bluuebunny/crossref_metadata_2025_split huggingface dataset:
Osteonecrosis of the Jaw in Patients with Bone Metastases Treated with Bisphosphonates: A Retrospective Study
Authors: Ibrahim Toni , Barbanti Francesca , Giorgio-Marrano Gianluca , Mercatali Laura , Ronconi Sonia , Vicini Claudio , Amadori Dino 
Published: March 2008

Abstract

Learning Objectives
After completing this course, the reader will be able to: Discuss the importance of treating patients with bone metastases using a multidisciplinary approach.Explain why bisphosphonates are a fundamental part of bone metastasis treatment.Evaluate the main features of ONJ and, in particular, its high risk factor.Describe the importance of ONJ prevention during bisphosphonate treatment.Emphasize the importance of interaction among the patient's dentist, surgeon, and oncologist for the management of ONJ.
CME Access and take the CME test online and receive 1 AMA PRA Category 1 Credit™ at CME.TheOncologist.com

Objective.
Bone metastases are a major cause of morbidity in cancer patients. Treatment includes bisphosphonates, which are also associated with avascular osteonecrosis of the jaw (ONJ). Our aim was to evaluate the correlation between bisphosphonates and ONJ.

Patients and Methods.
Of the 539 patients with bone metastases treated in our department from June 2002 to December 2006 with i.v. bisphosphonates, eight (1.5%) developed ONJ.

Results.
The eight patients with ONJ had all been given zoledronic acid, and two had also been treated with pamidronic acid. In four of the patients, ONJ was diagnosed during treatment, while in the remaining four it was diagnosed several months after therapy with bisphosphonates had ended. Six of these patients received local noninvasive treatment, of whom five progressed. Two showed apparent autolimitation of the disease. The remaining two patients underwent surgical resection and currently show no signs of relapse. All eight ONJ patients presented with various concomitant risk factors such as paradontopathy, dental extraction, or spontaneous avulsion.

Conclusions.
Our results show that ONJ can appear months after interruption of treatment and that a surgical approach can be used in suitable cases. Closer cooperation is needed among specialists to define guidelines for the prevention of ONJ in patients with bone metastases.
Ixabepilone: A Novel Antineoplastic Agent with Low Susceptibility to Multiple Tumor Resistance Mechanisms
Authors: Vahdat Linda 
Published: March 2008

AbstractLearning ObjectivesAfter completing this course, the reader will be able to: Evaluate the clinical significance of the lower susceptibility of epothilones to key mechanisms of drug resistance.Explain the key mechanisms of drug resistance to which epothilones display lower susceptibility.Describe the mechanism of action of ixabepilone.Describe how ixabepilone promotes tumor cell death through apoptosis.Identify six types of solid tumors in which ixabepilone has demonstrated single-agent activity.Discuss the preclinical and clinical activity of ixabepilone in chemotherapy-resistant tumors.CME Access and take the CME test online and receive 1 AMA PRA Category 1 Credit™ at CME.TheOncologist.comTumor resistance to chemotherapeutic agents ultimately leads to treatment failure in the majority of cancer patients. The identification of new agents that are less susceptible to mechanisms of tumor resistance could, therefore, bring significant clinical benefits to patients with advanced cancer. One new drug class of great interest in this respect is the epothilones and their analogues, which are microtubule inhibitors with low susceptibility to several mechanisms of drug resistance.Ixabepilone is an analogue of natural epothilone B with activity against a wide range of tumor types, including drug-resistant tumors. This is consistent with the preclinical activity of ixabepilone against human cancer cell lines resistant to taxanes and other agents. Taxane resistance in these cells may be acquired or primary and results from several mechanisms, such as overexpression of multidrug-resistance proteins and the βIII-tubulin isoform.Ixabepilone has demonstrated efficacy as monotherapy or in combination with capecitabine in anthracycline- and taxane-pretreated/resistant metastatic breast cancer (MBC), and has recently been approved for use in resistant/refractory MBC. Other epothilones, such as patupilone, KOS-1584, and ZK-EPO, are also being evaluated in drug-resistant cancers. Ixabepilone represents a new treatment option for MBC patients with cancers resistant to available chemotherapeutic agents.
Concept and Clinical Evaluation of Carrier-Mediated Anticancer Agents
Authors: Zamboni William C. 
Published: March 2008

Abstract
Major advances in the use of carrier vehicles delivering pharmacologic agents and enzymes to sites of disease have occurred over the past 10 years. This review focuses on the concepts and clinical evaluation of carrier-mediated anticancer agents that are administered i.v. or orally. The primary types of carrier-mediated anticancer agents are nanoparticles, nanosomes, which are nanoparticle-sized liposomes, and conjugated agents. Nanosomes are further subdivided into stabilized and nonstabilized or conventional nanosomes. Nanospheres and dendrimers are subclasses of nanoparticles. Conjugated agents consist of polymer-linked and pegylated agents. The theoretical advantages of carrier-mediated drugs are greater solubility, longer duration of exposure, selective delivery of entrapped drug to the site of action, superior therapeutic index, and the potential to overcome resistance associated with the regular anticancer agent. The pharmacokinetic disposition of carrier-mediated agents depends on the physiochemical characteristics of the carrier, such as size, surface charge, membrane lipid packing, steric stabilization, dose, and route of administration. The primary sites of accumulation of carrier-mediated agents are the tumor, liver, and spleen, compared with noncarrier formulations. The drug that remains encapsulated in or linked to the carrier (e.g., the nanosome or nanoparticle) is an inactive prodrug, and thus the drug must be released from the carrier to be active. The factors affecting the pharmacokinetic and pharmacodynamic variability of these agents remain unclear, but most likely include the reticuloendothelial system, which has also been called the mononuclear phagocyte system. Future studies need to evaluate the mechanism of clearance of carrier-mediated agents and identify the factors associated with the pharmacokinetic and pharmacodynamic variability of carrier agents in patients and specifically in tumors.
Critical Review of Nonsurgical Treatment Options for Stage I Non-Small Cell Lung Cancer
Authors: Haasbeek Cornelis J.A. , Senan Suresh , Smit Egbert F. , Paul Marinus A. , Slotman Ben J. , Lagerwaard Frank J. 
Published: March 2008

Abstract

Learning Objectives
After completing this course, the reader will be able to: Discuss the current results obtained with primary resection in stage I NSCLC.Describe clinical outcomes with nonsurgical techniques such as stereotactic radiation therapy and radiofrequency ablation.Identify potential advantages and drawbacks of these nonsurgical techniques.Assess which patients would benefit most from these techniques.
CME Access and take the CME test online and receive 1 AMA PRA Category 1 Credit™ at CME.TheOncologist.com
Surgery has traditionally been regarded as the treatment of choice for patients with stage I non-small cell lung cancer. However, the morbidity and mortality associated with surgery in elderly patients with considerable comorbidity remains of concern, as are the poor 5-year survival rates. Until recently, conventional radiation therapy was the only alternative curative treatment option for patients who were unfit for surgery, but with lower local control rates that were inferior to those with surgery. However, a growing body of clinical data on outcomes with newer nonsurgical treatment options such as stereotactic radiation therapy (SRT) and radiofrequency ablation (RFA) is now available.
SRT is a noninvasive method showing a 2-year local control rate in excess of 85% in both T1 and T2 tumors after three to eight fractions of high-precision radiotherapy. Despite the use of very high radiation doses, high-grade toxicity is limited to approximately 5% of patients. Percutaneous RFA is an invasive method showing 2-year local control rates of approximately 64% in smaller tumors, but results are poorer in lesions ≥3 cm. Compared with SRT, a higher procedure-related morbidity and mortality rate has been reported, mainly caused by pneumothorax and hemorrhage. Although data from randomized trials of conventional radiotherapy versus SRT or RFA are not available, the use of SRT is becoming widespread for patients who are unfit for surgery. Reported 2-year local control rates after SRT are comparable with those achieved with surgery, and prospective randomized trials comparing surgery with SRT in patients who are fit to undergo surgery are now being planned.
Prolonged Versus Standard Gemcitabine Infusion: Translation of Molecular Pharmacology to New Treatment Strategy
Authors: Veltkamp Stephan A. , Beijnen Jos H. , Schellens Jan H.M. 
Published: March 2008

Abstract

Learning Objectives
After completing this course, the reader will be able to: Describe the molecular pharmacology of nucleoside analogues.Explain transport, metabolism, and elimination in relation to the activity of gemcitabine.Describe the clinical pharmacology of gemcitabine in relation to its rate of administration.
CME Access and take the CME test online and receive 1 AMA PRA Category 1 Credit™ at CME.TheOncologist.com
Gemcitabine is frequently used in the treatment of patients with solid tumors. Gemcitabine is taken up into the cell via human nucleoside transporters (hNTs) and is intracellularly phosphorylated by deoxycytidine kinase (dCK) to its monophosphate and subsequently into its main active triphosphate metabolite 2′,2′-difluorodeoxycytidine triphosphate (dFdCTP), which is incorporated into DNA and inhibits DNA synthesis. In addition, gemcitabine is extensively deaminated to 2′,2′-difluorodeoxyuridine, which is largely excreted into the urine. High expression levels of human equilibrative nucleoside transporter type 1 were associated with a significantly longer overall survival duration after gemcitabine treatment in patients with pancreatic cancer.
Clinical studies in blood mononuclear and leukemic cells demonstrated that a lower infusion rate of gemcitabine was associated with higher intracellular dFdCTP levels. Prolonged infusion of gemcitabine at a fixed dose rate (FDR) of 10 mg/m2 per minute was associated with a higher intracellular accumulation of dFdCTP, greater toxicity, and a higher response rate than with the standard 30-minute infusion of gemcitabine in patients with pancreatic cancer.
In the current review, we discuss the molecular pharmacology of nucleoside analogues and the influence of hNTs and dCK on the activity and toxicity of gemcitabine, which is the basis for clinical studies on FDR administration, and the results of FDR gemcitabine administration in patients. These findings might aid optimal clinical application of gemcitabine in the future.
Should Urogenital Atrophy in Breast Cancer Survivors Be Treated with Topical Estrogens?
Authors: Trinkaus Mateya , Chin Sheray , Wolfman Wendy , Simmons Christine , Clemons Mark 
Published: March 2008

Abstract

Learning Objectives
After completing this course, the reader will be able to: Describe the urogenital consequences of antiestrogen treatment among women with a prior diagnosis of breast cancer and the effects that these side effects have on quality of life and medication compliance.Advise on the standard treatment of urogenital atrophy, including alternatives to topical estrogen replacement, in the non–breast cancer and breast cancer populations.Evaluate the evidence for the current recommendations of estrogen replacement therapy among women with a prior diagnosis of breast cancer.
CME Access and take the CME test online and receive 1 AMA PRA Category 1 Credit™ at CME.TheOncologist.com
Breast cancer survivors represent a unique patient population with a high prevalence of menopausal symptoms. Given the improved longevity of cancer patients, the consequences of menopause have become an increasingly important and challenging management issue. To date, considerable attention has been paid to the management of menopausal vasomotor symptoms and bone health among breast cancer patients. As a result, numerous nonhormonal treatment options have been developed for the management of these issues. The treatment of urogenital symptoms among this population is poorly understood and relatively understudied. Although systemic or topical estrogen replacement is the most effective method for treating hypoestrogenemic urogenital symptoms, women with a prior diagnosis of breast cancer are cautioned from taking exogenous estrogens in order to avoid a potential contribution to recurrent breast cancer risk. This review focuses on the urogenital consequences of estrogen deprivation therapy in breast cancer patients and provides practitioners with a simple guide of current and future strategies for managing these symptoms.
Familial Risks for Cancer as the Basis for Evidence-Based Clinical Referral and Counseling
Authors: Hemminki Kari , Sundquist Jan , Lorenzo Bermejo Justo 
Published: March 2008

Abstract

Learning Objectives
After completing this course, the reader will be able to: Describe the relative risk (using the standardized incidence ratio) of various familial cancers defined by the affected family member.Evaluate family history as a risk factor for all cancers, not only the ones for which mutation or PSA testing is recommended.Critically assess the accuracy of reported family histories.
CME Access and take the CME test online and receive 1 AMA PRA Category 1 Credit™ at CME.TheOncologist.com

Objective.
Reliable, clinically useful data on familial risks have not been available for all types of cancer, and familial aggregations of cancers, which are not known to belong to an inherited cancer syndrome, are often overlooked by medical referral systems. We provide uniform data on familial risks in all common cancers.

Methods.
The nationwide Swedish Family-Cancer Database includes 11.5 million individuals, born in 1932 and later, along with their parents. Standardized incidence ratios (SIRs) were calculated for age-specific familial risks in offspring.

Results.
The familial risks for offspring cancer were increased at 24 of 25 sites when a parent was diagnosed with concordant cancer, at 20 of 24 sites when a sibling was affected, and at 14 of 16 sites when a parent and at least one other sibling were affected. Among the offspring of affected parents, testicular cancer showed the highest risk, 4.52, followed by Hodgkin's disease (3.95) and esophageal cancer (3.36). At many sites, the risks between siblings were higher than those between offspring and affected parents, probably in part because of childhood environmental effects.

Conclusions.
The data show convincingly that familial clustering is a common feature for all cancer sites. The results will be helpful in implementing evidence-based guidelines for clinical genetic counseling and in facilitating the recognition of familial risk at all levels of the general medical referral system.
Patterns of care and outcomes among elderly individuals with primary malignant astrocytoma
Authors: Barnholtz-Sloan Jill S. , Williams Vonetta L. , Maldonado John L. , Shahani Dilip , Stockwell Heather G. , Chamberlain Marc , Sloan Andrew E. 
Published: March 2008

Object
This study was undertaken to evaluate the association between age at diagnosis, patterns of care, and outcome among elderly individuals with anaplastic astrocytoma (AA) and glioblastoma multiforme (GBM).

Methods
Using the Surveillance, Epidemiology and End Results database, the authors identified 1753 individuals with primary GBM and 205 individuals with primary AA (diagnosed between June 1991 and December 1999) who were 66 years and older and whose records were linked to Medicare information. To facilitate gathering of prediagnosis comorbidity and postdiagnosis treatment information, only those individuals were included who had the same Medicare coverage for 6 months before and 12 months after diagnosis. The odds of undergoing various combinations of treatments and the associations with outcome were calculated by tumor type and age and adjusted by various predictors.

Results
Age was not associated with treatment differences in individuals with AA. Very elderly individuals (≥ 75 years old) with GBM were more likely to have biopsy only (odds ratio [OR] 2.53, 95% confidence interval [CI] 1.78–3.59), surgery only (OR 1.47, 95% CI 1.15–1.87), or biopsy and radiation (OR 1.39, 95% CI 1.07–1.82) and were less likely to receive multimodal therapy. Regardless of patient age or lesion histological characteristics, survival was decreased in patients treated with biopsy only. Individuals with GBM who had surgery only or biopsy and radiation had worse outcomes than individuals treated with surgery and radiation. There were no differences in survival by lesion histological characteristics. Very elderly individuals with malignant astrocytomas were more likely to receive limited treatment (most pronounced in individuals with GBM). Survival variation correlated with treatment combinations.

Conclusions
These findings suggest that in clinical neurooncology patient age is associated with not receiving effective therapies and hence worse prognosis.
Outpatient brain tumor surgery: innovation in surgical neurooncology
Authors: Boulton Mel , Bernstein Mark 
Published: March 2008

Object
Recent studies of conventional craniotomies and image-guided biopsies have afforded a solid characterization of surgical morbidity and the timing of its occurrence. This report outlines a novel 11-year experience with outpatient image-guided biopsy and outpatient craniotomy for supratentorial intraaxial brain tumors.

Methods
During the period between August 1996 and May 2007, 117 awake image-guided biopsies and 145 elective craniotomies for tumor resection were prospectively selected to be performed as outpatient procedures. Data were recorded for each patient regarding tumor histological type, reasons for admission if planned early discharge failed, and surgical complications.

Results
Successful discharge from the Day Surgery Unit was possible in 109 (93%) of 117 biopsy cases and 136 (94%) of 145 craniotomy cases (only 2 of which [1.5%] required unplanned readmission after discharge). Neurological worsening occurred in 5.1% of the patients who underwent image-guided biopsies, and in 5.5% of those who underwent outpatient craniotomies (based on intent-to-treat group analysis). No patient suffered an adverse event with alteration in outcome because of planned outpatient discharge.

Conclusions
Outpatient image-guided brain biopsy and outpatient craniotomy for tumor resection are safe and effective procedures in selected patients.
Identification of the optimal cortical target point for extracranial–intracranial bypass surgery in patients with hemodynamic cerebrovascular insufficiency
Authors: Peña-Tapia Pablo Gerardo , Kemmling Andre , Czabanka Marcus , Vajkoczy Peter , Schmiedek Peter 
Published: March 2008

Object
The objective of this report is to describe a new approach to identify the optimal cortical target point for extracranial–intracranial (EC–IC) bypass surgery, to reliably find suitable recipient vessels for the anastomosis.

Methods
Thirty consecutive patients (17 men and 13 women; mean age 54.6 ± 11.79 years [± standard deviation]) with hemodynamic cerebrovascular insufficiency due to stenoocclusive arterial disease underwent EC–IC bypass surgery. The end of the Sylvian fissure was identified preoperatively using a specially designed template and external landmarks. At surgery, a 3-cm trephination was made, centered over the target point as determined by the template. The number, diameter, and length of the exposed cortical arteries were assessed using photographs and indocyanine green (ICG) angiograms.

Results
At least 1 recipient artery appropriate for anastomosis (≥ 1 mm) was found in every craniectomy. The mean number of suitable recipient arteries per craniotomy was 2.09 ± 0.87, the mean diameter was 1.28 ± 0.24 mm, and the mean length 10.83 ± 4.87 mm. Bypass patency was confirmed by intraoperative ICG angiography, postoperative computed tomography angiography, and digital subtraction angiography, and reached 100%.

Conclusions
Performing a 3-cm craniectomy over the described target point, reliably allows access to suitable recipient arteries for EC–IC bypass surgery.
Cigarette smoking as a risk factor for recurrence of aneurysms treated by endosaccular occlusion
Authors: Ortiz Rafael , Stefanski Michael , Rosenwasser Robert , Veznedaroglu Erol 
Published: March 2008

Object
Aneurysms treated by endovascular coil embolization have been associated with coil compaction, and the rate of recanalization has been reported to be as high as 40%. The authors report the first published evidence of a correlation between aneurysm recanalization correlated with a history of cigarette smoking.

Methods
The authors conducted a retrospective chart review of all cases involving patients admitted to their institution from January 1, 2003, to December 31, 2003, for treatment of a cerebral aneurysm. Cases in which patients were treated with coil embolization were reviewed for inclusion. Coil compaction was defined as change in the shape of the coil mass. Aneurysm recanalization was defined as an increase in inflow to the aneurysm in comparison with baseline. The incidence of coil compaction and the relationship with cigarette smoking history were compared in patients with and without recurrence.

Results
A total of 110 patients qualified for inclusion. The odds ratio (OR) for aneurysm recanalization after endosaccular occlusion with respect to history of cigarette smoking was significant for the entire cohort (OR 4.53, 95% confidence interval [CI] 1.95–10.52) and especially for the female cohort (OR 3.72, 95% CI 1.45–9.54). The male cohort demonstrated a trend toward a direct correlation, but the sample size was not large enough for statistical significance (OR 7.50, 95% CI 1.02–55.00).

Conclusions
There was an increased risk of recanalization especially in patients with low-grade subarachnoid hemorrhage who had a history of cigarette smoking. These data suggest a correlation between cigarette smoking and aneurysm recurrence.