bluuebunny/crossref_metadata_2025_split huggingface dataset:
FDA Drug Approval Summary: Nelarabine (Arranon®) for the Treatment of T-Cell Lymphoblastic Leukemia/Lymphoma
Authors: Cohen Martin H. , Johnson John R. , Justice Robert , Pazdur Richard 
Published: June 2008

Abstract

Learning Objectives
After completing this course, the reader will be able to: Add nelarabine (Arranon®) to the armamentarium of drugs for T-cell lymphoblastic leukemia/lymphoma.Identify patients that are eligible for nelarabine therapy.Identify the nelarabine dose-limiting toxicity.Describe the FDA criteria for accelerated approval.
CME This article is available for continuing medical education credit at CME.TheOncologist.com

Purpose.
To describe the clinical trials leading to U.S. Food and Drug Administration (FDA) approval of nelarabine (Arranon®), a new purine analogue, for the treatment of patients with T-cell acute lymphoblastic leukemia (T-ALL) and T-cell lymphoblastic lymphoma (T-LBL) whose disease has not responded to or has relapsed following treatment with at least two chemotherapy regimens.

Experimental Design.
Two phase II trials, one conducted in pediatric patients and the other in adult patients, were reviewed. Patients were in their first or subsequent relapse and/or were refractory to first-line therapy. The dose and schedule of i.v. nelarabine in the pediatric and adult studies were 650 mg/m2 per day daily for 5 days and 1,500 mg/m2 i.v. on days 1, 3, and 5, respectively. Treatments were repeated every 21 days. Study endpoints were the rates of complete response (CR) and CR with incomplete hematologic or bone marrow recovery (CR*).

Results.
The pediatric efficacy population consisted of 39 patients who had relapsed after, or had been refractory to, two or more induction regimens. CR to nelarabine treatment was observed in five patients (13%) and CR+CR* was observed in nine patients (23%). The adult efficacy population consisted of 28 patients. CR to nelarabine treatment was observed in five patients (18%) and CR+CR* was observed in six patients (21%).
Neurologic toxicity was dose limiting for both pediatric and adult patients. Other severe toxicities included hematologic, hepatic, and metabolic laboratory abnormalities in pediatric patients and gastrointestinal and pulmonary toxicities in adults.

Conclusions.
On October 28, 2005, the FDA granted accelerated approval for nelarabine for treatment of patients with relapsed or refractory T-ALL/T-LBL after at least two prior regimens. This use is based on the induction of CR. The applicant will conduct postmarketing clinical trials to demonstrate clinical benefit, for example, survival prolongation.
Pediatric Nonrhabdomyosarcoma Soft Tissue Sarcomas
Authors: Spunt Sheri L. , Skapek Stephen X. , Coffin Cheryl M. 
Published: June 2008

Abstract

Learning Objectives
After completing this course, the reader will be able to: Evaluate the clinical features of NRSTS in pediatric patients.Identify the factors that influence the selection of treatment and the clinical outcomes of pediatric patients with NRSTS.Select an appropriate treatment strategy for pediatric patients with NRSTS.
CME This article is available for continuing medical education credit at CME.TheOncologist.com
The nonrhabdomyosarcoma soft tissue sarcomas (NRSTSs) are a heterogeneous group of mesenchymal cell neoplasms that account for about 4% of childhood cancers. Because each histologic subtype of NRSTS is rare, they have been poorly studied and little is known about their biology, natural history, or optimal treatment. Data from adults with soft tissue sarcomas provide some helpful insight, but adult and childhood NRSTSs differ considerably in the distribution of their histologic subtypes, and certain entities are known to behave differently in young children. The greater risks posed to children by treatment, particularly by radiotherapy, also must be considered in treatment planning for children. This article summarizes what is known to date about childhood NRSTS, including the epidemiology, pathogenesis, and clinical approach to diagnosis and treatment of these tumors.
Use of H215O-PET and DCE-MRI to Measure Tumor Blood Flow
Authors: de Langen Adrianus J. , van den Boogaart Vivian E. M. , Marcus J. Tim , Lubberink Mark 
Published: June 2008

Abstract

Learning Objectives
After completing this course, the reader will be able to: Discuss the principles of perfusion imaging with H215O-PET and DCE-MRI.Compare the differences between and the limitations of the two methods.Critically review publications on the use of both methods in monitoring response to anticancer therapy.
CME This article is available for continuing medical education credit at CME.TheOncologist.com
Positron emission tomography (PET) with H215O and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) provide noninvasive measurements of tumor blood flow. Both tools offer the ability to monitor the direct target of antiangiogenic treatment, and their use is increasingly being studied in trials evaluating such drugs. Antiangiogenic therapy offers great potential and, to an increasing extent, benefit for oncological patients in a variety of palliative and curative settings. Because this type of targeted therapy frequently results in consolidation of the tumor mass instead of regression, monitoring treatment response with the standard volumetric approach (Response Evaluation Criteria in Solid Tumors) leads to underestimation of the response rate. Monitoring direct targets of anticancer therapy might be superior to indirect size changes. In addition, measures of tumor blood flow contribute to a better understanding of tumor biology.
This review shows that DCE-MRI and H215O-PET provide reliable measures of tumor perfusion, provided that a certain level of standardization is applied. Heterogeneity in scan acquisition and data analysis complicates the interpretation of study results. Also, limitations inherent to both techniques must be considered when interpreting DCE-MRI and H215O-PET results. This review focuses on the technical and physiological aspects of both techniques and aims to provide the essential information necessary to critically evaluate the use of DCE-MRI and H215O-PET in an oncological setting.
Treating Anemia of Cancer with Every-4-Week Darbepoetin Alfa: Final Efficacy and Safety Results from a Phase II, Randomized, Double-Blind, Placebo-Controlled Study
Authors: Gordon David , Nichols Gwen , Ben-Jacob Ali , Tomita Dianne , Lillie Tom , Miller Carole 
Published: June 2008

Abstract
Darbepoetin alfa is an erythropoiesis-stimulating agent (ESA) approved for treating chemotherapy-induced anemia. This phase II, double-blind, placebo-controlled study examined the efficacy of darbepoetin alfa for treating anemia of cancer (AoC) in patients not receiving chemotherapy or radiotherapy. Patients were randomized 3:1 to receive darbepoetin alfa (6.75 μg/kg) or placebo every 4 weeks; the end of the study was at week 17. The primary endpoint was the percentage of patients with a hematopoietic response. Secondary endpoints included transfusion incidence and safety parameters. Efficacy analyses were performed on 162 patients in the darbepoetin alfa group and 56 patients in the placebo group. The Kaplan–Meier percentages of patients who achieved a hematopoietic response (darbepoetin alfa, 69%; placebo, 24%) or achieved the target hemoglobin (darbepoetin alfa, 85%; placebo, 50%) differed significantly between treatment groups. The transfusion incidence did not differ between treatment groups probably because of the low baseline transfusion rates in AoC patients. The incidence of adverse events (including on-study deaths) was similar in both groups. In conclusion, darbepoetin alfa appeared to be well tolerated and significantly increased hemoglobin levels in these AoC study patients.
Trastuzumab in the Adjuvant Treatment of Early-Stage Breast Cancer: A Systematic Review and Meta-Analysis of Randomized Controlled Trials
Authors: Dahabreh Issa J. , Linardou Helen , Siannis Fotios , Fountzilas George , Murray Samuel 
Published: June 2008

Abstract

Learning Objectives
After completing this course, the reader will be able to: Summarize the main characteristics and findings of randomized controlled trials evaluating trastuzumab for the adjuvant treatment of early-stage breast cancer.Use combined-effect estimates provided by meta-analysis to appraise the risks and benefits of trastuzumab treatment in the adjuvant setting.Identify the links between basic science and drug development that led to the successful clinical use of trastuzumab, as well as the gaps in the existing evidence base regarding its use in breast cancer treatment.
CME This article is available for continuing medical education credit at CME.TheOncologist.com

Background.
We performed a systematic review and meta-analysis to compare treatment outcomes for human epidermal growth factor receptor (HER)-2–positive breast cancer patients receiving adjuvant chemotherapy with or without trastuzumab.

Methods.
We identified randomized clinical trials comparing adjuvant chemotherapy with or without trastuzumab in patients with resectable breast cancer. Fixed-effects meta-analysis was used to combine data.

Results.
Five eligible trials were identified, reporting outcomes on 13,493 women. Fixed-effects analysis showed disease-free survival to be superior for trastuzumab-treated patients (risk ratio [RR], 0.62; 95% confidence interval [CI], 0.56–0.68). Superiority was also observed for patients receiving trastuzumab with respect to mortality (RR, 0.66; 95% CI, 0.57–0.77), locoregional recurrence (RR, 0.58; 95% CI, 0.43–0.77), and distant recurrence (RR, 0.60; 95% CI, 0.52–0.68). Patients receiving trastuzumab with chemotherapy had a higher risk for congestive heart failure (RR, 7.60; 95% CI, 4.07–14.18) and left ventricular ejection fraction decline (RR, 2.09; 95% CI, 1.84–2.37). A higher risk for central nervous system metastasis as the first recurrence event (RR, 1.60; 95% CI, 1.06–2.40) was also noted in patients receiving trastuzumab.

Conclusions.
The use of trastuzumab should be considered an integral part of the adjuvant therapy of HER-2–positive breast cancer patients.
Pediatric Central Nervous System Germ Cell Tumors: A Review
Authors: Echevarría Maria E. , Fangusaro Jason , Goldman Stewart 
Published: June 2008

Abstract

Learning Objectives
After completing this course, the reader will be able to: Discuss the basic epidemiology of pediatric CNS GCTs.Perform the diagnostic workup and full evaluation that is necessary when evaluating a patient with a suspected CNS GCT.Select among the different therapeutic alternatives employed in treating children with a CNS GCT.
CME This article is available for continuing medical education credit at CME.TheOncologist.com
Central nervous system (CNS) germ cell tumors (GCTs) represent approximately 3% of primary pediatric brain tumors and encompass a wide pathologic spectrum. CNS GCTs are most commonly located in the pineal and suprasellar regions of the brain and can be divided into major groups including germinomas and nongerminomatous GCTs (NGGCTs), with teratomas often considered a separate category. The clinical presentation varies by location and size, and it frequently includes endocrine abnormalities, visual changes, and signs of increased intracranial pressure. Neuroimaging studies cannot differentiate GCTs from other tumors, and therefore, the diagnosis usually requires histologic confirmation. The rare exceptions are the cases where characteristic elevations of tumor markers, including alpha-fetoprotein and/or β-human chorionic gonadotropin are documented in the serum and/or cerebrospinal fluid. In these cases, the imaging findings along with the tumor marker elevation may be diagnostic in themselves without the need for tissue confirmation.
Treatment and prognosis differ greatly between groups. Germinomas have a superior prognosis than NGGCTs. Five-year overall survival rates &gt;90% were reported initially with the use of craniospinal irradiation. More recently, the use of chemotherapy in addition to radiation therapy has afforded the ability to decrease the dose and volume of radiation therapy without affecting survival rates. NGGCTs are less radiosensitive than germinomas, but the use of adjuvant chemotherapy has improved survival rates in this group as well. The standard management for CNS GCTs remains controversial. Treatment regimens aimed to improve progression-free and overall survival times are ongoing.
Commentary: Let the Tail Wag the Dog: The Case for Radioimmunotherapy of Low-Grade Follicular Lymphoma
Authors: Plastaras John P. , Glatstein Eli , Schuster Stephen J. 
Published: June 2008

Abstract
This commentary reviews the Buchegger et al. manuscript published in this issue of The Oncologist. The authors concur with Buchegger et al. and advocate greater use of radioimmunotherapy in advanced-stage low-grade follicular lymphoma.
Establishing a minimum standard for collaborative research in federal environmental agencies
Authors: Matso Kalle E , Dix Molly O'Donovan , Chicoski Benjamin , Hernandez Debra L , Schubel Jerry R 
Published: June 2008

Abstract
There is a general consensus that—given the magnitude of the challenges facing our nation's natural resource managers—the rate, efficiency, and effectiveness of linking research to decision making must be enhanced. Many reports have touched on this issue, most of them culminating with the exhortation to “foster more interactions between scientists and users,” but very few documents provide details or assign responsibility to drive the interactions that most agree should happen. As a result, many natural science and engineering programs “talk the talk”—that is, they say they do collaborative research with intended users; however, upon inspection, few of them “walk the walk” by effectively supporting collaboration throughout the research process. Moreover, when called to support transition to application in specific ways, research agencies often balk, most often objecting that research programs cannot afford to take any support away from funding more research. They may also argue that science works best for society when it is freed from concerns related to application. In this paper we will 1) review the cultural conflict that often underlies disagreements about collaborative research, 2) offer details on the basic ingredients required to achieve a minimum standard for collaborative research, 3) suggest an approach for determining the appropriate level of support for collaborative research, given various research goals, and 4) recommend specific steps for motivating scientists and stakeholders to participate in collaborative research.
Work-Related Illness—Continued Progress Requires Better Metrics
Authors: Harrison Myron 
Published: June 2008

Abstract
Management systems depend upon accurate measures of outcomes in order to pursue continuous improvement. Work-related illnesses are defects or noncompliances in an occupational safety and health management system. The ascertainment of these incidents is very difficult due to the characteristics of illness. This paper describes the development of an indicator for "exposure incidents" that serves as a leading indicator for the risk of work-related illness.
Work-related illness – continued progress requires better metrics
"It ain’t what you don’t know that gets you into trouble. It’s what you know for sure, that just ain’t so." Mark Twain
Changes in Functional Walking Distance and Health-Related Quality of Life After Gastric Bypass Surgery
Authors: Tompkins James , Bosch Pamela R , Chenowith Rochelle , Tiede Judy L , Swain James M 
Published: June 2008

Background and PurposeEarly physical functional changes after gastric bypass surgery (GBS) are unclear, and the relationship between these changes and health-related quality of life (HR-QOL) has not been reported. We measured distances from a 6-minute walk test (6MWT) and scores on the 36-Item Short-Form Health Survey (SF-36) before and after GBS.Subjects and MethodsTwenty-five people undergoing GBS completed the SF-36 and 6MWT presurgically and at the 3-month and 6-month follow-up visits. Ratings of perceived exertion (RPE) were measured during 6MWTs.ResultsPresurgical walking distance (X̅±SD; 414.1±103.7 m) was 55%±14% of normative values. Distances increased significantly at 3 months (505.2±98.0 m) and at 6 months (551.5±101.2 m). Final RPEs decreased significantly, and HR-QOL improved significantly. Both physical and mental health components of the SF-36 improved significantly. Distance was inversely correlated with body mass throughout the study and positively correlated with the SF-36 Physical Component Summary change from 3 to 6 months.Discussion and ConclusionsImproved functional capacity was associated with enhanced HR-QOL. At 6 months, walking distances remained 75% of those for age-matched peers who had normal weight.
Rho-kinase inhibitor and Nicotinamide Adenine Dinucleotide PHosphate oxidase inhibitor prevent impairment of endothelium-dependent cerebral vasodilation by acute cigarette smoking in rats
Authors: Iida Hiroki , Iida Mami , Takenaka Motoyasu , Fukuoka Naokazu , Dohi Shuji 
Published: June 2008

Introduction. We previously reported that acute cigarette smoking can cause a dysfunction of endothelium-dependent vasodilation in cerebral vessels, and that blocking the angiotensin II (Ang II) type 1 (AT1) receptor with valsartan prevented this impairment. Our aim was to investigate the effects of a Rho-kinase inhibitor (fasudil) and a Nicotinamide Adenine Dinucleotide PHosphate (NADPH) oxidase inhibitor (apocynin) on smoking-induced endothelial dysfunction in cerebral arterioles. Method. In Sprague—Dawley rats, we used a closed cranial window preparation to measure changes in pial vessel diameters following topical acetylcholine (ACh) before smoking. After one-minute smoking, we again examined the arteriolar responses to ACh. Finally, after intravenous fasudil or apocynin pre-treatment we re-examined the vasodilator responses to topical ACh (before and after cigarette smoking). Results. Under control conditions, cerebral arterioles were dose-dependently dilated by topical ACh (10-6 M and 10-5 M). One hour after a one-minute smoking (1 mg-nicotine cigarette), 10-5 M ACh constricted cerebral arterioles. However, one hour after a one-minute smoking, 10-5 M ACh dilated cerebral pial arteries both in the fasudil pre-treatment and the apocynin pre-treatment groups, responses that were significantly different from those obtained without fasudil or apocynin pre-treatment. Conclusion. Thus, inhibition of Rho-kinase and NADPH oxidase activities may prevent the above smoking-induced impairment of endothelium-dependent vasodilation.
Primary hyperaldosteronism due to adrenal microadenoma: a curable cause of refractory hypertension
Authors: Myint Khin Swe , Watts Michaela , Appleton Derris S , Lomas David J , Jamieson Neville , Taylor Kevin P , Coghill Stuart , Brown Morris J 
Published: June 2008

The diagnosis of primary hyperaldosteronism due to microadenoma or unilateral adrenal hyperplasia can be challenging, since hypokalaemic alkalosis, high plasma aldosterone and a definite adenoma on imaging may all be absent. Method and result. We describe three cases of resistant hypertension (on > 5 antihypertensives) where hyperaldosteronism was suspected because of a suppressed plasma renin level despite treatment with multiple drugs which normally elevate renin. Renin mass was measured by a double-site chemi-immunoluminometric assay. All patients had normal plasma aldosterone levels. Hypokalaemia was present in the first two cases but computed tomography did not show clear cut adenomas.Adrenal vein sampling (AVS) revealed lateralisation (> 4 times higher aldosterone to cortisol ratio (ACR) on the affected than contra-lateral side).The third patient was normokalaemic and AVS showed only minimal lateralisation (ACR 1.3:1).The severe hypertension in all cases was reversed by adrenalectomy, with blood pressure falling to target despite withdrawal of all but one to two drugs. Conclusions. The robotic assay of renin mass permits rapid detection of patients in whom plasma renin is suppressed below the normal range. A suppressed plasma renin indicates abnormal Na+-retention, and — when not overcome by drugs such as angiotensin-converting enzyme-inhibitors or angiotensin receptor blockers — may be the only clue to a curable adrenal adenoma.AVS is required to demonstrate lateralisation of aldosterone secretion, justifying adrenalectomy.
Effect of losartan on exercise tolerance and echocardiographic parameters in patients with mitral regurgitation
Authors: Sekuri Cevad , Utuk Ozan , Bayturan Ozgur , Bilge Ali , Kurhan Ziya , Tavli Talat 
Published: June 2008

Objectives. The aim of this study was to assess the effects of losartan treatment on exercise tolerance and echocardiographic parameters in patients with mitral regurgitation (MR) secondary to mitral valve prolapse or rheumatic heart disease. Methods. Twenty-seven patients (14 males, 13 females, mean age 51±11, range 21—76) with moderate MR due to mitral valve prolapse or rheumatic heart disease were examined by means of Doppler echocardiography.The subjects were submitted to treadmill exercise tests using the modified Bruce protocol at baseline, after six hours and after the six-week treatment period to be evaluated based on their exercise tolerance. Mitral Regurgitant Volume (MRV), effective regurgitant orifice diameter, left atrial volume, left ventricle (LV) end-diastolic volume index, LV end-systolic volume index, LV ejection fraction (LVEF), left ventricle mass index were calculated at baseline and after six weeks of treatment with single dose of losartan (50 mg/day). Results. Total treadmill exercise time increased from 477.7±147.9 to 535.7±149.0 seconds after six hours (p<0.01) and to 559.6±142.8 seconds after six weeks of treatment. Also, metabolic equivalent values increased following six hours of first dose and six weeks of losartan treatment (from 10.9±2.9 to R11.8±3.1, p=0.006 and 12.4±3.1, p=0.002; respectively). However, peak exercise systolic blood pressure (BP) was reduced after six hours and six weeks of treatment, and resting diastolic BP did not change after six hours but reduced at the end of the treatment period. MR volume decreased significantly from 29.3±14.1 ml to 25.1±14.8 ml, (p=0.025) without significant change in regurgitant orifice diameter (0.72±0.37 cm vs. 0.66±0.37 cm, p=NS), left atrium diameter and area while LVEF increased from 51.70±13.37 to 54.11—11.75 (p=0.015) with losartan. Conclusion. We conclude that the angiotensin II receptor antagonist losartan improves exercise tolerance and echocardiographic parameters in patients with moderate MR.