tbuckley/cabot-search huggingface dataset:
Diagnostic procedures for non-small-cell lung cancer (NSCLC): recommendations of the European Expert Group
Authors: Manfred Dietel, Lukas Bubendorf, Anne-Marie C Dingemans, Christophe Dooms, Göran Elmberger, Rosa Calero García, Keith M Kerr, Eric Lim, Fernando López-Ríos, Erik Thunnissen, Paul E Van Schil, Maximilian von Laffert
Journal: Thorax (2015)

<h3>Background</h3> There is currently no Europe-wide consensus on the appropriate preanalytical measures and workflow to optimise procedures for tissue-based molecular testing of non-small-cell lung cancer (NSCLC). To address this, a group of lung cancer experts (see list of authors) convened to discuss and propose standard operating procedures (SOPs) for NSCLC. <h3>Methods</h3> Based on earlier meetings and scientific expertise on lung cancer, a multidisciplinary group meeting was aligned. The aim was to include all relevant aspects concerning NSCLC diagnosis. After careful consideration, the following topics were selected and each was reviewed by the experts: surgical resection and sampling; biopsy procedures for analysis; preanalytical and other variables affecting quality of tissue; tissue conservation; testing procedures for epidermal growth factor receptor, anaplastic lymphoma kinase and ROS proto-oncogene 1, receptor tyrosine kinase (ROS1) in lung tissue and cytological specimens; as well as standardised reporting and quality control (QC). Finally, an optimal workflow was described. <h3>Results</h3> Suggested optimal procedures and workflows are discussed in detail. The broad consensus was that the complex workflow presented can only be executed effectively by an interdisciplinary approach using a well-trained team. <h3>Conclusions</h3> To optimise diagnosis and treatment of patients with NSCLC, it is essential to establish SOPs that are adaptable to the local situation. In addition, a continuous QC system and a local multidisciplinary tumour-type-oriented board are essential.
Randomized, multicenter phase III study of ranpirnase plus doxorubicin (DOX) versus DOX in patients with unresectable malignant mesothelioma (MM)
Authors: M. Reck, M. Krzakowski, J. Jassem, C. Eschbach, J. Kozielski, J. J. Costanzi, U. Gatzemeier, K. Shogen, J. von Pawel
Journal: Journal of Clinical Oncology (2009)

7507 Background: Ranpirnase (Onconase), a novel ribonuclease with preclinical activity against various tumors, has led to a median survival of 8.3 ms (one year survival: 42%) in a multicentre phase II trial in chemonaive and pretreated pts whom met the Cancer and Leukemia Group B (CALGB) prognostic criteria for group 1–4 (Mikulski, J Clin Oncol 20, 2001). Methods: This multicenter controlled phase III trial compared efficacy and safety of Dox (one of the most active single agents when the study was planned) with or without ranpirnase. Primary endpoint was overall survival (OS), secondary endpoints included progression-free survival, response rate, safety and disease related symptoms. Eligibility criteria: histologically proven unresectable MM; CALGB group 1–4, ECOG PS 0–1, adequate organ function. Stratification was performed according to CALGB group and histology (epitheloid vs. non-epitheloid). One line of prior therapy was permitted. Between 08/01 and 09/07 413 eligible pts were randomized to DOX 60 mg/m 2 every 3 wks with or without ranpirnase 240 μg/m 2 weekly (cycle 1) and 480 μg/m 2 in subsequent cycles (maximum 6) if no severe toxicity had occurred. The study was designed to detect an increase of 4 ms (9 vs. 13) in median OS (MST) using a two-sided logrank test (α = 5%) with 90% power. Results: Both arms were well balanced (DOX + ranpirnase / DOX: 203/210 pts): Mean age 62.2/61.8 yrs; males 157/156; PS 0 52/60; PS 1 151/150; prior chemo 65/65 pts (pemetrexed 35/35; other chemo 30/30). CALGB groups 14/14 (1), 45/51 (2), 117/115 (3), 27/30 (4). In the intent to treat population (ITT) there was no significant difference in OS (MST: 11.1 vs 10.7 ms; HR 1.02, 95% CI 0.82–1.26) whilst in a preplanned analysis including 130 pretreated patients a significant advantage in survival in favor of DOX + ranpirnase was found (MST: 10.5 vs 9 ms; HR 1.49, 95% CI 1.02–2.17). The safety profile for both treatment arms was similar. Most frequent side effects reported for both treatment groups included nausea, fatigue and alopecia. Conclusions: Combination of ranpirnase and DOX is a safe and feasible treatment in unresectable MM and showed a significant impact on survival of pretreated patients compared to DOX alone. [Table: see text]
Identification of a Novel ALK G1123S Mutation in a Patient with ALK-rearranged Non–small-cell Lung Cancer Exhibiting Resistance to Ceritinib
Authors: Gouji Toyokawa, Eiko Inamasu, Shinichiro Shimamatsu, Tsukihisa Yoshida, Kaname Nosaki, Fumihiko Hirai, Masafumi Yamaguchi, Takashi Seto, Mitsuhiro Takenoyama, Yukito Ichinose
Journal: Journal of Thoracic Oncology (2015)
Does phenytoin does affect celecoxib pharmacokinetics in patients with newly diagnosed glioblastoma multiforme?
Authors: S. A. Grossman, J. Olson, T. Batchelor, D. Peereboom, G. Lesser, S. Desideri, X. Ye, T. Hammour, J. G. Supko
Journal: Journal of Clinical Oncology (2005)

2085 Background: Evidence impl icating cyclooxygenase-2 (Cox-2) in tumor angiogenesis has prompted evaluation of Cox-2 inhibitors in cancer treatment. Hepatic metabolism by cytochrome P450 2C9 (CYP2C9) is a major route of elimination for celecoxib. Several commonly used antiepileptics induce CYP2C9. This study was conducted to determine the effects of enzyme inducing antiepileptic drugs (EIAEDs) on the pharmacokinetics of celecoxib. Secondary objectives were to determine the safety of celecoxib in this setting and estimate survival when celecoxib was administered concurrently with radiation therapy in pts with newly diagnosed glioblastoma multiforme. Methods: Pts were divided into +EIAED and −EIAED groups. Celecoxib was begun one week before radiation. A 400 mg dose was taken on day 1 followed by 400 mg bid until tumor progression, dose limiting toxicity, or study withdrawal. No adjuvant chemotherapy was permitted. Pharmacokinetic samples were obtained from day 1 to week 6 and assayed using a validated LC/MS Method: Results: 35 pts (22 +EIAED and 13 -EIAED) were accrued in 9 months. 14 pts were women and 5 were African American. All +EIAED pts received phenytoin. The study closed before reaching 22 pts per cohort given the EORTC adjuvant temozolomide Results: Celecoxib therapy was well tolerated; no bleeding or renal toxicities were noted. One pt had grade 3–4 epigastic distress. Pharmacokinetic data is available for 14 +EIAED pts and 10 -EIAED pts. There was no significant difference (P = 0.66) between the maximum plasma concentration after the first dose of drug in the +EIAED (1.85 ± 0.71 μg/ml) and -EIAED (1.98 ± 0.48 μg/ml) groups. Similarly, the area under the plasma concentration-time profile from time zero to 24 hours was similar (P = 0.79) (+EIAED, 14.9 ± 5.7 μg · h/ml; −EIAED, 13.9 ± 9.1 μg · h/ml). Survival data remains immature as only 4 pts have died. Conclusions: Plasma pharmacokinetics of celecoxib are not significantly affected by concomitant EIAED administration. This drug was well tolerated. Survival will be presented as the data matures. No significant financial relationships to disclose.
Mean Overall Survival (Os) and Quality-Adjusted Time Without Symptoms or Toxicity (Q-Twist) of Nanoparticle Albumin-Bound Paclitaxel (Nab-P) Vs Conventional Solvent-Based Paclitaxel (Sb-P) in Metastatic Breast Cancer
Authors: J. Cortes, X. Ji, F. Lin, S. Whiting, A. Ko, M. Bravo, A. Fandi, M. Botteman
Journal: Annals of Oncology (2014)
Abstract 17642: Warfarin versus Dabigatran: The Coagulation Activity in the Left Atrium During Atrial Fibrillation Ablation
Authors: Naoaki Hashimoto, Takanori Arimoto, Yoshinori Yashiro, Tadateru Iwayama, Daisuke Ishigaki, Yu Kumagai, Satoshi Nishiyama, Hiroki Takahashi, Tetsuro Shishido, Takuya Miyamoto, Joji Nitobe, Hiroshi Aoyama, Tetsu Watanabe, Isao Kubota
Journal: Circulation (2014)

Background: Atrial fibrillation (AF) ablation is associated with the potential risk of periprocedural thromboembolic events. Previous studies suggested performing AF ablation with continuous warfarin reduced the risk of thromboembolic events, otherwise the safety and efficacy of periprocedural dabigatran was controversial. We aim to compare the differences of the coagulable state in the left atrium (LA) between the anticoagulation strategies. Methods: We divided 158 patients who underwent AF ablation into 3 groups: ablation with off warfarin (n=100, WF-off group), ablation with perioperative warfarin therapy (n=33, WF group), and ablation with dabigatran therapy (n=25, D group). Warfarin was stopped 1 day before the procedure in WF-off group. Uninterrupted warfarin therapy was used in WF group and interrupted only on the morning of the procedure with dabigatran in D group. During AF ablation, the blood samples from the LA obtained immediately after the trans-septal puncture before heparin administration in each groups. The D-dimer level and soluble fibrin monomer complex (SFMC) level in the LA were evaluated. Results: The prevalence of positive D-dimer (≥ 0.5 μg/ml) in the LA was observed 3% in WF group, 12% in D group, and 23% in WF-off group, respectively. SFMC levels in the LA were significantly lower in WF group compared with WF-off group (p&lt;0.01). SFMC levels in D group tended to be higher compared with WF group, but lower compared with WF-off group. Conclusions: The coagulation activity in the LA was lower with perioperative warfarin therapy than with dabigatran therapy. Even transient interruption of anticoagulant therapy may be associated with hypercoagulable status in the LA.
Abstract 15671: Direct Thrombin Inhibition with Dabigatran Attenuates Pressure Overload-Induced Cardiac Fibrosis and Diastolic Dysfunction in Mice
Authors: Anping Dong, liping yang, adrienne nguyen, paul mueller, andrew morris, susan smyth
Journal: Circulation (2012)

Introduction:  Thrombin, a multifunctional serine protease, exerts proinflammatory and profibrotic cellular effects that may contribute to cardiac remodeling and hypertrophy mediated by its high-affinity protease-activated receptor-1 (PAR-1). The aim of the present study was to investigate whether direct thrombin inhibition with dabigatran attenuates myocardial injury in the setting of pressure overload-induced heart failure.   Methods:  Transverse aortic constriction (TAC) surgery was performed in C57/BL6J male mice (10-12 weeks old) to generate pressure overload and cardiac hypertrophy. TAC or sham mice were randomly assigned receive chow supplemented with dabigatran etexilate (10 mg/gm) or placebo (TAC+dabigatran, TAC+placebo, sham+dabigatran, sham+placebo).   Results:  Dabigatran treatment significantly extend thrombin clotting time by 3.2 fold (p   Conclusion:  Our results indicate that dabigatran attenuated cardiac fibrosis in the setting of pressure overload and improved diastolic function by inhibiting thrombin activity and possibly through down-regulation of PAR-1 expression without effects on cardiomyocyte hypertrophy.
A prospective trial of prophylaxis and treatment (P+T) of acute tumor lysis syndrome (ATLS) with rasburicase (R) and nonalkaline hydration in children and adolescents (C+A) with intermediate- (Group B) and high-risk (Group C) mature B-NHL: A Children's Oncology Group report.
Authors: S. Goldman, J. C. Lynch, L. Harrison, M. S. Cairo
Journal: Journal of Clinical Oncology (2010)

9572 Background: The incidence of TLS and renal insufficiency (RI) in our past study in C+A with Group (GP) C B-NHL P+T with allopurinol and alkaline hydration was 26% and 27%, respectively (Cairo, Blood 2007). R is more effective than allopurinol in rapidly reducing hyperuricemia in C+A at high risk of ATLS. (Goldman/Cairo, Blood 2001). Objectives: To assess the toxicity, incidence of ATLS, RI and assisted renal support (ARS) of R added to COP reduction in C+A with GP B + C B-NHL. Methods: COP was administered as previously described (Cairo, Blood, 2007). R (0.2 mg/kg IV) was generously supplied by sanofi-aventis. Hydration (without sodium bicarbonate) was administered at 3 L/m2/day. Laboratory (LTLS) and Clinical (CTLS) were classified according to the Cairo- Bishop classification (BJH, 2004). Chemotherapy began between 4 and 24 hrs of the day 0 R dose. GFR (ml/min/1.73 m2) was calculated using the pediatric Schwartz formula. Results: Seventy-eight pts were evaluated for response to R with COP including GP B pts (Stage III/IV) that were subdivided into normal (NL < 2XULN) (n=23) and high (HI ≥ 2XULN) (n=20) LDH and 35 GP C pts. Mean and elevated (% pts ≥ 8 mg/dl) initial uric acid (UA mg/dl) were 4.5 ± 2 (8.2%), 9.6 ± 4.6 (47%) and 8.6 ± 5.0 (45%), in the three groups, respectively. 47% pts received optional doses of R prior to day 0 and no SAE were attributed to any R doses. Two/20 (10%) in GP B HI LDH and 4/35 (11%) in GP C presented with RI and required ARS prior to R + COP therapy. The incidence of LTLS was 0%, 25% and 17% and CTLS was 0%, 10%, and 11%, respectively. GFR improved from baseline thru day 7 in all three groups: GP B NL LDH (141 ±29 to 154 ± 34), GP B HI LDH (96 ± 40 to 168 ± 45) and GP C (108 ± 42 to 173 ± 64). Conclusions: R during COP reduction is well tolerated and highly effective in preventing and treating ATLS in C+A with FAB group B (stage III/IV) and C B-NHL. Although R added to COP prevents new onset CTLS and need for ARS, approximately 10% of C+A with GP B HI LDH or GP C B-NHL still present at diagnosis with RI and require ARS. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration sanofi-aventis sanofi-aventis
Sudden cardiac arrest on the football field of play—highlights for sports medicine from the European Resuscitation Council 2015 Consensus Guidelines
Authors: E B Kramer, L Serratosa, J Drezner, J Dvorak
Journal: British Journal of Sports Medicine (2015)

The European Resuscitation Council (ERC) 2015 Guidelines for Resuscitation were published recently. For the first time, these guidelines included a subsection on 'cardiac arrest during sports activities' in the section dealing with cardiac arrest in special circumstances, endorsing both the importance and unique nature of this form of cardiac arrest. This paper reviews four critical areas in the management of sudden cardiac arrest in a football player: recognition, response, resuscitation and removal from the field of play. Expeditious response with initiation of immediate resuscitation at the side of a collapsed player remains crucial for survival, and chest compressions should be continued until the automated external defibrillator (AED) has been fully activated, so that the sideline medical team response to the side of a non-contact collapsed player on the field of play, with AED and defibrillation, occurs within a maximum of 2 min from collapse.
Abstract P2-01-30: A new nomogram to predict axillary metastasis in breast cancer patients without axillary surgery
Authors: Valery Rodionov, Vlada Cometova, Sergey Panchenko, Sereda Idrisova, Yurij Savinov, Maria Rodionova
Journal: Cancer Research (2015)

Abstract Background: Several studies have concentrated on finding a combination of predictive parameters to establish a mathematical model that can identify patients with no axillary metastasis for whom routine lymph node dissection could be safely avoided. We developed a new model of nomogram (the Ulyanovsk Cancer Center axillary lymph node metastasis nomogram, UCC-ALNM nomogram); it employs clinically and pathologically relevant variables and offers possible advantages over the others nomograms. The purpose of the study: To assess the predictive power of UCC-ALNM nomogram. Methods: A total of 530 breast cancer patients treated between 2008 and 2010 were used as the modeling group for validating the UCC-ALNM nomogram. Clinical and pathologic features of patients were assessed by multivariable logistic regression to predict the presence of axillary metastasis in breast cancer patients. The predictive accuracy of our nomogram was measured by calculating the area under the receiver-operating characteristic (ROC) curve (AUC). Clinical factors included into analysis were: patient’s age and localization of the primary tumor. Pathological factors evaluated were: traditional pathological criteria (primary tumor size, histological type, tumor grade, HR- and Her-2 status) and new total pathological index (Ulyanovsk prognostic index - UPI), introduced by pathologists of the Ulyanovsk Regional Cancer Center. UPI is total score of six main pathological criteria that characterize the malignancy of epithelial tumors: degree of cellular differentiation, cellular polymorphism, mitotic activity, growth pattern, lymphovascular invasion, stromal reaction. Results: By the multivariate analysis, patient’s age (p=0.04), tumor size (p&amp;lt;0.001), UPI (p&amp;lt;0.001), PR (p&amp;lt;0.001) and Her2 status (p=0.02) were identified as independent predictors of axillary metastasis. The nomogram was then developed using the six variables associated with axillary metastasis: age, tumor size, PR, Her2, UPI. The new model was accurate and discriminating with an AUC of 0.7510 when applied to the modeling group. Conclusions: UPI is a new predictive factor of axillary metastasis in breast cancer patients. UCC-ALNM nomogram. Citation Format: Valery Rodionov, Vlada Cometova, Sergey Panchenko, Sereda Idrisova, Yurij Savinov, Maria Rodionova. A new nomogram to predict axillary metastasis in breast cancer patients without axillary surgery [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P2-01-30.
Duration of response to androgen deprivation therapy and survival after subsequent biochemical relapse in men initially treated with radical prostatectomy
Authors: F. J. Bianco, Z. A. Dotan, M. W. Kattan, P. A. Fearn, H. I. Scher, J. A. Eastham, P. T. Scardino
Journal: Journal of Clinical Oncology (2004)

4552 Background: Biochemical recurrence (BCR) is seen in 25–35% of patients after radical prostatectomy (RP). Without treatment the median time from BCR to metastases (Mets) is 7–8 years and from Mets to death is 5–6 years. Management of BCR varies, with some patients observed, some irradiated and some given androgen deprivation therapy (ADT). The duration of response to first line ADT, and of survival for those who progress with a rising PSA after ADT (CastratePSA), have not been well documented. Methods: Our Prostate SPORE database traced all PSA measurements in 4037 patients treated by RP alone from 1983 to 2003. BCR was defined as 3 rises in PSA or secondary treatment. The date of initiation of ADT was recorded. The duration of response to ADT was defined as time until a subsequent PSA rise in the presence of castrate testosterone levels or the absence of PSA response to ADT. Overall survival after CastratePSA was estimated by Kaplan Meier analysis. Results: Median time from BCR to ADT was 3.4 (95% CI, 2.5–4.3) years, and the actuarial probability of receiving ADT was 80% by 12 years after BCR. At the time of analysis 309 of 630 BCR patients had begun ADT: 255 before and 54 after clinical Mets. Median duration of response to ADT was 10.8 (95% CI, 10–11.5) yrs. In 85 patients (20 with ADT after Mets) the PSA subsequently rose (CastratePSA), and 62 of these have died, all from prostate cancer. Median survival after CastratePSA was 25.6 (range 6–54) months. Significant independent predictors of survival for patients with CastratePSA in multivariable analysis were PSA doubling time (p=0.05), PSA level before ADT (p=0.08) and duration of response to ADT (p=0.01). These variables were used to construct a prognostic nomogram for this disease state. Conclusions: For patients with BCR after RP the duration of response to ADT is long (median 10.8 yr) and some patients respond for >15 yr. Emergence of a CastratePSA state, noted by a rise in PSA with or without detectable metastases, carries an ominous prognosis, with median survival of 2 yr and no patient alive 5 yr later. No significant financial relationships to disclose.
The noncoding RNAs SNORD50A and SNORD50B bind K-Ras and are recurrently deleted in human cancer
Authors: Zurab Siprashvili, Dan E Webster, Danielle Johnston, Rajani M Shenoy, Alexander J Ungewickell, Aparna Bhaduri, Ross Flockhart, Brian J Zarnegar, Yonglu Che, Francesca Meschi, Joseph D Puglisi, Paul A Khavari
Journal: Nature Genetics (2015)
Abstract 20361: Statin-Induced Myopathy in Patients With Familial Hypercholesterolemia
Authors: Zahid Ahmad, Li Song, Jedrek Wosik, Preethi Mani, Elisabeth Petr, George McLeod, Shatha Murad, Abhimanyu Garg
Journal: Circulation (2014)

Introduction: Patients with familial hypercholesterolemia (FH) suffer from premature coronary heart disease (CHD) due to extreme elevations in low-density lipoprotein cholesterol (LDL-C). As such, they require high doses of potent statins, a major risk factor for developing statin-induced myopathy. Little is known, though, about other underlying factors predisposing them to statin-induced myopathy. Methods: We studied 272 genetically screened FH patients - ascertained from Dallas, TX, lipid specialty clinics - with and without a documented history of statin-induced myopathy (defined as developing muscle symptoms or elevated serum creatine kinase (CK) levels while taking a statin). Results: Statin-induced myopathy was diagnosed in 35% of FH patients; however, at the time of participation in our study, 73% of myopathy patients were taking statins (vs 79% of statin-tolerant patients; p = 0.37). Statin dosages were similar in the two groups except for rosuvastatin (20 mg/day in myopathy patients vs 40 mg/day in statin-tolerant patients; p &lt; 0.001). Myopathy patients were older (57 ± 11 vs 51 ± 14 years; p = 0.001), had lower BMI (29 ± 6 vs 31 ± 7 kg/m2; p = 0.01), suffered from less premature CHD (22% vs 34%; p = 0.006), and had less hypertension (57% vs 67%; p = 0.05). On-treatment LDL-C was higher in myopathy patients (141 ± 37, n = 63, vs 128 ±40 mg/dL, n= 148; p &lt; 0.01). No differences were identified in pretreatment LDL-C (253 ± 53 vs 263 ± 83 mg/dL; p = 0.57), gender (63% vs 57 % female; p = 0.3), % with diabetes (23% vs 29%; p = 0.38), % with LDL-receptor or apolipoprotein B mutations (26% vs 36%; p = 0.09), or baseline CK levels (median 103 vs 115; p = 0.10). Conclusions: Despite a history of statin-induced myalgia, most FH patients eventually tolerated statins and achieved up to 44% reduction in LDL-C levels. FH patients with increased age and lower BMI were more likely to be diagnosed with myopathy, consistent with prior reports that age and smaller body frame are risk factors. Also, FH patients lacking hypertension or premature CHD were diagnosed more often with myopathy, suggesting that patients without CHD risk factors complain more about muscle symptoms. In conclusion, statin-induced myopathy adds an additional - but manageable - challenge to the treatment of FH patients.
Clinical and molecular significance of microvascular inflammation in transplant kidney biopsies
Authors: Anjali Gupta, Pilib Ó. Broin, Yi Bao, James Pullman, Layla Kamal, Maria Ajaimy, Michelle Lubetzky, Adriana Colovai, Daniel Schwartz, Graciela de Boccardo, Aaron Golden, Enver Akalin
Journal: Kidney International (2015)
Primary Cutaneous Cryptococcus in a Patient With Multiple Sclerosis Treated With Fingolimod
Authors: Amy K. Forrestel, Badri G Modi, Sarah Longworth, Marissa B. Wilck, Robert G. Micheletti
Journal: JAMA Neurology (2016)

A 62-year-old woman with multiple sclerosis treated with fingolimod for 3 years presented to clinic with a tender nodule on the forehead that was diagnosed by a tissue culture as Cryptococcus neoformans. The patient was diagnosed with primary cutaneous cryptococcosis.