bluuebunny/crossref_metadata_2025 huggingface dataset:
Noninvasive Application of Alternating Electric Fields in Glioblastoma: A Fourth Cancer Treatment Modality
Authors: Gutin Philip H. , Wong Eric T.
Published: February 2020

Overview:

Tumor treating fields (TTF) therapy is a novel antimitotic, electric field–based treatment for cancer. This nonchemical, nonablative treatment is unlike any of the established cancer treatment modalities, such as surgery, radiation, and chemotherapy. Recently, it has entered clinical use after a decade of intensive translational research. TTF therapy is delivered to patients by a portable, battery-operated, medical device using noninvasive transducer arrays placed on the skin surface surrounding the treated tumor. TTF therapy is now a U.S. Food and Drug Administration (FDA)–approved treatment for patients with recurrent glioblastoma (GBM) who have exhausted surgical and radiation treatments. This article will introduce the basic science behind TTF therapy, its mechanism of action, the preclinical findings that led to its clinical testing, and the clinical safety and efficacy data available to date, as well as offer future research directions on this novel treatment modality for cancer.
Stereotactic Body Radiation Therapy for Hepatocellular Carcinoma
Authors: Dawson Laura A. , Hashem Sameh , Bujold Alexis
Published: February 2020

Overview:

Stereotactic body radiotherapy (SBRT), in which highly conformal potent radiation doses are delivered in fewer fractions than traditional radiation therapy (RT), is an increasingly popular treatment for hepatocellular carcinoma (HCC). The great majority of HCCs smaller than 6 cm and with Child-Pugh A liver function are controlled with SBRT with limited toxicity. Long-term local control is reduced in larger tumors, and toxicity is increased in patients with Child-Pugh B or C liver function. SBRT is an effective treatment for tumor vascular thrombi and can lead to sustained vascular recanalization. The first site of recurrence following SBRT is most often within the liver, away from the high dose volume, providing rationale for combining SBRT with regional or systemic therapies. Randomized trials of SBRT are warranted.
Overdiagnosis and Overtreatment of Breast Cancer
Authors: Alvarado Michael , Ozanne Elissa , Esserman Laura
Published: February 2020

Overview:

Breast cancer is the most common cancer in women. Through greater awareness, mammographic screening, and aggressive biopsy of calcifications, the proportion of low-grade, early stage cancers and in situ lesions among all breast cancers has risen substantially. The introduction of molecular testing has increased the recognition of lower risk subtypes, and less aggressive treatments are more commonly recommended for these subtypes. Mammographically detected breast cancers are much more likely to have low-risk biology than symptomatic tumors found between screenings (interval cancers) or that present as clinical masses. Recognizing the lower risk associated with these lesions and the ability to confirm the risk with molecular tests should safely enable the use of less aggressive treatments. Importantly, ductal carcinoma in situ (DCIS) lesions, or what have been called stage I cancers, in and of themselves are not life-threatening. In situ lesions have been treated in a manner similar to that of invasive cancer, but there is little evidence to support that this practice has improved mortality. It is also being recognized that DCIS lesions are heterogeneous, and a substantial proportion of them may in fact be precursors of more indolent invasive cancers. Increasing evidence suggests that these lesions are being overtreated. The introduction of molecular tests should be able to help usher in a change in approach to these lesions. Reclassifying these lesions as part of the spectrum of high-risk lesions enables the use of a prevention approach. Learning from the experience with active surveillance in prostate cancer should empower the introduction of new approaches, with a focus on preventing invasive cancer, especially given that there are effective, United States Food and Drug Administration (FDA)-approved breast cancer preventive interventions.
Encountering Grief in Patient Care
Authors: Gilewski Teresa
Published: February 2020

Overview:

Grief is essentially unavoidable and is a normal reaction to loss. Grief may be experienced by patients and their loved ones as well as by physicians and members of the health care team in response to the consequences of illness or death. Grief is typified by certain indicators that may significantly effect one's emotional and physical well-being. Although these indicators tend to follow a general pattern, there is variability among individuals. Complicated grief may require psychiatric intervention. Caring for the seriously ill or dying patient may be particularly challenging from an emotional level and may increase the risk of burnout. Recognition of these emotions is a critical aspect of providing compassionate care on a sustainable level. Various strategies may be beneficial in coping with grief, and the exploration of grief may provide greater insight into the humanistic basis of medicine.
Is Biopsy Safe in Children with Newly Diagnosed Diffuse Intrinsic Pontine Glioma?
Authors: Puget Stephanie , Blauwblomme Thomas , Grill Jacques
Published: February 2020

Overview:

Diffuse intrinsic pontine gliomas (DIPGs), with a median survival of 9 months, represent the biggest therapeutic challenge in pediatric neuro-oncology. Despite many clinical trials, no major improvements in treatment have been made over the past 30 years. In most cases, biopsy is not needed for diagnosis because DIPG diagnosis is based on a typical clinical picture with radiologic evidence on magnetic resonance imaging. Therefore, little data on newly diagnosed DIPG have been published and are confounded by including autopsy (i.e., postradiation therapy) cases. In most cancers, advancing to cure has been linked to the discovery of relevant biomarkers, only found by access to tissue. Therefore, to further understand the biology of DIPG, fresh tissue samples must be obtained at diagnosis. However, most neurosurgical teams are reluctant to perform biopsy in pediatric patients, citing potential risks and lack of direct benefit. Yet, in reviewing 90 patients with and the published data on brainstem biopsy, these procedures have a diagnostic yield and morbidity and mortality rates similar to those reported for other brain locations. In addition, the quality and quantity of the material obtained confirm the diagnosis and inform an extended molecular screen, including biomarker study—information important to designing next-generation trials with targeted agents. Stereotactic biopsies can be considered a safe procedure in well-trained neurosurgical teams and could be incorporated in well-defined protocols for patients with DIPG.
Uterine Sarcomas: Histology and Its Implications on Therapy
Authors: Hensley Martee L.
Published: February 2020

Overview:

Uterine sarcomas are rare cancers, they comprise only 5% of all uterine malignancies. There are about 2,000 cases of uterine sarcoma diagnosed annually in the United States. Uterine sarcomas may be categorized as either favorable-risk, low-grade malignancies with a relatively good prognosis or as poor-risk, high-grade cancers that carry a high risk for tumor recurrence and disease progression. Expert histologic review is critical for appropriate diagnosis and management. Uterine sarcoma histologies considered to carry a more favorable prognosis include low-grade endometrial stromal sarcomas and adenosarcomas. The high-grade sarcomas include high-grade leiomyosarcomas, high-grade undifferentiated endometrial sarcomas, and adenosarcomas with sarcomatous overgrowth. The favorable histology, low-grade uterine sarcomas may be cured with surgical resection of uterus-limited disease. These tumors are often hormone-sensitive, and treatment with hormonal therapies may be efficacious for patients with advanced, unresectable disease. High-grade uterine leiomyosarcomas and undifferentiated endometrial sarcomas carry a high risk for recurrence, even after complete resection of uterus-limited disease. No adjuvant intervention has been shown to improve survival outcomes. Advanced, metastatic disease is generally treated with systemic cytotoxic therapies, which may result in objective response but is not curative. Selected patients with isolated metastatic disease and a long disease-free interval may benefit from metastatectomy.
Targeting CD30 in Hodgkin Lymphoma: Antibody-Drug Conjugates Make a Difference
Authors: Diefenbach Catherine S. M. , Leonard John P.
Published: February 2020

Overview:

CD30 expression is characteristic of the malignant Reed-Sternberg cell in Hodgkin lymphoma (HL) and several other lymphoid malignancies, such as anaplastic large-cell lymphoma (ALCL). Although unconjugated anti-CD30 antibodies have had minimal therapeutic activity in patients with HL as single agents, the CD30-directed antibody-drug conjugate (ADC) brentuximab vedotin has demonstrated activity that has resulted in its recent regulatory approval for the treatment of patients with relapsed HL and ALCL. Approximately 75% of patients with recurrent HL achieve objective responses, with the principal toxicity being peripheral neuropathy. Ongoing studies are evaluating treatment with this agent as part of first-line therapy, for patients with relapsed disease, and for patients with resistant disease and limited other options. Brentuximab vedotin demonstrates the therapeutic value of antibody-drug conjugation and serves as a model of how a novel, targeted approach can be employed to potentially further improve outcomes in settings where curative chemotherapeutic regimens are already available.
Soy Isoflavones and Breast Cancer
Authors: Wu Anna H. , Lee Eunjung , Vigen Cheryl
Published: February 2020

The soybean and its products have been a staple in the Asian diet for centuries. Although intake of soy remains low in most Western populations, the use of soy isoflavone supplements has become commonplace, and an increasing number of food products contain soy ingredients. This review will present an updated summary of the observational results on soy isoflavones and risk of breast cancer development and outcome in patients with breast cancer. Results from soy intervention studies that have specifically examined the effects of soy on breast cell proliferation in breast tissues will be discussed. We will conclude by highlighting gaps in our knowledge on soy and breast cancer and issues that need to be addressed in future studies.
Bridging Science and Clinical Practice: How to Use Molecular Markers When Caring for a Patient with Brain Cancer
Authors: Rosenfeld Myrna R.
Published: February 2020

Technical advances in genomic and proteomic profiling and bioinformatics have resulted in the identification of a large number of possible prognostic, predictive, and diagnostic molecular markers in glial tumors. Increasingly, clinical trials are incorporating tissue analyses to prospectively and retrospectively study the value of these and yet-to-be defined markers. Once validated, markers form the basis for increasingly stringent classification schemes and the development of personalized, targeted therapies. Descriptions of molecular marker findings, many not validated as clinically relevant, are filling pathology reports, and patients arrive to clinic with the latest journal article requesting marker assessment. Although some practitioners may choose to incorporate these findings into clinical decision making, empirical data supporting these decisions is limited to a few specific circumstances. This article reviews three markers—codeletion of 1p/19q, methylation of the O6-methylguanine-DNA methyltransferase (MGMT) promoter, and the presence of IDH1/2 mutation—for which there exists high or moderate levels of evidence of current clinical utility for guiding diagnostic, prognostic, and treatment decisions.
How to Use Molecular Markers When Caring for a Patient with Brain Cancer: 1P/19Q as a Predictive and Prognostic Marker in the Neuro-oncology Clinic
Authors: van den Bent M. J.
Published: February 2020

Although the central role of 1p/19q codeletion in oligodendroglioma was established almost two decades ago, apart from clear prognostic significance the implications for clinical care have been less clear. This has changed with the long-term follow-up analysis of the EORTC and RTOG trials on procarbazine, lomustine, and vincristine (PCV) chemotherapy in anaplastic oligodendroglioma. These have shown that 1p/19q loss in these tumors is predictive of overall survival benefit of the addition of PCV chemotherapy to radiotherapy.
Communication in View of Limited Resources: International Perspective
Authors: Zwitter Matjaz
Published: February 2020

Low socioeconomic status is associated with several risk factors for cancer, including a higher risk of presentation with advanced and often incurable disease. Treating patients in areas with limited resources requires not only the goal of saving or prolonging life, but also to alleviate suffering, including physical, emotional, and social components. Because complete coverage of all costs for modern cancer management by local institutions or governments is not possible in most (if not all) areas, most patients with cancer have to contribute toward the costs of their treatment. However, the demand for financially sustainable health care leads to restrictions in the spectrum of available treatments and often results in the creation of waiting lists for people requiring treatment. Communication between patients and providers in such circumstances is often challenging, especially when coupled with patients who have limited or no health care insurance and/or lack any ability to pay for services. Ultimately, any treatment plan should take into account the risks, benefits, personal goals, and beliefs of the individual with cancer. In areas of limited resources, the financial burden of treatment placed on the patient and his or her family must also be a part of the conversation and decisions regarding therapy. Within these parameters, sharing information and options becomes an indispensable condition for communication and the foundation of trust in the doctor–patient relationship.
Peritoneal Mesothelioma: The Site of Origin Matters
Authors: Kindler Hedy Lee
Published: February 2020

The etiology, gender distribution, pathology, natural history, and treatment options for mesothelioma (MM) differ substantially depending on the site of origin. Peritoneal mesothelioma (MPeM) is a rare disease, comprising only approximately 10% to 15% of the 2,500 cases of MM diagnosed in the United States each year. Patients with MPeM are younger than patients with pleural MM, and a higher proportion, mostly women, are long-term survivors. Most MPeM is caused by asbestos exposure. Germ-line mutations of BAP1 (BRCA associated protein 1) can predispose to MM, uveal melanoma, and potentially other cancers. MPeM can be challenging to diagnose, and cytology is rarely helpful. Review by an experienced pathologist using a panel of at least two positive and two negative immunohistochemical stains is essential. The three major pathologic subtypes are epithelial, sarcomatoid, and biphasic. Most cases are epithelial; the others have a dismal prognosis. Two indolent subtypes of borderline malignant potential—well-differentiated papillary mesothelioma and benign multicystic mesothelioma—are more common in the peritoneum and are treated surgically. In highly selected patients receiving treatment at experienced referral centers, an aggressive locoregional strategy that combines cytoreductive surgery to remove all gross disease and hyperthermic intraperitoneal chemotherapy to treat residual microscopic tumors yields a 3-year survival of 60% and a median survival approaching 5 years, far better than expected from historic controls. This approach also provides durable palliation of malignant ascites in nearly all patients. Pemetrexed is the only U.S. Food and Drug Administration (FDA)–approved systemic chemotherapy for pleural MM. Largely on the basis of data from pharmaceutical registry studies, the activity of pemetrexed-based chemotherapy appears to be similar in pleural MM and MPeM.
The Role of JAK1/2 Inhibitors in the Treatment of Chronic Myeloproliferative Neoplasms
Authors: Keohane Clodagh , Mesa Ruben , Harrison Claire
Published: February 2020

In 2005, the description of the JAK2V617F mutation for the first time provided a molecular key to enable more rapid diagnosis and target for novel therapeutics in the myeloproliferative neoplasms. In 2007, the first-in-class agent INC18424, ruxolitinib, JAKafi, or JAKAVI was first tested in patients with intermediate-risk 2 or high-risk myelofibrosis regardless of whether they possessed the JAK2V617F mutation. Patients treated with this agent had major reduction in splenomegaly as well as impressive reduction, and in some cases resolution, of symptoms. This study was followed by the two Controlled Myelofibrosis Study with Oral JAK Inhibitor Therapy (COMFORT) trials (the first-ever phase III trials in myelofibrosis), which confirmed results in these aspects were superior to either placebo or standard care, and updated results show a survival advantage with this therapy. This paper discusses these results and data from other JAK inhibitors while speculating on the future of these therapies. It also reflects on the fact that the true targets and agents' mode of action are uncertain. Unlike targeted therapy for chronic myeloid leukemia (CML), these agents do not deliver molecular remission, and it is not clear whether their predominant benefit is mediated via JAK2, JAK1, or both. Nonetheless, the advent of the JAK inhibitor is a welcome advance and has made a dramatic improvement to the therapeutic landscape of these conditions.
The Role of Kinase Inhibitors in the Treatment of Patients with Acute Myeloid Leukemia
Authors: Smith Catherine C. , Shah Neil P.
Published: February 2020

Multiple small molecule kinase inhibitors are currently undergoing development for the treatment of acute myeloid leukemia (AML). Recently, selective and potent FLT3 inhibitors such as AC220 (quizartinib) have proven clinically effective in patients with AML with FLT3 internal tandem duplication (ITD) mutations, but inhibitors of other pathologically activated kinases in AML such as c-KIT and JAK2 have achieved less clinical success. Other classes of inhibitors currently undergoing clinical development target mediators of downstream signaling pathways such as mTOR and MEK or cell cycle machinery such as aurora kinases, PLK1, or cyclin-dependent kinases. Other than FLT3 inhibitors, most inhibitors have achieved only rare bone marrow responses, and kinase inhibitor therapy in AML remains investigational. Continuing efforts to develop kinase inhibitors for the treatment of AML will require careful selection of patients for clinical trials, translational studies to characterize responders, and investigation of combination therapy that may be capable of improving response rates and duration.
Lung Cancer in Developing Countries: Access to Molecular Testing
Authors: Ferreira Carlos Gil
Published: February 2020

The era of personalized medicine has come to the treatment of non-small cell lung cancer, and now molecular testing is part of the daily clinical decision, at least for patients with adenocarcinoma. Nevertheless, access to those tests is still very limited in the developing world. Developing countries must adapt their health care system to address that and grant access of patients with lung cancer to those tests. Because of several differences among developing countries, strategies will certainly vary from country to country. Issues such as generation of local molecular epidemiology data, quality control, education of health care professionals, development of innovative local and regional strategies, interconnection between regulatory pathways for the approval of drugs, and companion molecular tests are required.
Do We Need to Irradiate All Small Invasive Breast Cancers and DCIS?
Authors: White Julia
Published: February 2020

Breast radiotherapy after lumpectomy is considered standard for nearly all patients with invasive breast cancer and is recommended for many patients after lumpectomy for ductal carcinoma in situ (DCIS). However, there is recognition that lumpectomy alone can achieve optimal cancer control for some patients with invasive breast cancer and DCIS. Patients with breast cancers with lower risk of recurrence are less likely to derive benefit from breast radiotherapy. This review will focus on defining populations of patients with invasive breast cancer and DCIS with a low risk of recurrence post-lumpectomy and the evidence supporting omission of breast radiotherapy post-lumpectomy.
ASCO's International Programs and How You Can Become Involved
Authors: El Saghir Nagi S. , Assi Hussein A. , Pyle Doug
Published: February 2020

The American Society of Clinical Oncology (ASCO) is dedicated to serving its members and to reducing disparities in the treatment of patients with cancer and their outcome. ASCO has a portfolio of international programs called ASCO International that aims to improve clinical practice by sharing oncology knowledge through a network of ASCO members and partners. In order to achieve its goals, ASCO has an International Affairs Committee that oversees many programs that involve a global exchange of knowledge through courses and workshops, mentoring, initiatives promoting research, and specialty training standards. All of these programs depend on ASCO member volunteers in one capacity or another.
Histology and Fusion Status in Rhabdomyosarcoma
Authors: Rudzinski Erin R.
Published: February 2020

The International Classification of Rhabdomyosarcoma (ICR) has provided diagnostic criteria for rhabdomyosarcoma (RMS) and formed the basis of histologic risk stratification since its publication in 1995. However, the recognition of new variants of embryonal rhabdomyosarcoma (ERMS), shifts in the diagnostic criteria of alveolar rhabdomyosarcoma (ARMS), the increasing use of myogenin immunohistochemistry and recognition of the distinct biologic properties associated with fusion status all raised questions about the continued use of this classification system in the diagnosis and treatment of patients with RMS. Recent Children's Oncology Group Soft Tissue Sarcoma Committee analysis of histology and fusion status in the intermediate risk RMS study D9803 refined the histologic criteria of RMS. We validated the new diagnostic criteria against fusion status, allowing prospective examination of the prognostic value of histology compared with fusion status for risk-stratification of patients with RMS. This article summarizes the evolution of and current practices in the histologic and molecular classification of rhabdomyosarcoma.
Surgical Management and Minimally Invasive Approaches for the Treatment of Metastatic Sarcoma
Authors: Hohenberger Peter , Kasper Bernd , Ahrar Kamran
Published: February 2020

Soft tissue sarcomas describe a very heterogeneous group of soft tissue tumors mainly arising in the lower extremities. If diagnosed at an early stage and a complete resection of the primary tumor is achieved, the patients' prognosis is excellent. However, metastatic tumor spread is common with only limited treatment possibilities. Despite an improved insight into tumor biology of sarcomas, no notable improvement has been gained in the last 20 years regarding prognosis of patients. Metastatic lung disease has long been the preserve of systemic treatments, local treatments being considered in a purely palliative intention. Several studies have objectified benefit to the local treatment of metastases, especially in an oligometastatic state. The development of techniques for stereotactic radiotherapy on the one hand and the refusal or contraindication for surgery on the other hand inaugurated studies in this direction. Besides surgery and radiotherapy, other local modalities have been investigated in the last few years such as thermal therapy (radiofrequency and laser ablation) or combined modalities (isolated limb perfusion and deep-wave hyperthermia plus chemotherapy) to help patients with metastatic soft tissue sarcoma. Minimally invasive, image-guided therapies such as thermal ablation should be considered particularly in patients who are not suitable surgical candidates or may have exhausted all other viable surgical options. Some of these techniques will be reviewed in this article, and their value for the patients will be evaluated in the light of indication from tumor biology and technical feasibility. These highly selected and specific procedures should only be performed after decision making in an interdisciplinary sarcoma-board.
Selecting the Best Drugs for Phase I Clinical Development and Beyond
Authors: Loong Herbert H. , Siu Lillian L.
Published: February 2020

Attrition rates of drugs from human entry to regulatory approval are far higher in anticancer drugs than those for nononcology indications. In the era of molecular therapeutics that results from a deeper understanding in cancer biology and advancing technologies, the number of compounds available for clinical testing is likely to continue to increase. Although the main objectives of phase I trials are to characterize toxicities of new agents and to determine the recommended dose for phase II development, most phase I studies are now designed to provide some early signal on preliminary efficacy as secondary objectives. The “go-no-go” decision to further develop a drug, or not, is now often pushed forward to the phase I setting. Thus, there is a need for investigators to be able to critically review the preclinical data available in order to determine which drugs should advance on the developmental path. This review highlights the intrinsic characteristics of a drug and the relevant data to be collected during its preclinical assessment, which may maximize the chances of success in clinical testing and eventual regulatory approval.
Obesity and Its Impact on Breast Cancer: Tumor Incidence, Recurrence, Survival, and Possible Interventions
Authors: Ligibel Jennifer A. , Strickler Howard D.
Published: February 2020

A positive association between obesity and the risk of incident postmenopausal breast cancer has been consistently observed in epidemiologic studies. Although most studies of premenopausal women have not found a similar relationship between breast cancer and obesity, the prognosis for both pre- and postmenopausal breast cancer is substantially worse among obese than normal-weight individuals. Increasing evidence suggests that these associations may be mechanistically related to sex hormones, insulin, and certain adipokines. Insulin, for example, has important mitogenic/antiapoptotic activity in addition to its metabolic effects, and many breast tumors express high levels of the insulin receptor (IR)-A isoform. Further, the use of metformin, a diabetes medication that reduces insulin levels, has been epidemiologically associated with reduced breast cancer risk among patients with diabetes, and a recent observational study found a higher rate of pathologic complete responses among patients with diabetes and breast cancer who were using metformin. Formal clinical trials of metformin as adjuvant breast cancer therapy have been initiated and are ongoing. Similarly, the effect of lifestyle changes on breast cancer outcomes is actively being investigated. Several lifestyle intervention studies have demonstrated that weight loss, increased physical activity, and dietary changes are feasible in breast cancer populations, and that individuals who make lifestyle changes after breast cancer diagnosis experience several physical and psychologic benefits. In this article, the authors review the evidence linking obesity with breast cancer risk and outcomes and provide an overview of lifestyle intervention studies in patients with breast cancer.
Picking the Optimal Target for Antibody-Drug Conjugates
Authors: Mathur Rohan , Weiner George J.
Published: February 2020

Antibody-drug conjugates (ADCs) combine the cytotoxic potential of chemotherapeutic drugs with the specificity of monoclonal antibodies (mAbs). After many years of unfulfilled promise, the field of ADCs is experiencing resurgence as more is learned about each of the components of an ADC and how these components need to be combined to produce a successful therapeutic agent. Choosing an appropriate target for ADCs is a critical parameter that effects the efficacy, therapeutic window, and toxicity profile of ADCs. This review will focus on the concepts underlying the choice of the target, review specific current ADCs and their targets, and look to the future of ADCs.
Acquired Resistance to Targeted Therapies in Advanced Non-Small Cell Lung Cancer: New Strategies and New Agents
Authors: West Howard , Oxnard Geoffrey R. , Doebele Robert C.
Published: February 2020

Although the transition to molecularly defined patient subgroups in advanced non-small cell lung cancer (NSCLC) often leads to dramatic and prolonged responses to an inhibitor of an identified oncogenic mutation, acquired resistance eventually ensues. The optimal approach to management in that setting remains the subject of ongoing research, although it is possible to identify several points that distinguish it from traditional tenets based on conventional chemotherapy. Such patients are not equivalent to those who have progressed on first-line chemotherapy, and consideration of initiation of chemotherapy-based regimens as if the patient were being treated first line in the absence of an oncogenic mutation is a reasonable consideration. Acquired resistance is often partial; therefore, continued treatment with the same targeted therapy or another agent against the same target is a strategy favored by many experts, in part to minimize the risk of “rebound progression” that may occur when the targeted therapy is withdrawn. Progression within the central nervous system (CNS) may occur because of poor penetration of the systemic targeted therapy into the CNS, rather than true cellular resistance to the therapy itself; accordingly, local therapy for “brain only” progression with sustained targeted therapy for extracranial disease can be associated with prolonged disease control. Finally, patients with acquired resistance to a targeted therapy are ideal candidates for clinical trials when available, particularly when repeat biopsies of progressing lesions can help elucidate mechanisms of resistance and thereby lead to histologically and molecularly informed treatment decisions.
Biomarkers and Correlative Endpoints for Immunotherapy Trials: What Can We Learn in Lung Cancer from Other Tumor Types?
Authors: Morse Michael A. , Osada Takuya , Hobeika Amy , Patel Sandip , Lyerly H. Kim
Published: February 2020

Immunotherapies for lung cancer are reaching phase III clinical trial, but the ultimate success likely will depend on developing biomarkers to guide development and choosing patient populations most likely to benefit. Because the immune response to cancer involves multiple cell types and cytokines, some spatially and temporally separated, it is likely that multiple biomarkers will be required to fully characterize efficacy of the vaccine and predict eventual benefit. Peripheral blood markers of response, such as the ELISPOT assay and cytokine flow cytometry analyses of peripheral blood mononuclear cells following immunotherapy, remain the standard approach, but it is increasingly important to obtain tissue to study the immune response at the site of the tumor. Earlier clinical endpoints such as response rate and progression-free survival do not correlate with overall survival demonstrated for some immunotherapies, suggesting the need to develop other intermediary clinical endpoints. Insofar as all these biomarkers and surrogate endpoints are relevant in multiple malignancies, it may be possible to extrapolate findings to immunotherapy of lung cancer.
Stories We Tell One Another: Narrative Reflection and the Art of Oncology
Authors: Steensma David P.
Published: February 2020

Storytelling is a deeply human act—ancient, universal, and familiar. But in this data-driven “Information Age,” is there still room for narrative? As oncologists, we often feel overclocked, increasingly forced to microtask and live by the business world's mantra of “faster, cheaper, better,” while our carefully honed humanistic clinical skills are coldly commoditized into Relative Value Units, our aptitude measured with tools that emphasize form over substance. In such an environment, can we still afford the inefficiency of anecdotes? Some might argue that we no longer need patient and physician narratives to inform care; instead, accurate molecular subtyping of tumors, good pharmaceutical agents, and rigorous clinical trial results are enough. Yet stories and reflections about being a doctor or being a patient remain important and instructive even in this era of molecular cancer medicine, even in the face of our increasing reliance on high-tech diagnostics and narrowly targeted smart therapeutics. Amid the pressures of rapidly changing practice patterns and the daily emotional challenges of working with seriously ill and dying patients, the acts of reflection and storytelling can also help keep us sane. Here I discuss the persistent importance of narrative in the context of the “Art of Oncology” forum of the Journal of Clinical Oncology.
Thrombosis and Cancer: Emerging Data for the Practicing Oncologist
Authors: Lyman Gary H. , Khorana Alok A. , Falanga Anna
Published: February 2020

The American Society of Clinical Oncology (ASCO) recently updated clinical practice guidelines on the treatment and prevention of venous thromboembolism (VTE) in patients with cancer. Although several new studies have been reported, many questions remain about the close relationship between VTE and malignant disease. The risk of VTE among patients with cancer continues to increase and is clearly linked to patient-, disease- and treatment-specific factors. In general, VTE among patients with cancer is treated in a similar fashion to that in other patient populations. However, the greater risk of VTE in patients with cancer, the multitude of risk factors, and the greater risk of VTE recurrence and mortality among patients with cancer pose important challenges for surgeons, oncologists, and other providers.
Endocrine Resistance: What Do We Know?
Authors: Miller Todd W.
Published: February 2020

Adjuvant therapy with antiestrogens targeting estrogen receptor α (ER) signaling prevents disease recurrence in many patients with early-stage ER+ breast cancer. However, a significant number of cases exhibit de novo or acquired endocrine resistance. While other clinical subtypes of breast cancer (HER2+, triple-negative) have disproportionately higher rates of mortality, ER+ breast cancer is responsible for at least as many deaths because it is the most common subtype. Therefore, identifying mechanisms that drive endocrine resistance is a high clinical priority. A large body of experimental evidence indicates that oncogenic signaling pathways underlie endocrine resistance, including growth factor receptor tyrosine kinases (HER2, epidermal growth factor receptor [EGFR], fibroblast growth factor receptor 1/2 [FGFR], insulin-like growth factor-1 receptor [IGF-1R]/ insulin receptor [InsR]), PI3K/AKT/ mTOR, MAPK/ERK, Src, CDK4/CDK6, and ER itself. Combined targeting of ER and such pathways may be the most effective means to combat antiestrogen resistance, and clinical trials testing such strategies show promising results. Herein, we discuss pathways associated with endocrine resistance, biomarkers that may be useful to predict response to targeted agents, and avenues for further exploration to identify strategies for the treatment of patients with endocrine-resistant disease.
Defining the Pillars of Trade Union Freedoms: the Polish Example
Authors: Gołaś Jakub
Published: February 2020

The aim of the article is to present and characterise the essence of four fundamental pil-lars (the freedom of association, the self-governance, the independence and the equality) of trade union freedoms in the Polish legal system. The author presents such aspects as the classification of trade union freedoms or the characterisation of chosen specific union pillars. The article is based on the review of the relevant national legislation (in-cluding the Polish Constitution, international agreements and the Act on Trade of 23th May 1991), doctrine and judicature.
Art. 647(1) CC – Important Protection of Subcontractors in the Construction Works Contract or the Legislator’s Error?
Authors: Mańke Przemysław
Published: February 2020

The purpose of this article is to present and assess the impact of the regulation Art. 6471CC on subcontractors in the construction market and outline doubts in respect of the contents of the regulations. The first part of the article shows reasons why the regulation concerned was enforced – unfair practices in the construction services market which had a detrimental impact on subcontractors. Furthermore, selected doubts are presented, those associated with the contents of the regulation in question and raised by the doctrine and jurisdiction, for example, the legal nature of the investor’s consent or the investor’s joint and several responsibility. It is important to indicate the contrast between the unprob-lematic legislative process and doubts disclosed during its application. The author of this article also depicts two proposed modifications, which appeared in doctrine. The impor-tant issue for this article is also a description of the amended text of this regulation and comparison to the previous one. In conclusion, it should be emphasized that art. 6471 CC is really important for the polish legal system but both the previous content of this regula-tion and the present one aren’t sufficient to guarantee the lack of doubts in interpretation
The Legal Concepts of Online Commerce
Authors: Kotkowski Jakub
Published: February 2020

The aim of the study is to present the selected legal concepts of online commerce. Elec-tronic commerce is still a relatively young, and thus only emerging, field of legal and economic marketing. Nevertheless, it exerts a serious and enormous influence on the entirety of social, economic and legal relations on a global scale. Bearing in mind this as-sumption the author pays attention to the selected topics of online commerce that leads to a conclusion that the existing legal and jurisprudential traditions are able to adapt to new, specific challenges posed by the development of technological civilization.
Exploring research data management planning challenges in practice
Authors: Lefebvre Armel , Bakhtiari Baharak , Spruit Marco
Published: February 2020

Research data management planning (RDMP) is the process through which researchers first get acquainted with research data management (RDM) matters. In recent years, public funding agencies have implemented governmental policies for removing barriers to access to scientific information. Researchers applying for funding at public funding agencies need to define a strategy for guaranteeing that the acquired funds also yield high-quality and reusable research data. To achieve that, funding bodies ask researchers to elaborate on data management needs in documents called data management plans (DMP). In this study, we explore several organizational and technological challenges occurring during the planning phase of research data management, more precisely during the grant submission process. By doing so, we deepen our understanding of a crucial process within research data management and broaden our understanding of the current stakeholders, practices, and challenges in RDMP.
Photonic Crystal-Based All-Optical Half Adder with High Contrast Ratio
Authors: Pathak Priyanka , Zafar Rukhsar , Kanungo Vinay , Vyas Sandeep
Published: February 2020

Photonic crystal waveguides provide a way to manipulate the performance of an optical signal in an ultra-small volume and are quite viable in designing chip-based components that will work all-optically. Here, in this article an all-optical half adder is proposed. It is based on a square lattice photonic crystal waveguide in which silicon rods are arranged periodically. The photonic crystal offers a wide photonic band-gap in the desired region of telecommunication wavelength (i. e. near λ = 1550 nm. The performance of half Adder is measured using the contrast ratio and response time. The contrast ratio for sum and carry is 5.2 dB and 16.7 dB, respectively. The proposed half adder is miniaturized in size and having a footprint of 49 µm2 only. The total response time of the proposed adder is 1.4 picoseconds only. So, the device offers a high bit rate of 0.714 Tb/sec. The proposed half adder is an optimum choice for its application in on-chip optical integrated circuits.
Describing the Pearson 𝑅 distribution of aggregate data
Authors: Torres David J.
Published: February 2020

Ecological studies and epidemiology need to use group averaged data to make inferences about individual patterns.
However, using correlations based on averages to estimate correlations of individual scores is subject to an “ecological fallacy”.
The purpose of this article is to create distributions of Pearson R correlation values computed from grouped averaged or aggregate data using Monte Carlo simulations and random sampling.
We show that, as the group size increases, the distributions can be approximated by a generalized hypergeometric distribution.
The expectation of the constructed distribution slightly underestimates the individual Pearson R value, but the difference becomes smaller as the number of groups increases.
The approximate normal distribution resulting from Fisher’s transformation can be used to build confidence intervals to approximate the Pearson R value based on individual scores from the Pearson R value based on the aggregated scores.
Broadband wavelength demultiplexer using Fano-resonant metasurface
Authors: Mun Sang-Eun , Choi Chulsoo , Hong Jongwoo , Lee Byoungho
Published: February 2020

Fano resonance, one of the interesting resonance phenomena in physics, provides versatile applications when combined with a concept of metasurface in nanophotonics. Fano-resonant metasurface (FRM) is attracting a lot of attention due to its superior narrowband characteristics as well as design freedom of metasurfaces in nanoscale. However, only the control of apparent asymmetric spectral nature of Fano resonance has been focused at applications such as optical sensors, as the amplitude feature of Fano resonances is relatively easy to control and can be measured by an experimental setup. Here, a method for modulating the phase information of FRM by both simulation and experiment is demonstrated. As a proof of concept, an optical demultiplexer, which can divide four target wavelengths in different directions of free space, is verified experimentally. It covers a broadband wavelength range of more than 350 nm in the near-infrared region with extremely small full-width at half-maximum. This approach can offer the complete control of FRM for a wide range of applications, including optical multiplexers, routers, filters, and switches, beyond conventional applications that have been limited to the amplitude control of Fano resonance.
Generalized second-order slip for unsteady convective flow of a nanofluid: a utilization of Buongiorno’s two-component nonhomogeneous equilibrium model
Authors: Mousavi Seyed Mahdi , Dinarvand Saeed , Yazdi Mohammad Eftekhari
Published: February 2020

The unsteady convective boundary layer flow of a nanofluid along a permeable shrinking/stretching plate under suction and second-order slip effects has been developed. Buongiorno’s two-component nonhomogeneous equilibrium model is implemented to take the effects of Brownian motion and thermophoresis into consideration. It can be emphasized that, our two-phase nanofluid model along with slip concentration at the wall shows better physical aspects relative to taking the constant volume concentration at the wall. The similarity transformation method (STM), allows us to reducing nonlinear governing PDEs to nonlinear dimensionless ODEs, before being solved numerically by employing the Keller-box method (KBM). The graphical results portray the effects of model parameters on boundary layer behavior. Moreover, results validation has been demonstrated as the skin friction and the reduced Nusselt number. We understand shrinking plate case is a key factor affecting non-uniqueness of the solutions and the range of the shrinking parameter for which the solution exists, increases with the first order slip parameter, the absolute value of the second order slip parameter as well as the transpiration rate parameter. Besides, the second-order slip at the interface decreases the rate of heat transfer in a nanofluid. Finally, the analysis for no-slip and first-order slip boundary conditions can also be retrieved as special cases of the present model.
On the comparative analysis of French (ne) … que exceptives
Authors: Authier J.-Marc
Published: February 2020

This article takes a close look at recent proposals that French(ne) … queexceptives are hidden comparatives involving two silent elements: a covert n-word and a phonologically unrealizedautre‘other’ introducing a partially elided comparative clausal standard headed byque‘than’. I show that assuming the constant presence of an n-word in the exceptive construction allows us to provideinter aliaa scopal treatment of the fact that(ne) … queexceptives in modal contexts are systematically ambiguous between an exclusive reading and a minimal sufficiency reading. As regards the comparative analysis of exceptives, I demonstrate that while the locality of association problem raised by (Homer. 2015.Ne … queand its challenges. In Ulrike Steindl, Thomas Borer, Huilin Fang, Alfredo García Pardo, Peter Guekguezian, Brian Hsu, Charlie O’Hara & Iris Chuoying Ouyang (eds.),Proceedings of the 32nd West Coast Conference on Formal Linguistics, 111–120. Somerville, MA: Cascadilla Proceedings Project.) can be resolved by assuming that in French, the standard of comparatives can be clausal or just nominal, the fact that(ne) … quedisplays a lexically-encoded, conventionalized meaning dependency on focus that is absent from its alleged comparative maximal phonological realization casts some serious doubt on the viability of the comparative analysis of French exceptives. Finally, I examine a number of contexts in which the n-word component of(ne) … quemust be overt and argue that this constraint follows from the Intonational Phrase Edge Generalization.
Differential Impacts of Religious Cultural Competence on Students' Perceived Conflict with Evolution at an Evangelical University
Authors: Barnes M. Elizabeth , Werner Ruth , Brownell Sara E.
Published: February 2020

Evolution remains a controversial issue in the United States, particularly for evangelical Christians, who as a group have been a key player in anti-evolution education legislation. Religious cultural competence can be effective in decreasing undergraduate biology students' perceived conflict between religion and evolution. However, the impact on student populations who are particularly resistant to evolution is unknown. We explored the efficacy of culturally competent evolution education practices adapted for biology students in a genetics course at an evangelical Christian university. This included the presence of an instructor as a religious scientist role model who accepts evolution, and the use of the book The Language of God. We explored how this curriculum affected students' conceptions of religion and evolution using pre- and post-surveys. We found a differential impact of the curriculum: 31% of the students who indicated that there was a conflict between their religious beliefs and evolution changed their conceptions to be more in line with scientific evidence, but the remaining 69% did not. We describe reasons why, including students' perceptions of The Language of God. This research indicates the challenges of implementing culturally competent evolution education for evangelical students, given their strong commitment to biblical literalism and their lower likelihood of being convinced by scientific evidence for evolution.