audrey Uy-Evanado, Carmen Rusinaru, Eric C Stecker, Gregory Nichols, Karen Gunson, Jonathan Jui, Sumeet S Chugh
Journal: Circulation (2017)

Introduction: Heart failure with preserved ejection fraction (HFpEF) is an increasingly common condition, but the heterogeneous and complex nature of this condition prevents effective diagnosis and management. The majority of patients with HFpEF undergo electrical remodeling of the myocardium manifesting with ECG abnormalities. Hypothesis: HFpEF is associated with multiple abnormal ECG markers. Methods: A pooled analysis of prospectively identified sudden cardiac arrest (SCA) cases and geographical controls (69% with coronary disease) was performed from an ongoing community-based study in the US Northwest (catchment population ~1 million). Subjects were required to have an archived 12-lead ECG, echocardiographically-determined LVEF, and clinical history available for analysis. Using logistic regression, we evaluated 10 ECG parameters for association with HFpEF vs. normal subjects. HFpEF was defined as clinical history of HF with EF≥50%, and normal subjects were those with EF≥50% and no HF. Results: Indivi...