bluuebunny/crossref_metadata_2025 huggingface dataset:
Multidisciplinary Approach to Brain Metastasis from Melanoma; Local Therapies for Central Nervous System Metastases
Authors: Ramakrishna Naren , Margolin Kim A.
Published: February 2020

The overall treatment paradigm for melanoma brain metastases continues to evolve and reflects the relative radioresistance of this histology, as well as the effect of emerging systemic therapies with central nervous system (CNS) activity. Local therapies, including surgery, whole brain radiotherapy (WBRT), and stereotactic radiosurgery (SRS), play an important role in the multidisciplinary management of melanoma brain metastases. Treatment selection for local therapies must consider many factors: (1) size, number, and location of lesions, (2) presence or absence of neurological symptoms, (3) extracranial disease status, expected survival, age, and performance status, (4) prior treatment history, (5) expected treatment toxicities, and (6) predicted response to systemic therapies. The choice of treatment modalities for brain metastases is among the most controversial areas in oncology. There has been a trend toward reduced use of WBRT and increased reliance on SRS and surgery for melanoma brain metastases. Although no prospective randomized data exist comparing local therapies for melanoma brain metastases, several large retrospective studies suggest aggressive local treatment with modalities including surgery and SRS are associated with favorable outcomes in select patients. 1 , 2 Multidisciplinary collaboration is required to facilitate a treatment plan that balances reduction in risk of neurological death and symptomatic progression against the risk of treatment-related toxicity.
Global Initiatives to Enhance Cancer Care in Areas of Limited Resources: What ASCO Members Are Doing and How You Can Become Involved
Authors: Lichtman Stuart M.
Published: February 2020

Cancer is the leading cause of death worldwide. In 2008, 7.6 million deaths were attributable to cancer, representing 13% of all deaths. It is estimated that approximately 30% of cancer deaths are attributable to the five leading behavioral and dietary risks. These include high body mass index, low fruit and vegetable intake, lack of physical activity, and tobacco and alcohol use. A number of viral infections, such as hepatitis B and C and HPV, are responsible for approximately 20% of cancer deaths. Approximately 70% of cancer deaths occurred in low- and middle-income countries. Because of the increased numbers of elderly individuals and improved control of comorbidity, deaths from cancer worldwide are projected to continue rising, with an estimated 13.1 million deaths in 2030. To meet this need, the American Society of Clinical Oncology (ASCO) has evolved into a truly international organization. Over one-third of ASCO members practice in over 100 countries, representing the world's largest collection of expertise and insight into the treatment of cancer. More than one-half of ASCO's Annual Meeting attendees come from outside the United States. The Journal of Clinical Oncology is read by more than 24,000 subscribers worldwide and is available in a number of different languages. To fulfill its mission, ASCO has a number of international programs for sharing knowledge and providing the tools to assist clinicians worldwide in treating their patients. These programs include mentoring and knowledge exchange, education initiatives, and scientific and educational meetings. This provides ample opportunity for involvement to enhance cancer care worldwide.
CancerLinQ and the Future of Cancer Care
Authors: Sledge George W. , Miller Robert S. , Hauser Robert
Published: February 2020

Patients, health care providers, and payers all have a similar interest in a health care system that is both efficient and intelligent. The attributes of such a system are widely recognized: we want a system that provides widespread access to consistently high-quality, science-based medical care; we want that system to be efficient, avoiding unnecessary waste, while delivering the right treatments to the right patients in a timely fashion; we want a system that allows us to both learn from our experience and generate new knowledge that will inform future treatment options; and we want a system that is compassionate and caring. What we want from a health care system often runs up against real-life obstacles and challenges: a fragmented delivery system, varying levels (or lack of) insurance, a growing burden of regulation and paperwork, and an increasingly complex understanding of tumor biology and the therapeutic approaches derived from this biology. New challenges are on the horizon—emerging genomic and imaging technology, with their enormous cognitive and data burdens, and a looming demographic challenge, where inadequate personnel resources face an aging population and an explosion of new treatments. Not all problems have technologic solutions, but many of the issues described above have potential solutions related to information technology. ASCO's CancerLinQ, described in this article, is an evolving attempt by the Society to improve the quality and efficiency of cancer care, while supporting education and research in the cancer field.
Opportunities for Oncology in the Patient Protection and Affordable Care Act
Authors: Patel Kavita K. , Tran Lisa
Published: February 2020

The Patient Protection and Affordable Care Act (ACA) contains within it three significant legislative constructs: to enhance access to health care, improve quality, and decrease cost. Also known as the Triple Aim, these three simple, yet monumental, goals have been the object of actions to date as well as future implementation efforts. This article will identify sections of the legislation that would directly provide areas of opportunity to improve health and achieve the triple aim for the oncology profession.
Obesity and Inflammation: New Insights into Breast Cancer Development and Progression
Authors: Iyengar Neil M. , Hudis Clifford A. , Dannenberg Andrew J.
Published: February 2020

The importance of inflammation in promoting carcinogenesis and tumor progression is well recognized. Chronic inflammation caused by a variety of infectious agents can lead to the development of several common malignancies. Similarly, inflammatory bowel disease is a well-known risk factor for colorectal cancer. Much less is known about the link between inflammation and the development of breast cancer. Recent data suggest that obesity causes both in-breast and systemic inflammation that contribute to the development and progression of breast cancer. This observation has potentially important implications in terms of prevention and treatment of breast cancer, especially given the rising worldwide overweight and obesity rates. Inflamed white adipose tissue (WAT) within the breast is associated with elevated levels of proinflammatory mediators, enhanced expression of aromatase (the rate-limiting enzyme for estrogen biosynthesis), and increased estrogen receptor-α (ER-α)-dependent gene expression. Systemic consequences of obesity including altered adipokine levels, elevated circulating estrogen levels, and insulin resistance are also believed to play a role in the pathogenesis of breast cancer. Collectively, these findings suggest a significant role for inflammation in the pathogenesis of breast cancer in obese and overweight patients.
Green Tea Polyphenols and Cancer Chemoprevention of Genitourinary Cancer
Authors: Bailey Howard H. , Mukhtar Hasan
Published: February 2020

Green tea, which has higher concentrations of polyphenols than other teas, has been correlated with reduced risk of various malignancies with most data supporting a potential protective role in prostate neoplasia. Preclinical studies over the last 25 years implicate constituent green tea catechins, epigallocatechin-3-gallate (EGCG) being the predominant form, as the main mechanistic ingredient in the observed biologic effects, which vary from proapoptotic effects to inhibition of androgen receptor and signal transduction pathways. There have been few prospective clinical trials of green tea polyphenols (GTP), especially with well-characterized formulations and doses. Although there have been hints of beneficial clinical activity in prostate neoplasia, other studies have raised concerns about the limited bioavailability and very low target-tissue concentrations of GTPs. At present there is no proven role for GTP supplementation in the prevention of genitourinary (GU) malignancies, but novel GTP formulations and further clinical testing may still support a future for GTP supplementation in GU cancer prevention.
Marine-Derived Omega-3 Fatty Acids: Fishing for Clues for Cancer Prevention
Authors: Fabian Carol J. , Kimler Bruce F.
Published: February 2020

Omega-3 fatty acids (FA) are polyunsaturated essential FA with anti-inflammatory properties. The most potent are the marine-derived eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), which counteract the pro-inflammatory omega-6 FA. Americans take in an average of only 100 mg of EPA plus DHA per day resulting in a low omega-3:omega-6 intake ratio of 1:10 favoring inflammation. Cohort and/or case control studies suggest EPA and DHA are promising for breast, colon, and prostate cancer risk reduction. Mechanistic studies largely in preclinical models suggest EPA and DHA reduce synthesis of prostaglandin E2 and other inflammatory cytokines, decrease aromatase activity and proliferation, promote differentiation and apoptosis, and enhance insulin sensitivity. Animal models using 7% to 20% omega-3 added to chow are promising; however, this amount of omega-3 in a diet is unlikely to be acceptable to humans. The optimal EPA:DHA ratio or the lowest effective dose of EPA and DHA for cancer prevention is unclear, but it is likely to be more than 600 mg/day, which is six times the average American intake. Most phase II prevention trials use 1 to 3.3 g of EPA and DHA, which is safe and well tolerated. Two grams of EPA was associated with fewer polyps in individuals with familial adenomatous polyposis in a randomized, placebo-controlled trial. Identification of serum risk biomarkers modulated by EPA and DHA in healthy humans has remained elusive, but phase II prevention trials with tissue obtained for risk and response biomarkers are ongoing.
Antibody-Drug Conjugates in Hematologic Malignancies
Authors: Leslie Lori A. , Younes Anas
Published: February 2020

Antibody-drug conjugates (ADCs) are agents composed of a monoclonal antibody linked to cytotoxic molecules. By specifically delivering cytotoxic agents to cells expressing surface antigens of interest, ADC technology allows for the targeted use of highly toxic agents resulting in increased efficacy against malignant cells and decreased damage to normal tissue. Effector agents can be small molecules, radioisotopes, proteins, or bacterially derived toxins. Over the past several decades, ADCs have been evaluated in a variety of preclinical models of hematologic malignancies, as well as early-phase clinical trials with limited success. More recently, advancements in linkage technology, improvements in cytotoxin selection, and use of smaller conjugates containing partial rather than complete antibodies have drastically improved the potential clinical value of ADCs. In the future, ADC technology may be used to restore tumor suppressor activity, target the microenvironment, or replace nonfunctional enzymes. In this review we will discuss select ADCs in various stages of development for use in hematologic malignancies including lymphoma, multiple myeloma, and leukemia.
Surveillance and Monitoring in Breast Cancer Survivors: Maximizing Benefit and Minimizing Harm
Authors: Jochelson Maxine , Hayes Daniel F. , Ganz Patricia A.
Published: February 2020

Although the incidence of breast cancer has increased, breast cancer mortality has decreased, likely as a result of both breast cancer screening and improved treatment. There are well over two million breast cancer survivors in the United States for whom appropriate surveillance continues to be a subject of controversy. The guidelines from the American Society of Clinical Oncology (ASCO) and the American College of Physicians are clear: only performance of yearly screening mammography is supported by evidence. Although advanced imaging technologies and sophisticated circulating tumor biomarker studies are exquisitely sensitive for the detection of recurrent breast cancer, there is no proof that earlier detection of metastases will improve outcome. A lack of specificity may lead to more tests and patient anxiety. Many breast cancer survivors are not followed by oncologists, and their doctors may not be familiar with these recommendations. Oncologists also disregard the data. A plethora of both blood tests and nonmammographic imaging tests are frequently performed in asymptomatic women. The blood tests, marker studies, and advanced imaging techniques are expensive and, with limited health care funds, may prevent funding for more appropriate aspects of patient care. Abnormal marker studies lead to additional imaging procedures. Repeated CT scans and radionuclide imaging may induce a second cancer because of the radiation dose, and invasive procedures performed as a result of these examinations also add risk to patients without clear benefits. Improved adherence to the current guidelines can cut costs, reduce risks, and improve patient quality of life without adversely affecting outcome.
How Do Mechanisms of Hepatocarcinogenesis (HBV, HCV, and NASH) Affect Our Understanding and Approach to HCC?
Authors: Johnson Philip J.
Published: February 2020

The major etiologic factors for hepatocellular carcinoma (HCC), including chronic hepatitis B and C virus infections and nonalcoholic fatty liver disease, are now well established by epidemiologic investigations. The mechanisms by which these factors result in HCC have been extensively investigated but have not, to date, resulted in the development of specific therapeutic interventions. Other frequently occurring dysregulated pathways, including the Wnt/β-catenin signaling pathway, are proving difficult to target, but there are early suggestions that patients with “MET-high” HCC may benefit from the c-MET inhibitor tivantinib. Chronic inflammation and consequent cell damage and regenerative proliferation are common to all etiologic factors, and emerging evidence suggests that anti-inflammatory agents such as aspirin deserve further investigation as preventive agents.
Novel Therapeutics in Hepatocellular Carcinoma: How Can We Make Progress?
Authors: Kelley Robin K. , Venook Alan P.
Published: February 2020

Hepatocellular carcinoma (HCC) is the third leading cause of cancer death globally, and its prevalence and impact are even more profound because sorafenib is the only systemic therapy proven to prolong survival in patients with advanced disease. Randomized phase III trials of other novel targeted agents including sunitinib, linifanib, brivanib, and the combination of sorafenib plus erlotinib have failed to improve overall survival compared with sorafenib as a single agent in the first line setting, as well as compared with placebo in the second-line setting, in the case of brivanib. These negative studies are a sobering reminder of the challenges to clinical research in HCC, including the competing comorbidity of liver dysfunction, marked clinical and biologic heterogeneity, and the unreliability of surrogate endpoints to accurately predict survival. To address these challenges, HCC-specific phase I/Ib cohorts must be used to define the maximum tolerated dose and drug exposure in this organ dysfunction population with high background rates of adverse events and little tolerance for superimposed treatment-related toxicity. Pooled analyses of contemporary randomized trials and database studies should be undertaken to define the strongest prognostic factors for stratification in future phase III studies. Research blood and archival tumor specimens should be collected from patients on clinical trials to intensify the search for biomarkers of responsive or resistant subsets, in parallel with ongoing efforts to improve on radiographic response assessment. Collectively, these and other new strategies are needed to make progress in identifying active novel therapeutics for patients with HCC.
Managing Choices for Older Patients with Colon Cancer: Adjuvant Therapy
Authors: Wu Christina , Goldberg Richard M.
Published: February 2020

Colon cancer is among the most common cancers in the United States, and the median age of patients at diagnosis is 70. Medical oncologists are commonly asked to comprehensively evaluate elderly patients to estimate individual risk/benefit ratios for adjuvant treatment. Although 40% of patients with colon cancer are elderly, clinical trials enroll mainly younger patients. Consequently, we are forced to depend on subgroup analyses, observational studies, and personal experience to guide recommendations. Decision-making in adjuvant therapy for colon cancer is increasingly complex, as we subdivide patients with stage II to III colon cancer by molecular as well as anatomic staging to predict which are likely to benefit from chemotherapy and then whether the addition of oxaliplatin to 5-fluorouracil (5-FU) is worth the toxicity. It is likely that the tumor biology of younger and older patients differs, and more research is needed to dissect out the biologic heterogeneity of both the tumors and their elderly hosts to help guide treatment. We recognize that our evaluations should not solely be based on temporal age and factor physiology, pharmacology, psychology, functional status, and social support into these considerations. Older patients who are treated must be monitored closely for toxicities when undergoing treatment. Although there is a clear need for clinical trials in this population, treatment decisions confront us today in the absence of definitive evidence. How can we help our patients navigate through these important choices?
Beyond Trastuzumab and Lapatinib: New Options for HER2-Positive Breast Cancer
Authors: Zardavas Dimitrios , Cameron David , Krop Ian , Piccart Martine
Published: February 2020

HER2-positive breast cancer (BC) constitutes a molecular subtype of the disease with an aggressive biologic behavior. Trastuzumab revolutionized the treatment of this disease, changing its natural history. Lapatinib is active in the metastatic setting, approved for patients who were pretreated with trastuzumab. However, resistance to anti-HER2 agents is a major clinical issue, occurring in both early-stage and advanced disease, and new treatment options are clearly needed. An abundance of HER2-targeted agents are being clinically developed: monoclonal antibodies, small molecule inhibitors, and antibody drug conjugates (ADC). Combining HER2-targeted agents in regimens of dual HER2 blockade has already reached clinical practice in the metastatic setting, confirming the preclinical efficacy of enhanced HER2 inhibition. Promising results have been generated in the neoadjuvant setting, and large randomized trials are seeking evidence for dual HER2 blockade in the adjuvant setting. ADC represent another hope for improved treatment outcomes of HER2-positive BC, as exemplified by the positive results of clinical trials employing trastuzumab-DM1 (trastuzumab emtansine, T-DM1). Moreover, an understanding of the molecular mechanisms mediating resistance to HER2 blockade has opened new therapeutic avenues, with several targeted agents entering clinical trials. This paper presents the clinical data of the HER2-targeted agents under development, as well as an overview of the biologic rationale for the development of agents aimed at circumventing anti-HER2 resistance.
Treatment Algorithms for Hormone Receptor-Positive Advanced Breast Cancer: Applying the Results from Recent Clinical Trials into Daily Practice—Insights, Limitations, and Moving Forward
Authors: Wilson Sheridan , Chia Stephen K.
Published: February 2020

Hormone receptor–positive (HR+) breast cancer is the most prevalent subtype of breast cancer in both early- and advanced-stage disease. Thus, the treatment of HR+ breast cancer has had the greatest global influence in improving clinical outcomes overall. Although the first-line metastatic breast cancer (MBC) trials comparing a third-generation aromatase inhibitor (AI) to tamoxifen have favored the AI, one of the challenges in translating these findings into clinical practice stems from the influence of prior adjuvant endocrine therapy, particularly the increasing use of adjuvant AIs today, on the choice of endocrine agent in the advanced setting because of the development of acquired resistance. Because the majority of patients enrolled into these studies were either endocrine-treatment naïve or exposed to tamoxifen only, the “real-life” applicability of the evidence is unclear. Because a superior dose of the selective estrogen receptor (ER) downregulator fulvestrant has now been established, its role as first-line therapy is being re-established. We are now starting to see the promise realized with blocking cross-talking growth factor pathways in addition to the ER pathway. The greatest efficacy is seen with the mammalian target of rapamycin (mTOR) inhibitor everolimus in combination with exemestane and, perhaps to a lesser extent, anti-HER2–directed therapy in combination with an AI. Future gains will likely involve a greater understanding of the redundancy and compensation induced by blocking these pathways, trials involving blocking multiple pathways in addition to hormonal agents, and the molecular interrogation of the individual's tumor in search of predictive biomarkers and “actionable” genomic aberrations.
Rare Epithelial Tumors Arising in or near the Ovary: A Review of the Risk Factors, Presentation, and Future Treatment Direction for Ovarian Clear Cell and Mucinous Carcinoma
Authors: Jain Angela , Seiden Michael V.
Published: February 2020

Currently all advanced-stage epithelial ovarian cancers are treated with a total abdominal hysterectomy, bilateral oophorectomy, and complete tumor debulking surgery, followed by carboplatin and paclitaxel. This treatment recommendation is based on clinical trials that are mostly populated with women with high-grade serous carcinomas. Patients with mucinous or clear cell carcinomas of the ovary tend to present with earlier-stage disease, and may not require adjuvant chemotherapy; those with advanced-stage disease tend to have carboplatin-resistant disease. Patients with mucinous ovarian carcinoma have presentations and tumor biology that are similar to colorectal carcinomas and may benefit from colorectal regimens containing fluorouracil (FU) and oxaliplatin. Their tumors may also be KRAS wild-type or have HER2 amplification, and could benefit from drugs like cetuximab or trastuzumab. Patients with clear cell carcinoma of the ovary often harbor AIRD1a mutations, an early event in oncogenesis that is not a currently drugable target. Anecdotal cases and our biologic understanding of these malignancies suggest they might be preferentially sensitive to antiangiogenesis inhibitors. Focused international trials will be needed in both of these rare epithelial ovarian cancers to better define optimal treatment regimens.
Revisiting the Role of Radiation Treatment for Non-serous Subtypes of Epithelial Ovarian Cancer
Authors: Thomas G.
Published: February 2020

Except for its palliative use, radiation has been largely abandoned in the management of ovarian cancers because of the recognized efficacy of chemotherapy agents. Whole abdominal irradiation (WAR), however, has been shown to be of adjuvant and curative value in ovarian cancer with microscopic or minimal residual disease in the pelvis, the so-called “intermediate risk group.” Recent hypothesis generating data from the use of adjuvant radiation following adjuvant chemotherapy in ovarian cancer has shown an incremental survival benefit for the rarer non-serous ovarian subtypes including clear cell, endometrioid, and mucinous. No incremental benefit was observed for the more common serous subtype. A retrospective examination of early trials using WAR as the sole postoperative treatment in ovarian cancer has determined that the majority of patients in these studies and cured by radiation actually had the non-serous subtypes. The recognition that the non-serous subtypes differ from the serous cancers in their stage of presentation, their molecular characteristics, their response to classic chemotherapy, and their outcomes suggest the non-serous subtypes should be treated as rare and different cancers. In addition to specific targeting therapies that may be developed, radiation should be reconsidered as part of the treatment armamentarium for these diseases.
Oral Mucositis in Head and Neck Cancer: Risk, Biology, and Management
Authors: Sonis Stephen T.
Published: February 2020

Of the toxicities associated with conventional forms of treatment for head and neck cancers, probably none has such a consistent legacy as oral mucositis. 1 Despite the fact that mucosal injury was noted as far back as Marie Curie's first forays into therapeutic radiation, an effective intervention has yet to be developed. In addition to its historic link to radiation, new therapeutic strategies including induction chemotherapy often produce mucositis, and targeted therapies appear to alter mucositis risk and its severity and course. 2 The symptomatic effect of oral mucositis is profound. Disabling oral and oropharyngeal pain prevents patients from eating normally, requires opiate analgesics, and in some cases results in alteration or discontinuation of anticancer therapy. 3 Furthermore, the health and economic consequences of oral mucositis are far from trivial. The incremental cost of oral mucositis in patients with head and neck cancer exceeds $17,000 (USD). 4
National Cancer Plans: The French Experience
Authors: Khayat David
Published: February 2020

With a prediction of about 20 million cases and 10 million deaths occurring to 2020, cancer is becoming one of the most important challenges in the field of human health. National Cancer Control plans are effective tools to set up actions that, by their specificity in regard to the local epidemiology and resources, can break the rising curve of human toll that we are paying to this disease. In this article we present the French experience with the National Cancer Plans. We point out the most significant actions that were developed in the areas of prevention, screening, care, access to innovative treatments, and research.
Reducing Inequalities in Cancer Outcomes: What Works?
Authors: Bickell Nina A. , Paskett Electra D.
Published: February 2020

Despite efforts to reduce disparities in cancer outcomes among vulnerable populations, certain subgroups do not experience the gains made in the reduction of cancer incidence and mortality. In this article, we review recent trial data reporting on patient-, physician-, and system-centered interventions to improve quality and reduce disparities in cancer care spanning patient navigation to health reform. We conclude with data from a state that implemented a multitiered approach, targeting patient and systems barriers, that serves as a guide for future endeavors.
Novel Approaches to Treatment of Double-Refractory Multiple Myeloma
Authors: Lee Hans C. , Shah Jatin J. , Orlowski Robert Z.
Published: February 2020

Multiple myeloma (MM) refractory to both proteasome inhibitors and immunomodulatory agents (IMiDs; double-refractory myeloma) has a poor prognosis. With the more frequent use of these agents as part of initial therapy, and then in the maintenance setting until disease progression, such drug resistance is an emerging problem of great significance. New therapeutic strategies are clearly needed for this patient population, including the development of more potent agents within existing antimyeloma drug classes, exploration of rational combinations of both novel and conventional drugs, and validation of new myeloma drug targets. Several approaches have shown substantial promise, including use of the second-generation proteasome inhibitor carfilzomib and the third-generation IMiD pomalidomide, which led to the recent regulatory approval of both agents. In addition, the kinesin-spindle protein KSP inhibitor ARRY-520 has shown activity as a first-in-class drug in myeloma therapeutics, whereas the histone deacetylase (HDAC) inhibitors vorinostat and panobinostat have demonstrated efficacy when used in rational combinations. This overview provides a summary of novel agents that have shown activity in double-refractory myeloma in recent phase II and III clinical trials, and a framework for future studies that will help to improve outcomes in this patient population.
New Tools for Diagnosis and Monitoring of Multiple Myeloma
Authors: San-Miguel Jesús F. , Paiva Bruno , Gutiérrez Norma C.
Published: February 2020

This article reviews the most relevant techniques currently used for the evaluation of patients with multiple myeloma. Although bone marrow morphologic examination and electrophoretic analysis of the monoclonal paraprotein and conventional x-rays remain the “gold standard” techniques for fast, accurate, and cost-effective diagnosis, other assays such as molecular cytogenetics, immunophenotyping, MRI, and PET-CT may contribute to a better assessment of patients with myeloma. Here, we will discuss not only the contribution of each technique to differential diagnosis of monoclonal gammopathies, but also the value of each parameter for determining prognosis and for monitoring treatment efficacy. In addition, possible technical pitfalls inherent to each technique will be analyzed.
Understanding and Surviving the Transition to Value-Based Oncology
Authors: Cox John V. , Sprandio John D. , Barkley Ronald
Published: February 2020

This paper and the three presentations it supports are drawn from the theme of the 2012 Cancer Center Business Summit (CCBS): “Transitioning to Value-Based Oncology: Strategies to Survive and Thrive.” The CCBS is a forum on oncology business innovation, and the principal question the organizers address each year is “What are the creative, innovative, and best business models and practices that are being conceived or piloted today that may provide a responsible and sustainable platform for the delivery of cancer care tomorrow?” At this moment in health care—when so much is in flux and new business models and solutions abound—the oncology sector has a solemn responsibility: to forge the business models and relationships that will help to define a new cancer care value proposition and a sustainable health care system of tomorrow for the benefit of the patients it serves to get it “right.”
Perspectives on Electronic Prescribing and Terminologies
Authors: Liebovitz David
Published: February 2020

Electronic medical records provide potential benefits and also drawbacks. Potential benefits include increased patient safety and efficiency. Potential drawbacks include newly introduced errors and diminished workflow efficiency. In the patient safety context, medication errors account for significant patient harm. Electronic prescribing (e-prescribing) offers the promise of automated drug interaction and dosage verification. In addition, the process of enabling e-prescriptions also provides access to an often unrecognized benefit, that of viewing the dispensed medication history. This information is often critical to understanding patient symptoms. Obtaining significant value from electronic medical records requires use of standardized terminology for both targeted decision support and population-based management. Further, generating documentation for a billable encounter requires usage of proper codes. The emergence of International Classification of Diseases (ICD)-10 holds promise in facilitating identification of a more precise patient code while also presenting drawbacks given its complexity. This article will focus on elements of e-prescribing and use of structured chart content, including diagnosis codes as they relate to physician office practices.
The Advanced Practice Professionals' Perspective: Keys to a Good Working Relationship between Advanced Practice Professions and Physicians
Authors: Polansky Maura
Published: February 2020

A strong working relationship between advanced practice professionals (APPs) and supervising oncologists is essential for reducing medical errors, retaining employees, and improving work environments. Although there is rather limited data on the unique relationship of the APP and physician, fundamental communication skills—including open communication, mutual respect, establishing expectations, and working with mutual purpose—should be the foundation of these relationships. This paper addresses various aspects of relationship building between APPs and physicians with suggestions for establishing successful working relationships.
Targeting the PI3K/AKT/mTOR Pathway: Biomarkers of Success and Tribulation
Authors: Owonikoko Taofeek K. , Khuri Fadlo R.
Published: February 2020

PI3K/AKT/mTOR pathway is an established oncogenic driver in humans. Targeted biologic agents against components of this pathway have shown promising activity leading to the approval of the allosteric inhibitors of mTOR, everolimus, and temsirolimus for the treatment of advanced cancers of the kidney, breast, and pancreas. Despite the established and promising activity of this therapeutic strategy, the duration and quality of benefit remains suboptimal in unselected patients. Improved understanding of the biologic consequence of altered PI3K/AKT/mTOR signaling is informing the development of protein (phosphorylated forms of S6, AKT, eIF4e) and genetic ( PIK3CA mutation, PTEN loss of function, TSC1 and TSC2 mutation, PIK3CA-GS genetic profile) biomarkers to identify patients most likely to benefit from this therapeutic strategy. This review provides an overview of the biologic rational and promising results of protein and genetic biomarkers for selecting patients appropriate for therapy with inhibitors of this pathway.
Familial Gastric and Pancreatic Cancers: Diagnosis and Screening
Authors: Raymond Victoria M. , Stoffel Elena M.
Published: February 2020

Screening for gastric and pancreatic cancers in asymptomatic individuals is not routinely practiced in the United States. While there is insufficient evidence that general population screening would reduce morbidity and/or mortality associated with these cancers, the utility of screening for individuals at increased risk warrants further study. Clinical challenges include identifying high risk individuals who would be most likely to benefit from screening and determining which screening modalities and intervals would be most effective.
Mammographic Density and Risk of Breast Cancer
Authors: Boyd Norman F.
Published: February 2020

The radiographic appearance of the breast on mammography varies among women, and reflects variations in breast tissue composition and the different X-ray attenuation characteristics of these tissues. Fat is radiologically lucent and appears dark on a mammogram. Connective and epithelial tissues are radiologically dense and appear light. These variations in appearance are commonly described as the percentage of the breast image that is radiologically dense, or as percent mammographic density (PMD). There is now extensive evidence that PMD is a risk factor for breast cancer, with a 4- to 6-fold gradient in risk between women with 75% or more PMD compared with those with 10% or less. However, the accuracy of risk prediction in individual women is modest. The extent of PMD is associated inversely with greater age, parity, and weight, and is reduced by the menopause and by tamoxifen. PMD is positively associated with greater height, a family history of breast cancer, and is increased by combined hormone therapy. The relative risk associated with density is substantially larger than the relative risk of breast cancer associated with a family history of the disease or any of the menstrual and reproductive risk factors. It is estimated that the risks of breast cancer attributable to density of 50% or more may be 16% for all breast cancers. Although combined hormone therapy and tamoxifen respectively increase a decrease both PMD and breast cancer risk, there is as yet insufficient evidence to use PMD as a surrogate marker for breast cancer.
Antiangiogenic Therapy for Glioblastoma: The Challenge of Translating Response Rate into Efficacy
Authors: de Groot John , Reardon David A. , Batchelor Tracy T.
Published: February 2020

Glioblastoma are one of the mostly vascularized tumors and are histologically characterized by abundant endothelial cell proliferation. Vascular endothelial growth factor (VEGF) is responsible for a degree of vascular proliferation and vessel permeability leading to symptomatic cerebral edema. Initial excitement generated from the impressive radiographic response rates has waned due to concerns of limited long-term efficacy and the promotion of a treatment-resistant phenotype. Reasons for the discrepancy between high radiographic response rates and lack of survival benefit have led to a focus on identifying potential mechanisms of resistance to antiangiogenic therapy. However, equally important is the need to focus on identification of basic mechanisms of action of this class of drugs, determining the optimal biologic dose for each agent and identify the effect of antiangiogenic therapy on oxygen and drug delivery to tumor to optimize drug combinations. Finally, alternatives to overall survival (OS) need to be pursued using the application of validated parameters to reliably assess neurologic function and quality of life.
The NCI Community Oncology Research Program: What Every Clinician Needs to Know
Authors: McCaskill-Stevens Worta , Lyss Alan P. , Good Marge , Marsland Thomas , Lilenbaum Rogerio
Published: February 2020

Research in the community setting is essential for the translation of advances in cancer research into practice and improving cancer care for all populations. The National Cancer Institute is proposing a new community-based program, NCI Community Oncology Research Program (NCORP), which is the alignment of two existing programs, the Community Clinical Oncology Program, Minority-Based Community Clinical Oncology Program, and their Research Bases, and the National Cancer Institute's Community Cancer Centers Program. NCROP will support cancer control, prevention, treatment, and screening clinical trials and expand its research scope to include cancer care delivery research. Cancer disparities research will be integrated into studies across the continuum of NCORP research. Input from current NCI-funded community investigators provides critical insight into the challenges faced by oncology practices within various organizational structures. Furthermore, these investigators identify the resources, both administrative and clinical, that will be required in the community setting to support cancer care delivery research and to meet the requirements for a new generation of clinical research. The American Society for Clinical Oncology (ASCO) has initiated a forum to focus on the conduct of clinical research in the community setting. Resources are being developed to help practices in managing cancer care in community settings.
Cellular Composition of the Tumor Microenvironment
Authors: Ansell Stephen M. , Vonderheide Robert H.
Published: February 2020

In addition to malignant cells, the tumor microenvironment also includes nonmalignant cells, secreted proteins, and blood vessels that surround and support the growth of the tumor. Interactions between the various components of the tumor microenvironment are significant; tumor cells can change the nature of the microenvironment, and conversely, the microenvironment can affect how a tumor grows and spreads. The structure and composition of the tumor microenvironment varies among different types of cancers and between patients. This paper focuses on the composition and function of the tumor microenvironment in hematologic malignancies with a specific focus on B-cell lymphomas.
The International Legal Issue of Attribution of Conduct to a State – The Case Law of the International Courts and Tribunals
Authors: Stryjkowska Sylwia
Published: February 2020

The article aims to broaden the subject of the attribution of conduct to a State by pre-senting different grounds for attributing State responsibility. It surveys main the prin-ciples of attribution, which were affirmed in international judicial decisions and specifies circumstances which extend beyond the general rule under which States incur responsi-bility only for the conduct of its organs. The provisions of the Articles on the Responsi-bility of States for Internationally Wrongful Acts constitute a primary point of reference of the research and are followed by examples of their practical application.
The Development of the American Private Sector in Relation to International Law. From the First Artificial Satellite to The American Space Commerce Free Enterprise Act
Authors: Topolska Paulina
Published: February 2020

The active development of technology enbled mankind to realize new programs for the exploration of previously inaccessible areas of the universe hundreds of thousands of kilometers away. The emergence of this new field created the need to ensure its special legal regulation, which would correspond to the specific characteristics of this business. But now we have entered into a phase of re-evaluation of existing legislation of space and we must realise that alongside countries operating in space an has arisen entirely new entity - the private sector. Therefore it is necessary to ask ourselves whether the privatization and commercialization of outer space is legally possible and if it is not pre-cluded by existing treaties. The draft of the latest US Commercial Space Act is undoubt-edly a great advance for key areas of the private sector activity such as remote sensing and new space missions. It provides a sense of confidence for entrepreneurs by strictly regulating issues related to the supervision of private sector entities. However, on the in-ternational scene the question has arisen of whether this act is contrary to international law, especially principles contained in existing space law treaties.
A viscosity-type algorithm for an infinitely countable family of (f,g)-generalized k-strictly pseudononspreading mappings in CAT(0) spaces
Authors: Aremu Kazeem O. , Abass Hammed , Izuchukwu Chinedu , Mewomo Oluwatosin T.
Published: February 2020

In this paper, we propose a viscosity-type algorithm to approximate a common solution of a monotone inclusion problem, a minimization problem and a fixed point problem for an infinitely countable family of

(
f
,
g
)

{(f,g)}

-generalized k-strictly pseudononspreading mappings in a

CAT
⁢

(
0
)

{\mathrm{CAT}(0)}

space. We obtain a strong convergence of the proposed algorithm to the aforementioned problems in a complete

CAT
⁢

(
0
)

{\mathrm{CAT}(0)}

space. Furthermore, we give an application of our result to a nonlinear Volterra integral equation and a numerical example to support our main result. Our results complement and extend many recent results in literature.
Highly accurate and explainable detection of specimen mix-up using a machine learning model
Authors: Mitani Tomohiro , Doi Shunsuke , Yokota Shinichiroh , Imai Takeshi , Ohe Kazuhiko
Published: February 2020

Background

Delta check is widely used for detecting specimen mix-ups. Owing to the inadequate specificity and sparseness of the absolute incidence of mix-ups, the positive predictive value (PPV) of delta check is considerably low as it is labor consuming to identify true mix-up errors among a large number of false alerts. To overcome this problem, we developed a new accurate detection model through machine learning.

Methods

Inspired by delta check, we decided to conduct comparisons with the past examinations and broaden the time range. Fifteen common items were selected from complete blood cell counts and biochemical tests. We considered examinations in which ≥11 among the 15 items were measured simultaneously in our hospital; we created individual partial time-series data of the consecutive examinations with a sliding window size of 4. The last examinations of the partial time-series data were shuffled to generate artificial mix-up cases. After splitting the dataset into development and validation sets, we allowed a gradient-boosting-decision-tree (GBDT) model to learn using the development set to detect whether the last examination results of the partial time-series data were artificial mixed-up results. The model’s performance was evaluated on the validation set.

Results

The area under the receiver operating characteristic curve (ROC AUC) of our model was 0.9983 (bootstrap confidence interval [bsCI]: 0.9983–0.9985).

Conclusions

The GBDT model was more effective in detecting specimen mix-up. The improved accuracy will enable more facilities to perform more efficient and centralized mix-up detection, leading to improved patient safety.
Fast Bilinear Algorithms for Symmetric Tensor Contractions
Authors: Solomonik Edgar , Demmel James
Published: February 2020

In matrix-vector multiplication, matrix symmetry does not permit a straightforward reduction in computational cost.
More generally, in contractions of symmetric tensors, the symmetries are not preserved in the usual algebraic form of contraction algorithms.
We introduce an algorithm that reduces the bilinear complexity (number of computed elementwise products) for most types of symmetric tensor contractions.
In particular, it lowers the bilinear complexity of symmetrized contractions of symmetric tensors of order

s
+
v

{s+v}

and

v
+
t

{v+t}

by a factor of

(

s
+
t
+
v

)

!

s
!

⁢

t
!

⁢

v
!

{\frac{(s+t+v)!}{s!t!v!}}

to leading order.
The algorithm computes a symmetric tensor of bilinear products, then subtracts unwanted parts of its partial sums.
Special cases of this algorithm provide improvements to the bilinear complexity of the multiplication of a symmetric matrix and a vector, the symmetrized vector outer product, and the symmetrized product of symmetric matrices.
While the algorithm requires more additions for each elementwise product, the total number of operations is in some cases less than classical algorithms, for tensors of any size.
We provide a round-off error analysis of the algorithm and demonstrate that the error is not too large in practice.
Finally, we provide an optimized implementation for one variant of the symmetry-preserving algorithm, which achieves speedups of up to 4.58

×

\times

for a particular tensor contraction, relative to a classical approach that casts the problem as a matrix-matrix multiplication.
Skin cancer on Instagram: implications for adolescents and young adults
Authors: Basch Corey H. , Hillyer Grace C.
Published: February 2020

Given the popularity and reach of Instagram among American adolescents and young adults (AYA), the well-known influence of social media on the behaviors of youth, and the rising rates of melanoma in this age group, this study sought to examine and describe the content of a sample of Instagram posts related to skin cancer. At three different times, a search of Instagram was conducted using #skincancer as the hashtag. Descriptive analyses of Instagram characteristics and content was performed. Overall, content focused on prevention (33.3%), skin cancer treatment (29.3%) and preventive measures such as using sunscreen and protective gear (29.3%). Nearly one-quarter discussed the ABCDEs (Asymmetrical; Borders are irregular; Color is not even; Diameter is large; Evolving) of screening and detection. Instagram postings that covered skin cancer prevention (n = 50, 33.3%) more often discussed the role of sun exposure in the development of skin cancer (28.0% vs. 10.0%, p = 0.005) and use of sunscreen and protective gear (62.0% vs. 13.0%, p < 0.001). The findings of this study indicate that a considerable portion of the Instagram posts included in this study focused on prevention. Thus, indicating that Instagram could be used to promote health, particularly among AYA.