tbuckley/cabot-search huggingface dataset:
Adjuvant therapy utilization among stage III melanoma patients.
Authors: C. Lance Cowey, Sameer R. Ghate, Whitney C. Rhodes, Thomas Wilson, Briana Ndife, Janet L. Espirito, Rohit Borker, Jennifer R. Frytak, Antonio Reis Nakasato, Nicholas J. Robert
Journal: Journal of Clinical Oncology (2018)

e21574 Background: Adjuvant treatment options for stage III melanoma patients (pts) are increasing with the approval of new agents. Little has been reported about the real world treatment patterns in a modern patient population. This study evaluated clinical characteristics and treatment patterns in Stage III melanoma pts during the time when ipilimumab and interferon were the only FDA approved treatment options. Methods: A retrospective observational cohort study of pts diagnosed with stage III melanoma from 11/2015 to 03/2017, with follow-up through 09/2017 were analyzed. Data were obtained from The US Oncology Network/McKesson Specialty Health iKnowMed electronic health record (EHR) database. Demographics, clinical characteristics, and adjuvant treatment patterns were characterized. Results: 325 pts with stage III melanoma at diagnosis were identified. Patients were staged using AJCC 7th edition criteria. Median follow-up time was 11.4 months. 92 pts (28.3%) initiated adjuvant therapy (adj) while 233 (71.7%) were classified as watch and wait approach (WW), defined as no evidence of systemic treatment for 6 months post-diagnosis (p < 0.05). Overall, 34.2% of pts were stage IIIA (n = 111), 38.8% (n = 126) stage IIIB, 23.1% (n = 75) stage IIIC, and 4.0% (n = 13) stage III not otherwise specified (NOS). The proportion of pts who initiated adj by stage was 22.5%, 32.5%, 26.7%, and 46.2% for IIIA, IIIB, IIIC, and III NOS, respectively. Adj pts predominantly initiated ipilimumab (88.0%) versus interferon (12.0%) (p < 0.05). Median age was 60 years, (59 years adj vs. 61 WW, p = 0.17), and 58.8% were male (55.4% adj vs. 60.1% WW, p = 0.44). Most pts (91.4%) were Caucasian (91.3%, adj, 91.4% WW). Conclusions: The majority (71.7%) of pts with stage III melanoma were not treated with adj, regardless of substage. Understanding adjuvant treatment patterns among stage III melanoma pts is important as new treatment options become available for this population. Additional analyses to evaluate the impact of adj and WW on recurrence and survival are planned.
Comparing adherence levels of CLL treatment from both the patient and physician perspective in the U.S.
Authors: Brad Schenkel, Pam Hallworth, Alex Rider, Brian Macomson, Jacquelyn McRae
Journal: Journal of Clinical Oncology (2017)

e19009 Background: Prior research has shown that there is a lack of congruency between physicians and patients regarding choice of therapy in CLL care. The aim of this study was to look at whether there are any similar differences in regard to perceptions of drug adherence between a group of CLL patients and their corresponding physicians. Methods: From February to May 2016, the Adelphi CLL Disease Specific Programme (DSP) recruited US physicians who are responsible for treatment decision-making in CLL. Patient Record Forms (PRF) and Patient Self-Completion questionnaires (PSC) were completed by physicians and patients, respectively. Means and standard deviations (SD) were calculated for continuous variables, and proportions were calculated for categorical variables. Results: A total of 81 physicians and 326 patients participated in the CLL DSP. The majority of physicians were heme-oncologists (68%), male (79%), and practiced in both a hospital and office-based setting (86%). Physicians reported that 87% of their CLL patients were “always” or “almost always” adherent to their CLL treatment. However, only 42% of patients reported that they were “never” or “hardly ever” non-adherent to CLL treatment. Patients reported that their physicians addressed adherence in the following methods: physicians asked patients about adherence (56%), nurses/other staff assisted patients (23%), physician did not check (15%), pill checking (3%), materials/resources were given (1%), and other (2%). Three-quarters (75%) of physicians reported that they discussed adherence with their CLL patients consistently. Conclusions: In this study, patients’ and physicians’ perceptions of adherence with regard to CLL treatment were not aligned. Although most physicians reported consistent discussions about adherence with their patients, the majority of patients reported subpar adherence to CLL treatment. As more oncology medications, including those approved in CLL, are available in a pill or capsule formulation and thus self-administered, it will be increasingly important to make patients aware of the importance of adhering to their medication and including physicians and caregivers in this dialogue.
Modelling inherited cardiac disease using human induced pluripotent stem cell-derived cardiomyocytes: progress, pitfalls, and potential
Authors: Alain van Mil, Geerthe Margriet Balk, Klaus Neef, Jan Willem Buikema, Folkert W Asselbergs, Sean M Wu, Pieter A Doevendans, Joost P G Sluijter
Journal: Cardiovascular Research (2018)

Abstract In the past few years, the use of specific cell types derived from induced pluripotent stem cells (iPSCs) has developed into a powerful approach to investigate the cellular pathophysiology of numerous diseases. Despite advances in therapy, heart disease continues to be one of the leading causes of death in the developed world. A major difficulty in unravelling the underlying cellular processes of heart disease is the extremely limited availability of viable human cardiac cells reflecting the pathological phenotype of the disease at various stages. Thus, the development of methods for directed differentiation of iPSCs to cardiomyocytes (iPSC-CMs) has provided an intriguing option for the generation of patient-specific cardiac cells. In this review, a comprehensive overview of the currently published iPSC-CM models for hereditary heart disease is compiled and analysed. Besides the major findings of individual studies, detailed methodological information on iPSC generation, iPSC-CM differentiation, characterization, and maturation is included. Both, current advances in the field and challenges yet to overcome emphasize the potential of using patient-derived cell models to mimic genetic cardiac diseases.
Data harmonization hurdles, lessons learned, and recommendations: An imaging study.
Authors: Amrita Basu, Denise Warzel, Justin Kirby, Aras Eftekhari, Janice Knable, John Freymann, Ashish Sharma, Tony Kerlavage
Journal: Journal of Clinical Oncology (2018)

e18603 Background: Data harmonization refers to the processes that enable data from different sources and studies to be combined, queried, and analyzed. This process is becoming exceptionally onerous in healthcare research with data rapidly increasing in variety and volume from different sources without common data standards. Various institutional efforts have focused on designing strategies for data integration, but a lack of enforcement and incentives has resulted in low adoption. The Cancer Imaging Archive (TCIA), sponsored by the NCI Cancer Imaging program, is a growing repository of medical images submitted by investigators worldwide. DICOM standards are predominantly leveraged for archiving and querying the imaging data, but TCIA does not currently require adherence to standards for describing non-image supporting data. Examples of these data include clinical and diagnostic data, patient outcomes, biomarker results, and treatment details. Harmonization of these data would greatly increase the utility of TCIA to imaging researchers. Methods: We identified and retrospectively harmonized non-image supporting data from existing lung and brain image collections from TCIA. We used the Genomic Data Commons (GDC) clinical and specimen data elements as the target standards for our harmonization process. We engaged subject matter experts to help with mappings across terms that had been used for histologic type. This information was used to manually align the instance data values with target data values in the GDC elements to support our query use case. Results: We built a
P01.105 Clinical and imaging features of pseudoprogression in malignant glioma.
Authors: S F Winter, E J Vaios, A Muzikansky, M R Bussière, H A Shih, M Martinez-Lage, F Loebel, P Vajkoczy, J Dietrich
Journal: Neuro-Oncology (2018)

Pseudoprogression (PP) likely represents a unique phenomenon encountered in high-grade glioma patients within the first six months of combined chemoradiation. As PP mimics recurrent disease, patients may need a tissue biopsy to guide management. We here characterize the clinical and imaging features of biopsy-proven PP, aiming to establish pre-selection criteria for patients requiring biopsy. Clinical, radiographic, and histopathological data of patients with malignant glioma and biopsy-proven PP (defined as appearance ≤6 months post radiotherapy (RT) initiation) were retrospectively analyzed. The spatiotemporal pattern of each imaging event/lesion diagnosed as PP defined a region of interest (ROI) and was evaluated via standard T1+C weighted MRI sequences and spatially correlated to the RT treatment plan. Additional non-biopsied ROIs in the same patient with radiographic PP were included in the analysis. 24 patients with biopsy-proven PP were analyzed. All had high-grade gliomas, the vast majority of which were glioblastomas (WHO Grade IV; 87.5%). Tumor pathology revealed MGMT-promoter methylation in 53% (n=9/17), EGFR amplification in 33% (n=7/21) and IDH mutation in 6% (n=1/16). Patient male-to-female ratio was approximately 2:1 and median age at diagnosis was 57.5 years (range: 32 -76 years). All patients underwent RT, 83% had concurrent and adjuvant TMZ-based chemotherapy. Median OS from initial diagnosis was 2.2 years; 12.5% of patients reached 5-year OS. 27 individual radiographic ROIs (n=26 biopsy-proven, n=1 radiographically diagnosed) were analyzed in our cohort. While histopathology of most specimens revealed tissue necrosis, 27% (7/26) showed findings of treatment effect intermixed with foci of solid tumor. Median onset of PP from RT initiation was 2 months (range: 7.5 weeks - 6 months) and associated with new symptoms in over two-thirds of patients, most of which (75%) required steroid treatment.Most patients developed a single ROI (median=1; range: 1 - 5 ROIs) of non-nodular, ring-like enhancing appearance around the tumor resection cavity (RC). Individual ROI size was highly variable (median=3.7 cm2; range: 0.5 - 32 cm2; n=16/27) and only one-fourth of ROIs were located at a distance from the RC (range: 1,2 - 6 cm). Accordingly, 100% of ROIs were located within the main radiation field. PP was enriched in patients with glioblastoma, occurring mostly within 2 months after chemoradiation as a single, ring-like enhancing lesion of variable size. Lesions located to areas exposed to maximum therapeutic radiation dosages, and patients were typically symptomatic requiring anti-edematous therapy and/or surgical debulking. The considerable incidence of lesions with mixed pathology highlights the diagnostic challenge associated with this important neuro-oncological condition.
Transcatheter Mitral-Valve Repair in Patients with Heart Failure
Authors: Gregg W. Stone, JoAnn Lindenfeld, William T. Abraham, Saibal Kar, D. Scott Lim, Jacob M. Mishell, Brian Whisenant, Paul A. Grayburn, Michael Rinaldi, Samir R. Kapadia, Vivek Rajagopal, Ian J. Sarembock, Andreas Brieke, Steven O. Marx, David J. Cohen, Neil J. Weissman, Michael J. Mack
Journal: New England Journal of Medicine (2018)

Among patients with heart failure who have mitral regurgitation due to left ventricular dysfunction, the prognosis is poor. Transcatheter mitral-valve repair may improve their clinical outcomes.
The IBM Cancer Guidelines Navigator, a tool to standardize and raise the quality of cancer care in Sub-Saharan Africa.
Authors: Daniel Strauss, Mark Megerian, Joel Mangan, Alexandra Urman, Ching-Kun Wang, Megan Obrien, Fernando Jose Suarez Saiz
Journal: Journal of Clinical Oncology (2018)

e18556 Background: In Sub-Saharan Africa, cancer is a significant health burden and is expected to rise. Access to quality healthcare is a challenge exacerbated by the limited number of oncologists and limited access to treatment. Treatment guidelines are difficult to apply and advances in cancer care are difficult to implement. Practitioners and cancer management leaders in Africa recognized the need to develop and implement standardized evidence based management of cancer in Sub-Saharan Africa. Methods: To address these challenges, in 2016 the African Cancer Coalition (organization of more than 40 practicing cancer clinicians Sub-Saharan countries) collaborated with the American Cancer Society (ACS) and the National Comprehensive Cancer Network (NCCN) to create the NCCN Harmonized guidelines for Sub-Saharan Africa. These guidelines provide treatment options adapted to Sub-Saharan Africa. For timely and accurate access to these guidelines, IBM Health Corps worked with the coalition and partners to develop the IBM Cancer Guidelines Navigator using the Watson cognitive computing technologies platform. The IBM Cancer Guidelines Navigator is a clinical decision support system (CDSS) that will allow clinicians to input the clinical attributes of a case as defined by the guidelines. The IBM Cancer Guidelines Navigator will output the appropriate recommendations as stipulated by the guidelines with related supportive care information and relevant evidence publications. Results: This Watson powered solution covers 5 cancer types; cervical, Kaposi's sarcoma, B-Cell lymphoma, prostate and breast cancer. The treatment recommendations are multidisciplinary and include surgery, radiation and chemotherapy. The tool will be deployed in 6 countries initially and its use will be measured to see the impact it has in cancer care outcomes. Conclusions: By combining the efforts of harmonizing cancer treatment guidelines and promoting its availability and accessibility in a case-query format, it is expected that programs like this one will have impact in raising the quality of care and standardizing cancer care among a vulnerable population. Further research will be done on outcomes data and presented.
Chemotherapy toxicity risk score (CTRS) for treatment decision in older patients with advanced solid cancer.
Authors: Tomohiro F. Nishijima, Allison Mary Deal, Grant Richard Williams, Hanna Kelly Sanoff, Kirsten A Nyrop, Hyman B. Muss
Journal: Journal of Clinical Oncology (2017)

10030 Background: The decision whether to treat older patients (pts) with advanced cancer with standard (ST) or reduced therapy (RT) is complicated by heterogeneity in aging. Currently, clinical impression based largely on age and performance status, determines whether a pt is fit or unfit for ST. We evaluated the potential utility of the CTRS (Hurria JCO 2011) for treatment decision in older cancer pts. Methods: This is a prospective observational study of older pts (+65) receiving first-line chemotherapy for locally advanced or metastatic cancer for which combination chemotherapy is the standard of care. CTRS was calculated before therapy initiation assuming the pts received ST (combination therapy at the standard dose). Pts were categorized as high risk (CTRS ≥10; RT (dose reduced combination or single agent chemotherapy) deemed appropriate) or non-high risk (CTRS &lt;10; ST deemed appropriate) for grade 3-5 adverse events (gr3-5 AEs). Treatment decision was left to the treating physician who was blinded to the CTRS result. We estimated the agreement in chemotherapy choice (ST vs RT) between treating physician and CTRS using the kappa statistic. Results: 44 pts (median 71 years) with GI (68%), GU (14%), lung (14%) or HEENT (5%) cancer were enrolled. 29 pts received ST (11 had CTRS ≥10 and 18 had CTRS &lt;10) and 15 pts received RT (10 had CTRS ≥10 and 5 had CTRS &lt;10). The kappa statistic showed only modest agreement in chemotherapy choice (0.26, 95%CI = -0.01 to 0.54) between physician and CTRS. Gr3-4 AEs and hospitalization due to AE occurred in 50% and 29% of 42 pts with follow-up data, respectively. There was no fatal AE. Among pts receiving ST, pts with CTRS ≥10 had a significantly higher incidence of gr3-4 AEs and hospitalization than those with CTRS &lt;10 using Fisher's exact test (Table). In the RT group, there was no significant difference in incidence of gr3-4 AEs or hospitalization between pts with CTRS ≥10 and CTRS &lt;10. Conclusions: Incorporation of CTRS in treatment decision may increase the proportion of elderly pts with advanced cancer who receive tolerable treatment. [Table: see text]
TCT-99 Does valve in valve TAVR carry a higher risk for Diffusion-Weighted MRI brain lesions compared to native valve TAVI?
Authors: Christina Brinkmann, Amnon Eitan, Julian Witt, Timo Haselbach, Jan Stripling, Friedrich-Christian Rieß, Joachim Schofer
Journal: Journal of the American College of Cardiology (2018)
Abstract 470: Raf Kinase Inhibitors Activate ERK1/2 in Cardiomyocytes, Promoting Cardiac Hypertrophy <i>in vitro</i> and, in the Context of Angiotensin II-Induced Hypertension in Mice, <i>in vivo</i>
Authors: Daniel N Meijles, Michelle A Hardyman, Stephen J Fuller, Kerry A Rostron, Sam J Leonard, Peter H Sugden, Angela Clerk
Journal: Circulation Research (2017)

Introduction: ERK1/2 promote hypertrophy and are protective in the heart, but cause cancer in dividing cells. Raf kinases lie upstream of ERK1/2 and Raf inhibitors (e.g. SB590885 (SB), dabrafenib (Dab)) are in development/use for cancer. Paradoxically, in cancer cells, low concentrations of SB/Dab stimulate (rather than inhibit) ERK1/2. Hypothesis: Our hypothesis is that the heart is primed for Raf paradox signaling. Raf inhibitors have potential to activate ERK1/2 in cardiomyocytes and promote cardiac hypertrophy. Methods: Neonatal rat ventricular cardiomyocytes (NRVMs) were exposed to inhibitors. Dab or SB (3 or 0.5 mg/kg/d) were studied in 12 wk male C57Bl6 mice in vivo in the presence of angiotensin II (AngII, 0.8 mg/kg/d) (n=6-11) using osmotic minipumps. Effects were compared with vehicle controls. Echocardiography was performed (Vevo2100). M-mode images (short axis view) were analyzed; data for each mouse were normalized to the mean of 2 baseline controls. Kinase activities were assessed by immunoblotting or in vitro kinase assays. Results: SB (0.1 μM) or Dab (1 μM) activated ERK1/2 (2.3±0.1 fold; n=4) in NRVMs consistent with Raf paradox signaling. An explanation is that Raf kinases dimerise and submaximal inhibitor concentrations bind one Raf protomer, locking it in an active conformation but activating the partner. In accord with this, 0.1 μM SB increased Raf activities. High SB concentrations (1-10 μM) initially inhibited ERK1/2 in NRVMs, but ERK1/2 were then activated (1 - 24 h) and promoted hypertrophy. In vivo (24 h), Dab and SB activated the ERK1/2 cascade, increasing ANF (17.3 ± 3.1 fold) and BNP (4.5 ± 0.8 fold) mRNA (n=4/5). Over 3 d, Dab and SB increased fractional shortening in the presence of AngII (1.22±0.06; 1.17±0.08), relative to AngII alone (0.95±0.04), increased systolic left ventricular (LV) wall thickness, and reduced systolic LV volume and internal diameter (0.83±0.03 cf 0.97±0.02 for AngII alone). Conclusions: The heart is primed for Raf paradox signaling and Raf inhibitors activate ERK1/2 in cardiomyocytes, promoting hypertrophy. In vivo, Raf inhibitors enhance ERK1/2 signaling and hypertrophy in the context of hypertension, and cardiac hypertrophy may be increased in hypertensive cancer patients receiving Raf inhibitors.
Universal testing for hormonal status in breast cancer: Are we choosing wisely?
Authors: Taylor Maxwell Goller, Javier De Luca-Johnson, Hibba tul Rehman, Abiy Berhie Ambaye
Journal: Journal of Clinical Oncology (2017)

6583 Background: Characterizing estrogen receptor (ER) and progesterone receptor (PR) status has long been standard practice with newly diagnosed breast cancers. ER and PR expression suggests a more favorable prognosis and predicts tumor responsiveness to hormonal therapy. However, this testing comes with considerable cost. At our institution, the Medicare reimbursement rate for a single ER/PR assay is $310. With over 300,000 newly diagnosed breast cancers in the US each year, the total cost of ER/PR testing is close to 100 million dollars. Furthermore, the 2010 American Society of Clinical Oncology (ASCO) and the College of American Pathologists (CAP) guidelines suggest that up to 20% of ER/PR testing worldwide may be inaccurate with potential for false negative results. A falsely negative result could lead clinicians to not offer treatment with hormonal therapies. The purpose of this study was to investigate whether nuclear grade could be used to predict ER status, thus saving cost and reducing the potential for false negative test results and the inappropriate withholding of beneficial treatment. Methods: A retrospective analysis of prospectively collected data from the University of Vermont Breast Cancer Database identified all newly diagnosed breast cancers of any histologic type with available data on nuclear grade and ER status (2/2008-10/2016). The relationship between nuclear grade and ER status was analyzed (Table). Results: Nuclear grades 1 and 2 were associated with a significantly higher proportion of ER positive results than high nuclear grades (chi-square test p &lt;.001). Conclusions: Nuclear grade 1 and 2 breast cancers are nearly universally ER positive (99% and 97%, respectively). Thus, ER testing may be redundant in these tumors. Elimination of ER testing in nuclear grade 1 and 2 tumors could save tens of millions of dollars each year in the US alone. It could also reduce the potential for false negative test results and the inappropriate withholding of beneficial treatment. [Table: see text]