bluuebunny/crossref_metadata_2025 huggingface dataset:
Recurrence Rates in Patients With Cervical Cancer Treated With Abdominal Versus Minimally Invasive Radical Hysterectomy: A Multi-Institutional Retrospective Review Study
Authors: Uppal Shitanshu , Gehrig Paola A. , Peng Katherine , Bixel Kristin L. , Matsuo Koji , Vetter Monica H. , Davidson Brittany A. , Cisa M. Paige , Lees Brittany F. , Brunette Laurie L. , Tucker Katherine , Stuart Staley Allison , Gotlieb Walter H. , Holloway Robert W. , Essel Kathleen G. , Holman Laura L. , Goldfeld Ester , Olawaiye Alexander , Rose Stephen L.
Published: February 2020

PURPOSE

To compare the disease-free survival (DFS) between open and minimally invasive radical hysterectomies (RH) performed in academic medical institutions

METHODS

Retrospective multi-institutional review of patients undergoing RH for stage IA1 (with lymphovascular invasion), IA2, and IB1 squamous, adenocarcinoma, or adenosquamous carcinoma between January 1, 2010 and December 31, 2017.

RESULTS

Of 815 patients, open RH was performed in 255 cases (29.1%) and minimally invasive RH in 560 cases (70.9%). There were 19 (7.5%) recurrences in the open RH and 51 (9.1%) recurrences in the minimally invasive group ( P = .43). Risk-adjusted analysis revealed that minimally invasive RH was independently associated with an increased hazard of recurrence (aHR, 1.88; 95% CI, 1.04 to 3.25). Other factors independently associated with an increased hazard of recurrence included tumor size, grade, and adjuvant radiation. Conization before surgery was associated with lower recurrence risk (aHR, 0.4; 95% CI, 0.23 to 0.71). There was no difference in OS in the unadjusted analysis (HR, 1.14; 95% CI, 0.61 to 2.11) or after risk adjustment (aHR, 1.01; 95% CI, 0.5 to 2.2). Of 264 patients with tumors ≤ 2 cm on final pathology (excluding those with no residual tumor on final pathology), 2/82 (2.4%) recurred in the open RH group and 16/182 (8.8%) in the minimally invasive RH group ( P = .058). In propensity score matching analysis, 7/159 (4.4%) recurrences were noted in the open RH group and 18/156 (11.5%) in the minimally invasive RH group ( P = .019). Survival analysis revealed an increased risk of recurrence in the minimally invasive group in propensity-matched cohort (HR, 2.83; 95% CI, 1.1 to 7.18)

CONCLUSION

In this retrospective series, patients undergoing minimally invasive radical hysterectomy, including those with tumor size ≤ 2 cm on final pathology, had inferior DFS but not overall survival in the entire cohort.
Functional genetic analysis in a jawless vertebrate, the sea lamprey: insights into the developmental evolution of early vertebrates
Authors: York Joshua R. , McCauley David W.
Published: February 2020

Lampreys and hagfishes are the only surviving relicts of an ancient but ecologically dominant group of jawless fishes that evolved in the seas of the Cambrian era over half a billion years ago. Because of their phylogenetic position as the sister group to all other vertebrates (jawed vertebrates), comparisons of embryonic development between jawless and jawed vertebrates offers researchers in the field of evolutionary developmental biology the unique opportunity to address fundamental questions related to the nature of our earliest vertebrate ancestors. Here, we describe how genetic analysis of embryogenesis in the sea lamprey (Petromyzon marinus) has provided insight into the origin and evolution of developmental-genetic programs in vertebrates. We focus on recent work involving CRISPR/Cas9-mediated genome editing to study gene regulatory mechanisms involved in the development and evolution of neural crest cells and new cell types in the vertebrate nervous system, and transient transgenic assays that have been instrumental in dissecting the evolution of cis-regulatory control of gene expression in vertebrates. Finally, we discuss the broad potential for these functional genomic tools to address previously unanswerable questions related to the evolution of genomic regulatory mechanisms as well as issues related to invasive sea lamprey population control.
Studying convergent evolution to relate genotype to behavioral phenotype
Authors: Gallant Jason R. , O'Connell Lauren A.
Published: February 2020

Neuroscience has a long, rich history in embracing unusual animals for research. Over the past several decades, there has been a technology-driven bottleneck in the species used for neuroscience research. However, an oncoming wave of technologies applicable to many animals hold promise for enabling researchers to address challenging scientific questions that cannot be solved using traditional laboratory animals. Here, we discuss how leveraging the convergent evolution of physiological or behavioral phenotypes can empower research mapping genotype to phenotype interactions. We present two case studies using electric fish and poison frogs and discuss how comparative work can teach us about evolutionary constraint and flexibility at various levels of biological organization. We also offer advice on the potential and pitfalls of establishing novel model systems in neuroscience research. Finally, we end with a discussion on the use of charismatic animals in neuroscience research and their utility in public outreach. Overall, we argue that convergent evolution frameworks can help identify generalizable principles of neuroscience.
Symmetry and Systematic Enumeration of Twistane Derivatives. Global/Local Chirality and Global/Local RS-Stereogenicity Revisited by Fujita’s Stereoisogram Approach
Authors: Fujita Shinsaku
Published: February 2020

Fujita’s stereoisogram approach (S. Fujita, Mathematical Stereochemistry; De Gruyter: Berlin, 2015) has been applied to the discussion on the stereochemistry of twistane derivatives. In addition to chirality as the first kind of handedness, RS-stereogenicity is emphasized as the second kind of handedness, where an R-twistane skeleton and an S-twistane skeleton are recognized to be a pair of RS-diastereomers as a result of RS-stereogenicity. The contrast between global/local chirality and global/local RS-stereogenicity is clearly demonstrated by introducing the names, R-twistane and S-twistane, which are based on the globality of RS-stereogenicity. Among the five types of stereoisograms (type I to type V) as the full repertoire, there appear only type-I and type III stereoisograms during the discussions on twistane derivatives. Combinatorial enumeration of twistane derivatives are discussed on the basis of Fujita’s proligand method (S. Fujita, Combinatorial Enumeration of Graphs, Three-Dimensional Structures, and Chemical Compounds; University of Kragujevac, Faculty of Science: Kragujevac, 2013).
Characterization of Optical filters using Rutherford Backscattering Spectroscopy
Authors: Vlastou R. , Fokitis E. , Kalliabakos G. , Kokkoris M. , Kossionides E.
Published: February 2020

The composition and thickness of optical filters, especially designed for the Auger project, were measured using the RBS method. The aim of this project is to detect the extensive air showers, developed by the interaction of very energetic cosmic rays with the atmospheric air. This swarm of particles, moving at the speed of light through the atmosphere, ionizes the nitrogen atoms, which radiate UV photons in the range of 300-420 nm. This nitrogen fluorescence is subsequently detected by fluorescence detectors having optical filters placed in front of their photomultipliers with high transmittance in the region of 300-420 nm and low transmittance outside this region, in order to maximize the photon signal to background photon ratio. The required transmittance of the optical filters led to specific production techniques, such as the dielectric multi-layer thin film deposition on a substrate, using high-low index UV-transparent materials. In order to select the optimal deposition technique for the mass production of these filters, the RBS method has been used, among others, to provide information concerning the thickness of the individual layers and possible deviations from the desired stoichiometry.The optical filters presented in this work were made of 6 and 12 thin film layers of WOzjMgFi deposited on UV glass. The samples were bombarded with α-particles at EQ — 3MeV, provided by the 5.5 MV Tandem Accelerator at NCSR "Demokritos". The RBS spectra were analyzed utilizing the computer simulation code RUMP.
Oxygen Contamination of Multilayer TiNx — SiO2 — Si Structures found by Resonant RBS Analysis
Authors: Aslanoglou X. A. , Evangelou E. , Konofaos N. , Dimitriades Ch. , Kossionides E. , Kaliampakos G. , Kriembardis G.
Published: February 2020

Multi layer structures consisting of TiN — SiO2 — Si layers operating as MOS devices were constructed and tested for their electrical properties. RBS and resonance reaction analysis were performed for the characterisation of the structure of the devices. The results show a correlation between the structure found by RBS and the electrical performance of the devices.
Cross Section Measurements of the 89Y(p,γ)90Zr eaction in the energy range Ep=1.6-2.4 MeV.
Authors: Tsagkari P. , Skreti E. , Souliotis G. A. , Demetriou P. , Harissopulos S. , Paradellis T. , Hammer J. W. , Kunz R. , Angulo C. , Goriely S. , Rauscher T.
Published: February 2020

The total cross section of the nuclear reaction 89Y(p,7)90Zr has been measured over the proton energy range EP=1.6-2.4 MeV. The results are compared with the predictions of statistical model calculations
The Introduction of a new physical quantity and a corresponding scale for measuring the Radioecological Sensitivity of a certain area
Authors: Assimakopoulos P. A.
Published: February 2020

No abstract (available).
Nuclear mass systematics by complementing the Finite Range Droplet Model with neural networks
Authors: Athanassopoulos S. , Mavrommatis E. , Gernoth K. A. , Clark J. W.
Published: February 2020

A neural-network model is developed to reproduce the differences between experimental nuclear mass-excess values and the theoretical values given by the Finite Range Droplet Model. The results point to the existence of subtle regularities of nuclear structure not yet contained in the best microscopic/phenomenological models of atomic masses. Combining the FRDM and the neural-network model, we create a hybrid model with improved predictive performance on nuclear-mass systematics and related quantities.
Dispersive Correction to the p+16 0 Optical Montel Potential
Authors: Pantis G.
Published: February 2020

The optical model potential to p+16 0 scattering is derived by taking into account the polarization potential induced by the energy dispersion relation. The real part of the potential is derived by the RGM-method with the Volkov or Minnesota potential as a basis for the n-n force. It is shown that the polarization potential effects an adjustment of the parameters of the n-n force due to the constraints imposed by the energy dispersion relation.
Advanced Nuclear Physical Analytical Techniques
Authors: Papadopoulos N. N. , Ochsenkühn K. M.
Published: February 2020

Among the modern analytical methods, the nuclear analytical techniques, and especially neutron activation analysis, pay an important role in accurate and sensitive analysis. The capabilities of this technique and its application range have broadened lately with the development and employment of a combination of special more or less novel sub-techniques. These techniques are (a) bss-free counting gamma-ray spectrometry, (b) radioactive decay compensation and (c) repeated activation and measurement. The first technique permits short-time measurements at high count rates in multielement activation analysis with a wide nuclide concentration and half-life range, while by the other two techniques the counting statistics can be improved considerably especially in short-lived nuclide analysis. Thus, because of the high throughput rate, more customers can be served even far from the reactor site by mailing the samples and getting the analytical results back.
Inelastic cross sections in relativistic deuterons on Lead reactions
Authors: Zamani M. , Stoulos S. , Fragopoulou M. , Krivopustov M.
Published: February 2020

The inelastic cross section of deuterons hitting a Lead target has been determined by the beam attenuation technique. A spallation neutron source based on Lead target has been irradiated with 1.6 and 2.5 GeV deuterons. Solid state nuclear track detectors as well as the activation method were used in order to obtain the neutron and proton distribution along the surface of the source. The attenuation coefficient was estimated by fitting the experimental data taking into account the build up effect and the beam attenuation. Using the attenuation coefficient, the interaction length and then the inelastic cross section of deuterons on Lead reaction have been determined.
Monte Carlo simulation of a NaI detector in the aquatic environment
Authors: Bagatelas C. , Tsabaris C. , Kokkoris M. , Papadopoulos C. T. , Vlastou R.
Published: February 2020

NaI(Tl) crystals are used in many marine applications for continuous measurements with buoy operation and autonomous in situ measurements in seawater. Monte Carlo simulations were performed using the GEANT4 code for the investigation of the γ-ray absorption in water in different spherical geometries and for the efficiency of a NaI(Tl) detector of different radionuclides in the aquatic environment. In order to test the reliability of these simulations, experimental values of the NaI(Tl) detector efficiency were deduced using a special tank filled with water and reference single gamma ray sources (99mTc, 137Cs and 40K). The cascade reference source 111In was also diluted in tank for comparison with the reproduction spectra of its cascade lines as provided with the GEANT4 code. The results are in good agreement with the simulated ones within uncertainties.
МАРКЕТИНГОВЫЕ СТРАТЕГИИ В ПОТРЕБИТЕЛЬСКОЙ КООПЕРАЦИИ
Authors: Mishchenko Tatyana Leonidovna
Published: February 2020

Резюме. В современных условиях хозяйствования актуальность взаимодействия рыночного субъекта с внешней средой часто порождает проблемные ситуации, которые не всегда своевременно и эффективно решаются. И в данной связи на помощь приходит маркетинг и его стратегии. Формирование и использование маркетинговых стратегий способствует эффективному ведению бизнеса. В современной экономике именно маркетинг обеспечивает коммерческую выгоду рыночному субъекту. Правильно выбранная маркетинговая стратегия позволяет рыночным субъектам занимать прочные конкурентные позиции на рынке среди аналогичных предложений. В большинстве потребительских кооперативов отсутствует практика разработки маркетинговой стратегии, а потому многие из них не в состоянии выжить в жесткой конкурентной борьбе. Кроме того, выбор маркетинговых стратегий для разных субъектов рынка носит неоднозначный характер, что связано с миссией и целью каждой организационно-правовой формы, а потому требует глубоких исследований и анализа. В статье представлен алгоритм разработки маркетинговой стратегии для субъектов потребительской кооперации.Цель – определение процесса разработки маркетинговой стратегии в потребительском кооперативе.Метод или методология проведения работы: в статье использовались системный метод, общенаучные методы, эмпирического наблюдения, а также экономико-статистического анализа.Результаты: определены основные маркетинговые стратегии для роста конкурентного преимущества потребительской кооперации.Область применения результатов: полученные результаты целесообразно применять в потребительской кооперации и в экономических субъектах, осуществляющих сельскохозяйственную деятельность.
КОНСТРУКТИВНЫЕ ОСОБЕННОСТИ КОНСТАТИРУЮЩЕЙ ЧАСТИ СРАВНИТЕЛЬНЫХ КОНСТРУКЦИЙ (НА МАТЕРИАЛЕ ЛИТЕРАТУРНОГО ТВОРЧЕСТВА ПИСАТЕЛЕЙ-ВРАЧЕЙ)
Authors: Mirzoeva Valentina Mikhaylovna , Kuznetsova Anzhelika Alimovna , Vitlinskaya Lyudmila Grigorevna , Volovich Mayya Il’inichna
Published: February 2020

Состояние вопроса. Цель работы заключается в исследовании формального устройства и структурных особенностей констатирующей части однокомпаративных конструкций на материале литературного творчества писателей-врачей. Данные синтаксические единицы остаются до сих пор подробно не описанными, а рассматриваются, как правило, в связи с конструкциями сравнительно-уподобительного типа, что оставляет в тени существенные признаки описанных в данной статье синтаксических единиц.Методология проведения работы. Исследование опирается прежде всего на соединение лингвистического описания, наблюдения со статистическим анализом, что позволяет получить достоверную информацию о лексико-грамматических свойствах компаратива, его конструктивных и функциональных особенностях.Результаты. Доказано, что в констатирующей части однокомпаративных предложений сравнительное отношение всегда представлено полнее, чем в уподобительно-сравнительных моделях. По своему строению данная синтаксическая конструкция может функционировать в качестве самостоятельного предложения, не утрачивая сравнительного значения. Описана семантическая полифункциональность членов констатирующей части однокомпаративных предложений и обосновано их отличие от сравнительных синтаксических единиц с признаками включения. Наблюдение за функционированием однокомпаративных предложений в литературном творчестве писателей-врачей выявило функционально-семантические свойства субстантивированного местоимения это, конструкции с которым оказались более частотными в художественных и публицистических текстах писателей-врачей.Область применения результатов. Полученные результаты могут быть использованы не только для дальнейших исследований сравнительных конструкций русского языка, но и применены в качестве теоретического материала в курсе изучения синтаксиса художественного текста.
THE TEACHER'S ROLE IN INCREASING EMPLOYABILITY SKILLS OF THE DRAWING BUILDING ENGINEERING VOCATIONAL HIGH SCHOOL STUDENTS
Authors: Ridlo Alrosyid , Jumintono Jumintono , Achsan Bambang Noor
Published: February 2020

The process of preparing students on vocational education that includes the development of skills, competency, understanding, attitudes, work habits and the appreciation needed by workers to enable them to work successfully in their fields should be of interest to educators in vocational education institutions. Early observations of science and the emphasis on authentic assessment suggested that the 2013 curriculum for vocational high school is a renewal or innovation of the previous curriculum. The research is done through descriptive-qualitative re-search method. The population in this study is all teachers of vocational subject vocational competence of building drawing techniques in Bantul Regency. The technique of collecting data through an interview, observation, and documentation, data is analyzed to get a description about research object. The results showed that the selection of strategies and learning approaches should be studied closely, especially in relation to their relevance to learning missions, learning objectives, students' potential and characteristics, and environ-mental resources. Vocational teachers have at least four important roles in developing students' employability skills, namely the role of teachers as demonstrators, as mediators, as evaluators and as competent individuals. Implementation of the 2013 curriculum learning on the competence of building drawing techniques from several previous studies can be concluded to be implemented adequately.
The establishment of breastfeeding in the small-for-gestational-age baby
Authors: Dooks Emma , Owens David , Stacey Tomasina
Published: February 2020

Background

Term babies born smaller than expected for a given gestation are at greater risk of short- and long-term health conditions. Breastmilk is the optimum nutrition for all babies and offers specific protection from the risks that follow from being born small for gestational age.

Aim

To explore breastfeeding outcomes for babies born with a birthweight below the 10th centile.

Methods

Data were collected on all women giving birth in one maternity unit in the north of England over a year. Method of feeding at three time points was compared between small-for-gestational-age and appropriately grown babies.

Findings

Small-for-gestational-age babies were significantly less likely to be breastfeeding at discharge from hospital and community services compared to larger babies.

Conclusion

This study suggests that small-for-gestational-age babies are disadvantaged in establishing breastfeeding.
Extraction of the mandibular canine tooth in dogs
Authors: Oxford Matthew
Published: February 2020

The mandibular canine is a large tooth that often leaves a sizeable defect when extracted. An open extraction is therefore usually the most appropriate technique as this will allow a more controlled loosening of the tooth. This technique will also permit suitable closure of the extraction site.
Spoof surface plasmonic transmission line with high isolation and low propagation loss
Authors: Singh Surya Prakash , Tiwari Nilesh Kumar , Akhtar M. Jaleel
Published: February 2020

A novel compact spoof surface plasmonic (SSP) transmission line (TL) consisting of a stem-shaped periodic structure is proposed to achieve high field confinement in the higher frequency range (microwave to terahertz). The dispersion characteristic of the proposed stem-shaped SSP unit cell exhibits much lower asymptotic frequency and higher field confinement than the conventional coplanar waveguide (CPW) and the rectangular SSP unit cell structure without increasing the overall transverse dimension, i.e., improved signal propagation performance with reduced cross-sectional area. The numerical study of the multi-conductor line based on the proposed stem-shaped SSP unit cell shows that it has improved propagation and isolation features in comparison to the conventional TL structures. Here, the improved isolation is characterized in terms of the mutual coupling (MC) between the two adjacent lines designed using the stem-shaped SSP unit cell, which is not found to significantly increase with an increase in the coupling length unlikely in the conventional TLs. For the proposed SSP-based multi-conductor line, the MCs for 1.6, 2.25, and

4.15

λ

coupling lengths with fixed separation of

0.175

λ

are found to be 22,

−

19.8

, and

−

17.55

d
B

, respectively.
Blastocystis spp. subtype 10 infected beef cattle in Kamal and Socah, Bangkalan, Madura, Indonesia
Authors: Suwanti Lucia Tri , Susana Yuli , Hastutiek Poedji , Suprihati Endang , Lastuti Nunuk Dyah Retno
Published: February 2020

Background and Aim: Blastocystis spp. is a gastrointestinal parasite that can infect both humans and animals and has the potential to become a zoonotic parasite. This study analyzed a subtype (ST) of Blastocystis spp. that had infected beef cattle in Kamal and Socah, Bangkalan, Madura, Indonesia.

Materials and Methods: Fresh stool samples were collected from 108 beef cattle at Kamal and Socah, Bangkalan, Madura, Indonesia. Blastocystis spp. were detected both morphologically and genetically based on the 18S rRNA gene. The morphology of Blastocystis spp. from the stool samples and cultured samples were observed under a light microscope. Blastocystis spp. from 20 positive cultures were amplified through polymerase chain reaction, and the resultant sequences were identified by ST.

Results: One hundred and eight (100%) fecal samples from the fresh or cultured stools were positive morphologically for Blastocystis spp. Molecularly, all 20 of the samples selected for DNA analysis were found to be Blastocystis spp. ST 10.

Conclusion: Based on morphological and molecular detection, the prevalence of Blastocystis spp. infection in beef cattle within Kamal and Socah, Bangkalan, Madura, Indonesia, was high. About 100% were non-zoonotic parasites. This was the first report of Blastocystis spp. ST 10 found in infected beef cattle in Kamal and Socah, Bangkalan, Madura, Indonesia.
PRACTICE OF DIMENSIONAL IN THE IMPLEMENTATION OF THE METHODOLOGY OF GROUP INTERCHANGEABILITY
Authors: Galkin M. G. , Smagin A. S.
Published: February 2020

The subject of consideration in this article is the process of modeling the dimensional relationships at the Assembly stage using a single-circuit graph size scheme, which describes the mechanism of the individual parts of the conjugation in the implementation of the Assembly area group interchangeability methodology, reflecting the specific conditions of production. In the context of dimensional modeling, calculation procedures are considered on the basis of the developed mathematical model, which can be applied to both single-circuit and multi-circuit size schemes with dependent size chains. In particular, for the conditions of large-scale production, the algorithm for determining the scattering field of the assembled parts sizes by sorting them into size groups is considered. The design procedure is considered on the concrete example which describes a variant of completing of details with rather wide tolerances in the Assembly unit meeting the set criterion of working capacity.
WE ARE PROUD OF OUR PAST, WE MAKE THE GLOBAL FUTURE. THE MAIN STAGES OF DEVELOPMENT OF THE SCIENTIFIC RESEARCH INSTITUTE OF INTROSCOPY
Authors: Artemiev B. V. , Bobrov V. T. , Galkin D. I. , Efimov A. G. , Matveev V. I. , Monahov O. E. , Shubochkin A. E.
Published: February 2020

The short essay on the history, which begins in 1964, of the Research Scientific Institute of Introscopy (hereinafter referred to as the Institute) is presented. The main stages of the establishment and development of the Institute are considered. Over the years, dozens of world-famous scientists have worked in the Institute, more than 770 types of diagnostic devices and stationery equipment for all sectors of the national economy have been developed, more than 620 monographs and 3300 scientific articles have beenpublished, more than 5100 copyright certificates and patents for inventions have been registered. The Institute provided significant assistance in the establishment of Departments of Non-Destructive Testing at a number of universities in the Russia/USSR (MPEI, MIREA, etc.) for the training of high-ranking engineers in the field of non-destructive testing and introscopy. The devices and equipment invented and designed at the Institute were mass-produced at many enterprises in the Russia/USSR (Elektrotochpribor factory, Volna Production Association, Introscope JSC (Chisinau), Aktyubrentgen JSC factory (Aktobe), Tochpribor KhPO (Kharkov), Veda Production Association (Kiev), SKB Gazpriboravtomatika (Moscow), Kontrolpribor plant (Moscow),Sevkavrentgen plant (Maisky).
The Appropriate Extent of Surgery for Early-Stage Breast Cancer
Authors: Morrow Monica
Published: February 2020

Overview:

Attitudes regarding the appropriate extent of surgery for breast cancer and the effect of surgery on breast cancer–specific survival have varied over time. Failure to maintain local control is associated with decreased survival, but the extent of surgery necessary for local control has decreased as other treatment modalities, such as radiotherapy and systemic therapy, have become more widely used. Both endocrine therapy and chemotherapy considerably reduce rates of local recurrence in the breast, as well as the incidence of contralateral breast cancer, and as efficacy in reducing metastatic disease increases, so does the benefit in reducing local recurrence. The excellent rates of local control in the ACOSOG Z11 trial after elimination of axillary dissection in patients with positive sentinel nodes receiving whole-breast irradiation and systemic therapy are a model for reducing surgical morbidity in the era of multimodality therapy.
Postmastectomy Radiation and Partial Breast Irradiation
Authors: Zellars Richard C.
Published: February 2020

Overview:

Between 1997 and 1999, three modern postmastectomy radiation therapy (PMXRT) trials were published. These trials showed a significant benefit with respect to local control and survival in women who received adjuvant radiation after mastectomy. Despite two decades of follow-up, reanalyses, meta-analyses and vigorous and often acrimonious debate, questions about the benefit of PMXRT in women with one to three positive lymph nodes (LNs) remain unanswered for many. This persistent debate has limited the use of PMXRT. A treatment concept certain to be as vigorously debated as that of PMXRT is that of partial breast irradiation (PBI). However, unlike PMXRT, the acceptance of PBI, by community physicians, has been nothing short of meteoric and represents the first major shift in the local therapy paradigm in more than 10 years. Herein, information will be presented that will suggest we are nearing the end of one debate—PMXRT in patients with one to three positive LNs—and beginning another—appropriateness of PBI.
Limitations of Adaptive Clinical Trials
Authors: Buyse Marc
Published: February 2020

Overview:

Adaptive designs are aimed at introducing flexibility in clinical research by allowing important characteristics of a trial to be adapted during the course of the trial based on data coming from the trial itself. Adaptive designs can be used in all phases of clinical research, from phase I to phase III. They tend to be especially useful in early development, when the paucity of prior data makes their flexibility a key benefit. The need for adaptive designs lessened as new treatments progress to later phases of development, when emphasis shifts to confirmation of hypotheses using fully prespecified, well-controlled designs.
Adjuvant Treatments for Localized Advanced Gastric Cancer: Differences among Geographic Regions
Authors: Kang Yoon-Koo , Yoo Changhoon
Published: February 2020

Overview:

After much debate, adjuvant therapy has become the standard of care worldwide for resected localized gastric cancer. However, geographic differences exist in standard adjuvant treatments: postoperative chemoradiation in North America, perioperative chemotherapy in the United Kingdom, and postoperative chemotherapy in East Asia. Now that D2 gastrectomy has been recognized as the optimal surgery for localized gastric cancer in the West as well as in Asia, the standard adjuvant treatments used in the West may need to be reconsidered. One of the most important issues in adjuvant therapy for localized gastric cancer is how to improve the clinical outcomes of current standard treatments. Recent Cancer and Leukemia Group B (CALGB) and AMC studies suggest that simply intensifying chemotherapy by adding more agents or prolonging treatment duration is insufficient. However, new strategies like early initiation of chemotherapy and/or intraperitoneal chemotherapy may further improve the current standard adjuvant therapy. In the era of targeted therapy, the role of biologic agents for gastric cancer should also be explored in the adjuvant setting. With a deeper understanding of the molecular biology of gastric cancer, adjuvant therapy for patients with localized gastric cancer can be optimized and individualized.
State-of-the-Art Management for the Patient with Castration-Resistant Prostate Cancer in 2012
Authors: Sartor Oliver
Published: February 2020

Overview:

Much progress has been made in metastatic castration-resistant prostate cancer (CRPC), and multiple new U.S. Food and Drug Administration (FDA)-approved survival-prolonging drugs are now available. In 2004, docetaxel/prednisone was the first therapy shown to prolong survival. In 2010 and 2011, sipuleucel-T, cabazitaxel/prednisone, and abiraterone/prednisone were FDA approved. Two new agents, radium-223 and MDV-3100, have recently reported large phase III trials prolonging overall survival and will be submitted for regulatory approval in 2012. One can now begin to ask, is there an optimal sequence for therapies in metastatic CRPC? Despite the recent progress, there is much we do not know and virtually no information on this important question. We know that abiraterone/prednisone and cabazitaxel/prednisone are appropriate choices for a patient after receiving docetaxel, but we do not know what, if anything, represents the optimal sequence for abiraterone and cabazitaxel. In fact we do not understand how one therapy may affect the response to a subsequent therapy. We are also aware that the pre- and postdocetaxel spaces represent regulatory rather than biologic divisions. In addition, despite the proven role of docetaxel/prednisone, many patients with CRPC are not considered to be suitable for chemotherapy, and worldwide many never receive any form of chemotherapy. What is the optimal management for these patients? Taken together it is reasonable to assess patient preferences, prior therapies and response/tolerance to prior therapies, burden of disease, comorbidities, current symptoms, drug toxicities, out-of-pocket costs, etc., in clinical decision making. Given the many factors we do not know, it is hard to be dogmatic in approaching the therapeutic options for the patient with CRPC. We will likely soon move beyond the current sequencing paradigm and begin to assess new combinations in a systematic and rational fashion. Perhaps one day, in the not too distant future, we will develop molecular “stratification systems” to better guide therapeutic choices in CRPC.
The New National Cancer Institute National Clinical Trials Network
Authors: Grubbs Stephen S.
Published: February 2020

Overview:

The National Cancer Institute (NCI) Cooperative Group Program has been reviewed by three published studies in the last 7 years evaluating the efficiency and effectiveness of this national oncology clinical trials system. The recommendations for improvement from these reports have prompted NCI to transform the Cooperative Group Program into a new NCI National Clinical Trials Network (NCTN) to improve the efficiency of large clinical trials and increase the speed of cancer translational research. The new NCTN offers community-based clinical investigators new opportunities to advance cancer research in their community setting but also presents challenges in promoting community-based research.
Opportunities and Pitfalls of Targeted Therapeutic Combinations in Solid Tumors
Authors: Mateo Joaquin , Ong Michael , Yap Timothy A. , de Bono Johann S.
Published: February 2020

Overview:

Recent advances in cancer biology have led to the discovery and development of chemical compounds and drugs that target specific cellular receptors, mediators, or effectors that are central to oncogenic survival, growth, and invasion. However, the complexity of tumor biology makes it is unrealistic to expect an antitumor therapeutic to be successful based on the inhibition of a single target or even a lone signaling pathway. Therefore, the potential success of such “targeted therapies” is likely to require the development of multiagent combinations. Combination strategies have a greater likelihood of addressing issues with genetically complex tumors, potentially avoiding drug resistance mechanisms through the inhibition of escape signaling pathways and slowing the development of newly resistant tumor cells. Combination regimes also have the potential of enhancing target inhibition through synergistic antitumor effects and minimizing drug-related toxicities to patients. However, numerous challenges to developing these combinations exist. This review will focus on the opportunities and pitfalls of developing novel targeted drug combinations, with a particular focus on early-phase drug development, where the greatest challenges exist, analyzing key points for the design and development of clinical trials for combinations of targeted agents.
Initial Management of Low-Risk Pediatric Fever and Neutropenia: Efficacy and Safety, Costs, Quality-of-Life Considerations, and Preferences
Authors: Sung Lillian
Published: February 2020

Overview:

Initial management options for pediatric low-risk fever and neutropenia (FN) include outpatient compared with inpatient management and oral compared with intravenous therapy. Single-arm and randomized trials have been conducted in children. Meta-analyses provide support for the equivalence of outpatient and inpatient approaches. Outpatient oral management may be associated with a higher risk of readmission compared with outpatient intravenous management in children with FN, although other outcomes such as treatment failure and discontinuation of the regimen because of adverse effects were similar. Importantly, there have been no reported deaths among low-risk children treated as outpatients or with oral antibiotics. Costs, whether derived directly or through cost-effectiveness analysis, are consistently reduced when an outpatient approach is used. Quality of life (QoL) and preferences should be considered in order to evaluate different strategies, plan programs, and anticipate uptake of outpatient programs. Using parent-proxy report, child QoL is consistently higher with outpatient approaches, although research evaluating child self-report is limited. Preferences incorporate estimated QoL, but, in addition, factor in issues such as costs, fear, anxiety, and logistical issues. Only approximately 50% of parents prefer outpatient management. Future research should develop tools to facilitate outpatient care and to measure caregiver burden associated with this strategy. Additional work should also focus on eliciting child preferences for outpatient management. Finally, studies of effectiveness of an ambulatory approach in the real-world setting outside of clinical trials are important.
Curative-Intent Treatment for Colorectal Liver Metastases: A Medical Oncologist's Perspective
Authors: Saltz Leonard B.
Published: February 2020

Overview:

Resection or ablation of CRC liver metastases can be offered with curative intent in some, but not all patients in whom resection is technically possible. Chemotherapy can improve the potential for cure to some degree, either in the adjuvant or neoadjuvant setting, or, in relatively rare circumstances, by converting truly unresectable disease into resectable. Careful and realistic patient selection, with an individualized and realistic assessment of curative potential, is key to providing each patient with the means to make realistic treatment choices.
Measuring and Improving Value of Care in Oncology Practices: ASCO Programs from Quality Oncology Practice Initiative to the Rapid Learning System
Authors: Jacobson Joseph O. , Neuss Michael N. , Hauser Robert
Published: February 2020

Overview:

Rising cancer care costs are no longer sustainable. Medical oncologists must focus on providing the maximum value to their patients; improving short-term, intermediate and long-term outcomes; and managing overall costs. Accurate measurement of outcomes and overall cost is essential to informing providers and institutions and in the quest for continuous improvement in value. The ASCO Quality Oncology Practice Initiative (QOPI) is an excellent tool for sampling processes of care in medical oncology practices. To achieve the larger goal of improving the value of cancer care, ASCO is investing in the development of a Rapid Learning System, which will leverage emerging information technologies to more accurately measure outcomes (including those reported by the patient) and costs, resulting in highly efficient, effective, and safe cancer care.
Ethics of Biopsy in Children with Newly Diagnosed Diffuse Intrinsic Pontine Glioma
Authors: Foreman Nicholas K.
Published: February 2020

Overview:

To understand the ethical dilemmas that beset this issue of biopsy in children with newly diagnosed diffuse intrinsic pontine glioma, one must understand both the history behind it and the current dominant interpretation of ethics through the medium of the institutional review boards. It is also important to understand that this article represents the author's personal viewpoint. At a consensus meeting to discuss the issue of biopsies in Diffuse Intrinsic Pontine Glioma (DIPG) at the National institutes of Health held in the fall of 2011, there were a variety of opinions expressed.
Evaluation of Patients with Disseminated or Locoregionally Advanced Thyroid Cancer: A Primer for Medical Oncologists
Authors: Colevas A. Dimitrios , Shah Manisha H.
Published: February 2020

Overview:

Historically, patients with thyroid cancers are managed by endocrinologists, surgeons and radiation oncologists. Due to recent progress in this field with advances in treatment of thyroid cancer, medical oncologists are now commonly involved in care of patients with advanced thyroid cancers. In this manuscript, we describe general principles in management of patients with various types of thyroid cancers including differentiated, medullary and anaplastic thyroid cancers.
Are Oncologists Accountable Only to Patients or Also to Their Families? An International Perspective
Authors: Surbone Antonella , Baider Lea
Published: February 2020

Overview:

In most societies, health professionals traditionally carry responsibility only toward their patients. However, this is not the case in all cultures. In the contemporary practice of oncology in Western cultures, there is a shift toward assuming broader responsibility for patients with cancer' families during the illness course, the grieving stage, and in cancer prevention and genetic counseling. Traditional family, community, and religious values play a central role in determining people's perceptions and attitudes toward life and death as well as toward caregiving for a sick relative. The meaning of cancer illness within the family culture is thus influenced not only by each individual's values and beliefs but also by the family's makeup and dynamics, as well as their taboos and secrets. Global cancer care should therefore be directed at the family as a unit, while respecting patient autonomy and privacy. This reappraisal of our traditional understanding of physicians' duty as solely directed at the patient is reflected in the recent US trend toward a patient- and family-centered care approach. An additional challenge for oncology professionals is to integrate and tailor interventions toward the needs of both care recipients and caregivers and relate it to this dyad as the basic and enduring unit of care.
What Is the Best Strategy for Incorporating New Agents into the Current Treatment of Follicular Lymphoma?
Authors: Smith Sonali M.
Published: February 2020

Overview:

Although there is increasing knowledge about the pathobiology of follicular lymphoma (FL), the incorporation of new agents is challenged by the long clinical course and inherent heterogeneity of the disease. Furthermore, a longstanding concept in FL is that although most patients have an indolent initial phase of disease, this is typically followed by sequentially shorter remission durations and justifies the continued intense search for new rationally designed agents. Ideally, there would be personalized prognostic tools, preemptive target identification, and means to predict response in individual patients. Short of having these tools, one conceptual approach is to consider FL as a series of clinical disease states divided between treatment-naïve (low tumor burden and high tumor burden), relapsed (typically still chemoimmunotherapy-sensitive), and multiply relapsed (usually chemoimmunotherapy-resistant) disease. By applying what is known about the biology of FL along with the available agents, new treatment options can be better defined and tested within these clinical contexts. During the last few years, novel chemotherapeutics, biologic agents, monoclonal antibodies, antibody drug conjugates, and maintenance strategies are all either replacing or adding onto existing strategies. These new agents and approaches challenge the notion of inevitably shorter response durations, and offer hope of improved clinical outcomes compared with traditional sequential cytotoxic therapy.
Molecular Testing of Non–Small Cell Lung Carcinoma Biopsy and Cytology Specimens
Authors: Wistuba Ignacio I.
Published: February 2020

Overview:

During the past decade, substantial progress has been made in the characterization of molecular abnormalities in non–small cell carcinoma (NSCLC) tumors that are being used as molecular targets and predictive biomarkers for selection of targeted therapy. These recent advances in NSCLC targeted therapy require the analysis of a panel of molecular abnormalities in tumor specimens, including gene mutations (e.g., EGFR, KRAS, BRAF, DDR2), gene amplifications (e.g., MET, FGFR1), and fusions (e.g., EML4-ALK) by applying different methods to tumor tissue (biopsy) and cell (cytology) samples. However, the biopsy and cytology samples available for molecular testing in advanced metastatic NSCLC tumors are likely to be small specimens, including core needle biopsies and/or fine needle aspiration, which may limit the molecular and genomic analysis with currently available methods and technologies. In this process, the role of the pathologist is becoming increasingly important to adequately integrate both routine histopathologic assessment and molecular testing into the clinical pathology for proper tumor diagnosis and subsequent selection of the most appropriate therapy.
Glioblastoma: Biology, Genetics, and Behavior
Authors: Brat Daniel J.
Published: February 2020

Overview:

Glioblastoma (GBM) is a highly malignant, rapidly progressive astrocytoma that is distinguished pathologically from lower-grade tumors by necrosis and microvascular hyperplasia. The global pattern of growth changes dramatically with the development of GBM histology and is characterized by hypoxia-driven peripheral expansion from a growing necrotic core. Necrotic foci present centrally in GBM and are typically surrounded by “pseudopalisading” cells—a configuration that is relatively unique and long recognized as an ominous prognostic feature. Theses pseudopalisades are severely hypoxic, overexpress hypoxia inducible factor-1 (HIF-1), and secrete proangiogenic factors, such as vascular endothelial growth factor (VEGF) and interleukin 8 (IL-8). The microvascular hyperplasia that emerges in response promotes peripheral tumor expansion. Recent evidence suggests that pseudopalisades represent a wave of tumor cells actively migrating away from central hypoxia that arises following a vascular insult. Vaso-occlusive and prothrombotic mechanisms in GBM could readily explain the presence of pseudopalisading necrosis in tissue sections, the rapid peripheral expansion on neuroimaging, and the dramatic shift to an accelerated rate of clinical progression as a result of hypoxia-induced angiogenesis. The genetic alterations that coincide with progression to GBM include amplification of epidermal growth factor receptor (EGFR), deletion of CDKN2A, and mutation or deletion of PTEN. Other diagnostic and prognostic tests used in neuro-oncology include assessment of 1p/19q, MGMT promoter methylation, IDH1, and p53. More recently, the Cancer Genome Atlas data have indicated that there are four robust transcriptional classes of GBM, referred to as proneural, neural, classical, and mesenchymal. These classes have genetic associations and may pave the road for future development of targeted therapies.