tbuckley/cabot-search huggingface dataset:
Abstract 13172: Transverse Versus Longitudinal Electrical Propagation Within the Atrioventricular Node During Dual Pathway Conduction
Authors: Youhua Zhang
Journal: Circulation (2013)

Introduction: We have discovered and validated that AV node dual pathway conduction results in His electrogram alternans (HEA), which indicates dual inputs instead of a final common pathway from AV node into the His bundle. We hypothesized that fast pathway (FP) propagates in a direction across AV nodal fibers orientation, while slow pathway (SP) propagates longitudinally along fibers orientation. This transverse versus longitudinal propagation results in functional dissociation in distal node and dual inputs into the His bundle. Methods: Action potentials (AP) from multiple locations in the superior and inferior AV nodal domains were obtained to monitor electrical propagation during A1A2 programmed pacing in 8 rabbit hearts. Dual pathway conduction was confirmed by HEA. Results: AV nodal fibers were generally aligned longitudinally along the AV conduction axis. During FP conduction at basic beat A1, electrical excitation propagated in a superior to inferior direction across major fibers orientation (Figu...
ERCC1 polymorphism in patients with locally advanced head and neck squamous cell carcinoma treated with concomitant chemoradiation: Prevalence and impact on treatment efficacy
Authors: O. Abboud, X. Weng, L. Guertin, É. Bissada, Z. Abou Chacra, P. Nguyen-Tan, B. Fortin, J. Tabet, M. Audet, D. Soulieres
Journal: Journal of Clinical Oncology (2009)

6032 Background: Excision repair cross-complementation group 1 (ERCC1) is a gene coding for the nucleotide excision repair complex. Its increased expression and polymorphism at codon 118 have been linked to poor response to chemotherapy or chemoradiation in several types of cancer. ERCC1 removes the cisplatin adducts on the DNA of cells and its polymorphism appears to be a marker of chemotherapeutic resistance to platinum-based therapy. Objectives: To determine the prevalence of the polymorphism of ERCC1 (codon 118) in patients with locally advanced HNSCC treated with concomitant platinum-based chemoradiation therapy with or without prior surgery, and its effect on eficacy evaluated by locoregional control, disease-free survival and overall survival. Methods: Prospective data on efficacy was available on 460 consecutive patients treated with concomitant chemoradiation in our institution with a minimal follow-up of 2 years. Of these, 230 fixed and paraffin embedded biopsies or surgical specimens were collected. DNA was extracted from specimens and polymorphism of codon 118 was determined using a PCR technique. All analysis were performed using Kaplan-Meier survival curves, Fisher's test for categorical data and log-rank statistics for failure times. Results: DNA extraction was successful in 222 patients. Polymorphism mapping was possible in 178 specimens. Genotypic distribution in the population was the following : AAT/AAT:40% (Gr1), AAC/AAT: 48%(Gr2), AAC/AAC: 12% (Gr3). At 3 years, evaluation of efficacy for Gr1, Gr2, and Gr3 was determined. Locoregional control was respectively 77%, 83%, and 67% (p = NS), DFS was 58%, 68% and 55% (p=NS), and OS was 70%, 69%, and 70% (p = NS). Conclusions: ERCC1 polymorphism did not have an impact in our population on response to chemoradiation therapy. It can be postulated that ERCC1 does not seem to discriminate patients for whom another treatment option should be sought for patients with locally advanced SCCHN. Further data will be presented at the meeting including a multivariate analysis using different markers tested in our laboratory (KRAS, MGMT methylation, etc). No significant financial relationships to disclose.
Pharmacokinetic (PK) and phase I study of sorafenib (S) for solid tumors and hematologic malignancies in patients with hepatic or renal dysfunction (HD or RD): CALGB 60301
Authors: A. A. Miller, D. J. Murry, K. Owzar, D. R. Hollis, G. K. Abou-Alfa, A. Desai, J. Hwang, M. Villalona-Calero, E. C. Dees, L. D. Lewis, M. J. Ratain
Journal: Journal of Clinical Oncology (2007)

3538 Background: We sought to characterize the PK and determine a tolerable dose of S in patients with HD or RD. Methods: Patients with performance status 0–2 and pathologically proven solid tumors, multiple myeloma, or non-Hodgkin’s lymphoma, for whom standard therapy was exhausted, were assigned to one of 9 cohorts: [1] Bilirubin (B) =ULN and SGOT =ULN and creatinine clearance (CC) =60 ml/min; [2] B &gt; ULN but = 1.5 x ULN and/or SGOT &gt; ULN; [3] CC between 40 and 59 mL/min; [4] B &gt; 1.5 x ULN to = 3 x ULN (any SGOT); [5] CC between 20 and 39 mL/min; [6] B &gt; 3 x ULN to 10 x ULN (any SGOT); [7] CC &lt; 20 mL/min; [8] albumin &lt; 2.5 mg/dL (any B/ SGOT); and [9] hemodialysis. S was administered po as a 400 mg test dose on day 1 with blood sampled before and 1, 2, 3, 4, 6, 24, and 168 hrs afterwards for PK. Total S concentrations were fit to a 2-compartment model and population parameters from previous studies were utilized. On day 8, continuous daily po S started with dose escalation in groups of at least 3 evaluable patients. Dose-limiting toxicity (DLT) by day 29 was defined as: grade 4 neutrophils or platelets; B = 1.5 x baseline in HD and = 2.5 x ULN in RD; CC reduction by &gt; 20 mL/min in RD and &gt;10 mL/min in HD; grade = 3 nausea/vomiting/diarrhea despite optimal supportive care; or any other grade = 3 non-hematologic toxicity. Results: Between 1/05 and 12/06, 146 patients (target 150) were registered but 12 never started therapy. With the exception of cohorts 6 and 7, at least 12 patients per cohort were evaluable. The dose level in each cohort with DLT in less than one third of patients was: [1] 400 mg bid; [2] 400 mg bid; [3] 400 mg bid; [4] 200 mg bid; [5] 200 mg bid; [6] not even 200 mg every third day tolerable; [7] n/a; [8] 200 mg qd; and [9] 200 mg qd. All DLT was non-hematologic: 9 of 12 events in patients with HD were increase in B; other DLT included abdominal pain, rash, fatigue, nausea/vomiting, hand-foot syndrome, congestive heart failure, diarrhea, hemorrhage, and hypertension. PK data are available for 51 patients. Apparent S clearance was: highly variable, median 5.69 (range 1.27 - 19.98) L/hr; not related to age, body weight, or sex; and not different among cohorts. Conclusions: Apparent S clearance does not depend on cohort. We propose the above empiric starting doses by cohort. No significant financial relationships to disclose.
Novel Prognostic Model Of Primary Mediastinal Large B-Cell Lymphoma (PMBL): A Multicenter Cooperative Retrospective Study In Japan
Authors: Tomohiro Aoki, Koji Izutsu, Ritsuro Suzuki, Chiaki Nakaseko, Hiroshi Arima, Kazuyuki Shimada, Makoto Sasaki, Jun Takizawa, Kinuko Mitani, Tadahiko Igarashi, Yoshinobu Maeda, Fumihiro Ishida, Nozomi Niitsu, Ken Ohmachi, Hirotaka Takasaki, Naoya Nakamura, Tomohiro Kinoshita, Shigeo Nakamura, Michinori Ogura
Journal: Blood (2013)
Comparison of prevalence of pain symptoms and completion rates using a patient-reported outcomes (PRO) tool of pain in palliative and curative patients.
Authors: Sabrina Yeung, Catherine Brown, Andrea Perez Cosio, Yvonne Leung, Mindy Liang, Gursharan Gill, Samantha Sarabia, Aixin Liu, Lauren Wong, Doris Howell, Geoffrey Liu
Journal: Journal of Clinical Oncology (2015)

78 Background: Regular self-reporting of symptoms using validated computerized assessment tools can improve individualized symptom management. Yet there are concerns that palliative patients who may benefit most from such self-reporting may be reluctant to adopt such approaches or have barriers to proper reporting. We compared actual prevalence and completion rates of a PRO-tool between patients being managed with a palliative (PAL) or curative intent (CUR). Methods: A pain PRO-tool was administered cross-sectionally using tablet technology across outpatient clinics in a comprehensive cancer centre. Questions were adapted from the Brief Pain Inventory (BPI) and Edmonton Symptom Assessment System (ESAS), recording responses on pain severity and interference in life. PRO-tool completion rates and prevalence of pain symptoms were compared between CUR and PAL. Results: Of 200 patients, 82 were PAL and 118 were CUR; median age was 60 (21-86) years; 48% were female. A greater proportion of PAL were found with gastrointestinal, gynecological and lung cancers than CUR (p = 0.04). Each question had greater than 95% completion rates for both groups, capturing a wide range of scores. 16% of PAL reported no pain as their worst pain in the last 24 hours as opposed to 31% of CUR (p = 0.02). 82% (PAL) and 68% (CUR) reported their average pain as being at least “some pain” (p = 0.03), and there were no differences in the proportion of patients reporting interference with their general activity between PAL and CUR (p &gt; 0.05). Presence of current pain was equivocal when assessed via the ESAS adapted question (76% PAL vs 66% CUR, p = 0.16), but was significantly different when assessed using the BPI adapted question (72% PAL vs 56% CUR; p = 0.02). Conclusions: A Pain PRO-tool was completed with similarly high rates in PAL and CUR patients. As expected, prevalence of recent and current pain was high in both groups, and in some instances, higher in PAL than CUR patients. These results suggest that a Pain PRO-tool could be implemented with ease in the palliative setting, and would capture pain comprehensively.
Phase II study of tivozanib, an oral VEGFR inhibitor, in patients with recurrent glioblastoma.
Authors: Xuezhu Cai, Vyshak Chandra, Yangming Ou, Kyrre E. Emblem, Alona Muzikansky, John Evans, Jayashree Kalpathy-Cramer, Jorg Dietrich, Andrew S. Chi, Patrick Y. Wen, Bruce R. Rosen, Tracy Batchelor, Elizabeth Robins Gerstner
Journal: Journal of Clinical Oncology (2015)

2025 Background: Tivozanib, an oral, pure VEGFR tyrosine kinase inhibitor is an anti-angiogenesis drug which aims to modulate the tumor blood supply. This phase II study was designed to test the effectiveness of tivozanib on tumor vasculature in patients with recurrent GBM. Methods: Ten adult patients with recurrent GBM, median age of 62 (range 51-73), were enrolled on a Simon 2-stage design study and treated with tivozanib 1.5mg daily, 3 weeks on/1 week off in 28 day cycles. Brain MRI was done at baseline and after each cycle. The enhancing tumor and surrounding area of abnormal FLAIR hyperintensity were outlined and median tumor cerebral blood flow (CBF) and cerebral blood volume (CBV) values were derived from dynamic susceptibility contrast MRI to assess the performance of tivozanib. Vessel architectural imaging (VAI) was used to measure tumor vessel calibers and relative oxygen saturation. A t-test was used to compare baseline MRI parameters to the pre-cycle 3 visit. A univariate Cox model was used to test the association of each MRI parameter with time to progression. Results: Best MacDonald criteria responses were: CR (1), PR (1), SD (4), PD (4) and the median duration of response was only 3.6 mo (1.7-3.8mo) so the study was stopped per planned stopping rule. One patient was taken off study for unacceptable skin toxicity and nine patients for progressive disease. Given the dropout rate, only data up to cycle 3 was included in this analysis. There was no statistically significant change in enhancing tumor volume (p = 0.70), FLAIR volume (p = 0.31), or median CBV (p = 0.13) or median CBF (p = 0.54) within the enhancing tumor. Within the FLAIR hyperintensity, median CBV (p = 0.12) and median CBF (p = 0.41) also did not change significantly. No parameter was associated with time to tumor progression. VAI showed no change in vessel calibers or tissue oxygenation. Conclusions: Tivozanib was well tolerated but most patients progressed rapidly. The majority of patients had no significant change in tumor enhancement and perfusion imaging demonstrated insignificant changes in tumor and peritumoral blood volume, flow, vessel caliber, and oxygenation, suggesting that this anti-angiogenic agent had limited impact on brain tumor vasculature. Clinical trial information: NCT01846871.
A Retrospective Study of Risk Factors for Radiation Pneumonitis of Definitive Chemoradiotherapy for the Treatment of Locally Advanced Lung Cancer By Emphysema Quantification
Authors: S. Tokunaga, M. Tachihara, H. Koyama, Y. Ejima, H. Shinke, D. Tamura, H. Otera, K. Kobayashi, Y. Funada, R. Sasaki, Y. Ohno, Y. Nishimura
Journal: Annals of Oncology (2014)
Complex variant translocation t(1;2) with TPM3-ALK fusion due to cryptic ALK gene rearrangement in anaplastic large-cell lymphoma
Authors: Reiner Siebert, Stefan Gesk, Lana Harder, Doris Steinemann, Werner Grote, Brigitte Schlegelberger, Markus Tiemann, Iwona Wlodarska, Verena Schemmel
Journal: Blood (1999)
Inhibition of Promutagen Activation by the Antioxidants Butylated Hydroxyanisole and Butylated Hydroxytoluene
Authors: R H McKee, A M Tometsko
Journal: JNCI Journal of the National Cancer Institute (1979)

Butylated hydroxyanisole (BHA) and butylated hydroxytoluene (BHT) exhibited antimutagenic activity in the Salmonella typhlmurlum reversion test. Both BHA and BHT reduced reversion induced by chemicals requiring metabolic activation for effectiveness. However, they did not affect reversion induced by direct-acting mutagens. These results suggested that BHA and BHT may inhibit the metabolic activation processes and demonstrated that the S. typhlmurlum reversion test may be used to identify inhibitors of the neoplastic process.
Temozolomide in the treatment of progressive low-grade glioma
Authors: N. S. Silva, V. Paes, J. Galeana, A. P. Pascalicchio, C. Galvão, S. Cavalheiro
Journal: Journal of Clinical Oncology (2005)

8525 Background: The optimal treatment for low-grade glioma is still controversial. Temozolomide has been shown to be active in gliomas. The goals of this study are to determine the efficacy and side-effects profile of this agent. Methods: We report on the results of temozolomide for the treatment of patients with progressive low-grade gliomas in our institution during the time-period March 2001 - November 2004. Seventeen patients with low-grade glioma have been treated to date, three of whom previously received chemotherapy. Age ranged from 1,8 y to 18,5 y (m: 8,9 y); M/F 10/7; diencephalic - 11; medullary - 2; posterior fossa 1;dissemineted - 3 (gliomatosis); astro I - 14; astro II - 1; oligodentroglioma - 2. Temozolomide was administered orally, in a fasting state, once a day for 5 consecutive days dose of 200mg/m2/d repeat.every 28 days. Response was assessed by MRI every 4 cycles. Hormonal evaluation and aphtalmologic evaluations were performed reagularly. Clinical benefit was evaluated measuring seizure control and modification of Karnofsky performance status. Results: Partial and minor response were observed in 6/17 patients, stable disease in 7/17; progressive disease in 3/17. Vision improvement was noticed in 2/17 patients. Toxicity: 11/17 patients had nausea/vomiting; 3/17 grade 2 and 3 thrombocytopenia, 1/17 grade 3 hepatic toxicity shown by a reversible increave of liver transaminases. Conclusions: Temozolomide showed activity in low-grade glioma with low toxicity and excellent quality of life. No significant financial relationships to disclose.
Cost implications of intravenous bevacizumab treatment in patients with renal cell carcinoma (RCC): A retrospective claims database analysis
Authors: E. Dial, M. Duh, A. Fournier, L. Antras, D. Rodermund, M. P. Neary, W. K. Oh
Journal: Journal of Clinical Oncology (2009)

5112 Background: Angiogenesis inhibitor (AI) therapies are promising novel treatments for patients with RCC. However, IV therapy may impose transportation burdens for patients, infection risk from IV catheters and increased costs. The incremental costs associated with IV vs. oral administration of selected AI therapies (oral sunitinib or sorafenib, or IV bevacizumab off-label) for the treatment of RCC were evaluated. Methods: Patients with ≥ 2 RCC claims (ICD-9 189.0, 198.0) were identified from a large US commercial health insurance claims database from 1/02 to 12/07. Patients receiving bevacizumab (N=109) were matched 1:1 to patients receiving sorafenib or sunitinib, and observed from their first AI therapy claim until the last treatment date. Inpatient, outpatient and pharmacy costs were calculated on a per- patient per-month (PPPM) basis over the treatment period. Cost comparisons between the IV AI group and each separate oral AI group were performed using multivariate Tobit regressions for each category separately, adjusting for age, gender, region, health plan, time from first RCC claim and first metastasis claim to treatment initiation. Results: Mean total medical cost was $13,351, $6,998, and $8,213 PPPM for bevacizumab, sorafenib, and sunitinib, respectively (p&lt;0.05 for equality). Adjusted incremental total medical cost for the bevacizumab group was $5,045 PPPM higher than for sorafenib (p&lt;0.05), and $4,902 PPPM higher than for sunitinib (p&lt;0.05). Bevacizumab patients incurred higher incremental PPPM outpatient services cost by $7,687 and $7,995 compared to sorafenib and sunitinib, respectively (both p&lt;0.05) largely driven by the cost of bevacizumab itself. Conclusions: Patients with RCC treated with bevacizumab incur an incremental $58,826 to $60,546 total medical cost per patient per year compared to those treated with sunitinib or sorafenib. Oral AI therapies may result in cost savings to patients and healthcare payers over IV therapies. [Table: see text] [Table: see text]
Platinum concentration in bladder tissue treated with neoadjuvant chemotherapy and pathologic response.
Authors: Elizabeth A. Guancial, Deepak Kilari, Edward M. Messing, Eric S. Kim
Journal: Journal of Clinical Oncology (2015)

341 Background: Platinum (Pt) resistance is a major limitation in the treatment of muscle-invasive bladder cancer (MIBC), for which Pt-based chemotherapy remains the standard of care. Reduced intratumoral drug accumulation is an important mechanism of platinum resistance. Our previous studies in lung cancer demonstrate significant correlation between tissue Pt concentration and tumor response to neoadjuvant chemotherapy (NAC). Tissue Pt concentration was measured in bladder specimens exposed to Pt-based NAC and correlated to pathologic response. Methods: A cohort of 19 clinically annotated, archived frozen bladder specimens from MIBC patients treated with three to four cycles of Pt-based NAC was identified [pT0 (pathologic complete response, pCR), n=4; pTis or pT1 (pathologic partial response, pPR), n=6; &gt;/= pT2 (minimal pathologic response/progression), n=9]. Two cystectomy specimens from MIBC patients treated with Pt-based adjuvant therapy were used as controls. Non-tumor bearing adjacent bladder tissue (“normal”) was identified in cystectomy specimens by a genitourinary pathologist. Total Pt concentration in normal tissue was measured by flameless atomic absorption spectrophotometry. Three group Kruskal-Wallis tests were used to compare the distributions of Pt concentrations by pathologic response (pCR, pPR, minimal response/progression). Mann-Whitney non-parametric two-sided tests were used for two group comparisons. Results: Total Pt concentration in normal adjacent bladder tissue differed by tumor pathologic response (p=0.011). Specimens with a pCR had the highest Pt concentrations compared to those with a pPR (p=0.0095) or no response/progression (p=0.0196). There was no significant difference in Pt levels between PR and no response/progression group (p=0.37). Conclusions: Our findings suggest that enhanced Pt accumulation may be an important determinant of Pt sensitivity. Studies investigating factors that modulate intracellular Pt concentration, such as expression of influx/efflux Pt transporters, may serve as predictive biomarkers and promote increased use of Pt-based NAC.
Fatal and Nonfatal Occupational Injuries Involving Wood Chippers—United States, 1992-2002
Journal: JAMA (2005)

Tree damage from storms and routine tree-trimming operations prompt the need for disposing of branches and brush. Mobile wood chippers shred branches and tree trimmings into mulch. Branches are fed into a chute, in which rotating blades macerate the wood. Mobile chippers pose potential dangers to operators, who can become caught in the feed mechanism and pulled into the rotating chipper knives or struck by the hood of the machine while it is being opened or closed with the knives still rotating. This report summarizes data describing fatal and nonfatal injuries related to occupational wood chipper use, which indicate that those working with mobile wood chippers are at risk for serious injury and death, but that these injuries can be prevented through proper training, machine maintenance, and the use of personal protective equipment.
Zoledronic acid for the prevention of bone loss in patients with previously untreated lymphoma undergoing chemotherapy
Authors: V. D. Cataldo, M. A. Thompson, B. B. Toth, P. Sanjorjo, S. J. Bourgeois, B. N. Bekele, C. Jimenez, W. A. Murphy, S. A. Byfield, F. B. Hagemeister
Journal: Journal of Clinical Oncology (2009)

e20611 Background: Treatment of lymphoma with alkylating agents and steroids causes bone loss and increased fracture risk. In addition, over half of all untreated lymphoma patients are osteopenic or osteoporotic at diagnosis. Pamidronate reduces bone loss and risk of vertebral fractures in lymphoma patients undergoing chemotherapy (CT). However, the effects of the more potent bisphosphonate (BP) zoledronic acid (ZA) in this setting are unknown. Therefore, we report on a phase III trial evaluating the effect of ZA on bone mineral density (B) in patients with newly-diagnosed lymphoma undergoing CT. Methods: In total, 72 patients will be randomized to either the control arm [calcium carbonate (1,200 mg orally/day) plus vitamin D (400 IU orally/day)], or the BP arm [calcium carbonate and vitamin D as in the control arm plus ZA (4 mg IV at baseline and at 6 months)]. The primary endpoint is the absolute change in B of the lumbar spine (LS) and femoral neck (FN) at baseline and 12 months. Results: Thus far, 112 patients have been screened for enrollment. Twenty-seven patients (24.1%) failed screening due to periodontal disease, a predetermined exclusion criterion of the study. To date, 14 patients in the control arm and 9 patients in the BP arm have completed the one-year follow up period including baseline and one-year B evaluations. Comparing patients in the control arm to those in the BP arm, the average absolute change in B at the LS was -0.048 g/cm 2 vs. 0.0093 g/cm 2 (p=0.005), at the left FN was -0.039 g/cm 2 vs. 0.0074 g/cm 2 (p=0.01), and at the right FN was -0.043 g/cm 2 vs. 0.0211 g/cm 2 (p&lt;0.001), respectively. There have been no therapy-related serious adverse events or skeletal fractures in either arm. Conclusions: ZA in combination with calcium carbonate and vitamin D improves the B of patients with lymphoma undergoing CT. Given the incidence of below-average pre-treatment B and the known deleterious effects of lymphoma therapy on bone density, baseline B evaluation is warranted in all lymphoma patients. The high rate of periodontal disease in this patient population emphasizes the need for careful dental evaluation prior to BP therapy given the well-described, albeit rare, risk of osteonecrosis of the jaw from ZA. [Table: see text]