bluuebunny/crossref_metadata_2025 huggingface dataset:
Using Akaike's information theoretic criterion in mixed-effects modeling of pharmacokinetic data: a simulation study
Authors: Olofsen Erik , Dahan Albert
Published: May 2014

Akaike's information theoretic criterion for model discrimination (AIC) is often stated to "overfit", i.e., it selects models with a higher dimension than the dimension of the model that generated the data. However, with experimental pharmacokinetic data it may not be possible to identify the correct model, because of the complexity of the processes governing drug disposition. Instead of trying to find the correct model, a more useful objective might be to minimize the prediction error of drug concentrations in subjects with unknown disposition characteristics. In that case, the AIC might be the selection criterion of choice.

We performed Monte Carlo simulations using a model of pharmacokinetic data (a power function of time) with the property that fits with common multi-exponential models can never be perfect - thus resembling the situation with real data. Prespecified models were fitted to simulated data sets, and AIC and AICc (the criterion with a correction for small sample sizes) values were calculated and averaged. The average predictive performances of the models, quantified using simulated validation sets, were compared to the means of the AICs. The data for fits and validation consisted of 11 concentration measurements each obtained in 5 individuals, with three degrees of interindividual variability in the pharmacokinetic volume of distribution.

Mean AICc corresponded very well, and better than mean AIC, with mean predictive performance. With increasing interindividual variability, there was a trend towards larger optimal models, but with respect to both lowest AICc and best predictive performance. Furthermore, it was observed that the mean square prediction error itself became less suitable as a validation criterion, and that a predictive performance measure should incorporate interindividual variability.

This simulation study showed that, at least in a relatively simple mixed effects modelling context with a set of prespecified models, minimal mean AICc corresponded to best predictive performance even in the presence of relatively large interindividual variability.
Tourism industry employing personal experience marketing tools
Authors: Кривошеева Татьяна , Krivosheeva Tatiana , Хаванова Наталья , Khavanova Natalya , Осокин Вадим , Osokin Vadim
Published: May 2014

With the concept of the experience economy in place, the evolution of the exchange object has made a step further to integrate experiences, calling forth a need for a marketing complex which would reflect the experiences and manage them. The concept of experience marketing was established and developed alongside the development of the concept of experience economy. Many scientists view tourism as a sector of service economy, which suggests that, as applied to the tourism industry, the experience marketing instrument will promote a sustained development of tourist service consumer catering activities.
Global tourism development trends: impact on marketing
Authors: Вапнярская Ольга , Vapnyarskaya Olga , Ульянченко Людмила , Ulyanchenko Lyudmila
Published: May 2014

With Russian enterprises and organizations operating in the sphere of tourism integrated into the global tourist service market, Russian tourist market players increasingly come under the influence of global tourist factors and development trends. At the marketing activity planning stage, especially when creating tourist service offers, companies are to take into account the common factors regulating and determining global tourist demand. The article provides an analysis of the major global tourism development trends, which, according to the authors, are to provided for by marketing decision-makers primarily in regards inbound tourism. The authors conclude that the trends included in the analysis are potentially influential at regional and micro levels.
Evolutional trends of retail risk assessment
Authors: Черникова Людмила , Chernikova Lyudmila , Новичков Николай , Novichkov Nikolay , Фаизова Гузель , Faizova Guzel
Published: May 2014

The article deals with the evolutionary trends of retail risk assessment. The authors present an analysis of the historical perspective on retail banking development and assessment methods. The methods of private entity borrowing capacity assessment are evolving on an ongoing basis due to changes in legislation, the development of information technologies and growing active-bank-operations-related risks. The analysis as conducted by the authors has revealed an evolution of the methods ensuring the enhancement and maintenance of the quality of retail assets. The authors claim that scoring is to be considers with due regard to the significance of the technological component, and dwell on their vision of this definition.
THE ALUMINIUM PRICE FORECASTING BY REPLACING THE INITIAL CONDITION VALUE BY THE DIFFERENT STOCK EXCHANGES
Authors: Lascsáková Marcela , Nagy Peter
Published: May 2014

In mathematical models, for forecasting prices on commodity exchanges different mathematical methods are used. In the paper the numerical model based on the exponential approximation of commodity stock exchanges was derived. The price prognoses of aluminium on the London Metal Exchange were determined as numerical solution of the Cauchy initial problem for the 1st order ordinary differential equation. To make the numerical model more accurate the idea of the modification of the initial condition value by the aluminium price (stock exchange) was realised. The derived numerical model was verified by determining the influence of the length of the initial condition drift on the accuracy of the obtained prognoses. The types of the initial condition drift during different movements of aluminium prices were studied. The most accurate prognoses were the most often obtained by using the longest initial condition drift. In this type of drift the initial condition value was replaced by aluminium stock exchange in the month in which the absolute percentage error of the prognosis had at least selected value. The advantage of this drift was manifested especially in the stable price course and within larger changes in prices. If there was price fluctuating within the observing period, in the next forecasting the most accurate was the drift the initial condition value of which had been replaced by the price that was the nearest to the stock exchange price evolution.
FORMABILITY OF AUSTENITIC STAINLESS STEEL 316 SHEET IN DYNAMIC STRAIN AGING REGIME
Authors: Hussaini Syed Mujahed , Singh Swadesh Kumar , Gupta Amit Kumar
Published: May 2014

Dynamic strain aging region for austenitic stainless steel 316 was investigated from room temperature to 650°C at constant strain rates of 1x10-2, 1x10-3 and 1x10-4 sec-1. Characteristics indicators of serrated plastic flow were observed in the temperature range of 400°C to 600°C at these strain rates. Strain rate sensitivity of the material is found to be negative in this region. Study of fracture surface of tensile test specimen by scanning electron microscope revealed that ductility in this region decreased. The limiting drawing ratio of sheet metal is the indicator of formability in deep drawing. LDR of the sheet metal was estimated by performing the deep drawing of different diameter blanks in finite element simulation software LS-DYNA in DSA temperature region. It was observed that in DSA region, formability of sheet metal decreased. These simulations are validated and compared with experimental results.
IDENTIFICATION OF FACTORS CAUSING NITRIDATION OF CRUDE STEEL IN BOF BEFORE TAPPING
Authors: Buľko Branislav , Demeter Jaroslav , Kijac Jozef , Demeter Peter
Published: May 2014

Determination of factors and measuring their impact on the amount of nitrogen in the metal is key attribute when optimizing technological and operational measures tending to minimize, respectively prevent of the final steel nitridization. Knowing the rate of influence of individual factors on the nitrogen content in the metal is crucial in dealing with prediction of the quantity for the production and processing stages of steel production in a closed production cycle. In this paper, factors determining nitrogen content in crude steel before tapping, using Cohen´s distribution table and graphical expression are presented. Influence of after-blows on nitrogen content is well known, but there are other factors which affect steel nitridization before tapping from oxygen converter.
MANUFACTURABILITY VERIFICATION AND COMPARISON OF QUALITY PARAMETERS OF SHAPED SURFACE
Authors: Tomáš Miroslav , Draganovska Dagmar , Hudák Juraj , Ižol Peter
Published: May 2014

The paper describes stamping punch production from the view manufacturability and quality of stamping punch active surfaces. The tin car-body stamping punch has been chosen as a subject of experimental work. The experimental stamping punch has been made out of Textit and production stamping punch has been made out of tool steel X210Cr12. Milling strategies has been proposed and verified using CAM software SolidCAM considering the maximum Scallop Height. The roughness parameters Ra and Rz measured on selected areas of stamping punch shaped surface were compared to Scallop Height. Manufactured areas on shaped surface were optically evaluated as well. The application of proposed procedure is shown as an example of manufacturability for experimental and production stamping punch designed for complex parts production.
STRESS ANALYSIS IN CYLINDRICAL SPECIMENS MADE FROM 34CrMo4 USING DIC
Authors: Štamborská Michaela , Losertová Monika , Mareš Vratislav , Horsák Lukáš
Published: May 2014

The stress analysis using digital image correlation was carried out on cylindrical tensile specimens made from low carbon 34CrMo4 steel. The results obtained by conventional tensile test were compared with the results obtained by digital image correlation. The true stresses were evaluated from the compiled true stress-strain diagrams and compared with the engineering stresses. The average values of the yield stress and tensile strength reached of 945±15 MPa and 1039±5 MPa, respectively. Thus, parameters obtained from tensile test were plotted in the engineering diagrams that represent often starting diagrams for engineering practice. Based on results of digital image correlation the possibility of construction of the true stress-strain diagrams is discussed with regard to more exact values of stress for use in practice. The evaluation and compilation of the true stress-strain diagrams were carried out by means of image correlation software Vic 2D.
CORROSION PROPERTIES OF SELECTED ALUMINIUM ALLOYS IN MODEL ELECTROLYTES
Authors: Lacková Petra , Hagarová Mária , Cervová Jana
Published: May 2014

The paper deals with the corrosion properties and corrosion resistance of aluminium alloys types of AlCu (EN AW 2017), AlMgSi (EN AW 6012) and AlZn (EN AW 7075) with heat treatment T3 (solution treatment, forming and natural aging). The basic corrosion characteristics were quantified by measurement of corrosion potential measured against the saturated calomel electrode and weight losses of exposed samples in the environment of distilled water and in solution SARS. The samples of aluminium alloys were immersed in above-mentioned environments for one minute for a period of six months. Furthermore, an extra evaluation of corrosion of exposed aluminium samples was carried out by means of metallographic analysis. The exposed sample surfaces were evaluated using a microscope.
EFFECT OF ELECTRODEPOSITION TEMPERATURE ON CORROSION RESISTANCE OF CALCIUM PHOSPHATE
Authors: Pastorek Filip , Hadzima Branislav , Omasta Miroslav , Mhaede Mansour
Published: May 2014

Electrodeposition process of calcium phosphate (CaP) was performed at various temperatures on AZ31 magnesium alloy and the influence on corrosion resistance of the alloy covered by CaP was investigated by electrochemical tests supported by photodocumentation. The electrodeposition treatment was performed by potential controlled method in water solution of Ca(NO3)2.4H2O, NH4H2PO4 and H2O2. The difference in the process of CaP formation at various temperatures was described using diagrams of current density time dependence. Corrosion measurements were performed in 0.9% NaCl solution at 22 ± 2 °C using electrochemical impedance spectroscopy. According to corrosion resistance results, the optimal temperature for CaP electrodeposition process was chosen.
RESEARCH ON HIGH TEMPERATURE PROPERTIES OF IRON ORE MATERIALS
Authors: Pustějovská Pavlína , Jursová Simona
Published: May 2014

The paper deals with reducibility of metallurgical pellets. They were tested by ISO 4695:2007 to determine their reducibility in CO environment at 950°C and ISO 4696-2:2007 to determine their disintegration index after reduction at 550°C. The paper presents the results of reduction process. It compares them with reducibility of other material such as iron ore and sinter. The paper interprets the effect of reduction on phase composition of pellets and the content of bounded water. The thermoplastic properties present physic-chemical changes of feedstock during its descent in the shaft of blast furnace aggregate. The mechanical solidity characterizes the capability of material to be resistant against the pressure, the crash, the fall and the abrasion.
An Empirical Analysis of Price, Quality, and Incumbency in Procurement Auctions
Authors: Tunca Tunay I. , Wu D. J. , Zhong Fang (Vivian)
Published: May 2014

The use of multiattribute auctions for procurement of products and services when both price and quality matter is becoming more frequent. Such auctions often employ scoring rules and are open ended in winner determination. Yet there is a significant gap in the literature on the efficiency of these procurement mechanisms. In this paper, providing a theoretical model and utilizing data from legal service procurement auctions, we study how open-ended scoring auctions can be used effectively in procurement and demonstrate the roles supplier quality and incumbency play in this process. We demonstrate that open-ended auctions can generate substantial savings to a buyer without compromising quality. We study the underlying mechanism and show how the auction format can work to achieve such performance. We find that the buyer's revealed preferences significantly differ from her stated preferences. Finally, we contribute to the understanding of the role of incumbency in procurement auctions by providing evidence that what may be perceived as incumbency bias can in fact be a revelation of preference for quality.
Everyday creativity in design process
Authors: Lloyd Peter , Jones Derek
Published: May 2014

The study of creativity in design has tended to emphasize its value and location in the individual designer as part of a statistically outlying population rather than as a normal characteristic of an entire population. Theories of creativity have generally stressed either its mysterious, gift-like qualities to an individual or as a constructed relationship between consumer and designer. This article, in developing a third view of creativity in design as a ‘normal’ phenomenon, describes a study of 1038 student design assignments obtained from a distance-learning course in Design Thinking. The article shows how normal distributions of design outputs can result from a large population following a structured design process. We argue that the creativity displayed is a natural result of the ‘grammar’ of that process. Seen in this way creativity becomes less of an individual ‘gift’ to a select minority, as generally understood, but an everyday occurrence to problems of design.
Molecular Profiling and Commercial Predication Assays in Ovarian Cancer: Still Not Ready for Prime Time?
Authors: Kohn Elise C.
Published: May 2014

Short of early detection to allow curative primary intervention, the other major barrier to further success in treatment of ovarian cancers is matching the best treatment to the proper ovarian cancer type and to the individual patient. There are several decades of experience applying in vitro chemoresponse testing for solid tumors including ovarian cancer. This concept, first described in 1979, has yet to receive level one evidence supporting its application, despite the testing of numerous assays commercially as well as in academic centers and its use for tens of thousands of patients at a significant cost. The approach—rather than undergoing rigorous scientific examination—is now being muddied by the development of commercial molecular profiling assays from which treatment suggestions are provided. Molecular profiling as a research tool has added value to our understanding and treatment of patients with ovarian cancer. Morphologic and histochemical characterizations coupled now with increasing knowledge of ovarian cancer type-specific molecular patterns is improving our ability to properly diagnosis ovarian cancer type and thus guide therapy. With the exception of the role of germ-line and possibly somatic BRCA1 and BRCA2 mutations and their true predictiveness for probable response to poly(ADP-ribose) polymerase inhibition, molecular typing and profiling has yet to identify druggable molecular targets in ovarian cancer. Its use should be continued as a research and learning tool, and its results should be subjected to clinical trial validation. For very different reasons, neither chemoresponse assays nor molecular profiling are ready for prime time, yet.
Surgery in the HPV Era: The Role of Robotics and Microsurgical Techniques
Authors: Ridge John A.
Published: May 2014

Retrospective studies suggested that head and neck cancers associated with human papilloma virus (HPV) are more frequently cured than those caused by substance use. The Eastern Cooperative Oncology Group (ECOG) subsequently confirmed the observation in a prospective trial. Most HPV-initiated cancers arise in the oropharynx. Survival differences between patients with cancers caused by HPV and those caused by alcohol and tobacco use persist despite modern treatment. The impression that treatment intensification has resulted in improved survivorship may well be attributable to an increasing proportion of patients with cancers caused by HPV infection. Unsatisfactory results for cancers attributable to substance use and encouraging improvements in tumor control for patients with HPV-initiated cancers have led to dissatisfaction with the current nonsurgical management paradigm. Ongoing advances in surgical techniques permit transoral resection of oropharyngeal cancers, thus limiting exposure-related morbidity and permitting ready recovery in terms of speech and swallowing. Transoral laser microsurgery (TLM) is increasingly employed and transoral robotic surgery (TORS) has dramatically popularized surgical treatment of oropharyngeal cancers. Resection affords the opportunity to increase local control at the primary site and surgical management of neck allows risk-based stratification of postoperative radiation therapy. Case series from several institutions show encouraging results. Transoral surgical resection is safe, can be undertaken with acceptable morbidity, and provides comparable locoregional control to that achieved with chemoradiation. Prospective trials for patients with HPV-initiated cancers, as well as those referable to substance use, are underway.
Molecular Monitoring and Mutations in Chronic Myeloid Leukemia: How to Get the Most out of Your Tyrosine Kinase Inhibitor
Authors: Baccarani Michele , Soverini Simona , De Benedittis Caterina
Published: May 2014

The course of chronic myeloid leukemia (CML) and the response to treatment with tyrosine kinase inhibitors (TKIs) are best monitored and assessed using two molecular tests: the first is real-time quantitative reverse transcription-polymerase chain reaction (RQ-PCR), which measures the size of residual disease that is expressed as BCR-ABL1% (the ratio between BCR-ABL1 and a control gene) and the other is mutational analysis by Sanger sequencing, which checks for the presence of BCR-ABL1 kinase domain point mutations. Both tests are technically demanding and require a high level of specialization and standardization. RQ-PCR, when performed on a regular basis, allows for the defining of molecular response (MR) levels as log reduction from a standardized baseline: major molecular response (MMR or MR3) that is the best predictor of survival; and the deeper molecular response (MR4, MR4.5, and MR5) that is necessary to enroll a patient in a trial aiming at treatment-free remission (TFR). Mutational analysis, to be performed in case of failure or warning by Sanger sequencing, allows for screening of the BCR-ABL1 kinase domain for mutations conferring resistance to TKIs. Since different mutations have different degrees of sensitivity to each of the currently available TKI, the knowledge of BCR-ABL1 kinase domain–mutation status is necessary for subsequent treatment choice. Optimal patient management requires that MR and mutational information be rationally interpreted at both the technical and at the biologic level, and put into context—therapeutic decisions also take into account other factors, such as age, comorbidities, side effects, compliance, and treatment-related complications.
Models of Cancer Survivorship Health Care: Moving Forward
Authors: Oeffinger Kevin C. , Argenbright Keith E. , Levitt Gill A. , McCabe Mary S. , Anderson Paula R. , Berry Emily , Maher Jane , Merrill Janette , Wollins Dana S.
Published: May 2014

The population of cancer survivors in the United States and worldwide is rapidly increasing. Many survivors will develop health conditions as a direct or indirect consequence of their cancer therapy. Thus, models to deliver high-quality care for cancer survivors are evolving. We provide examples of three different models of survivorship care from a cancer center, a community setting, and a country-wide health care system, followed by a description of the ASCO Cancer Survivorship Compendium, a tool to help providers understand the various models of survivorship care available and integrate survivorship care into their practices in a way that fits their unique needs.
Electronic Health Records (EHRs): Supporting ASCO's Vision of Cancer Care
Authors: Yu Peter , Artz David , Warner Jeremy
Published: May 2014

ASCO's vision for cancer care in 2030 is built on the expanding importance of panomics and big data, and envisions enabling better health for patients with cancer by the rapid transformation of systems biology knowledge into cancer care advances. This vision will be heavily dependent on the use of health information technology for computational biology and clinical decision support systems (CDSS). Computational biology will allow us to construct models of cancer biology that encompass the complexity of cancer panomics data and provide us with better understanding of the mechanisms governing cancer behavior. The Agency for Healthcare Research and Quality promotes CDSS based on clinical practice guidelines, which are knowledge bases that grow too slowly to match the rate of panomic-derived knowledge. CDSS that are based on systems biology models will be more easily adaptable to rapid advancements and translational medicine. We describe the characteristics of health data representation, a model for representing molecular data that supports data extraction and use for panomic-based clinical research, and argue for CDSS that are based on systems biology and are algorithm-based.
Integrative Oncology: An Overview
Authors: Deng Gary , Cassileth Barrie
Published: May 2014

Integrative oncology, the diagnosis-specific field of integrative medicine, addresses symptom control with nonpharmacologic therapies. Known commonly as “complementary therapies” these are evidence-based adjuncts to mainstream care that effectively control physical and emotional symptoms, enhance physical and emotional strength, and provide patients with skills enabling them to help themselves throughout and following mainstream cancer treatment. Integrative or complementary therapies are rational and noninvasive. They have been subjected to study to determine their value, to document the problems they ameliorate, and to define the circumstances under which such therapies are beneficial. Conversely, “alternative” therapies typically are promoted literally as such; as actual antitumor treatments. They lack biologic plausibility and scientific evidence of safety and efficacy. Many are outright fraudulent. Conflating these two very different categories by use of the convenient acronym “CAM,” for “complementary and alternative therapies,” confuses the issue and does a substantial disservice to patients and medical professionals. Complementary and integrative modalities have demonstrated safety value and benefits. If the same were true for “alternatives,” they would not be “alternatives.” Rather, they would become part of mainstream cancer care. This manuscript explores the medical and sociocultural context of interest in integrative oncology as well as in “alternative” therapies, reviews commonly-asked patient questions, summarizes research results in both categories, and offers recommendations to help guide patients and family members through what is often a difficult maze. Combining complementary therapies with mainstream oncology care to address patients' physical, psychologic and spiritual needs constitutes the practice of integrative oncology. By recommending nonpharmacologic modalities that reduce symptom burden and improve quality of life, physicians also enable patients to play a role in their care. Critical for most patients, this also improves the physician-patient relationship, the quality of cancer care, and the well-being of patients and their families.
Lynch Syndrome 101 (Years, That Is)
Authors: Lindor Noralane M.
Published: May 2014

Lynch syndrome was described over a century ago but information on the medical consequences and optimal management of this disorder continue to amass and evolve. This brief overview highlights the gene-specific and site-specific cancer penetrance and management options for those with Lynch syndrome.
Obligations of an Academic and Clinical Oncologist: Historical Reflections
Authors: Johnson David H.
Published: May 2014

Obligations are derived from one's core values—those fundamental, enduring, deeply held beliefs that guide one's everyday actions. Gandhi stated it more eloquently than I ever could: “Your beliefs become your thoughts, your thoughts become your words, your words become your actions, your actions become your habits, your habits become your values, your values become your destiny.”1So what are the obligations of the academic oncologist and clinician? I believe there are a few indubitable and fundamental obligations: professionalism, patient care, stewardship, maintenance of knowledge, productivity, and mentorship). I might add that I do not see these obligations as unique to the academician but rather applicable to all physicians.
Colorectal Cancer: All Hands on Deck
Authors: Venook Alan P. , Weiser Martin R. , Tepper Joel E.
Published: May 2014

The past 50 years has seen substantial progress in our understanding of and in the management of colorectal cancer (CRC). Surveillance colonoscopy with resection of premalignant polyps has led to a decreased incidence of CRC even though compliance with the recommendations is suboptimal. Epidemiologic and genetic information allow us to identify individuals at risk for cancer and should allow us to prevent the disease in many individuals. Patients diagnosed with metastatic CRC live much longer than in the past, and some with metastatic disease are cured. This is attributed to many factors, including cross-sectional imaging that identifies metastases earlier, new surgical and radiation techniques, and numerous new chemotherapies. Higher resolution imaging modalities have improved the ability to find limited and resectable metastatic disease; surgical advances include laparoscopic-assisted procedures and safer and more extensive hepatic resection; and radiation techniques allow for higher dose and less morbidity. Biologic therapies have not yet been maximized, but we are learning when and where some should be used. Soon we expect to be staging patients by biologic and genetic characteristics rather than by gross pathology—treating patients based on biologic features but preferably identifying people at risk and preventing CRC altogether.
Targeted Alpha-Particle Immunotherapy for Acute Myeloid Leukemia
Authors: Jurcic Joseph G. , Rosenblat Todd L.
Published: May 2014

Because alpha-particles have a shorter range and a higher linear energy transfer (LET) compared with beta-particles, targeted alpha-particle immunotherapy offers the potential for more efficient tumor cell killing while sparing surrounding normal cells. To date, clinical studies of alpha-particle immunotherapy for acute myeloid leukemia (AML) have focused on the myeloid cell surface antigen CD33 as a target using the humanized monoclonal antibody lintuzumab. An initial phase I study demonstrated the safety, feasibility, and antileukemic effects of bismuth-213 (213Bi)-labeled lintuzumab. In a subsequent study, 213Bi-lintuzumab produced remissions in some patients with AML after partial cytoreduction with cytarabine, suggesting the utility of targeted alpha-particle therapy for small-volume disease. The widespread use of 213Bi, however, is limited by its short half-life. Therefore, a second-generation construct containing actinium-225 (225Ac), a radiometal that generates four alpha-particle emissions, was developed. A phase I trial demonstrated that 225Ac-lintuzumab is safe at doses of 3 μCi/kg or less and has antileukemic activity across all dose levels studied. Fractionated-dose 225Ac-lintuzumab in combination with low-dose cytarabine (LDAC) is now under investigation for the management of older patients with untreated AML in a multicenter trial. Preclinical studies using 213Bi- and astatine-211 (211At)-labeled anti-CD45 antibodies have shown that alpha-particle immunotherapy may be useful as part conditioning before hematopoietic cell transplantation. The use of novel pretargeting strategies may further improve target-to-normal organ dose ratios.
Managing Cumulative Expectations in Oncology: Challenges and Potential Solutions
Authors: Abernethy Amy P. , Grubbs Stephen S.
Published: May 2014

The dedication of oncologists to their patients is undeniable. Patients given what can be a devastating diagnosis look to their physician for hope, guidance, and answers. The physician, in turn, must assimilate information from a staggering amount of resources and outlets and then form a plan that satisfies current practices and guidelines while still being consistent with the most current regulations set by a multitude of sources for oversight. Do all this for every patient in a time in which the number of new and continuing patients is ever increasing, and it is hardly surprising that the shocking overload can lead to physician burnout and, quite possibly, poorer patient care. Overload, be it information, task, knowledge, or expectation, is real, and to avoid succumbing, cancer care providers need to acknowledge that the problem exists by identifying the sources and admit that the problem of overload is out of control. Only then can providers begin to realize what can and can not be done, so that they can focus attention on what they are doing when they are doing it—an application of mindfulness. To take control of the avalanche of incoming information, providers need to make good use of filters, set time aside to evaluate inbound intelligence, and identify and (importantly) rely on a narrow set of trusted resources. Although strategies on coping with overloads abound, the physician needs to be diligent in applying the available options to keep burnout at bay.
Value of Cancer Care: Ethical Considerations for the Practicing Oncologist
Authors: Jagsi Reshma , Sulmasy Daniel P. , Moy Beverly
Published: May 2014

The value of cancer care has emerged at the center of a national discourse on fiscal responsibility and resource allocation. The cost of cancer care is rising at a higher pace than any other area of health care. As we struggle to address this unsustainable rise in cancer expenditures, oncology providers are forced to examine our practice patterns and our contributions to the overall health care cost burden. This article provides an oncologist-centered examination of our duties to individual patients and how they may seem at odds with our duties to society. It also discusses how oncology providers can do their part to contain health care costs while honoring their professional obligation to do their best for each patient.
Beyond Stage I Germ Cell Tumors: Current Status Regarding Treatment and Long-Term Toxicities
Authors: Haugnes Hege Sagstuen , Stephenson Andrew J. , Feldman Darren Richard
Published: May 2014

Approximately 20% to 40% of patients with germ-cell tumors (GCT) will need advanced medical treatment because of relapse or initial metastatic disease. The survival and recommended treatment for men with metastatic disease varies according to histology, primary and metastatic sites, and the level of prechemotherapy tumor markers. For patients with a good prognosis, three cycles of bleomycin, etoposide, and cisplatin (BEP) or four cycles of etoposide, and cisplatin are recommended. For patients with intermediate- and poor prognosis, four cycles of bleomycin, etoposide, and cisplatin remains the preferred treatment option, although a switch to a more intensive regimen can be considered a new alternative. A major advance in salvage therapy for GCT in the last 5 years was the development of a new risk classification system. Initial salvage treatment includes both high-dose chemotherapy and standard-dose chemotherapy. There is clear consensus that patients with residual masses larger than 1 cm should undergo postchemotherapy retroperitoneal lymph node dissection (PC-RPLND); however, the role of PC-RPLND in patients with serologic and radiographic complete response to first-line chemotherapy is controversial. The rationale for PC-RPLND in patients with small residual masses is discussed, and only a small minority of advanced nonseminoma GCT (NSGCT) patients are suitable candidates for observation after first-line chemotherapy. Post-treatment long-term toxicity has emerged as an important issue for GCT survivors. Examples of late effects are secondary nongerm-cell cancers and cardiovascular disease, which represent the most severe and potentially life-threatening effects of cancer treatment. Follow-up of cancer survivors should include recommendations for maintaining a healthy lifestyle to reduce the risk of serious long-term and late effects of treatment.
The Geriatrics and Genetics behind Bladder Cancer
Authors: Milowsky Matthew I. , Kim William Y.
Published: May 2014

Bladder cancer is a disease of older patients who often have multiple comorbidities. Although cisplatin-based combination chemotherapy is the standard of care in the neoadjuvant and metastatic settings, outcomes remain poor, and approximately half of patients are ineligible for cisplatin where treatment options are severely limited. Recent comprehensive genome sequencing studies have defined the mutational spectra of high-grade urothelial carcinoma of the bladder. Although there is a high prevalence of potentially actionable genomic alterations, whether these events represent true oncogenic vulnerabilities has yet to be confirmed. Given the demographics and genetics, we propose that bladder cancer represents an ideal model to study the potential of targeted therapy in older patients who are too often unable to receive cisplatin-based therapy and where novel treatment strategies are desperately needed.
Personalizing Therapy for Older Adults with Lymphoid Malignancies: Options and Obstacles
Authors: Wildes Tanya M. , Goede Valentin , Hamlin Paul
Published: May 2014

Increasing age is both a risk factor for and a negative prognostic factor in lymphoid malignancies. The disparities in outcomes between older and younger adults with lymphoid malignancies may reflect age-related differences in treatment and in biology of disease. Lymphomas in older adults are biologically more aggressive. Only small age-related differences in the frequency of cytogenetic abnormalities are seen in multiple myeloma. No major differences in the biology of chronic lymphocytic leukemia (CCL) are seen across the age spectrum. Chemotherapy and immunotherapy in older adults with lymphoid malignancies are marked by greater vulnerability to toxicity of therapy. Excessive toxicity can result in poorer outcomes, either directly through treatment-related mortality, or through decreased dose intensity. Thus, new approaches to predict toxicity of therapy and stratified treatment algorithms based on risk of toxicity are needed. Herein we detail some of the promising approaches to predicting toxicity and tailoring treatment for older adults with lymphoid malignancies.
Management of Vulvar and Vaginal Melanomas: Current and Future Strategies
Authors: Leitao Mario M.
Published: May 2014

Melanomas arising in the vulva and vagina are rare and therefore there is minimal data specific to these malignancies. Data are often extrapolated from other cutaneous melanomas, which may or may not be appropriate. Surgery remains the primary treatment modality at initial diagnosis and in select recurrent cases. Wide local excision of the primary lesion not requiring an exenteration, along with sentinel lymph node (SLN) mapping, should be routinely considered in vulvar melanomas. Local excision and SLN mapping is difficult and often not considered for vaginal melanomas. Primary exenterative procedures should not be routinely offered. In locally advanced cases potentially requiring an exenterative procedure, radiation therapy with or without concurrent immunotherapy is a consideration. The role of adjuvant therapy remains unclear. Surgery or radiation therapy can be considered in recurrent cases. Systemic chemotherapy agents have a modest response rate with associated poor survival outcomes. Novel immunotherapeutic and targeted agents have been reported to improve survival in melanoma and should be considered in cases of vulvovaginal melanoma. All cases should be tested for at least c-KIT and BRAF V600E mutations. Patients with vulvovaginal melanomas should be strongly encouraged to participate in clinical trials.
Novel Approaches to Improve the Treatment of Rare Gynecologic Cancers: Research Opportunities and Challenges
Authors: Ledermann Jonathan A. , Ray-Coquard Isabelle
Published: May 2014

More than 50% of all gynecologic cancers can be classified as rare tumors (defined as an incidence of fewer than six per 100,000). Improved understanding of the molecular pathogenesis of tumors increases the proportion of rare tumors and creates challenges in optimizing the design of clinical trials. Novel trial designs are needed to take forward the development of new treatments in rare tumors. This requires international partnerships, harmonization of treatment, and collaboration to overcome the regulatory barriers to conducting international trials. Although randomized trials can be done in many tumor types, there are some for which conducting even single-arm studies may be challenging. For these tumors, robust collection of data through national and/or international registries could lead through audit to improvements in the treatment of rare tumors.
Survivorship in Gynecologic Cancer: Enduring the Treatment toward a New Normal
Authors: Duska Linda R. , Fader Amanda N. , Dizon Don S.
Published: May 2014

Women are living longer after a cancer diagnosis because of advances in early detection and treatment. However, although our ability to effectively treat gynecologic malignancies has improved, survivors of gynecologic cancer often face profound physical, emotional, sexual, and psychosocial challenges as a result of their cancer diagnosis and treatment. In this article, we discuss how patient comorbidities (i.e., obesity) and cancer treatment effects may adversely affect sexual health outcomes, gastrointestinal function, and general health among survivors of gynecologic cancer. The importance of a multidisciplinary, patient-centered approach to survivorship care is emphasized.
A Value Framework in Head and Neck Cancer Care
Authors: de Souza Jonas A. , Seiwert Tanguy Y.
Published: May 2014

The care of head and neck squamous cell carcinoma has greatly evolved over the past 30 years. From single modality to a multidisciplinary care, there has also been a concurrent increase in treatment intensity, resulting, at many times, in more zealous regimens that patients must endure. In this article, we apply Porter's value model as a framework to balance survival, toxicities, cost, and trade-offs from a patient's perspective in head and neck cancer. This model defines value as the health outcome per dollar achieved. Domains and outcomes that are important to patients, including not only survival or short-term quality of life, but also functional outcomes, recovery, sustainability of recovery, and the lasting consequences of therapy are included in this framework. Other outcomes that are seldom measured in head and neck cancer, such as work disability and financial toxicities, are also included and further discussed. Within this value model and based on evidence, we further discuss de-escalation of care, intensity-modulated radiation therapy, newer surgical methods, and enhancements in the process of care as potential approaches to add value for patients. Finally, we argue that knowing the patient's preferences is essential in the value discussion, as the attribute that will ultimately provide the most value to the individual patient with head and neck cancer.
Surveillance Imaging for Lymphoma: Pros and Cons
Authors: Lynch Ryan C. , Zelenetz Andrew D. , Armitage James O. , Carson Kenneth R.
Published: May 2014

There is no international consensus on the optimal frequency or duration of computed tomography or positron emission tomography scanning for surveillance in patients who achieve complete remission after initial therapy for lymphoma. Although some clinical practice guidelines suggest periodic imaging is reasonable, others suggest little or no benefit to this practice. From a theoretical perspective, the frequency and duration of surveillance imaging is largely dependent upon the lymphoma subtype. Aggressive lymphomas with a fast growth rate will require surveillance more frequently and for a shorter duration compared to the indolent lymphomas. Historically, relapse has been detected in a majority of patients based upon clinically evident signs and symptoms. Currently, no study has demonstrated an overall survival difference for patients with relapse detected by imaging as opposed to clinical evaluation, although one study did demonstrate a lower second-line International Prognostic Index in patients with relapse detected by surveillance imaging. Enthusiasm for this finding has been tempered by recent studies highlighting the potential long-term risk of secondary malignancies because of ionizing radiation exposure from diagnostic imaging. These factors along with the significant costs associated with diagnostic imaging have contributed to an ongoing debate regarding the relative costs, risks, and benefits of radiographic surveillance. Herein we present perspectives for and against routine surveillance imaging in an effort to facilitate a better understanding of the issues relevant to what is ultimately a clinical decision made by an oncologist and his or her patient.
Developments in the Treatment of Locally Advanced and Metastatic Squamous Cell Carcinoma of the Skin: A Rising Unmet Need
Authors: Palyca Paul , Koshenkov Vadim P. , Mehnert Janice M.
Published: May 2014

Squamous cell carcinoma of the skin (SCCS) is a common malignancy with potentially devastating consequences in patients with locally advanced or metastatic disease. Its rising incidence, primarily a result of an aging population and increased ultraviolet (UV) radiation exposure, characterize an emerging unmet need. A firm understanding of the biology of this disease, likely distinct from that of other squamous malignancies because of the influence of UV radiation, is necessary in the evaluation of treatment paradigms. Careful recognition of high-risk features pertaining to tumor and host characteristics is paramount to proper management. However, a lack of standardization in guidelines in this regard creates a challenge for physicians. Questions persist regarding additional evaluation and treatment for advanced disease such as the roles for sentinel lymph node biopsy and the adjuvant use of radiation and chemotherapy. With respect to advanced disease, multiple combinations of chemotherapy have been tested with variable success, but no rigorous randomized studies have been conducted. In addition, EGFR inhibitors such as cetuximab and erlotinib have displayed antitumor activity and as such, warrant further investigation. In sum, the treatment of locally advanced and metastatic SCCS is a ripe area for clinical investigation. This article summarizes the current understanding of disease biology and emerging questions in the management of this disease.
Update on the Biology and Clinical Management of Merkel Cell Carcinoma
Authors: Thakuria Manisha , LeBoeuf Nicole R. , Rabinowits Guilherme
Published: May 2014

Merkel cell carcinoma (MCC) is a rare but aggressive neuroendocrine cutaneous malignancy, with a predilection for sun-exposed sites in elderly patients. Despite an incidence 30 times less than that of melanoma, its disease-specific mortality is three times higher. Management of MCC remains challenging because of a limited understanding of its molecular biology, lack of prospective clinical trials, and limitations associated with retrospective reviews of therapeutic options. With the recent discovery of an associated human polyomavirus, significant progress has been made in the understanding of the pathogenesis of this malignancy. With this progress, there has been increasing optimism regarding new tools in the therapeutic armamentarium to fight this deadly disease. Here we present an overview on MCC with an emphasis on the most recent biologic discoveries and the rationale for novel targeted and immunotherapies.
Frontline Approach to Metastatic BRAF-Mutant Melanoma Diagnosis, Molecular Evaluation, and Treatment Choice
Authors: Chapman Paul B. , Hauschild Axel , Sondak Vernon K.
Published: May 2014

An estimated 76,100 patients will be diagnosed with invasive melanoma in the United States in 2014, and 9,710 patients will die from the disease. In almost all cases, the cause of death is related to the development of widespread metastatic disease. Although death rates from most types of cancer have steadily decreased in the United States –a 20% decrease during two decades from a peak of 215.1 deaths per 100,000 population in 1991 to 171.8 in 2010 –death rates from melanoma have steadily increased during the same time, especially among males. The news regarding melanoma is far from all bad. Increases in our understanding of the human immune system have led to the development of new immunotherapeutic drugs such as ipilimumab, which has been shown to improve survival in phase III trials in metastatic melanoma, and anti-programmed death 1 (anti-PD1) antibodies, recently hailed by ASCO as one of the past year's most noteworthy clinical cancer advances. However, no discovery has influenced and, indeed, transformed the management of metastatic melanoma more than the identifıcation of activating mutations in the BRAF gene in the mitogen-activated protein kinase (MAPK) pathway, which occur in about half of cutaneous melanomas and can be targeted with small molecule inhibitors of the BRAF protein, the downstream MEK protein, or both. This article will address how patients with metastatic melanoma are evaluated for their mutation status and how the presence of a targetable mutation influences therapeutic decisions regarding systemic therapy and even surgery.