tbuckley/cabot-search huggingface dataset:
Factors affecting specimen accrual in a community hospital biobank.
Authors: Sameer Tolay, C Simon Shelley
Journal: Journal of Clinical Oncology (2014)

e20570 Background: Community hospital biobanks are important contributors to several cancer genome programs. In an effort to improve the specimen accrual, we sought to determine cancer patients’ attitudes and knowledge about donating tissue for research. Methods: We mailed questionnaires to 500 patients who had undergone cancer surgery at our hospital in the year 2012. Results: Response rate was 43.4% (217/500). Only 36/217 respondents were aware of the biobank (BB), 32 of whom had consented to tissue collection. Of the 181/217 who were not aware, 120 believed that they would have consented had they been aware, 46 were not sure, and 15 would have refused. Most respondents (174/217) saw possible benefit for others as the most important reason for consenting. 41/217 patients believed there is a potential for misuse of their tissue or personal information, 17 did not want to deal with any extra issues, and 11 did not understand the concept. None cited religious or cultural beliefs as factors influencing their decision. Conclusions: Majority of the people were unaware of the concept of BB but if made aware, most of them would have consented primarily to help other cancer patients. Lack of patient awareness is an important difference between a smaller community hospital and a bigger quaternary setting. With increasing participation of smaller centers towards international cancer genome programs, improving patient awareness could be a major step in increasing specimen accrual. Despite being unaware, most patients showed good understanding of the concept of BB. The fear of misuse or commercial use of their tissue and personal information was their biggest apprehension. Hence, even a small, informative conversation addressing this issue could help allay patient fears about tissue donation. Total patients 500 Patients responded n= 217 Patients aware of biobank Consented Did not consent 36 32 4 Patients not aware of biobank Would have consented Not sure Would have refused 181 120 46 15 Reasons to consent Treatment of others Personal treatment 174 69 Patients expressing apprehensions Misuse of tissue/personal information Dealing with extra issues Didn't understand the concept Tissue handling Too much Paperwork No role in research Wrong circumstances 60 41 17 11 08 06 06 04
Role of antiemetic prophylaxis for breast cancer (BC) patients treated with anti-HER2 or anti-VEGF monoclonal antibodies.
Authors: Massimiliano Alu, Giuseppe Bronte, Antonio Russo, Antonella Usset, Sceila Affronti, Giovanni Orlando, Maria Antonietta AspanÃƒÂ², Silvana Bavetta, Paolo Amari, Giuseppe Galanti, Vincenzo Adamo, Livio Blasi
Journal: Journal of Clinical Oncology (2014)

e20705 Background: To date the anti-emetic prophylaxis based on the combination of 5HT3-antagonists and corticosteroids is mandatory for high and moderate emetogenic cytotoxic agents. This approach significantly reduced the early onset nausea and vomiting associated with chemotherapy (CT). This effect is fundamental to achieve a completion of planned treatment both in the adjuvant and metastatic setting of BC pts. Methods: A search for clinical records of BC pts was performed in our center to identify those, who were treated with CT and monoclonal antibodies (moAbs), such as trastuzumab or bevacizumab, concomitantly (Con) or sequentially (Seq). The patients were stratified according with the kind of anti-emetic prophylaxis they received during the treatment with moAbs, i.e. corticosteroid plus 5HT3-antagonist (C-A) or corticosteroid alone (C). This study aims to explore the usefulness of 5HT3-antagonists in those patients treated with moAbs without concomitant CT. Results: 65 patients were selected retrospectively. Median age was 56, (range 32-80). 25 pts were treated with adjuvant therapy for early breast cancer, 40 received CT for advanced BC. 61 pts were evaluable for nausea and vomiting incidence. The stratification of pts according with the kind of anti-emetic prophylaxis (C-A vs C alone) and kind of moAbs and CT combination (Con vs Seq) provided 12 pts receiving C-A for Con therapy, 8 pts receiving C for Con therapy, 23 pts receiving C-A for Seq therapy and 18 pts receiving C for Seq therapy. 4 pts reported early onset nausea and vomiting associated with chemotherapy. Grade 1 and 2 nausea and vomiting was observed in 2 pts receiving C-A for Con therapy; grade 1 nausea and vomiting was observed in 2 patients receiving C for Con therapy. Conclusions: This retrospective analysis suggests that the use of 5HT3 antagonists for the anti-emetic prophylaxis in BC pts during moAbs-based treatment is not necessary. Indeed the incidence of nausea and vomiting in those pts receiving C-A is similar to those receiving C alone in the same arm of treatment (Con and Seq). This consideration could be useful for the design of prospective clinical trials and for the compilation of pharmacoeconomics-based recommendations.
Utilization of a 358-gene panel to molecularly profile solid tumors for association with target-based therapeutic agents.
Authors: Karen Elizabeth Rasmussen, Ramlah Nehring, Guru Ananda, Grace A. Stafford, Vivek Phillip, Susan Mockus, Anuj Srivastava, Allen Simons, Charles Donnelly, Krishna Karuturi, Douglas Hinerfeld, Vanessa Spotlow, Micaela Lundquist, Xiaoan Ruan, Carol J. Bult, Sean Scott, Tara Love, Dan R. Richards, Edison T. Liu
Journal: Journal of Clinical Oncology (2014)

e22117 Background: Matching the mutational profile of a patient’s tumor with appropriate targeted agents is a goal of personalized medicine in oncology. While the targeted therapeutic armamentarium in oncology remains limited, the number of therapies entering clinical trials is continually increasing. We interrogated a variety of solid tumors with the JAX Cancer Panel, comprised of 358 cancer-related genes, to determine the frequency of mutations associated with an approved or investigational drug. Methods: Genomic DNA was extracted from macro dissection-enriched FFPE tissue sections, followed by enrichment of target exons by hybrid-capture (Agilent Technologies). Illumina HiSeq 2500 or MiSeq sequencers generated 150bp paired-end sequence reads. Mutational analysis was performed using the Clinical Genomics Analytical (CGA) pipeline, developed at the Jackson Laboratory (JAX), linking the NGS QC Toolkit, BWA, and the Picard/GATK tool kit for QC, alignment, and variant discovery. Variant characterization and annotation were conducted with Ingenuity Clinical. Quality metrics for scoring a mutation were at least 400X average coverage of the targeted genomic interval with >90% covered at no less than 100X. Results: 113 cases covering a range of diagnoses and including both primary tumors and metastases were analyzed using the CLIA compliant JAX Cancer Panel. Tumors contained an average of 133 genetic variants [Range: 43-406], of which an average of 4 variants (Range: 3-12) were deemed clinically actionable. Markers were identified associated with response or resistance to an average of 13 approved drugs [range 0-42] and 14 clinical trials [range 0-31]. The top quartile were associated with 32 actionable drugs [Range: 8-46; Mean: 21] and 30 clinical trials [Range: 0-31; Mean: 14]. The mean coverage for >90% was at least 480X [range: 432-1377X], with >92% of the targets being covered by at least 100 reads. The sensitivity and specificity for SNPs and indels were >97% at 10% allele frequency. Conclusions: The JAX 358 gene Cancer Panel is a sensitive mutation detection assay that yields, on average, 4 potentially actionable variants per tumor.
Abstract 16145: Significance of High-sensitivity Cardiac Troponin T Levels Between the Limit of Blank and the Limit of Detection in the General Population: A Meta-analysis
Authors: Ravi Parikh, Stephen L Seliger, James de Lemos, Vijay Nambi, Robert Christenson, Colby Ayers, Wensheng Sun, John S Gottdiener, Lewis H Kuller, Christie M Ballantyne, Christopher deFilippi
Journal: Circulation (2015)

Introduction: A substantial minority of asymptomatic individuals will have very low but measurable levels of cardiac troponin T using a high sensitive assay (hs-cTnT). It is controversial if levels in this range provide physiologic and prognostic information. We hypothesized that hs-cTnT levels between the limit of blank (LOB) (3 ng/L) and limit of detection (LOD) (5 ng/L) are associated with increased incidence of heart failure (HF) and cardiovascular death compared to levels below the LOB (&lt;3 ng/L). Methods: hs-cTnT was measured in subjects without prevalent HF from the Cardiovascular Health Study (CHS), Atherosclerosis Risk in Communities (ARIC) study, and Dallas Heart Study (DHS). Participants were divided into two groups: levels below the LOB (n=7272) and levels between the LOB and LOD (n=3451). Cross sectional and longitudinal associations with demographics, traditional cardiovascular risk factors, and cardiovascular outcomes were made. A fixed-effect meta-analysis was performed using regression coefficients and variance estimates from fully adjusted models from all three cohorts. Results: Participants with hs-cTnT between the LOB and LOD were older, more likely to be male, and had higher prevalence of cardiovascular risk factors and structural abnormalities such as higher coronary artery calcium score and left ventricular mass. A meta-analysis of the three cohorts showed participants with hs-cTnT between the LOB and LOD were at increased risk of new-onset HF (HR=1.18, 95% CI: 1.02, 1.38) and cardiovascular death (HR=1.29, 95% CI: 1.06, 1.57) after adjusting for demographics and traditional risk factors when compared to participants with hs-cTnT below the LOB (Figure). Conclusions: hs-cTnT levels between the LOB and LOD are associated with a higher prevalence of traditional risk factors, cardiac pathology, and worse outcomes compared with levels below the LOB. Therefore, in general population cohorts, hs-cTnT should be reported down to the LOB.
Leucine for the Treatment of Transfusion Dependence in Patients with Diamond Blackfan Anemia
Authors: Adrianna Vlachos, Evangelia Atsidaftos, Ellen Muir, Zora R. Rogers, Mohammad Lufti Lababidi, Waseem Alhushki, Jason E. Farrar, Bertil Glader, Barbara Gruner, Helge Hartung, Christine M. Knoll, Grzegorz Nalepa, Anupama Narla, Arun Ranjan Panigrahi, Colin A. Sieff, Kelly J. Walkovich, Jeffrey M Lipton
Journal: Blood (2018)
Does adjuvant oxaliplatin affect the sphincter function in patients with locally advanced rectal cancer (LARC) treated with preoperative chemoradiotherapy followed by low anterior resection (LAR) with total mesorectum excision (TME)?
Authors: Fernando Arias, Gemma Asin, Itxaso Mora, Koldo Cambra, Berta Ibañez, Fernando Mañeru, Antonio Viudez, Irene Hernandez, Leire Arbea, Marta Errasti, Marta Barrado, Clara Eito, Miguel Ciga, Ruth Vera, Miguel A Dominguez
Journal: Journal of Clinical Oncology (2014)

e14585 Background: The objective of the study is to determine if the addition of oxaliplatin administered postoperatively influences on sphincter function in patients with locally advanced rectal cancer (LARC). Methods: We have reviewed 51 patients with LARC treated at our center with low anterior resection (LAR) and without colostomy from 2004 and free of local relapse at the time of the study. Anal sphincter function was assessed by Wexner´s incontinence score (0 to 20 points, being punctuation inversely proportional to sphincter function). Mean time from LAR to fecal function assessment was 58 months (25 to 96 months). All questionnaires were completed between January 2010 and December 2012. Patients’ characteristics such as age, stage, distant to the anal margin, radiotherapy dose to sphincter, and Wexner’s incontinence score, were summarized using descriptive statistics. Comparisons of these variables between the subgroups of patients who did or did not received oxaliplatin were carried out using the Mann-Withney test or the X2trend test. Multivariate linear regression models were fitted to assess the relationship between the use of oxaliplatin and incontinence, and to evaluate if the use of oxaliplatin modifies the effect of radiotherapy on incontinence. Results: The median incontinence score was seven points (0-20). About 40% of the patients (21/51) received oxaliplatin in the adjuvant CT. No difference was found in the median Wexner incontinence score between the groups according to the use of oxaliplatin (p=0.929). The other variables did not differ among the subgroups (age p=0.127; distance to the anal margin p=0.859; mean radiotherapy doses p=0.135) except for stage (p=0.028, being higher in the group with oxalipatin). Multivariate model results suggest that there is no relationship between the use of oxaliplatin and incontinence (p=0.974). Neither the data suggest that the oxaliplatin modify the effect of radiation, in relation to the incontinence degree (interaction term with mean dosesk, p=0.723). Conclusions: Our results show that, in these patients, adjuvant oxaliplatin does not affect negatively this function
Integrated Proteomic and Phosphoproteomic Analysis Reveal Novel Targets and Suggest Rationale for Ibrutinib Efficacy in UM-CLL
Authors: Laura Beckmann, Valeska Berg, Clarissa Dickhut, Johannes Bloehdorn, Jasmin Bahlo, Sandra Robrecht, Malte Hülsemann, Stefan Loroch, Olaf Merkel, Kirsten Fischer, Clemens-Martin Wendtner, Stephan Stilgenbauer, Albert Sickmann, Michael Hallek, René Zahedi, Lukas P. Frenzel
Journal: Blood (2018)
Tinagl1 Suppresses Triple-Negative Breast Cancer Progression and Metastasis by Simultaneously Inhibiting Integrin/FAK and EGFR Signaling
Authors: Minhong Shen, Yi-Zhou Jiang, Yong Wei, Brian Ell, Xinlei Sheng, Mark Esposito, Jooeun Kang, Xiang Hang, Hanqiu Zheng, Michelle Rowicki, Lanjing Zhang, Weichung J. Shih, Toni Celià-Terrassa, Yirong Liu, IIeana Cristea, Zhi-Ming Shao, Yibin Kang
Journal: Cancer Cell (2019)
Abstract 17: Association of Race and Sex with Cardiovascular Disease and Non-Cardiovascular Disease Mortality: The REasons for Geographic and Racial Differences in Stroke study
Authors: Gabriel S Tajeu, Monika M Safford, George Howard, Rikki M Tanner, Paul Muntner
Journal: Circulation (2017)

Introduction: Black Americans have higher rates of cardiovascular disease (CVD) mortality compared with whites. Differences in sociodemographic, psychosocial, CVD, and other risk factors may explain increased mortality risk. Methods: We analyzed data from 29,015 REasons for Geographic and Racial Differences in Stroke study participants to determine factors that may explain the higher hazard ratio for CVD and non-CVD mortality in blacks compared with whites. Cause of death was adjudicated by trained investigators. Within age-sex sub-groups, we used Cox proportional hazards regression with progressive adjustment to estimate black:white hazard ratios. Results: Overall, 41.0% of participants were black, and 54.9% were women. Over a mean follow-up of 7.1 years (maximum 12.3 years), 5,299 participants died (1,797 CVD and 3,502 non-CVD deaths). Among participants &lt; 65 years of age, the age and region adjusted black:white hazard ratio for CVD mortality was 2.28 (95% CI: 1.68-3.10) and 2.32 (95% CI: 1.80-3.00) for women and men, respectively, and for participants ≥ 65 was 1.54 (95% CI: 1.30-1.82) and 1.35 (95% CI: 1.16-1.57) for women and men, respectively ( Table ). The higher black:white hazard ratios for CVD mortality were no longer statistically significant after multivariable adjustment, with the largest attenuation occurring with sociodemographic and CVD risk factor adjustment. Among participants &lt; 65 years of age, the age and region adjusted black:white hazard ratios for non-CVD mortality were 1.51 (95% CI: 1.24-1.85) and 1.76 (95% CI: 1.46-2.13) for women and men, respectively, and for participants ≥ 65 was 1.12 (95% CI: 1.00-1.26) and 1.34 (95% CI: 1.20-1.49) for women and men, respectively. The higher black:white hazard ratios for non-CVD mortality were attenuated after adjustment for sociodemographics. Conclusions: Black:white differences are larger for CVD than non-CVD causes of death. The increased CVD mortality for blacks compared with whites is primarily explained by sociodemographic and CVD risk factors.
A multicenter, open-label, single-arm, phase 2 study of the S1P inhibitor sonepcizumab (LT1009) in patients with previously treated metastatic renal cell carcinoma (mRCC).
Authors: Rupal Satish Bhatt, Sumanta Kumar Pal, Harry A. Drabkin, John D. Hainsworth, Andrew Dorr, Michael B. Atkins, James Walter Mier, Xiaoen Wang, Roger Allen Sabbadini, Dario Paggiarino
Journal: Journal of Clinical Oncology (2014)

TPS4605 Background: Sphingosine-1-phosphate (S1P), a key component of the sphingolipid signaling cascade, is a pleiotropic tumorigenic growth factor. S1P promotes tumor growth by stimulating cell proliferation, metastasis and cell survival while promoting tumor-associated angiogenesis by supporting the migration and survival of endothelial cells needed to form new blood vessels. Cancer cells promote conditions that favor the production of S1P through upregulation of sphingosine kinase (SphK) which appears responsible for release of S1P into the extracellular compartment. Data thus far implicate the type 1 isoform of SphK in chemoresistance and in the enhanced tumorigenicity adaptations to hypoxia, all of which correlate with poor patient outcomes in several cancer types. Sonepcizumab (LT1009) is a humanized murine-derived monoclonal antibody directed at S1P. Sonepcizumab slowed the progression of several orthotopic and subcutaneous human tumors in nude mice, including sunitinib-resistant renal tumors. Sonepcizumab was safe and well tolerated in a completed phase 1 study in 28 pts with advanced solid tumors up to 24 mg/kg weekly. Based on these data, we hypothesize that sonepcizumab may be effective in pts with advanced mRCC who failed previous therapies. Methods: A two-part, multi-center, open label phase 2 study is in progress to evaluate safety, tolerability, efficacy, and the pharmacokinetics (PK) and pharmacodynamics (PD) of sonepcizumab as a single agent when given at the dose of 24 mg/kg weekly in pts with previously treated mRCC. Two cohorts will be enrolled and dosed at the phase 1 maximum tolerated dose (MTD) of 24 mg/kg. If at least 12 out of the first 22 pts are progression-free at 2 months, then a second cohort will be enrolled for a total of approximately 60 pts. Key eligibility criteria include prior therapy with a VEGF/VEGFR targeted therapy (an mTOR inhibitor and/or prior immunotherapy are also permitted for a total of no more than 3 prior therapies); The primary endpoint is PFS. Secondary endpoints include response rate and serum PD biomarkers, including S1P. Clinical trial information: NCT01762033.
Correlation between risk benefit index and uptake of breast cancer chemoprevention.
Authors: Parijatham S. Sivasubramanian, Katherine D. Crew, Kevin Kalinsky, Dawn L. Hershman, Matthew A. Maurer, Heather Greenlee, Laura L. Reimers, Mary Beth Terry
Journal: Journal of Clinical Oncology (2014)

1568 Background: Chemoprevention with antiestrogens, tamoxifen and raloxifene, is under-utilized partly due to concerns regarding side effects such as uterine cancer and thromboembolism. Tamoxifen is indicated for women with ductal and lobular carcinoma in situ (DCIS/LCIS) and has a favorable risk-benefit ratio for high-risk women under age 50. For women 50 years and older, a Risk Benefit Index (RBI) developed by Freedman et al. takes into account a woman's age, race, breast cancer risk, and prior hysterectomy. We examined the correlation between RBI and chemoprevention uptake among high-risk women. Methods: From 2007 to 2013, new high-risk women seen at an urban, academic breast clinic were enrolled. Eligibility for chemoprevention included a 5-yr Gail risk≥1.67%, DCIS/LCIS, or BRCA mutation. RBI scores for tamoxifen and raloxifene based upon published algorithm tables were calculated for high-risk women ≥50 yrs and classified as strong/moderate evidence of benefits outweighing risks and benefits do not outweigh risks. Women with DCIS/LCIS/BRCA mutation and age<50 were excluded from the analysis. Results: Among 403 women enrolled, 311 (77%) were eligible for chemoprevention. Among women with DCIS/LCIS/BRCA mutation and age<50, 62% (124/201) and 31% (10/32) took an antiestrogen, respectively. Among 60 women with an RBI score, 82% had strong/moderate benefit; 33% took an antiestrogen with 65% in agreement with their RBI score. Among women who did not take an antiestrogen, 80% would have had a benefit to raloxifene or both. Conclusions: Among high-risk women who took an antiestrogen, the majority of treatment decisions were in agreement with their RBI score. Most women who refused an antiestrogen would have benefited. High-risk postmenopausal women now have the option of aromatase inhibitors, which may improve the risk-benefit profile for chemoprevention. Took tamoxifen Took raloxifene Took neither Total, N (%) Strong/moderate benefit for both 0 3 6 9 (15) Strong/moderate benefit for raloxifene 4 9 26 39 (65) Strong/moderate benefit for tamoxifen 1 0 0 1 (2) No benefit for both 1 2 8 11 (18) Total, N (%) 6 (10) 14 (23) 40 (67) 60 (100)
OC-075 Impact of pre-existing biliary stents on eus staging in patients with a head of pancreas mass
Authors: NL Bekkali, MK Nayar, SJ Johnson, L Thornton, A Darne, B Haugk, J Leeds, RM Charnley, KW Oppong
Journal: Gut (2017)

Introduction  Self-expanding metal stents (SEMS) are superior to plastic stents (PS) for pre-operative drainage of the common bile duct (CBD) and are increasingly preferred. Endoscopic ultrasound (EUS) has a role in staging particularly of tumours that are borderline operable on CT. Biliary stents can cause acoustic shadowing and artefacts thereby reducing the view of the posterior aspect of the tumour and its relationship to local vessels. SEMS have a larger cross-sectional profile and may cause more shadowing than PS. There are to date no published studies of the impact of biliary stents on EUS staging. The aim of this study is to assess whether the presence of a biliary stent impairs the accuracy of linear EUS staging.  Method  The study group comprised all patients with head of pancreas (HOP) mass undergoing EUS biopsy between January 2013 and June 2016. Staging information was obtained from the EUS report. Staging was considered accurate when EUS had the same staging with respect to the major vessels (SMV, SMA and PV) as per outcome of surgery or multidisciplinary consensus following imaging review. Any statement indicating inability to fully image the tumour margins due to stent was classified as indicative of inaccurate staging. Accuracy of vascular staging between the stented and unstented group was analysed using Chi-square test.  Results  A total of 835 patients underwent EUS for a solid pancreatic mass of which 382 had a mass in the HOP. Median age was 67 [25-86] yrs and 326 (85%) were male. At time of EUS, 232 of 382 (61%) patients had no stent and 150 (39%) patients had stents in the CBD; 97 (65%) SEMS and 53 (35%) PS. Staging wasn’t required in 74 patients and reports were not available in 14; 260 had documented EUS staging. Overall staging accuracy was 247/297 (83%); accurate in 39/76 (51%) SEMS patients, 37/43 (86%) with PS and 171/178 (96%) unstented patients. Staging outcomes were significantly different between SEMS compared to the PS group (p=0.0003) and the unstented group, p=0.0001. Difference in staging between plastic stent and the unstented group was also significant, p=0.03.  Conclusion  Our results show a significant impact of SEMS and plastic stents on EUS staging. The effect is greatest with SEMS. We therefore recommend that patients in whom EUS staging is indicated, who also require biliary drainage, should have EUS performed before stent placement and if biliary drainage must be performed before EUS, plastic stents should be considered.  Disclosure of Interest  None Declared