tbuckley/cabot-search huggingface dataset:
Frequency and risk factors for tyrosine kinase inhibitor–associated cardiotoxicity.
Authors: Peter J. Hurley, Suma Konety, Qing Cao, Charles Oertli, Srilakshmi Vankina, Anne Hudson Blaes
Journal: Journal of Clinical Oncology (2016)

6596 Background: Tyrosine kinase inhibitors (TKI) are cancer drugs associated with cardiovascular events in clinical trials. There are limited data on the frequency of these complications in clinical practice. We aim to describe the frequency of cardiovascular events for patients taking the following TKI: axitinib, dasatinib, imatinib, lapatinib, nilotinib, pazopanib, regorafenib, sorafenib, or sunitinib. Methods: We performed a retrospective case-control study of 354 subjects treated with TKI and 354 controls (matched by age, gender, and cancer diagnosis when available) not treated with TKI at the University of Minnesota from 2011-2014. We reviewed the subject’s medical record to describe the frequency of cardiovascular events defined as minor (Common Terminology Criteria for Adverse Events version 4.0 [CTCAE v4.0] grade 1-3) or serious (CTCAE v4.0 grade 4-5). Results: Each group had a median age of 58 years and included 181 (51.1%) males and 173 (48.9%) females. History of diabetes, smoking, hyperlipidemia (HLD), hypertension (HTN), congestive heart failure (CHF), coronary artery disease (CAD), atrial fibrillation, and chronic obstructive pulmonary disease (COPD) was similar between groups. HTN was the most common co-morbidity (41.8% in the TKI group vs. 41.2% in the control; p = 0.88). The cumulative incidence of any cardiovascular event at 12-months was greater for the TKI group (6%, CI 3-11%) than the control (0%, CI 0-2%) (p < 0.01). The frequency of minor events was similar between groups (3.7% TKI group vs 4.2% control group; p = 0.70), however serious events occurred more frequently in the TKI group (2.3%) compared to the control (n = 1, 0.3%) (p = 0.02). History of HLD, CHF, CAD, or COPD was associated with increased risk of a cardiovascular event (Table). Conclusions: TKI are associated with an increased risk of serious cardiovascular events. Particular attention should be given to patients on TKI with a history of HLD, CHF, CAD, or COPD as they are at higher risk for cardiovascular events. Risk of cardiovascular event by baseline characteristic. Baseline Characteristic Odds Ratio 95% Confidence Interval P-value HLD 1.94 0.99-3.80 0.05 CHF 11.03 4.58-26.56 < 0.01 CAD 4.60 2.11-10.04 < 0.01 COPD 5.22 1.99-13.69 < 0.01
The telomerase inhibitor imetelstat in patients (pts) with intermediate-2 or high-risk myelofibrosis (MF) previously treated with Janus kinase (JAK) inhibitor: A phase 2, randomized study.
Authors: Ayalew Tefferi, Naseema Gangat, Dietger Niederwieser, Jan Van Droogenbroeck, Maria R. Baer, Jean-Jacques Kiladjian, Ronald Hoffman, Guido Finazzi, Francisco Cervantes, Jason R. Gotlib, Shireen Sirhan, Jane Apperley, Angélique Langlois, Ying Wan, Laurie Jill Sherman, Souria Dougherty, Faye Feller, Olatoyosi Odenike
Journal: Journal of Clinical Oncology (2016)

TPS7079 Background: MF is a Philadelphia chromosome negative myeloproliferative neoplasm, with a relatively poor prognosis. Ruxolitinib, a JAK1/JAK2 inhibitor, is the only approved therapy for MF, and there are no approved treatment options for pts who fail ruxolitinib. There is a great unmet need for effective therapy for this pt population. Imetelstat sodium is a 13-mer oligonucleotide that specifically targets the RNA template of human telomerase and is a potent competitive inhibitor of telomerase enzymatic activity (Asai et al, Cancer Res 2003; Herbert et al, Oncogene 2005). A pilot study of imetelstat therapy in MF demonstrated complete and partial remissions, including some molecular remissions (Tefferi et al, N Engl J Med2015). Based on the novel mechanism of action imetelstat may provide clinical benefit to pts with intermediate-2 or high-risk MF with refractory/relapsed disease after JAK inhibitor therapy. Methods: This is a randomized (1:1), single-blind, multicenter, phase 2 study of two dosing regimens of imetelstat (9.4 mg/kg or 4.7 mg/kg IV, every 3 weeks) in approximately 200 adult pts with DIPSS intermediate 2 or high-risk MF who had progressive disease during or after JAK inhibitor therapy. Pts must have a diagnosis of primary, post-essential thrombocythemia, or post-polycythemia vera MF, measurable splenomegaly, active symptoms of MF, and hematology and biochemical lab parameters within protocol limits. An interim review for safety, early efficacy, and exposure-response analysis is planned after 20 pts have been randomized in each arm for at least 12 weeks. The primary endpoints of this study are to evaluate the spleen response rate (proportion of pts achieving ≥ 35% reduction in spleen volume) and symptom response rate (proportion of pts achieving ≥ 50% reduction in total symptom score) at week 24. Secondary endpoints include safety, treatment response per modified IWG MRT criteria for MF (Tefferi et al, Blood 2013), duration of responses, overall survival, and pharmacokinetic and pharmacodynamic relationships. Study sites opened in June 2015 and the study is currently open to accrual. Clinical trial information: NCT02426086.
Fecal metabolome and microflora differences between colorectal cancer patients and healthy adults.
Authors: Tiffany Weir, Robert Frederick Marschke, Regina J. Brown, Joanne O'Malia, Erica Dickson, Marlon Bazan, Amy Sheflin, Adam Heuberger, Erica Borresen, Stefan Pettine, Elizabeth Ryan
Journal: Journal of Clinical Oncology (2013)

11050 Background: High throughput genomic technologies such as 454 pyrosequencing and metabolomics platforms are now available to explore the relationships between gastrointestinal microflora, metabolism and colorectal cancer (CRC). Recent efforts to characterize the colorectal cancer microbiome have led to the identification of numerous bacteria whose presence or absence is associated with diseased tissue. Methods: Stool samples were collected from 10 healthy adults and 11 colorectal cancer patients prior to surgery at the University of Colorado Health-Poudre Valley Hospital in Fort Collins, CO. Fecal samples were processed for isolation of microbial DNA and sequenced using the 454 pyrosequencing platform. Metabolites were extracted using acidified water for short chain fatty acids (SCFA) and 3:2:2 isopropanol:acetonitrile:water to obtain global metabolite profiles utilizing Gas Chromatography-Mass Spectrometry (GC-MS). Results: There were no significant differences in the overall microbial community structure associated with disease state, but several bacterial genera, particularly butyrate-producing species, were under-represented in the CRC samples, while a mucin-degrading species, Akkermansia muciniphila, was about 4-fold higher in CRC (p&lt;0.01). Consequently, the chemoprotective SCFA, butyrate, was significantly lower in CRC samples than in those from healthy adults (p&lt;0.0001) and GC-MS profiling revealed that there were higher levels of amino acids in stool samples from CRC patients and higher poly and monounsaturated fatty acids in stool from healthy adults (p&lt;0.01). Conclusions: This systems biology approach may allow us to identify functional groups of gastrointestinal bacteria and their associated metabolites as novel therapeutic and chemopreventive targets. The Colorado Agricultural Experiment Station, Shipley Foundation and the NIH R03CA150070 supported this work.
Morbidity, mortality and cost associated with venous thromboembolism among hospitalized breast cancer patients: Results from national inpatient sample.
Authors: Sushil Ghimire, Ramesh Kumar Pandey, Sirjana Basnet Pandey, Rashmi Dhital, Dilli Ram Poudel, Daniel A. Forman
Journal: Journal of Clinical Oncology (2018)

e13573 Background: Venous thromboembolism (VTE) is an important cause of morbidity and mortality among hospitalized cancer patients. We aimed to study prevalence of VTE and its impact among hospitalizations in patients with breast cancer (BC). Methods: We used the National Inpatient Sample (NIS) database from 2001 to 2013 to identify adults ( > = 18 yrs) with BC as well as presence of VTE using ICD-9 codes and compared demographic characteristics and in-hospital outcomes between BC with and without VTE. Regression analysis was used to calculate odds of association. Results: 267,714 (3.01%) of a total of 8,880,681 hospitalized breast cancer patients had associated VTE. Demographic characteristics including age, race, comorbidity index and gender are shown in the table. BC patients with VTE had a longer mean length of stay (LOS) (7.16 days vs 4.54 days, OR 2.6 (CI 2.5 – 2.7), p < 0.001), higher average cost of hospitalization ($14518 vs $10513, OR 1.4 (CI 1.3 – 1.5), p < 0.001) and higher inpatient mortality (5.67% vs 2.92%, OR 2.0 (CI 1.9 – 2.1), p < 0.001). Factors associated with higher odds of VTE were male sex, African-American race, higher comorbidity index and use of chemotherapy based on multivariate analysis. Interestingly, smoking and female sex were associated with lower odds of occurrence of VTE. Conclusions: VTE in BC is associated with increased mortality, longer hospitalization and higher cost. Effective measures to reduce the VTE among the BC patients could help improve in-hospital outcomes. VTE No VTE DVT PE Age (yrs) 69.26 69.18 69.56 68.25 Female (%) 98.79 98.79 98.73 98.95 Race: Caucasian 75.79 79.37 74.34 76.92 African American 15.24 10.75 16.00 14.96 Others 8.96 9.88 9.66 8.12 Charlson comorbidity Index (%) < = 2 52.15 63.66 3 8.62 9.40 > = 4 39.22 26.93 Mean LOS (days) 7.16 4.54 7.48 6.48 Mortality 5.67% 2.92% 4.35% 8.15% Cost of hospital stay ($) 14517.77 10512.85 14906.57 13566.18 Factors associated with VTE: Multivariate regression, OR (CI) Smoking Chemotherapy Age Female Race Charlson Comorbidity Index AA Others 3 4 0.90 (0.87 – 0.92) 1.49 (1.42- 1.1.56) 1.00 (1.003 – 1.004) 0.76 (0.70- 0.83) 1.40(1.36– 1.44) 0.92(0.87 – 0.96) 1.10(1.05 – 1.14) 1.72(1.67 – 1.78)
Management of conjunctival malignancies at a quaternary care center: Outcomes and potential for quality improvement.
Authors: Tim Sotman, Michael Ryan Folkert
Journal: Journal of Clinical Oncology (2016)

e18095 Background: Conjunctival melanoma (CM) and squamous cell carcinoma (SCC) are ocular malignancies (OMs) with high rates of recurrence and morbidity. Optimal surgical management includes excisional biopsy and cryotherapy, but recurrence after excision is common; even with histologically clear surgical margins, 5-year recurrence rates are 11-21% SCC and 26% for CM. Evidence demonstrating the efficacy of adjuvant radiotherapy (RT) for CM and SCC has been shown, and to determine feasibility for a prospective trial investigating the use of adjuvant radiotherapy at our institution, we undertook a chart review of all patients with CM or SCC at our institution from 2004 to present. Methods: Following IRB approval, charts were reviewed for all patients with conjunctival malignancies at our institution. A total of 31 patients (32 eyes) were identified with histologically-confirmed CM or SCC, and patient characteristics, treatment patterns, and outcomes were assessed. Statistical analysis was performed with SPSS version v21. Results: Of the 32 OMs identified, 8 (25%) were CM and 24 (75%) were SCC. Median follow-up was 42.9 months. For patients who did not undergo upfront exenteration, 9 (28.1%) experienced local recurrence, and all underwent surgical salvage at first recurrence, 6 with re-excision and 3 with exenteration. The 5-year recurrence rate after surgical excision and cryotherapy was 37.5% ± 34.2% for CM and 11.5% ± 16% for SCC. Adjuvant or salvage RT was administered in 4 (12.5%) of patients; no patients failed locally after RT. Exenteration was required in 10 (31.3%) patients; as initial management in 6 patients and salvage treatment in 5 patients. The 5-year exenteration rates were 46.4 ± 40.2% (CM) and 33.2 ± 23.8% (SCC). Conclusions: Conjunctival malignancies are rare, even in a quaternary care center such as our institution. In our experience, rates of recurrence and exenteration appear to be higher than those in other large published series, which could reflect a referral base with more advanced disease on presentation and/or limited use of adjuvant therapies. Based on these findings, an adjuvant conjunctival RT protocol is under development to reduce rates of local recurrence.
Epidermal maturation, vitamin C and hyaluronan metabolism
Authors: L. Hämäläinen, E. Kärkkäinen, P. Takabe, L. Rauhala, G. Bart, R. Kärnä, S. Pasonen-Seppänen, S. Oikari, M.I. Tammi, R.H. Tammi
Journal: British Journal of Dermatology (2018)

Epidermis, the surface layer of human skin, is formed by cells called keratinocytes. They divide (making more cells) in the deeper parts of the skin and gradually move towards the surface. Keratinocytes eventually form a layer of dead cells on the skin's surface, and this layer is the main protective barrier against things that might damage or irritate the skin, such as chemicals and germs. A viscous substance called hyaluronan surrounds keratinocytes in the lower, living cell layers. All kinds of injuries to the epidermis, like wounding, infection, and sunburn, trigger a strong inflammatory response by keratinocytes. This response includes increased division of keratinocytes, and their movement to help the injury site recover, as well as increased hyaluronan production and turnover. In many skin diseases the keratinocyte injury‐response is excessive, or even completely unfounded, and harmful. Therefore, factors and treatments that calm down this reaction are potential medicines for some skin diseases. This study from Kuopio, Finland, studied hyaluronan metabolism (i.e. breakdown) in a special model developed in the laboratory, in which keratinocytes separate to produce a normal‐looking epidermis. This model allowed the researchers to demonstrate that vitamin C suppresses both production and degradation of hyaluronan in the epidermis. Since rapid hyaluronan metabolism is an indicator of inflammation, vitamin C – which is an antioxidant ‐ might have a use for suppressing this reaction in keratinocytes. This study calls for more work on the vitamin's mechanism of action, and possible roles in clinical practice.
Impact of National Cancer Institute (NCI) Community Cancer Centers Program (NCCCP) and NCI Community Oncology Research Program (NCORP) on clinical trial (CT) activities in a community cancer center.
Authors: Mehmet Sitki Copur, Mary Gulzow, Yuzhen Zhou, Sarah Einspahr, Jennifer Scott, Lauren Murphy, Brenda Broekemeier, Julie Splattstoesser, Ryan C. Ramaekers, David Crockett, Dron Gauchan, Douglas Clark, Angela Mae Obermiller, Max Norvell
Journal: Journal of Clinical Oncology (2018)

e18500 Background: Within past decade NCI has implemented two major initiatives to improve CT participation and quality of cancer care in the community setting. Catholic Health Initiatives (CHI) St. Francis Cancer Treatment Center in Grand Island Nebraska was one of the privileged community cancer centers to participate in both programs. Methods: During the last 3 years of NCCCP and first 3 years of NCORP, data on CT activities including number/percent of patients, underserved populations on CTs, number/type of CTs, staffing, organizational infrastructure/linkage to National Clinical Trials Network (NCTN), and access to cancer treatment (CRx), cancer control/prevention (CC/P), cancer care delivery (CCDR) trials were gathered and compared. Results: CT enrollment increased from 512 (30%) during NCCCP to 518 (36%) during NCORP (P = 0.0005). All patients were rural Nebraskans, 70% older than 60. Total CTs increased from 45 during NCCCP to 125 during NCORP. Major increases in NCTN trials/accruals were seen during NCORP. Staffing increased by two. Organizational infrastructure/linkage to cooperative group (CG) trials was with CALGB through an academic affiliation and academic IRB during NCCCP and with ECOG-ACRIN, SWOG, NRG, ALLIANCE through CHI-NCORP and central IRB of NCI and/or CHI during NCORP. Conclusions: Participation in both NCI programs positively impacted CT related activities and expanded research with enhanced access to quality cancer care. NCORP provided a robust NCTN linkage resulting in a record high CT portfolio. This preliminary comparison between two strong NCI initiatives may help for design of future programs. Activity July 2011-June 2014 Last 3-year NCCCP July 2014-June 2017 First 3-year NCORP P # Staff (FTE) 7 9 0.02* ∑ # Accruals (range) 512 (140-230) 518 (107-213) ∑% Accruals (range) 30 (26-34) 36 (23-42) 0.0005* ∑ # CG Trials / ∑ # Accruals 23 / 36 98 / 151 0.09 # CRx / # Accruals 18 / 26 81 / 114 0.03* # CC/P / # Accruals 2 / 8 11 / 21 0.41 # CCDR / # Accruals 0 3 / 16 0.25 # Biospecimen / # Accruals 3 / 2 3 / 0 0.91 # Industry / # Accruals 10 / 9 18 / 27 0.33 # Investigator Initiated / # Accruals 12 / 467 9 / 340 0.96 ∑ 45/512 125/518
Financial toxicity associated with conflict-induced cross-border travel for cancer care: Experience of Iraqi patients in Lebanon.
Authors: Deborah Mukherji, Mac Skelton, Raafat Alameddine, Omran Saifi, Miza Salim Hammoud, Marilyne Daher, Maya Charafeddine, Walid Faraj, Sally Naji Temraz, Ali Shamseddine, Layth Y.I. Mula-Hussain, Mohammed Saleem, Kadhim Faruq Namiq, Omar Dewachi, Ghassan Abu Sitta
Journal: Journal of Clinical Oncology (2018)

6562 Background: Conflict-induced cross-border travel for cancer care is commonly observed in the Middle East region. There has been very little research conducted on the impact this has on patients or on how cancer centers can adapt their services to meet the needs of this population. This study examines the experience of Iraqi patients with cancer seeking care in Lebanon at the American University of Beirut Medical Center (AUBMC). The aim of this study was to understand the social and financial context of conflict-related cross-border travel for cancer diagnosis and treatment. Methods: After IRB approval, 60 Iraqi patients and caregivers were recruited and interviewed. For background epidemiological data regarding the population of patients seeking cancer care at AUBMC, the diagnoses of adult patients with Iraqi nationality were reviewed from January 2013 to December 2016. Results: For the retrospective sample, the total number of patients was 1284 with 40% presenting with advanced solid tumors. The prospective data emphasized the difficulties around access to the necessary financial resources for cancer treatment abroad as well as patterns of mobility. Fifty four respondents (90%) reported high levels of financial distress. Patients relied upon the sale of possessions (48%), homes (30%) and vast networks to raise funds for treatment. Thematic analysis revealed several key drivers for undergoing cross-border treatment, including (1) the conflict-driven exodus of Iraqi oncology specialists; (2) destruction of hospitals or road blockages; (3) referrals by Iraqi doctors to Lebanese hospitals (4) geographical proximity of Lebanon and (5) lack of diagnostic equipment, radiotherapy machines, and reliable provision of chemotherapy in Iraqi hospitals. Conclusions: As a phenomenon distinct from medical tourism, conflict-related deficiencies in healthcare at home force patients with limited financial resources to undergo treatments in neighboring countries. We highlight the importance of shared decision-making and taking the unique socioeconomic status of this population of patients into account when planning treatment.
Abstract 20288: Characteristics of Monomorphic Ventricular Tachycardia in Adult Patients With Isolated Ventricular Noncompaction Undergoing VT Ablation
Authors: Yanhui Li, Yumei Xue, Jianhua Yu, Zulu Wang, Chengyang Jiang, Mbai Mackenzi, Venkatakrishna Tholakanahalli, Jian-Ming Li
Journal: Circulation (2017)

Introduction: VT was associated with sudden cardiac death (SCD) in isolated ventricular noncompaction (IVNC). The electrophysiological characteristics of these VTs were unknown Methods: Seven patie...
Patterns of care and outcome of germ cell tumours (GCT) in an Australian high-volume centre.
Authors: Malmaruha Arasaratnam, Bavanthi Balakrishnar, Megan Crumbaker, Sandra Turner, Amy Hayden, Andrew Brooks, Manish Patel, Howard Gurney
Journal: Journal of Clinical Oncology (2018)

e16534 Background: GCT accounts for 1-2% of all malignancies and are the most common invasive cancer in men aged between 15 to 34 years. Treatment is associated with high cure rate, but at the cost of long term morbidity. We analysed patients with GCT treated in a high-volume cancer centre in Australia to evaluate disease presentation, treatment practices and outcome. Methods: This is a retrospective analysis of 611 patients diagnosed with GCT in the Sydney West Cancer Network between 1990 to 2013. Data collected includes demographics, risk factors, disease characteristics, treatment administered, secondary malignancies and survival outcomes. Results: The median age was 33 years (range 14 to 85). The primary tumour site was the testis in 589 (96.3%), mediastinal in 11 (1.8%), and retroperitoneal in 9 (1.5%). History of undescended testis was in 48 (7.9%) and family history of GCT in 30 (4.9%). Pure seminoma was seen in 334 (54.7%), with 273 (82.0%) of these being stage I. Initial treatment in stage I seminoma was active surveillance in 69 (25%), radiotherapy in 178 (65%), and chemotherapy in 24 (9%). Non-seminomatous GCT (NSGCT) was diagnosed in 277 (45.3%), with 162 (58.5%) stage 1. Initial treatment in stage I NSGCT was active surveillance in 127 (78%), adjuvant radiotherapy in 3 (2%), and adjuvant chemotherapy in 29 (18%). Metastatic disease at presentation was seen in 163 (26.7%); 55 (33.7%) seminoma and 108 (66.3%) NSGCT. Sites of metastases were; lymph node only in 112 (68.7%), lung and node only in 30 (18.4%) and non-pulmonary visceral sites in 12 (7.4%). The most commonly used chemotherapy regimen was BEP (bleomycin, etoposide, cisplatin) in the advanced setting. With a minimum of 4 years of follow up in all patients, 18 (2.9%) have died from GCT and 72 (11.8%) from all causes. 27 have developed a second cancer (solid tumour 25; acute leukaemia 2). Conclusions: To our knowledge, this is the largest testicular cancer series from Australasia and data are comparable to published series from other countries.