tbuckley/cabot-search huggingface dataset:
Trends in Nationwide Herpes Zoster Emergency Department Utilization From 2006 to 2013
Authors: Erica D. Dommasch, Cara J. Joyce, Arash Mostaghimi
Journal: JAMA Dermatology (2017)

The effect of vaccination on emergency department (ED) utilization for herpes zoster (HZ) has not been examined to date.To determine trends in US ED utilization and costs associated with HZ.The Nationwide Emergency Department Sample data set was examined for temporal trends in the number of visits and costs for treatment of HZ in EDs in the United States from January 1, 2006, through December 31, 2013. Cases of HZ were identified using validated International Classification of Diseases, Ninth Revision-Clinical Modification diagnosis codes. Patients were stratified by age: less than 20 years (varicella vaccine recommended), 20 to 59 years (no vaccine recommended), and 60 years or older (HZ vaccine recommended). Population-based rates were estimated using sampling weights.Population-based incidence rates of HZ-related ED visits, charge for ED services, and total charges.A total of 1 350 957 ED visits for HZ were identified between 2006 and 2013, representing 0.13% of all US ED visits. Of these patients, 563 200 (51.7%) were male; mean (SE) age was 54.0 (0.1) years. Between 2006 and 2013, the percentage of HZ-related ED visits increased from 0.13% to 0.14% (8.3%). This growth was driven by patients aged 20 to 59 years (increase of 22.8% [from 0.12% to 0.14% of ED visits]) while the proportion of ED HZ visits decreased for patients aged less than 20 years and 60 years or older, from 0.03% to 0.02% (-39.6%) and from 0.28% to 0.25% (-10.9%), respectively. For all age groups, there was an increase from 2006 to 2013 in overall adjusted total (from $92.83 to $202.47 million) and mean charges (from $763 to $1262) for HZ-related ED visits.The number of ED visits and total cost associated with HZ increased between 2006 and 2013. Greater use was driven by an increased number of visits by patients aged 20 to 59 years, but populations recommended for vaccination (<20 and ≥60 years) demonstrated decreased ED utilization. Per-visit and total costs increased across all age groups. Vaccination may be associated with a reduction of ED utilization. Further research is required to confirm these results and examine the drivers of increased ED costs.
<i>EIF1AX</i> and <i>NRAS</i> Mutations Co-occur and Cooperate in Low-Grade Serous Ovarian Carcinomas
Authors: Dariush Etemadmoghadam, Walid J. Azar, Ying Lei, Tania Moujaber, Dale W. Garsed, Catherine J. Kennedy, Sian Fereday, Chris Mitchell, Yoke-Eng Chiew, Joy Hendley, Raghwa Sharma, Paul R. Harnett, Jason Li, Elizabeth L. Christie, Ann-Marie Patch, Joshy George, George Au-Yeung, Gisela Mir Arnau, Timothy P. Holloway, Timothy Semple, John V. Pearson, Nicola Waddell, Sean M. Grimmond, Martin Köbel, Helen Rizos, Ivan B. Lomakin, David D.L. Bowtell, Anna deFazio
Journal: Cancer Research (2017)

Low-grade serous ovarian carcinomas (LGSC) are associated with a poor response to chemotherapy and are molecularly characterized by RAS pathway activation. Using exome and whole genome sequencing, we identified recurrent mutations in the protein translational regulator EIF1AX and in NF1, USP9X, KRAS, BRAF, and NRAS RAS pathway mutations were mutually exclusive; however, we found significant co-occurrence of mutations in NRAS and EIF1AX Missense EIF1AX mutations were clustered at the N-terminus of the protein in a region associated with its role in ensuring translational initiation fidelity. Coexpression of mutant NRAS and EIF1AX proteins promoted proliferation and clonogenic survival in LGSC cells, providing the first example of co-occurring, growth-promoting mutational events in ovarian cancer. Cancer Res; 77(16); 4268-78. ©2017 AACR.
Endotracheal Leiomyoma Mimicking Malignancy on 18F-FDG PET/CT in a Patient With Papillary Thyroid Carcinoma
Authors: Jae Pil Hwang, Seung-Won Lee, Jeong Ja Kwak, Jung Mi Park
Journal: Clinical Nuclear Medicine (2017)

Endotracheal leiomyoma is a rare benign lesion, accounting for approximately 1% of tracheal tumors, and generally occurs in the lower respiratory tract. Because its growth causes airway obstruction symptom, surgical treatment is generally suggested after detection. We report a case with leiomyoma of the cervical endotracheal space showing intense FDG uptake on F-FDG PET/CT mimicking malignancy in a 79-year-old woman with papillary thyroid carcinoma.
Gastrostomie per cutanée (GPE) chez les malades ne pouvant consentir, pourquoi? pour qui? comment? Résultats d'une enquête chez les gastro-entérologues (GE) de Midi-Pyrénées
Authors: L Escudié, JL Payen, F March, M Carreiro, C Seigneuric
Journal: Endoscopy (2006)

Nous avons tous, un jour, dans notre pratique endoscopique, placé une GPE chez un patient incapable de donner son consentement éclairé.
Circulating tumor cells as an early detection tool for BRCA positive women?
Authors: Georg Pfeiler, Maria Bernathova, Zsuzsanna Bago-Horvath, Thomas Helbich, Alex Farr, Christian F. Singer, Margaretha Rudas, Muy-Kheng Maria Tea, Tanja N. Fehm
Journal: Journal of Clinical Oncology (2016)

e13025 Background: Women with BRCA mutation have a high risk to develop breast and ovarian cancer. Even though intensive radiologic breast cancer screening is successful in this group of patients, surgery and systemic treatment will not be prevented. Several clinical trials have shown that detection of circulating tumor cells (CTC) in adjuvant treated breast cancer patients are a good prognostic tool and might be reason enough to re-start treatment. In this prospective study we investigated the presence of CTCs and their possible predictive value regarding any cancer diagnosis in cancer-free women with germline BRCA mutation. Methods: In 2009, cancer-free women with BRCA germline mutation, without previous bilateral prophylactic mastectomy, were included in the study. Before blood sample donation, all women were screened by mammography and breast-MRI as well as vaginal ultrasonography, and CA-12.5 assessment. All samples underwent immunomagnetic enrichment using the AdnaTest BreastCancerSelect (AdnaGen AG, Germany) within 4h after blood withdrawal. Patients were followed by mammography and breast-MRI as well as vaginal ultrasonography, and CA-12.5 if applicable. Results: A total of 10 patients with a median age of 45 years (35-54 years), all harboring BRCA germline mutation were enrolled. The median follow-up was 5.8 years, last breast-MRI and mammography were performed in 2014/2015. Five patients (50%) have had a prophylactic bilateral salpingo-ovarectomy plus hysterectomy, all before 2009. 2 patients developed a vulvar lichen sclerosus, 1 with and 1 without salpingo-ovarectomy, respectively. CTCs were detected in 1 out of 10 (10%) women. The cells were detected in 2 separately analyzed blood samples and were positive for Her-2, Akt-2, Twist1, PI3Ka and ALDH1. Annually mammography and breast-MRI were without any signs of malignancy in this patient. At the end of 2014 the patient underwent bilateral prophylactic mastectomy showing benign histology. Since 2009, no other patient underwent breast surgery or was diagnosed with any kind of cancer. Conclusions: Circulating tumor cells were detected in 1 out of 10 BRCA.positive cancer-free patients, but did not lead to cancer diagnosis with a follow-up of more than 5 years.
Factors associated with non use of adjuvant trastuzumab in older patients with HER2+ breast cancer.
Authors: Ines Vaz Luis, Nancy U. Lin, Nancy Lynn Keating, William Thomas Barry, Joyce Lii, Harold J. Burstein, Eric P. Winer, Rachel A. Freedman
Journal: Journal of Clinical Oncology (2016)

601 Background: Although adjuvant trastuzumab for human epidermal growth factor (HER2)+ breast cancer (BC) is highly efficacious regardless of age, the real world use of trastuzumab for older patients is not known. Methods: We used Surveillance, Epidemiology and End Results (SEER) Medicare data to identify patients aged ≥66 with stage I-III HER2+ BC diagnosed in 2010-2011(when HER2 was available). Multivariable logistic regression examined characteristics associated with trastuzumab non use. Results: Among 1900 women, 77% were ≤ age 80, 76% had a comorbidity score=0, 6% had history of congestive heart failure (CHF), 72% had hormone receptor (HR)+BC, and 15% had stage III disease. Overall, 51% did not receive adjuvant trastuzumab and 30% did not receive any systemic therapy. Older age, CHF, favorable disease characteristics (lower stage, HR+), black race, and low socio-economic status were strongly associated with non use of trastuzumab (Table). Even among patients with higher risk cancers, a substantial proportion were not treated with trastuzumab, including patients with stage III disease AND the following characteristics: HR- (24%), comorbidity score=0 (25%), black race (46 %) and age 66-70 (18%). Conclusions: Many older patients do not receive adjuvant trastuzumab-based therapy and 30% of all patients received no systemic therapy for their cancers. Although treatment omission may be appropriate in specific cases, we noted substantial disparities in trastuzumab use, even among patients with higher risk disease, suggesting that a significant proportion of patients who would be expected to benefit from trastuzumab are not receiving treatment. Strategies to optimize and standardize care for older patients with HER2+ disease are urgently needed. Trastuzumab non use. Variable % Adjusted OR 95% CI Age 66-70 40 1.0 71-75 42 1.1 0.8-1.4 76-80 55 2.2 1.6-3.0 ≥80 73 5.1 3.3-7.9 Race/Ethnicity White 51 1.0 Black 64 2.0 1.5-2.7 Median income Lowest 57 1.0 Highest 48 0.7 0.6-0.9 Prior CHF Yes 74 1.0 No 50 1.8 1.2-2.6 Stage Ia 76 1.0 Ib 56 0.3 0.1-0.9 II 42 0.2 0.1-0.3 III 32 0.1 0.1-0.2 Grade High 40 1.0 Intermediate 58 1.7 1.4-2.2 Low 81 5.0 3.5-6.3 HR + 54 1.0 - 45 0.8 0.7-0.9 Adjusted by geography, education, tumor size, nodes, comorbidity.
Phase I trial of the combination of the multikinase inhibitor nintedanib plus letrozole: A window of opportunity trial in adjuvant hormone-receptor positive breast cancer (HRPBC).
Authors: Laura Medina Rodriguez, Juan Antonio Guerra, Diego Malon, Rodriguez Laura, Ramon Colomer, Miguel Quintela-Fandino
Journal: Journal of Clinical Oncology (2016)

TPS615 Background: In a 290 HRPBC patient series we found a 7.9% of cases harbouring FGFR1 amplification, associated to a 5.5-fold increase in relapse risk. In vitro data with a panel of 5 HRPBC cell lines with and 4 without FGFR1 amplification revealed that hormonal deprivation (preclinical model of aromatase inhibition) abrogated cell growth by > 90% in FGFR1-negative cell lines but less than 50% in the remainder. Nintedanib is a multikinase inhibitor of VEGFR1-4, PDGFRA/B and FGFR1/3, and has activity in several malignancies. Its anti FGFR1 effects are less studied than its antiangiogenic effects. In vitro it lacked effect against FGFR1-negative lines but induced 40-70% growth inhibition in the amplified ones. Only the combination of hormonal deprivation and nintedanib induced > 90% cell growth inhibition in FGFR1-amplified cell lines. The data were confirmed in a FGFR-1 amplified xenograft model controlled by sorafenib (antiangiogenic without anti-FGFR1 activity). FGFR inhibitors have not shown high activity in HRPBC patients with FGFR1 amplification; our data suggest that the combination with aromatase inhibitors is required. Methods: Multicentric, phase I, dose escalation study followed by an expansion cohort. Dose-escalation: 3+3 design with fixed dose of letrozole (2.5 mg/d) and escalating levels of nintedanib, starting in 150 mg/b.i.d. (maximum of 250 mg/b.i.d.), on a continuous schedule. Pharmacokinetics (PK) profile and blood samples for determining FGF23 (pharmacodynamic engagement of FGFR1), will be drawn on days 1, 15 and 28 of first cycle. Expansion cohort: 10 patients, treated with the recommended phase II dose (RP2D) for 1 month (optional 6 months). FGF23 will be determined on days 1, 15, 29 and monthly thereafter. Objectives: Primary: determine the RP2D based in the toxicity and PK profiles; assess PD engagement (expansion); secondary: toxicity and safety (in both phases). Key inclusion criteria: Postmenopausal HRPBC women > 18 years old with negative HER2 that have been receiving adjuvant treatment with letrozole for less than 6 months at the inclusion date. Patient enrollment started in August 2015. Clinical trial information: NCT02619162.
Oncologists' estimates of expected survival time and scenarios for survival: accuracy in the ALTG NITRO trial of 1st line chemotherapy for advanced non–small-cell lung cancer.
Authors: Annette Tognela, David Espinoza, Andrew Davidson, Matthew MK Chan, Brett Gordon Maxwell Hughes, Michael J. Boyer, Karen P. Briscoe, Stephen Begbie, Nick Muljadi, Xanthi Coskinas, Nick Pavlakis, Michael Millward, Martin R. Stockler, Belinda E. Kiely
Journal: Journal of Clinical Oncology (2016)

9074 Background: We have proposed that best, worst, and typical scenarios for survival, based on simple multiples of an individual’s expected survival time (EST) estimated by their oncologist, are a useful way of formulating and explaining prognosis in advanced cancer. The aim of this study was to determine the accuracy and prognostic significance of such estimates in a multicenter, randomized trial. Methods: Oncologists recorded their estimate of the ‘expected survival time’ at baseline in each of 372 patients recruited in the NITRO trial. We hypothesized that oncologists’ estimates of EST would be well-calibrated (~50% of patients living longer or shorter than EST) and imprecise ( < 33% living within 0.75 to 1.33 time their EST), but provide accurate scenarios for survival time (~10% dying within a quarter of their EST, 10% living longer than 3 times their EST, and 50% living for half to double their EST). We also hypothesized that oncologists’ estimates of EST would be independently significant predictors of survival in a multivariable Cox model adjusting for traditional prognostic factors selected in the first 250 participants recruited, and validated in the remaining 122. Results: Oncologists’ estimates of EST were well calibrated (51% of patients lived longer than their EST), but imprecise (24% lived within 0.75 to 1.33 times their EST). Scenarios based on the oncologists’ estimates were accurate: 9% of patients died within ¼ of their EST, 12% lived longer than 3 times their EST, and 53% lived from half to double their EST. Oncologists’ estimates of EST were independently significant predictors of overall survival (HR 0.92, 95% CI 0.88 to 0.96, p < 0.001) in Cox models accounting for ECOG performance status, liver metastases, neutrophil to lymphocyte ratio, and anaemia. Conclusions: Oncologists’ estimates of EST were well calibrated, imprecise, and independently significant predictors of survival above and beyond traditional prognostic factors. Best, worst and typical scenarios for survival based on EST were remarkably accurate, and are a good solution to the problem of estimating prognosis in advanced cancer. Clinical trial information: ACTRN12608000588392.
Functionally Null <i>RAD51D</i> Missense Mutation Associates Strongly with Ovarian Carcinoma
Authors: Barbara Rivera, Massimo Di Iorio, Jessica Frankum, Javad Nadaf, Somayyeh Fahiminiya, Suzanna L. Arcand, David L. Burk, Damien Grapton, Eva Tomiak, Valerie Hastings, Nancy Hamel, Rabea Wagener, Olga Aleynikova, Sylvie Giroux, Fadi F. Hamdan, Alexandre Dionne-Laporte, George Zogopoulos, Francois Rousseau, Albert M. Berghuis, Diane Provencher, Guy A. Rouleau, Jacques L. Michaud, Anne-Marie Mes-Masson, Jacek Majewski, Susanne Bens, Reiner Siebert, Steven A. Narod, Mohammad R. Akbari, Christopher J. Lord, Patricia N. Tonin, Alexandre Orthwein, William D. Foulkes
Journal: Cancer Research (2017)

RAD51D is a key player in DNA repair by homologous recombination (HR), and
Incidental germline findings identified in a somatic genomic sequencing program for advanced cancer patients.
Authors: Neda Stjepanovic, Philippe L. Bedard, Amit M. Oza, Blaise Clarke, Monika K. Krzyzanowska, Raymond Woo-Jun Jang, Neesha C. Dhani, Natasha B. Leighl, Abha A. Gupta, Christine Elser, Jeanna McCuaig, Melyssa Aronson, Spring Holter, Kara Semotiuk, Lailah Ahmed, Lisa Wang, Tracy Stockley, Suzanne Kamel-Reid, Lillian L. Siu, Raymond Kim
Journal: Journal of Clinical Oncology (2016)

1532 Background: Next generation sequencing (NGS) of tumor DNA is used to match precision cancer therapies. Germline DNA is often co-analyzed to aid in tumor variant interpretation, but may identify a previously unrecognized hereditary cancer syndrome (HCS). We reviewed germline variants and analyzed patients' (pts) preferences in learning about HCSs discovered through an institutional somatic NGS program (NCT01505400). Methods: Advanced cancer pts with ECOG ≤ 1 were offered tumor-germline NGS using the Illumina TruSeq Amplicon Cancer Panel with 48 cancer genes designed specifically for somatic profiling. This also included the HCS genes: APC, ATM, CDH1, CDKN2A, KIT, MET, MLH1, PTEN, RB1, RET, SMAD4, SMARCB1, STK11, TP53, and VHL. All pts were provided with an optional IRB-approved consent for return of incidental germline pathogenic/likely pathogenic variants in HCS genes with appropriate genetic counselling. Results: From Aug/2013 to Nov/2015, 1937 pts were enrolled. Median age was 59, 67% were women and 18% had prior genetic testing. 1817 pts (94%) consented to be informed of incidental germline results and 103 pts (5%) declined, with no statistically significant differences based on age, sex, race or prior genetic testing. Of 1538 pts (85%) who successfully underwent NGS testing of tumor and germline, eight were found to have pathogenic germline variants in HCS genes. Three pts were previously clinically identified: one with Familial adenomatous polyposis (APC) and two with Li-Fraumeni syndrome (LFS, TP53). Five pts had previously unrecognized germline pathogenic variants: three in TP53 (LFS), of which only one fulfilled Chompret's criteria, and one in SMARCB1 (schwannomatosis) in the absence of syndrome features. One harbored a TP53variant at 16% allele frequency suggesting an acquired event in blood, rather than LFS. Conclusions: Interest in the return of germline results is high among pts with advanced cancers who undergo somatic profiling. Despite not conducting comprehensive analysis of all potential germline variants, a number of HCSs were still incidentally identified, supporting the involvement of genetic counselling in somatic profiling programs.
Résultats et impact thérapeutique de l'examen par vidéo-capsule endoscopique dans les saignements digestifs inexpliqués
Authors: K Vahedi, X Dray
Journal: Endoscopy (2006)

l'objectif de l'étude était d'évaluer la rentabilité diagnostique et l'impact thérapeutique de l'examen par vidéo-capsule endoscopique (VCE) dans l'exploration des saignements digestifs inexpliqués (SDI).
Performance of mutation risk prediction models in a racially diverse multi-gene panel testing cohort.
Authors: Gregory Idos, Katherine G Roth, Leah Naghi, Charite Nicolette Ricker, Julie Culver, Duveen Sturgeon, Kerry Kingham, Rachel Koff, Nicolette M. Chun, Courtney Rowe-Teeter, Anne-Renee Hartman, Brian Allen, Brent Evans, Meredith Mills, Christine Hong, Kevin McDonnell, Uri Ladabaum, James M. Ford, Stephen B. Gruber, Allison W. Kurian
Journal: Journal of Clinical Oncology (2017)

1523 Background: Mutation carrier prediction models are clinically useful tools for identifying candidates for genetic counseling and testing. Consensus guidelines recommend germline genetic testing for those with a carrier probability (CP) of approximately 5% or higher. However, prediction models may perform less well among racial/ethnic minorities. Our hypothesis is that pathogenic mutations (PM) are identifiable in a clinically meaningful fraction of racially/ethnically diverse patients with a CP of &lt; 5%. Methods: We conducted a multicenter prospective clinical trial of patients undergoing cancer-risk assessment using a 25 gene panel, which include APC, ATM, BARD1, BMPR1A, BRCA1, BRCA2, BRIP1, CDH1, CDK4, CDKN2A, CHEK2, EPCAM, MLH1, MSH2, MSH6, MUTYH, NBN, PALB2, PMS2, PTEN, RAD51C, RAD51D, SMAD4, STK11, TP53. Patients were recruited from August 2014 to November 2016 at three centers. Patients were enrolled if they met standard clinical criteria for genetic testing or were predicted to have a ≥2.5% probability of inherited cancer susceptibility using validated prediction models. We evaluated the CP of patients with a PM in BRCA1, BRCA2, and/or a mismatch repair (MMR) gene using the following models: (1) BRCApro, (2) MMRpro and (3) PREMM 1,2,6 . Results: Of 2000 patients enrolled in this cohort, 80.6% are female (n = 1612). Regarding race/ethnicity, the cohort is 40.1% Non-Hispanic White (n = 802), 37.4% Hispanic (n = 748), 11.5% Asian (n = 230), 3.9% Black (n = 78), and 7.1% Other (n = 142). Among 241 (12.1%) patients who tested positive for a pathogenic mutation, 76 (31.5%) patients had a BRCA1 or BRCA2 mutation. Of those, 52 (68.4%) patients had a BRCApro CP of &lt; 5%. Thirty-eight (15.8%) patients had a pathogenic mutation in an MMR gene: 19 (50.0%) had an MMRpro CP of &lt; 5%, while 13 (34.2%) had a PREMM 1,2,6 CP of &lt; 5%. The racial/ethnic distribution of BRCA1/2 or MMR mutation carriers is similar to that of the whole cohort. Conclusions: In a diverse cohort of patients undergoing 25-gene multiple-gene panel testing, half or more carriers of BRCA1/2 or MMR mutations had a CP of &lt; 5%, the consensus guideline-recommended cutoff for genetic testing. These results support a lower threshold for genetic testing guidelines. Clinical trial information: NCT02324062.