tbuckley/cabot-search huggingface dataset:
Association of exercise with late mortality in adult survivors of childhood cancer: A report from the Childhood Cancer Survivor study.
Authors: Jessica Scott, Nan Li, Qi Liu, Yutaka Yasui, Wendy Leisenring, Paul C. Nathan, Todd M. Gibson, Saro Armenian, Tormod Nilsen, Kevin C. Oeffinger, Kirsten K. Ness, Scott Adams, Leslie L. Robison, Gregory T. Armstrong, Lee Jones
Journal: Journal of Clinical Oncology (2018)

10512 Background: Adult survivors of childhood cancer are at excess risk for late mortality compared to the general population. Whether exercise attenuates this risk is not known. Methods: We examined the association between self-reported vigorous exercise [metabolic equivalent-hrs/week (MET-h/wk)] and cause-specific late mortality among 15,450 adult survivors participating in the Childhood Cancer Survivor Study using multivariable piecewise exponential regression analysis to estimate rate ratios (RR). Longitudinal change in vigorous exercise was evaluated among a subset of 5689 survivors. Results: During a median follow-up of 10 years (interquartile range: 15 years), 1063 deaths (811 health-related, 120 recurrence/progression of primary cancer, 132 external/unknown causes) were documented. At 15 years the cumulative incidence of all-cause mortality was 11.7% (95% CI, 10.57-12.80) for 0 MET-h/wk, 8.6% (95% CI, 7.42-9.72) for 3 to 6 MET-h/wk, 7.4% (95% CI, 6.23-8.57) for 9-12 MET-h/wk, and 8.0% (95% CI, 6.50-9.45) for 15-21 MET-h/wk (P < 0.001). There was a significant inverse association across quartiles of exercise and all-cause mortality after adjusting for chronic health conditions and treatment exposures (Ptrend= 0.023). Among a subset of 5689 survivors, increased exercise (+7.9 ± 4.4 MET-h/wk) over an 8-year period was associated with a 40% reduction in all-cause mortality rate compared with maintenance of low exercise (RR = 0.60; 95% CI, 0.44 to 0.82, p = 0.01). Conclusions: Vigorous exercise in early adulthood and increased exercise over eight years is associated with lower risk of late mortality in adult survivors of childhood cancer.
Establishment and characterization of a circulating tumor cell line from a breast cancer patient.
Authors: Pan Zhao, Chang Zou, Hong Hu, Cai neng Zhong, Ya yuan Zhang, Dong xian Zhou, Wen bin Zhou
Journal: Journal of Clinical Oncology (2018)

e13062 Background: Circulating tumor cells (CTCs) are rare tumor cells disseminated in peripheral blood from either original tumor sites or metastatic sites. Current studies on CTCs are mainly focused on its diagnosis and prognosis significances, although controversial results were reported elsewhere. Actually, as a few studies showed that CTCs would be a kind of intriguing drug targets and would be more beneficial for cancer patients if its genomic and proteomic information were deciphered dynamically. However, the rarity, challenging isolating as well as the primary culture procedures limited analysis of CTCs insightfully. Methods: In the present study, we aimed to isolate and characterize CTCs from breast cancer patients. Here we showed that a CTCs cell line was established and characterized from the peripheral blood of a patient with metastatic ER-positive breast cancer by negative enriching method combined with adherent culture methods. Results: Cytokeratin but not CD45 were positively immune-stained in this CTCs cell line, named as CTC-3 cell line hereafter, as shown by FISH approach. CD133-positive cells in about 1% in this cell lines as found in flowcytometry analysis. Larger nuclear/cytoplasm ratio, higher colony formation capacities and spheroids formation capacities were found in CTC-3 cells as compared with that of breast cancer cell line MCF-7. CTC-3 cells showed faster replication rate as compared with that of MCF-7 both in vitro and in vivo. Besides, short tandem repeat (STR) analysis showed that the similarity of CTC-3 and MCF-7 on the standard site alignment is less than 20% and that of CTC-3 and PBMCs from the donor is more than 90%, which indicated that CTC-3 might be a new breast cancer cell line. Conclusions: In summary, in this study a CTCs-derived breast cancer cell line is established, which could provide a source to better decipher the information of cancer as well as screening precision medicine for the current donor patient with breast cancer and might open up a novel avenues towards monitoring the progression and developing personally treatments for breast cancer patients.
TCT-874 Coronary Microvascular Function During STEMI: Real Time Absolute Dynamic Microvascular Resistance in an Experimental Porcine Model Using Controlled Flow Infusion
Authors: Robert Schwartz, Esther Gerteis, Jonathan Schwartz, Martin Rothman, Jon Hoem, Oliver Bludau, Blathnaid Feldman, Nikola Cesarovic, Mareike Gastl
Journal: Journal of the American College of Cardiology (2018)
What factors drive the choice of a genetic test? A prospective study of the preferences of women with ovarian cancer.
Authors: Brittany Anne Davidson, Jonathan Foote, Jessie Ehrisman, Jui-Chen Yang, Shelby D. Reed, Reed Johnson, Paula S. Lee, Angeles Alvarez Secord, Andrew Berchuck, Laura Jean Havrilesky
Journal: Journal of Clinical Oncology (2018)

e13621 Background: Although genetic testing is recommended for women with epithelial ovarian cancer (EOC), little is known about patient preferences for the various testing options. Our objective was to measure relative preferences for features of genetic testing in women with EOC referred for genetic counseling. Methods: 100 women with EOC and planned referral for genetic testing were recruited to participate in a survey to elicit their preferences for 5 attributes of single gene vs multigene genetic testing, each presented with 2-4 levels: out-of-pocket cost ($0, $100, $250, $1,000), probability of identifying a deleterious mutation (60%, 80%, 88%) or a variant of uncertain significance (VUS) (5%, 20%, 40%), sample requirements (blood or saliva) and turn-around time (1, 2 or 4 weeks). Subjects viewed an educational video and were then asked to choose between 2 unlabeled testing scenarios, each with variations in the levels displayed, with 13 iterations of this task. We used a mixed logit regression to model patients’ choices as a function of attribute levels and to obtain log-odds estimates indicating the preference weights for each attribute level. Results: 94 EOC patients were enrolled; 68 (76.4%) subsequently presented for a genetic counseling appointment. 46 (48.9%) had a family history of breast and/or ovarian cancer. Test cost was the most important attribute and assigned an importance weight of 10, followed by the ability of a test to detect deleterious mutations (importance weight 8.8) or VUS (4.9). Sample requirements (0.4) and turnaround time (0.1) did not significantly drive the choice of a genetic test. Subjects valued an improvement from 60 to 88% in the probability of detecting a deleterious mutation at $877 (CI: $583-$1226). Similarly, subjects valued an improvement in detecting a VUS from 5% to 40% at $492 (CI: $305-$718). At subsequent genetics consultation, 55/68 (80.9%) subjects chose multigene testing, 8/68 (11.8%) chose BRCA1/2 testing only and 5/68 (7.4%) declined testing. Conclusions: Low out of pocket cost of testing and a high detection rate for both informative/deleterious and uninformative/variant mutations are preferred by patients with EOC who are considering genetic testing.
Mutant NPM1 Maintains the Leukemic State through HOX Expression
Authors: Lorenzo Brunetti, Michael C. Gundry, Daniele Sorcini, Anna G. Guzman, Yung-Hsin Huang, Raghav Ramabadran, Ilaria Gionfriddo, Federica Mezzasoma, Francesca Milano, Behnam Nabet, Dennis L. Buckley, Steven M. Kornblau, Charles Y. Lin, Paolo Sportoletti, Maria Paola Martelli, Brunangelo Falini, Margaret A. Goodell
Journal: Cancer Cell (2018)
P04.37 The dielectric properties of malignant glioma tissue
Authors: M A Proescholdt, A Haj, C Doenitz, A Brawanski, Z Bomzon, H Hershkovich
Journal: Neuro-Oncology (2018)

Recently, tumor treating fields (TTFields) have been established as an effective new approach for the treatment of newly diagnosed GBM. One of the most crucial parameters defining the treatment efficacy of TTFields is the electric field intensity. Essentially, the higher the electric field intensity, the higher the tumor cell killing that can be achieved by TTFields. The electric properties of the normal intracranial compartments (cerebrospinal fluid, blood, white and grey mater) are well established, allowing the prediction of the electric field distribution by finite element mesh modelling. In contrast, there is no data available about the electric properties of tumor tissue, which leads to a lack of information regarding the electric field intensity within the tumor. In this study we will determine the dieclectric properties of malignant glioma by analyzing resected tissue following a fast acquisition protocol. To account for the intratumoral heterogeneity, different regions of the tumor will be sampled and analyzed separately. Twenty patients with high grade glioma currently being recruited. Tissue probes are acquired from the infiltration zone, vital tumor area, and perinecrotic compartment identified intraoperatively using neuronavigation, intraoperative ultrasound and fluorescence guidance. From each region, five tissue probes are sampled. Immediately after acquisition, the tissue is immediately to avoid artifacts by temperature change, change of fluid composition as well as post resection ischemia. A cylindrical fragment is dissected from each tissue sample and is placed into a cylindrical cell with a known diameter. Two parallel electrodes are placed on both sides of the sample and the thickness of the tissue is measured using a micrometer. The impedance is recorded at frequencies 20Hz-1MHz using a software specificly developed for this study, which controls the LCR meter (Keysight Technologies, Santa Rosa, USA). The measured impedance is then translated into dielectric properties of the sample (conductivity and relative permittivity) based on the parallel plate model, the recorded complex impedance and the geometry of the samples. Each tissue probe will be fixed, H&E stained and histologically analyzed for tumor cell count and specific tissue features (infiltration into normal brain, vital tumor area, necrosis). The study has received a positive vote from the Ethical Board of the University Regensburg Medical Center. The first patients are being recruited, the actual results will be evaluated and presented during the meeting.
Abstract 16434: Atrial Fibrillation Is Associated With Significative Functional Tricuspid Regurgitation In Patients With Left Ventricular Dysfunction
Authors: Giovanni Benfari, Clemence Antoine, Wayne L Miller, Hector I Michelena, Vuyisile T Nkomo, Maurice Enriquez-Sarano
Journal: Circulation (2016)

Introduction: Functional tricuspid valve regurgitation (FTR) is common in patients with left ventricular (LV) dysfunction and is usually ascribed to pulmonary hypertension (PHTN) or to reduced ejec...
Building "bridges": Use of participatory design to create an electronic tool to improve management of chemotherapy toxicities.
Authors: Rebecca M. Prince, Laura Parente, Anthony Soung Yee, Melanie Lynn Powis, Katherine Enright, Sonal Gandhi, Eva Grunfeld, Rashida Haq, Amna Husain, Monika K. Krzyzanowska
Journal: Journal of Clinical Oncology (2016)

e21586 Background: There is growing interest in leveraging technology to solve clinical problems in healthcare. Patients (pts) receiving chemotherapy have high symptom needs that can negatively impact patients’ quality of life and healthcare utilization. We sought to develop an initial prototype of an electronic tool to facilitate remote management of chemotherapy toxicities. Methods: Our participatory design method consisted of user needs assessment through ethnographic field study and focus groups. Thematic analysis through ideation sessions and time-of-day exercises allowed identification of overarching issues. These themes informed iterative development of a tablet-based prototype, which was user-tested and refined over 2 rounds. Oncology pts, caregivers, and health care providers (HCPs) including oncologists, oncology nurses, and primary care physicians participated in all stages of development and testing. Results: Fifteen pts with a variety of tumor types, 1 caregiver, and 12 HCPs participated in the needs assessment. Most themes were common to both pts and HCPs: gaps and barriers in the current system, need for decision aids, improved communication and options in care delivery, secure access to credible information in a timely manner and integration into existing systems. Additionally, pts identified missed opportunities, care not meeting their needs, feeling overwhelmed and anxious, and wanting to be more empowered; HCPs identified accountability as an issue. These themes informed development of a tablet-based prototype called ‘bridges’ which includes symptom tracking, self-management advice, and HCP communication. The module was well received during usability testing with 10 pts and 11 HCPs, but challenges were recognized including integration of the tool into existing workflows and care teams, provision of standardized symptom management advice, privacy and consent issues, and the need for patient specific information. Conclusions: An electronic tool that integrates just-in-time self-management advice and HCP support into routine care may address some of the gaps in the current system for managing chemotherapy toxicities.
Impact of metformin on survival and mTOR pathway in head and neck cancer.
Authors: Shuchi Gulati, Changchun Xie, Randall Butler, Trisha Wise-Draper
Journal: Journal of Clinical Oncology (2016)

e17514 Background: Head and neck squamous cell carcinomas (HNSCCs) have been shown to exhibit activation of the PI3K–mTOR pathway, which is important for cellular proliferation and survival. The hypoglycemic agent, metformin, has been shown to inhibit mTOR signaling both in-vivo and in-vitro. However, retrospective analyses investigating the anti-cancer activity of metformin have been conflicting. Given that metformin is cheap, has a good safety profile and is easy to administer, many clinicians are pursuing its use prospectively to determine predicted anti-cancer properties. Here we investigate outcome of non-diabetic (NDM) and diabetic (DM) patients on metformin vs other hypoglycemic agents. Methods: Retrospective analysis of 500 HNSCC patients at University of Cincinnati (Jan 2009-Jan 2015) was performed. NDM and DM patients on metformin or other anti-diabetic agents were included. Kaplan-Meier method was used to calculate overall survival (OS) and progression free survival (PFS) and 95% CI. Cox model was used to test association between metformin (or diagnosis of DM) and OS (or PFS) (SAS version 9.4). IHC analysis for mTOR downstream activity will be done on samples from patients from the DM group on metformin, DM group not on metformin and NDM group. Results: Of the 500 patients, 187 had advanced (stage III/ IV) HNSCC, majority were Caucasian (87%) and smokers (77%). Median age at diagnosis was 59 years. 51 of these patients had DM, of which 76% (39) were on metformin. OS (adjusted for age, sex, stage) for patients on metformin had a slight trend toward better outcome vs those not on metformin (HR 0.8; p-value 0.6; 25th percentile OS was 1081 vs 880 days). Interestingly PFS was improved in NDM patients (25thpercentile PFS of 1192 vs 457 days), but this did not translate into an OS benefit. IHC analysis of downstream mTOR effectors is underway. Conclusions: This retrospective study shows a trend toward better OS in patients on metformin compared to those not on metformin, although the results are limited due to insufficient follow-up and are not significant. Molecular analysis may reveal insight to patients more likely to respond to metformin. Prospective ongoing trials will be imperative to determine the clinical benefit of the addition of metformin.
Persistent high levels of circulating effector memory T cells and anti-nuclear antibodies in metastatic melanoma patients who experience durable CRs to immunotherapy after the cessation of treatment.
Authors: Megan Wheelden, Jeremy Haley, Todd Schell, Kathleen M Kokolus, Diane Hershock, Carol Mallon, Heath B. Mackley, Jeffrey Michael Sivik, Joseph J. Drabick
Journal: Journal of Clinical Oncology (2018)

e21576 Background: Checkpoint blockade therapies have dramatically improved the prognosis for metastatic melanoma patients, with overall response rates reported as high as 35%. These regimens have significantly improved the durable complete response (CR) rate with patients showing dramatic control of widespread metastatic disease that persists after stopping therapy. However, most patients fail to experience a CR, and the underlying basis for what contributes to CRs remains poorly defined. In this study, we evaluated the immune parameters of long-term metastatic melanoma survivors who received immunotherapy to identify characteristics associated with durable responses. Methods: Metastatic melanoma patients that received immunotherapy and experienced a long-term CR were identified (12 patients). Control samples were collected from patients with non-metastatic melanoma who were without disease after treatment with surgery, radiation, and/or high dose interferon (10 patients). Both groups were over 1 year out from treatment. CBC differentials, anti-nuclear antibody testing, and flow cytometric staining of T cell subsets were performed. Results: No significant differences were found in the frequencies of major subsets of PBMCs between long-term immunotherapy survivors and controls. In addition, there were no differences in overall frequencies of total CD4 or CD8 T cells, or among CD4 regulatory T cells. However, the proportion of effector memory CD4 T cells was significantly higher in long-term survivors (p = 0.0028), with a corresponding decrease in the proportion of naïve and central memory phenotype CD4 T cells. In addition, we found that a significant proportion of long-term survivors had high ANA titers while no control patients had detectable ANAs (p = 0.0255). Conclusions: These results suggest that expansion of the effector memory subset of CD4 T cells correlates with durable CRs in metastatic melanoma patients who received immunotherapy even after the therapies have been discontinued. We postulate that this particular immunophenotypic pattern may have prognostic value.
Predictors of progressive disease (PD) and subsequent outcomes in metastatic renal cell carcinoma (mRCC) patients (pts) treated with nivolumab (nivo).
Authors: Haris Zahoor, Pedro C. Barata, Xuefei Jia, Brian P Hobbs, Allison Martin, Kimberly D Allman, Laura S. Wood, Petros Grivas, Timothy D. Gilligan, Jorge A. Garcia, Moshe Chaim Ornstein, Brian I. Rini
Journal: Journal of Clinical Oncology (2018)

e16563 Background: Nivo is approved for the treatment (tx) of refractory mRCC. Predictors of PD on nivo and outcomes in such pts are lacking. Methods: A retrospective analysis of pts with clear cell mRCC who received nivo at Cleveland Clinic (2015-2017) was performed. PD was defined per RECIST v1.1 or clinical. Univariate analyses (UVA) and multivariate analyses (MVA) were used to identify potential predictors of progression-free survival (PFS) and overall survival (OS). Recursive partitioning method was used to identify cut-off values for neutrophil to lymphocyte ratio (NLR) and eosinophil counts. Results: Ninety pts with median age of 67 (33-83), 74% men, and 83% good to intermediate IMDC score were included. Median number of prior systemic tx were 2 (range, 1-6). Median OS and PFS were 15.8 and 4.8 months, respectively. PD was found in 56 (62%) pts and 23/56 (41%) pts had new organ sites of metastases (mets), with brain (8/23; 35%) being the most common. Twelve pts received treatment beyond progression (TBP) and among 6 pts with available data, 3 (50%) had any tumor shrinkage (2, 17%; 1, 29%). Of 56 pts with PD, 28 (50%) were able to initiate subsequent tx, mainly with axitinib (14/28, 50%) and cabozantinib (6/28, 21%). Pts who were unable to initiate subsequent tx were transitioned to hospice in most cases (23/28, 82%). In MVA, presence of pleural mets at baseline (HR, 1.86; 95% CI, 1.00-3.45; p = 0.049) and higher ( > 4.2) baseline NLR (HR, 1.76; 95% CI, 1.01-3.06; p = 0.047) were associated with increased risk of progression, whereas higher ( > 0.1 k/uL) baseline eosinophil count was associated with lower risk of progression (HR, 0.51; 95% CI, 0.28-0.91; p = 0.024). Presence of pleural mets at baseline also conferred higher risk of death (HR, 2.83; 95% CI, 1.33-5.88; p = 0.007). Conclusions: Brain was the most common site of PD in pts treated with nivo, and only half of pts progressing on nivo were able to initiate subsequent tx. The risk of PD increased with a higher baseline NLR and reduced with a higher baseline eosinophil count. The presence of pleural mets at baseline was associated with higher risk of progression and death.
A patient navigation program to enhance access to care for undeserved patients with a suspicion or diagnosis of cancer in Mexico City.
Authors: Alexandra Bukowski, Enrique Soto Perez De Celis, Wendy A Ramos-López, Patricia Rojo-Castillo, Jesus Armando Sanchez- Gonzalez, Oscar Sánchez-Gutiérrez, Lorena Viramontes-Aguilar, Bernardo Davila-Davila, Samuel Ahumada Tamayo, Sandra San Miguel, Jacqueline Alcalde-Castro, Paul E. Goss, Yanin Chavarri Guerra
Journal: Journal of Clinical Oncology (2017)

6544 Background: High cancer mortality rates in developing nations are partially driven by advanced stages at diagnosis and limited access to care. In Mexico, the interval from problem identification to start of treatment can be up to 7 months, mostly due to healthcare system delays. We implemented a patient navigation (PN) program aimed at reducing time to referral to cancer centers for patients (pts) with a suspicion or a diagnosis of cancer seen at a public general hospital in Mexico City. Methods: Pts age &gt; 18 seen at Hospital General Ajusco Medio in Mexico City who required referral to a cancer center were enrolled. Baseline demographic, economic and psychosocial data were collected. A Patient Navigator assisted pts with scheduling; paperwork; obtaining results in a timely manner; transportation; and with other cultural barriers. The goal of the PN program was for at least 70% of enrolled patients to obtain a specialized appointment at a cancer center within the first 3 months from enrollment. Results: 53 pts (median age 54, range 19-80; 51% female) were included between 01/16 and 12/16. 19% (n = 10) had breast/GYN, 19% (n = 10) GU, 19% (n = 10) endocrine, 19% GI (n = 10) and 14% (n = 13) other tumors. All the pts were uninsured, 59% (n = 30) had less than middle school education, 80% (n = 41) were unemployed and 96% (n = 49) had a monthly household income of &lt; $360 USD. 54% (n = 28) reported deprivation in at least one basic living need (education, running water, toilet, electricity or flooring). The most commonly identified barriers to healthcare access were financial (73%, N = 37), lack of transportation (47%, N = 24), fear (37%, N = 19) and poor communication with healthcare workers (35%, N = 18). Mean time to referral was 11 days (range 0–46, SD 11.2) and mean time to cancer specialist appointment 26 days (range 1–94, SD 21.18). 92% of pts successfully obtained appointments at a cancer center in &lt; 3 months. Conclusions: Compared with previously reported data, this PN program shortened time to referral to a cancer center for pts with a suspicion or diagnosis of cancer in Mexico City. PN represents a potential solution to overcome barriers to healthcare access for underserved pts with cancer in developing countries.