tbuckley/cabot-search huggingface dataset:
Abstract P450: Young Women with Increased Cardiovascular Disease Risk Burden have Poor Health Literacy
Authors: Tracy K Paul, Robert R Sciacca, Juviza K Rodriguez, Elsa-Grace V Giardina
Journal: Circulation (2014)

Introduction: Young women are thought to have low cardiovascular disease (CVD) risk; however, mortality due to ischemic heart disease has actually risen among women aged 35-44 years. We hypothesized that young women with increased CVD risk burden are more likely to misperceive body image and less likely to practice healthful behaviors. Methods: To determine CVD risk burden among young women (aged 18-49 years) of a primarily urban population, 569 women visiting outpatient medical clinics were assessed. Anthropometric measures [height, weight, waist, body mass index (BMI)], attitudes towards weight, and lifestyle behavior were determined. Body image self-perception was assessed using validated silhouette scales. Increased CVD risk burden was defined as presence of hypertension, diabetes mellitus, tobacco use, hyperlipidemia, and/or obesity. Results: Participants were Hispanic (62.7%; 357/569); non-Hispanic White (20.7%; 118/569); non-Hispanic Black (8.9%; 51/569) and Asian/other ethnicity (7.5%; 43/569); mean age was 35.9 years ± 8.1 and income $39,828 ± $20,229. BMI categories were: obese (BMI ≥ 30 kg/m 2 , 27.4%; 155/569); overweight (BMI 25.0 - 29.9 kg/m 2 , 29.0%; 164/569); normal (BMI 18.5 - 24.9, 41.2%; 233/569); and underweight (BMI ≤ 18.4; 2.3%; 13/569). Women without CVD risk burden were the reference standard. Nearly half (47.7%; 271/569) had increased CVD risk burden; and 33.5% (190/569) had ≥ 1 CVD risk factor, exclusive of obesity, including hypertension (18.0%), hyperlipidemia (11.5%), current tobacco use (10.2%), and diabetes mellitus (5.8%). Women with increased CVD risk were less likely to correctly identify body size (48.3% vs. 69.4%, p&lt;0.0001). They were more likely to be concerned about weight (82.0% vs. 65.8%, p =0.01) and actively trying to lose weight (77.3% vs. 65.4%, p=0.03). But, they were less likely to read nutrition labels when making food choices (29.4% vs. 17.9%, p=0.03) and more likely to cite cost (18.7% vs. 12.1%, p=0.03) and difficulty implementing a weight loss regimen (22.2% vs. 15.6%, p=0.05) as barriers to losing weight. Most, regardless of CVD risk burden, knew blood pressure, cholesterol, and blood sugar status. However, women with increased CVD risk burden were less likely to know cholesterol level (81.4% vs. 88.8%, p=0.02). Fewer obese women knew that tobacco contributes to CVD risk compared to non-obese women (92.3% vs. 96.6%, p=0.04). Conclusion: Paradoxically, though aware of their CVD risk factors and with heightened weight concerns, young women with increased CVD risk burden misperceive their body size and lack healthy behavior knowledge. A disconnect exists between this group’s recognition of their underlying risk and ability to modify their lifestyle to decrease CVD risk burden.
Activation state (phosphorylated) EGFR and STAT3 as prognostic markers in resected non-small cell lung cancer (NSCLC)
Authors: T. Cortas, R. Eisenberg, P. Fu, J. Robke, J. A. Kern, A. Dowlati
Journal: Journal of Clinical Oncology (2005)

7090 Background: Epidermal Growth Factor Receptor (EGFR) has been extensively evaluated in NSCLC with approximately 70% of formalin-fixed paraffin-embedded (FFPE) specimens positive on immunohistochemistry (IHC). The total EGFR expression has failed to demonstrate prognostic importance. Activation of EGFR results in downstream STAT-3 activation. We hypothesized that activation (phosphorylated) state (pEGFR, pSTAT-3) rather than total mass protein will have prognostic value in NSCLC. Methods: 105 patients underwent lung resection for NSCLC at University Hospitals of Cleveland from 1998–2001 with FFPE samples evaluable for analysis. A database with patient characteristics (TNM stage, gender, age, time to recurrence, and survival) was established. pEGFR and pSTAT-3 antibodies were used for IHC. Specimens were divided into negative, 1+ (>5% of tumor cells showing + staining), 2+ or 3+ staining. Cox proportional hazard model was used for multivariate analysis. Results: Median age was 71years. 55% (58/105) were female. 63% had adenocarcinoma. Stage breakdown was as follows: stage I: 57%, stage II: 29%, stage III: 14%. Only 31% of the specimens were + for pEGFR (higher in squamous 44% compared to adenocarcinoma 28%). pSTAT-3 + staining was seen in 39% of samples. There was a significant positive correlation between pEGFR and pSTAT-3 (p=0.028). No such correlation was seen with pERK or pAKT. After controlling for age, sex, stage and pSTAT3, the hazard of dying for patients with + pEGFR was 1.64 times higher compared to negative pEGFR (p = 0.121). The estimated 5 year Kaplan-Meier probabilities of overall survival (OS) was 60.2% for pEGFR negative versus 46.9% for pEGFR positive patients. Conclusions: Although total EGFR is commonly expressed in NSCLC (∼70%), the activation form (pEGFR) is seen in only 1/3 of patients. There is a trend toward worse survival in early stage NSCLC that express pEGFR. pEGFR and pSTAT-3 were commonly co-expressed compatible with known signal transduction pathway in lung cancer. The use of activated rather than total mass receptors should be further evaluated as prognostic and predictive factors for response to EGFR-targeted therapies. (Supported by American Cancer Society) No significant financial relationships to disclose.
Outpatient administration of high-dose methotrexate for osteosarcoma treatment in Brazil
Authors: C. R. Macedo, A. M. Cappellano, D. T. Noguchi, A. P. Martinho, C. G. Dias, C. G. Dias, R. C. Malheiros, A. H. Dutra, M. Grings, A. L. Pires, A. S. Petrilli
Journal: Journal of Clinical Oncology (2009)

10038 Background: We describe the experience with outpatient administration of high dose methotrexate (HDMTX) and leucovorin rescue for osteosarcoma treatment at Instituto de Oncologia Pediátrica. Methods: HDMTX (12g/m 2 ) is administered as part of the Brazilian Osteosarcoma Treatment Group Protocol in an ambulatory basis. Daily MTX serum levels and fluid controls follows until the serum level is &lt;0,2 μ/L. Families were oriented to measure urinary pH and volume, PO intake and to adjust leucovorin dose as needed. To achieve treatment adherence, a family education program was developed. Concomitantly to HD chemotherapy, low dose oral cyclophosphamide and MTX (metronomic treatment) were provided to metastatic (M) patients. This is a retrospective analysis of the HDMTX courses administered between 2006 and 2008. Results: Out of 341 HDMTX infusions, administered to 42 patients, 42.5% had abnormal serum levels at hour 24, 8.8% at hour 48 and 33.2% at hour 72. After required interventions, 2.9% (n = 8) had serum levels &gt;0.2 μ/L at hour 72 leading to delayed excretion. Of these, 7 had also creatinine elevation and main adverse events were mucositis, reversible transaminasis elevation and one sepsis. In the overall analysis, other toxicities included mucositis grade II (20%), nefrotoxicity (5.6%) and neutropenia grades III and IV (25.4%). Serious adverse events of seizure, allergic reaction, and Steven Johnson's Syndrome lead to suspension of future HDMTX administration in 4 patients (01 metastatic). The main differences found between M and non-M patients were 16.8% versus 8.7% of leucopenia grade IV and 12.1% versus 6.6% of anemia grades III and IV. Conclusions: Similar to other authors’ experience, outpatient administration of HDMTX lead to elevated serum levels in 42.5% of the infusions, demonstrating the importance of a well trained staff and early introduction of supportive therapies to avoid associated toxicities. To a developing country, this approach helps lowering treatment costs and infection risks and increases patient adherence to treatment, with acceptable toxicities, even with the introduction of metronomic treatment. No significant financial relationships to disclose.
Abstract 17186: In Vivo Platelet Activation in Impaired Glucose Tolerance and During Progression of Type 2 Diabetes: a Cross-sectional and Longitudinal Study
Authors: Flavia Ciaffardini, Giovanni Davì, Patrizia Di Fulvio, Gloria Formoso, Rossella Liani, Francesca Pagliaccia, Carlo Patrono, Giovanna Petrucci, Dario Pitocco, Bianca Rocca, Francesca Santilli, Paola Simeone, Luigi Tanese, Romina Tripaldi, Natale Vazzana, Francesco Zaccardi
Journal: Circulation (2014)

Introduction: Impaired glucose tolerance (IGT) reflects the progression from normoglycemia to type 2 diabetes mellitus (DM). IGT and DM are associated with high cardiovascular disease (CVD) morbidity and mortality. Hypothesis: Enhanced platelet activation has been previously reported in DM, but whether this pertains to IGT is unknown. Methods: We investigated in vivo platelet activation, as reflected by the urinary excretion of 11-dehydro-TXB2 (TXM), in IGT and DM patients with a diagnosis documented either &lt;12 months (new-DM) or ≥12 months (established-DM) from study entry. Patients were studied repeatedly up to 46 months to assess changes in platelet activation over time. Some patients were given standard 500 kcal meals at 8am, 1 and 6pm and TXM was measured repeatedly during a 12-hr period. Results: We enrolled 49 IGT patients (19M, age 56±9 yrs), 59 new-DM (36M, 61±10 yrs) and 61 established-DM (34M, 62±7 yrs, DM duration 9.7±6.1 yrs) patients diagnosed according to the ADA criteria, not on antiplatelet drugs. Median TXM values at study entry were comparably enhanced in the 3 groups (1,189 [897-1,503], 1,277 [897-1,870], and 1,217 [885-1,494] pg/mg creatinine in IGT, new- and established-DM, respectively; p=0.39). Urinary TXM excretion showed limited intra-subject variability over time, as shown in the Figure. There was no convincing evidence of a circadian variation in TXM excretion. Two-hour, post-meal glucose variations (8-10am or 1-3pm) did not affect subsequent TXM values. Conclusions: We conclude that the potential benefits and risks of antiplatelet therapy should be considered in IGT management, because persistent platelet activation might contribute to CVD progression and its thrombotic complications. Given the stability of high TXM excretion in DM, this non-invasive biomarker of platelet activation should be tested as a predictor of vascular events during long-term follow-up.
Rapid elimination kinetics of free PSA and hK2 following initiation of GnRH-antagonist treatment of aggressive Prostate Cancer
Authors: D. Ulmert, A. Serio, H. I. Scher, M. Seandel, D. Frankel, A. Vickers, T. Kold Olesen, H. Lilja
Journal: Journal of Clinical Oncology (2008)

5171 Background: Presently the sum (tPSA) of complex (cPSA) and free PSA (fPSA) is used when evaluating the effect of prostate cancer treatment. PSA-forms display large discrepancies in metabolic pathways and elimination rates from blood due to significant differences in size, character and treatment. Prior studies of serial blood samples taken subsequent to radical prostatectomy (RP) showed that cPSA decrease is very slow as opposed to fPSA that is rapidly eliminated in exponential fashion. Previous studies of GNRH-agonist treated patients showed that all prostate kallikrein forms decrease in a similarly slow exponential manner. Access to serial samples taken after treatment with a novel GnRH-antagonist (Degarelix) allowed us to investigate the elimination profile of prostate kallikrein-forms after the rapid castration induced by this drug. Material and methods: Serial bloods (1, 3, 7, 14, 21 and 28 days after treatment initiation) were from 24 prostate cancer patients following the initiation of treatment with the GnRH-antagonist. 2/24 had localized disease, 15/24 locally advanced, 6/24 generalized and 1/24 was non-classified. PSA-forms were measured with a commercial assay and hK2 with a research prototype assay. Results: Geometric mean levels (ng/mL) of tPSA, cPSA, fPSA and hK2 at baseline were 42.6 (SD 48.0), 36.5 (SD 36.5), 6.10 (SD 7.99) and 1.30 (SD 2.84), respectively. 22/24 patients had castrate levels (<0.5 ng/ml) after 24 hours, and 24/24 after 72 hours. All kallikrein-forms declined in an exponential fashion after degarelix administration, a much faster elimination rate could be observed for free PSA and hK2 compared to tPSA (or cPSA). At day 3 and day 7, the percent decline in hK2 and fPSA from pre-treatment levels was significantly higher than that of tPSA (or cPSA). Conclusion: The fast onset of action of the GnRH-antagonist and the subsequent decline in PSA lead to a profile in the reduction of prostate kallikreins that is similar to the decline seen after RP. The faster decline of free forms reflects the effect of testosterone elimination more accurately and promptly than tPSA. Monitoring with fPSA and hK2 may provide more reliable option to assess response to treatment after rapid onset of castration. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Ferring Pharmaceuticals Arctic Partners
Chronic Myelogenous Leukemia
Authors: Susan O'Brien, Camille N. Abboud, Mojtaba Akhtari, Jessica Altman, Ellin Berman, Daniel J. DeAngelo, Steven Devine, Amir T. Fathi, Jason Gotlib, Madan Jagasia, Joseph O. Moore, Javier Pinilla-Ibarz, Jerald P. Radich, Vishnu V.B. Reddy, Neil P. Shah, Paul J. Shami, B. Douglas Smith, David S. Snyder, Meir Wetzler, Furhan Yunus
Journal: Journal of the National Comprehensive Cancer Network (2012)

OverviewChronic myelogenous leukemia (CML) accounts for 15% of adult leukemias.The median age of disease onset is 67 years; however, SEER statistics show that CML occurs in all age groups.In 2010, an estimated 4870 cases were diagnosed in the United States, and 440 patients died of the disease. 1 CML is a hematopoietic stem cell disease, characterized by a reciprocal translocation between chromosomes 9 and 22, resulting in the formation of the Philadelphia chromosome (Ph).This translocation t(9;22) results in the head-to-tail fusion of the breakpoint cluster region (BCR) gene on chromosome 22 at band q11 and the Abelson murine leukemia (ABL) gene located on chromosome 9 at band
Alemtuzumab in T-cell large granular lymphocytic leukaemia: interim results from a single-arm, open-label, phase 2 study
Authors: Bogdan Dumitriu, Sawa Ito, Xingmin Feng, Nicole Stephens, Muharrem Yunce, Sachiko Kajigaya, Joseph J Melenhorst, Olga Rios, Priscila Scheinberg, Fariba Chinian, Keyvan Keyvanfar, Minoo Battiwalla, Colin O Wu, Irina Maric, Liqiang Xi, Mark Raffeld, Pawel Muranski, Danielle M Townsley, Neal S Young, Austin J Barrett, Phillip Scheinberg
Journal: The Lancet Haematology (2015)
Phase I/II trial of metronomic chemotherapy with daily dalteparin and cyclophosphamide, twice-weekly methothrexate, and daily prednisone (DalCMP) as therapy for metastatic breast cancer (MBC).
Authors: B. A. Sousa, R. A. Buckman, M. Clemons, S. F. Dent, N. S. Wong, R. Kerbel, D. J. Sutherland, U. Emmenegger, S. Gardner, K. I. Pritchard
Journal: Journal of Clinical Oncology (2010)

1152 Background: We recently published data on 41 patients (pts) treated with DalCMP (JCO 2009). We have now accrued additional pts to further compare responses in pts treated or not with prior anthracycline (A) and taxane (T) based regimens. Methods: Pts with measurable MBC received daily sc dalteparin (5,000UI), po cyclophosphamide (50mg), twice weekly po methothrexate (2.5mg BID) and daily po prednisone (5mg). Primary study endpoint was clinical benefit rate (CBR) (i.e., complete response [CR] + partial response [PR] + prolonged stable disease for ≥ 24 weeks [pSD]). Secondary endpoints included time to progression (TTP), duration of response (DOR), and overall survival (OS). Pts were in group 1 (no prior chemotherapy for metastatic disease) or group 2 (prior A and T for metastatic disease, or prior adjuvant A and T if relapse < 1 year, or prior adjuvant A and prior T for metastatic disease). Adverse events were assessed by common toxicity criteria version 2 (CTCAE). Kaplan-Meier methods and log rank test were used for time to event outcomes. Exact confidence intervals (CI) and Fisher's Exact test were used for proportions. Results: Between Oct 2003 and Sept 2008, 92 eligible pts were recruited from two cancer centers in Ontario, Canada, 44 in group 1 and 48 in group 2. There were 2 cases of grade (G) 4 toxicity (anemia, leukopenia). G3 toxicity included transient elevation of liver transaminases in 21 pts and fatigue in 7. Efficacy results are shown in the Table. Conclusions: Metronomic DalCMP is safe, well tolerated, and clinically active in MBC. Group 1 (no prior A/T) n=44 Group 2 (prior A/T) n=48 p value Response CR- 1 (2.2%) CR- none 0.15 PR-5 (11.4%) PR-3 (6.2%) D-14 (31.8%) SD-8 (16.7%) pSD-5 (11.4%) SD-5 (10.4%) D-19 (43.2%) PD-32 (66.7%) CBR (%) 25 (CI 95%: 13.2-40.3) 16.7 (CI 95%: 7.5-30.2) 0.44 TTP (median, wks) 15.7 (CI 95%: 7.4-22.1) 7.8 (CI 95%: 7.0-14.7) 0.16 OS (median, wks) 73.5 (CI 95%: 48.0- 86.8) 31.7 (CI 95%: 26.4- 57.0) 0.051 Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Pfizer
Presence of bone marrow micrometastasis (BMM) in breast cancer patients predicts a poor-prognosis pattern of first distant metastasis: Results from the pooled analysis
Authors: S. Braun, F. D. Vogl, K. Pantel
Journal: Journal of Clinical Oncology (2006)

567 Background: As a putative surrogate marker of ubiquitous distant metastasis, which is assessable both at initial diagnosis of breast cancer and during adjuvant therapy, BMM would be a valuable end-point marker for adjuvant clinical trials. Methods: Based on individual pt data of 4,686 breast cancer pts with a 10-year follow-up (median, 62 months), we analyzed distant disease-free survival (DDFS) of BMM+/BMM− pts, and looked specifically into sites of first metastatic relapse, expressed as bone metastasis-free (BFS), visceral metastasis-free (VFS), and multiple metastasis-free survival (MFS; i.e., simultaneous diagnosis of bone and visceral metastases). We performed Kaplan-Meier analysis and computed incidence rates (IR)/ incidence rate ratios (IRR) for the occurrence of metastasis at different sites. Results: BMM were detected in 1,432 (30.6%) of pts overall and significantly more often in pts with subsequent diagnosis of distant metastasis as compared to those who survived without metastases (48.5% vs. 26.0%, P&lt;0.001). BMM+ pts had a significantly shorter DDFS than BMM- pts (IRR 2.36; 95%CI, 2.07–2.69; P&lt;0.001). This was also true when we analyzed either bone (IRR 2.73; 95%CI, 2.27–3.29; P&lt;0.001) or visceral metastases only (IRR, 2.48; 95%CI, 2.11–2.91; P&lt;0.001). Among 952 pts with occurrence of distant metastasis, IR of such an event was 1.28-fold (95%CI, 1.12–1.46; P&lt;0.001) higher in BMM+ pts than in BMM- pts. Among 462 BMM+ pts (but not among those 490 BMM- pts), IRs for MFS were significantly increased as compared to both VFS (IRR 1.72; 95%CI, 1.36–2.18; P&lt;0.001) and BFS (IRR 1.85; 95%CI 1.21–2.06; P=0.001). IR for BFS of BMM+ patients (1.08; 95%CI 0.87–1.34) was not significantly increased over VFS. Conclusion: Our data provide conclusive evidence that presence of BMM predicts an early onset and a poor prognosis pattern of overt distant metastasis. With the similar likelihood of the occurrence of subsequent metastasis in bone and at visceral sites, BMM appears to be a marker of generalized tumor cell spread. No significant financial relationships to disclose.
The value of surveillance computed tomography scans of the pelvis in patients with head and neck primary melanomas.
Authors: G. C. Alvarado, N. E. Papadopoulos, W. Hwu, A. Y. Bedikian, J. Homsi, J. Myers, Y. Bronstein, R. L. Bassett, P. Hwu, K. B. Kim
Journal: Journal of Clinical Oncology (2010)

e19035 Background: Computed tomography (CT) scans can be of great value to assess distant metastases in melanoma patients with a high risk for tumor recurrence; yet, this potential benefit must be balanced with the cost, discomfort and the radiation exposure associated with the scans. There is a lack of convincing evidence for the benefit of pelvic CT scans in patients with head and neck primary melanomas. We conducted a retrospective study to evaluate the frequency of pelvic metastases as the first site of metastasis in patients with head and neck primary melanomas, in order to justify the use of the pelvic CT scan as a routine staging imaging study. Methods: We searched our institution's patient database for patients with histolologically confirmed head and neck primary melanomas and selected patients with adequate follow up who had a first appointment between January 2002 and January 2005. Results: We identified 146 patients who met our selection criteria. The median age was 59.5 years, and 73% were male. Although scalp (40%) and face (32%) were the most common sites of the primary melanoma, 16% had a primary in the mucosal surface of the sinus and mouth, or conjunctiva. Seventy-five percent of the patients had either stage I or II melanoma at the time of the diagnosis, and 2% had stage IV disease at initial diagnosis. At the median follow-up duration of 49 months, 110 (75%) had developed recurrences, and the median time to the first recurrence was 13 months. A total of 82 (56%) eventually developed distant metastases with only 10 (7%) developing metastases in the pelvis, among which none had pelvic metastases as the first site of recurrence. With 0 missed pelvic metastases among 146 patients, the probability that the true rate of missed metastases is at least 5% is 0.0006. Conclusions: Our study suggests that pelvic CT scans may not be necessary as a routine staging examination in patients with head and neck primary melanomas, even in those with high risk for recurrence and/or metastasis. No significant financial relationships to disclose.
An evaluation of in-patient management of refractory or severe chemotherapy-induced diarrhea.
Authors: L. V. Smith, S. Shah, P. G. Kwan
Journal: Journal of Clinical Oncology (2010)

e13126 Background: Chemotherapy-induced diarrhea (CID) is a common complication of cancer treatment, which can result in significant morbidity and mortality. American and Canadian guidelines recommend octreotide as first-line treatment option for the management of refractory or severe CID. Methods: This was a retrospective study that evaluated the management of CID in hospitalized patients at VA North and Central Texas Health Care Systems. Patients were eligible for study if they were admitted to the hospital due to 5-FU or CPT-11 related diarrhea. Patients were required to have received chemotherapy within 30 days of hospital admission. Objectives of the study were to evaluate the adherence to the CID guideline recommendations and morbidity and mortality associated with the management of CID. Results: Total of 28 patients were identified eligible for the study with mean age of 66 years. Fifty-seven percent of the patients had late onset (> 24 hours after chemotherapy) diarrhea and 64% had loperamide prior to the hospital admission. In-patient only 1 (4%) of the patients received octreotide as first-line treatment for the management of refractory or severe CID. Intravenous fluid was administered to 25 (89%) and antibiotics to 8 (29%) of the patients. Twenty-three of 28 (82%) patients achieved complete response (CR). Median time to complete resolution of diarrhea was 4 days and the mean length of hospital stay was 6.3 days. At 30 days from hospital admission overall mortality rate was 11%. Patients who achieved CR in 3 or less days had no 30 days mortality compared with 19% (p=0.24) for patients who did not achieve CR by day 3. Conclusions: Delay in complete resolution of refractory or severe CID may increase risk of mortality. Chemotherapy-induced diarrhea in the in-patient setting is not managed according to the guideline recommendations and there is a significant need for education and awareness of morbidity and mortality associated with CID. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Novartis