bluuebunny/crossref_metadata_2025 huggingface dataset:
Gastric Adenocarcinoma: An Update on Genomics, Immune System Modulations, and Targeted Therapy
Authors: Lee Jeeyun , Bass Adam J. , Ajani Jaffer A.
Published: October 2018

Gastric adenocarcinoma (GAC) is a global health burden on all societies, and it was the third-leading cause of cancer-related mortality in 2012, causing 723,000 deaths worldwide. The prognosis of patients with metastatic GAC remains poor, with a median overall survival of less than 1 year in patients treated with currently available therapies. A limited number of therapeutic agents is currently available. Recent additions to the armamentarium include trastuzumab and ramucirumab, which have shown some survival advantage when added to cytotoxic(s). Genomic analyses have defined various genotypes of GACs. The novel genomic knowledge can lead to discovery of novel targets and novel therapeutic agents. In this update, we focus on the current genomic data, targeted therapies including immune system modulators, and expand on HER2/neu testing and the use of agents against this target. Several other facets of GAC and its therapy are not to be included in this review but have been discussed elsewhere.
Lung Cancer Screening With Low-Dose CT: Implementation Amid Changing Public Policy at One Health Care System
Authors: Begnaud Abbie , Hall Thomas , Allen Tadashi
Published: October 2018

Screening for lung cancer with low-dose CT has evolved rapidly in recent years since the National Lung Screening Trial (NLST) results. Subsequent professional and governmental organization guidelines have shaped policy and reimbursement for the service. Increasingly available guidance describes eligible patients and components necessary for a high-quality lung cancer screening program; however, practical instruction and implementation experience is not widely reported. We launched a lung cancer screening program in the face of reimbursement and guideline uncertainties at a large academic health center. We report our experience with implementation, including challenges and proposed solutions. Initially, we saw less referrals than expected for screening, and many patients referred for screening did not clearly meet eligibility guidelines. We educated primary care providers and implemented system tools to encourage referral of eligible patients. Moreover, in response to the Centers for Medicare & Medicaid Services (CMS) final coverage determination, we report our programmatic adaptation to meet these requirements. In addition to the components common to all quality programs, individual health delivery systems will face unique barriers related to patient population, available resources, and referral patterns.
Multimodal Rectal Cancer Treatment: In Some Cases, Less May Be More
Authors: Garcia-Aguilar Julio , Glynne-Jones Rob , Schrag Deborah
Published: October 2018

A series of clinical trials in the last several decades has resulted in the development of multimodality treatment of locally advanced rectal cancer that includes neoadjuvant (preoperative) chemoradiotherapy, total mesorectal excision, and postoperative adjuvant chemoradiotherapy. Owing to this regimen, patients with locally advanced rectal cancer have better survival rates than patients with colon cancer, but at the cost of substantial morbidity and reduced quality of life. The challenge is to identify treatment approaches that maintain or even improve oncologic outcomes while preserving quality of life. We have identified different tumor characteristics that are associated with recurrence and probability of survival for locally advanced rectal cancer. This risk stratification, based on baseline clinical staging and tumor response to chemoradiotherapy, has led us to question whether all patients with locally advanced rectal cancer require every component of the multimodal regimen. In this article, we will review recent evidence that some patients with locally advanced rectal cancer can be spared one or more treatment modalities without compromising long-term oncologic outcomes and while preserving quality of life.
Discussing the Evidence for Upstream Palliative Care in Improving Outcomes in Advanced Cancer
Authors: Nickolich Myles S. , El-Jawahri Areej , Temel Jennifer S. , LeBlanc Thomas W.
Published: October 2018

Palliative care has received increasing attention at the American Society of Clinical Oncology (ASCO) Annual Meeting since the publication of its provisional clinical opinion on the topic in 2012. Despite frequent discussion, palliative care remains a source of some controversy and confusion in clinical practice, especially concerning who should provide it, what it encompasses, and when and how it can help patients and their families. In this article, we provide a formal definition of palliative care and review the state of the science of palliative care in oncology. Several randomized controlled trials now show that palliative care improves important outcomes for patients with cancer. Related outcome improvements include a reduction in symptoms, improved quality of life, better prognostic understanding, less depressed mood, less aggressive end-of-life care, reduced resource utilization, and even prolonged survival. As such, ASCO recommends early integration of palliative care into comprehensive cancer care for all patients with advanced disease and/or significant symptom burden. Our aim is that this summary will facilitate greater understanding about palliative care and encourage further integration of palliative care services into cancer care. More research is needed to illuminate the mechanisms of action of palliative care and to improve the specificity of palliative care applications to unique scenarios and populations in oncology.
Approach to Oligometastatic Prostate Cancer
Authors: Bernard Brandon , Gershman Boris , Karnes R. Jeffrey , Sweeney Christopher J. , Vapiwala Neha
Published: October 2018

Oligometastatic prostate cancer has increasingly been recognized as a unique clinical state with therapeutic implications. It has been proposed that patients with oligometastases may have a more indolent course and that outcome may be further improved with metastasis-directed local ablative therapy. In addition, there are differing schools of thoughts regarding whether oligometastases represent isolated lesions—where targeted therapy may render a patient disease free—or whether they coexist with micrometastases, where targeted therapy in addition to systemic therapy is required for maximal clinical impact. As such, the approach to the patient with oligometastatic prostate cancer requires multidisciplinary consideration, with surgery, radiotherapy, and systemic therapy potentially of benefit either singularly or in combination. Indeed, mounting evidence suggests durable disease-free intervals and, in some cases, possibly cure, may be achieved with such a multimodal strategy. However, selecting patients that may benefit most from treatment of oligometastases is an ongoing challenge. Moreover, with the advent of new, highly sensitive imaging technologies, the spectrum based on CT of the abdomen and pelvis and technetium bone scan of localized to oligometastatic to widespread disease has become increasingly blurred. As such, new MRI- and PET-based modalities require validation. As some clinical guidelines advise against routine prostate-specific antigen screening, the possibility of more men presenting with locally advanced or de novo oligometastatic prostate cancer exists; thus, knowing how best to treat these patients may become more relevant at a population level. Ultimately, the arrival of prospective clinical data and better understanding of biology will hopefully further inform how best to treat men with this disease.
Challenges and Opportunities in Delivering High-Quality Cancer Care: A 2016 Update
Authors: Ganz Patricia A. , Hassett Michael J. , Miller David C.
Published: October 2018

Herein, both the rationale and scope of current initiatives aimed at improving the quality of cancer care delivery in the United States are described. First, we discuss a recent report from the Institute of Medicine that issued a strong call for both the development of quality measures in oncology and implementation of a learning health care system in which data and experience from clinical practice can inform continuous improvements in cancer care. Second, we review the multiple, diverse initiatives that are underway to identify, test, and validate quality measures for the entire spectrum of cancer care. Finally, we discuss regional quality improvement collaboratives as one successful approach to creating a cycle of quality measurement, identification of best practices, and implementation of changes in practice patterns that ultimately yield improved care and outcomes for patients with cancer.
New Targets and New Agents in High-Risk Multiple Myeloma
Authors: Nooka Ajay K. , Lonial Sagar
Published: October 2018

Advances in the treatment of multiple myeloma have resulted in dramatic improvements in outcomes for patients. The newly emerging profiling of mutations emerging as a consequence of large prospective sequencing studies such as the CoMMpass Study or other efforts from European investigators are not further helping to define the place and role for personalized medicine in myeloma. While mutations such as NRAS, KRAS, and BRAF do occur in myeloma, it is not clear that targeting them as a single drug strategy will result in meaningful responses or durations of response. Personalized medicine in multiple myeloma at this time likely entails the use of risk-based approaches for maintenance therapy, the use of current biology-based treatments such as proteasome inhibitors, and immunomodulatory agents, with an eye towards the use of mutation-specific treatments in the setting of minimal residual disease or in concert with biology-based treatments overall.
Biomarkers for Immunotherapy: Current Developments and Challenges
Authors: Spencer Kristen R. , Wang Jianfeng , Silk Ann W. , Ganesan Shridar , Kaufman Howard L. , Mehnert Janice M.
Published: October 2018

Immunotherapy has revolutionized cancer therapy and has been named the cancer advance of the year for 2016. Checkpoint inhibitors have demonstrated unprecedented rates of durable responses in some of the most difficult-to-treat cancers; however, many treated patients do not respond, and the potential for serious side effects exists. There is a growing need to identify biomarkers that will improve the selection of patients who will best respond to therapy, further elucidate drug mechanisms of action, and help tailor therapy regimens. Biomarkers are being explored at the soluble, cellular, and genomic levels, and examples in immunotherapy include serum proteins, tumor-specific receptor expression patterns, factors in the tumor microenvironment, circulating immune and tumor cells, and host genomic factors. The search for reliable biomarkers is limited by our incomplete understanding of how immunotherapies modify the already complex immune response to cancer, as well as the contribution of immuno-editing to a dynamic and inducible tumor microenvironment and immune milieu. Furthermore, there has been little extension of any candidate assay into large, prospective studies, and the lack of standardization in measurement and interpretation restricts their validity. Both tumor-infiltrating lymphocytes and PD-L1 expression within the tumor microenvironment have been recognized as having both prognostic and predictive value for patients treated with immunotherapy. Alternately, a larger panel of gene signatures, chemokines, and other factors that correlate with response has been proposed. In this article, we will explore the status of current biomarker candidates.
Tissue-Agnostic Drug Development
Authors: Flaherty Keith T. , Le Dung T. , Lemery Steven
Published: October 2018

The U.S. Food and Drug Administration (FDA) has approved drugs to treat patients with tumor types based on a single anatomic site, such as renal cell carcinoma or melanoma, rather than on a biomarker alone. This standard approach is based on a number of factors, including heterogeneity of drug effects in different biomarker-positive tumor types. Additionally, drug development for some drugs was primarily directed toward a specific genomic abnormality in a specific tumor type (e.g., drugs for anaplastic lymphoma kinase [ALK] fusion-positive non–small cell lung cancer). In such cases, differences in biology, differences in natural histories of different cancers, differences in mutation frequencies among cancers, or differences in concomitant therapies may have necessitated diverse development considerations. As described in U.S. regulations [21 CFR 201, CFR 201.57(c)(2)], the indications and usage section of drug labeling “must state that a drug is indicated for the treatment, prevention, mitigation, cure, or diagnosis of a recognized disease or condition or of a manifestation of a recognized disease or condition, or for the relief of symptoms associated with a recognized disease or condition.” Such regulations, however, do not require that disease be defined solely as a specific tumor type. This manuscript will highlight scientific/biologic issues, clinical trial designs, and regulatory issues pertaining to the development of drugs agnostic of tumor type. Although the manuscript will discuss regulatory considerations as understood by the authors regarding tissue-agnostic drug development, it should not be considered formal or binding FDA guidance or policy.
Clinical Pathways and the Patient Perspective in the Pursuit of Value-Based Oncology Care
Authors: Ersek Jennifer L. , Nadler Eric , Freeman-Daily Janet , Mazharuddin Samir , Kim Edward S.
Published: October 2018

The art of practicing oncology has evolved substantially in the past 5 years. As more and more diagnostic tests, biomarker-directed therapies, and immunotherapies make their way to the oncology marketplace, oncologists will find it increasingly difficult to keep up with the many therapeutic options. Additionally, the cost of cancer care seems to be increasing. Clinical pathways are a systematic way to organize and display detailed, evidence-based treatment options and assist the practitioner with best practice. When selecting which treatment regimens to include on a clinical pathway, considerations must include the efficacy and safety, as well as costs, of the therapy. Pathway treatment regimens must be continually assessed and modified to ensure that the most up-to-date, high-quality options are incorporated. Value-based models, such as the ASCO Value Framework, can assist providers in presenting economic evaluations of clinical pathway treatment options to patients, thus allowing the patient to decide the overall value of each treatment regimen. Although oncologists and pathway developers can decide which treatment regimens to include on a clinical pathway based on the efficacy of the treatment, assessment of the value of that treatment regimen ultimately lies with the patient. Patient definitions of value will be an important component to enhancing current value-based oncology care models and incorporating new, high-quality, value-based therapeutics into oncology clinical pathways.
More Medicine, Fewer Clicks: How Informatics Can Actually Help Your Practice
Authors: Patt Debra A. , Bernstam Elmer V. , Mandel Joshua C. , Kreda David A. , Warner Jeremy L.
Published: October 2018

In the information age, we expect data systems to make us more effective and efficient—not to make our lives more difficult! In this article, we discuss how we are using data systems, such as electronic health records (EHRs), to improve care delivery. We illustrate how US Oncology is beginning to use real-world evidence to facilitate trial accrual by automatic identification of eligible patients and how big data and predictive analytics will transform the field of oncology. Some information systems are already being used at the point of care and are already empowering clinicians to improve the care of their patients in real time. Telehealth platforms are being used to bridge gaps that currently exist in expertise, geography, and technical capability. Optimizing virtual collaboration, such as through virtual tumor boards, is empowering communities that are geographically disparate to coordinate care. Informatics methods can provide solutions to the challenging problems of how to manage the vast amounts of data confronting the practicing oncologist, including information about treatment regimens, side effects, and the influence of genomics on the practice of oncology. We also discuss some of the challenges of clinical documentation in the modern era, and review emerging efforts to engage patients as digital donors of their EHR data.
The Oncology Care Model: Perspectives From the Centers for Medicare & Medicaid Services and Participating Oncology Practices in Academia and the Community
Authors: Kline Ron , Adelson Kerin , Kirshner Jeffrey J. , Strawbridge Larissa M. , Devita Marsha , Sinanis Naralys , Conway Patrick H. , Basch Ethan
Published: October 2018

Cancer care delivery in the United States is often fragmented and inefficient, imposing substantial burdens on patients. Costs of cancer care are rising more rapidly than other specialties, with substantial regional differences in quality and cost. The Centers for Medicare & Medicaid Services (CMS) Innovation Center (CMMIS) recently launched the Oncology Care Model (OCM), which uses payment incentives and practice redesign requirements toward the goal of improving quality while controlling costs. As of March 2017, 190 practices were participating, with approximately 3,200 oncologists providing care for approximately 150,000 unique beneficiaries per year (approximately 20% of the Medicare Fee-for-Service population receiving chemotherapy for cancer). This article provides an overview of the program from the CMS perspective, as well as perspectives from two practices implementing OCM: an academic health system (Yale Cancer Center) and a community practice (Hematology Oncology Associates of Central New York). Requirements of OCM, as well as implementation successes, challenges, financial implications, impact on quality, and future visions, are provided from each perspective.
Gastric Cancer in Southern Europe: High-Risk Disease
Authors: De Mello Ramon Andrade
Published: October 2018

Gastric cancer is an aggressive disease. Several risk factors are involved in gastric cancer pathogenesis, likely Helicobacter pylori (H. pylori) infection, genetic factors in hereditary syndromes, lifestyle, and diet. However, well-implemented screening strategies are lacking in most countries, including those in Southern Europe. Nevertheless, gastric cancer outcomes are better in some Southern European countries than in others, likely because of the incidence and distribution of different histologic types. Robotic surgery has been gaining favor as a treatment of early-stage disease, and the need for perioperative chemotherapy or adjuvant chemoradiotherapy (CRT) for locally advanced disease has been debated. In the metastatic setting, trastuzumab in combination with chemotherapy has helped to extend survival compared with chemotherapy alone for HER2-positive disease. This article will describe how gastric cancer is assessed and treated in Southern Europe in an attempt to correlate these approaches from a global perspective.
Cancer Care and Control as a Human Right: Recognizing Global Oncology as an Academic Field
Authors: Eniu Alexandru E. , Martei Yehoda M. , Trimble Edward L. , Shulman Lawrence N.
Published: October 2018

The global burden of cancer incidence and mortality is on the rise. There are major differences in cancer fatality rates due to profound disparities in the burden and resource allocation for cancer care and control in developed compared with developing countries. The right to cancer care and control should be a human right accessible to all patients with cancer, regardless of geographic or economic region, to avoid unnecessary deaths and suffering from cancer. National cancer planning should include an integrated approach that incorporates a continuum of education, prevention, cancer diagnostics, treatment, survivorship, and palliative care. Global oncology as an academic field should offer the knowledge and skills needed to efficiently assess situations and work on solutions, in close partnership. We need medical oncologists, surgical oncologists, pediatric oncologists, gynecologic oncologists, radiologists, and pathologists trained to think about well-tailored resource-stratified solutions to cancer care in the developing world. Moreover, the multidisciplinary fundamental team approach needed to treat most neoplastic diseases requires coordinated investment in several areas. Current innovative approaches have relied on partnerships between academic institutions in developed countries and local governments and ministries of health in developing countries to provide the expertise needed to implement effective cancer control programs. Global oncology is a viable and necessary field that needs to be emphasized because of its critical role in proposing not only solutions in developing countries, but also solutions that can be applied to similar challenges of access to cancer care and control faced by underserved populations in developed countries.
Screening and Treating Prostate Cancer in the Older Patient: Decision Making Across the Clinical Spectrum
Authors: Morgans Alicia K. , Dale William , Briganti Alberto
Published: October 2018

Treatment of the growing geriatric patient population is increasingly being recognized as a necessary priority of the oncology community. As the most common cancer among men in developed countries, prostate cancer afflicts a sizable portion of elderly men. Caring for this population requires knowledge of aspects of disease presentation, screening strategies, treatment approaches, and survivorship care considerations unique to the geriatric population. In this article, we review characteristics of prostate cancer screening and treatment decision making for localized disease in elderly men, including a discussion of the biology of disease in the elderly population. We also review best practices for providing treatment for localized and recurrent disease in an elderly population, including engaging in a basic geriatric assessment to determine fitness for treatment, eliciting information about patient preferences and support systems, and balancing treatment decisions in the context of these factors using the resources of a multidisciplinary care team. We then consider complications of prostate cancer survivorship related to systemic treatment in the elderly population of men with this disease. Finally, we emphasize the importance of engaging patients in treatment decision making across the spectrum of disease to personalize treatment plans and provide optimal care.
Tumor Evolution, Heterogeneity, and Therapy for Our Patients With Advanced Cancer: How Far Have We Come?
Authors: El-Deiry Wafik S. , Taylor Barry , Neal Joel W.
Published: October 2018

The clinical and molecular heterogeneity of various cancer types is well documented. In the era of precision oncology whereby molecular profiling of tumors is incorporated into clinical care, both intra- and intertumoral molecular and genetic heterogeneity have been described. Together, they impact patient treatment and outcomes. Host genetics and the tumor microenvironment impact on tumor evolution and heterogeneity through variations in immune cell infiltration, stromal variations, and selection pressures from hypoxia or nutrient stress, among others. Tumor progression and exposure to therapeutic agents lead to further molecular evolution and heterogeneity that is clinically relevant. Moreover, tumors that evolve after diagnosis and as a function of therapy generally become more aggressive and refractory to available therapeutics, including targeted agents and immunotherapy. The evolving clinical and molecular heterogeneity of patient tumors can be explored with various clinical and research-based specimens and testing such as pre- and post-treatment biopsies; serial liquid biopsies; single cell analysis; PDX and organoid models; anatomic, functional, and molecular imaging; and rapid postmortem studies. Other factors that influence tumor heterogeneity include immune checkpoints, cancer stem cells, therapy-acquired resistance mechanisms that may occur through secondary mutations, and adaptive responses. Modern technologic advances for tumor characterization provide opportunities to understand tumor evolution and its impact on clinical outcomes to improve therapeutic regimens. Characterization of novel targets and development of effective therapeutics are needed to target heterogeneity and the evolution of resistance mechanisms.
Perspectives on the Use of Clinical Pathways in Oncology Care
Authors: Chiang Anne C. , Ellis Peter , Zon Robin
Published: October 2018

Pathways and guidelines are valuable tools to provide evidence-based care in oncology. Pathways may be more restrictive than guidelines because they attempt (where possible) to reduce cost, add efficiency, and remove unwarranted variability. Pathways offer an opportunity to measure, report, and improve quality of care; they can drive to evidence-based targeted therapy where appropriate; they can enhance efficiency through standardization; and, finally, they can be a vehicle to enhance participation in clinical trials. Pathway implementation requires understanding and commitment on the part of the physician and leadership as they may initially disrupt workflow, but ultimately have the ability to enhance patient care. ASCO criteria have been published for the development and implementation of high-quality oncology pathway programs. Future challenges for pathways include incorporation of molecular testing and appropriate targeted care in a real-time precision oncology approach.
Practice Model for Advanced Practice Providers in Oncology
Authors: Cairo Jamie , Muzi Mary Ann , Ficke Deanna , Ford-Pierce Shaunta , Goetzke Katrina , Stumvoll Diane , Williams Laurie , Sanchez Federico A.
Published: October 2018

According to ASCO, the number of practicing oncologists has remained stable despite growth demands, leading to an overall shortage in many areas of the country. Nurse practitioners and physician assistants are advanced practice providers (APPs) who can assist in the provision of support and care to patients with cancer, but the role of the APP in the oncology setting has not been well defined. There exists a variety of different practice patterns for APPs who work in oncology, and the lack of role definition and absence of an established practice model are considered leading causes of APP attrition. According to the American Academy of Nurse Practitioners, it has been well demonstrated that, when nurse practitioners are allowed to work to the full scope of their education and preparation, there are notable cost reductions and quality improvements in patient care. The focus of APP education and training is on health promotion, disease prevention, and primary care medical management, but most APPs have limited exposure to management of cancer in patients. With this in mind, Aurora Cancer Care developed a practice model for APPs who work in oncology. The goal of the model is to enhance the quality of care delivered to patients and provide a stimulating work environment that fosters excellent collaborative relationships with oncologist colleagues, supports professional growth, and allows APPs to practice to the full extent of their licensure.
Standard and Genomic Tools for Decision Support in Breast Cancer Treatment
Authors: Henry N. Lynn , Bedard Philippe L. , DeMichele Angela
Published: October 2018

Over the past few decades, comprehensive characterization of the cancer genome has elucidated pathways that drive cancer and mechanisms of resistance to therapy and provided important insights for development of new therapies. These advances have resulted in the development of prognostic and predictive tools for use in clinical settings, which can assist clinicians and patients in making informed decisions about the benefits of established therapies. In early-stage breast cancer, multiparameter genomic assays are now available for decision making about the duration of adjuvant endocrine therapy and the use of adjuvant chemotherapy. Similarly, in metastatic disease, there are multiple commercially available next-generation sequencing options for identifying genetic alterations in tumors that may be targeted with a drug. Although these tools hold great promise for providing precision medicine, it can be difficult for the treating physician to evaluate their clinical utility and appropriately select tools for individual clinical situations. This review summarizes the currently available genomic tools in breast cancer, the data underlying their clinical validity and utility, and how they can be used in conjunction with standard clinicopathologic data for making adjuvant and metastatic treatment decisions.
Optimal Management of Early and Advanced HER2 Breast Cancer
Authors: Hurvitz Sara A. , Gelmon Karen A. , Tolaney Sara M.
Published: October 2018

Approximately 15%–20% of breast cancer is HER2 positive, and patients with this subtype of disease historically had worse outcomes than patients with HER2-negative disease. However, the introduction of HER2-directed therapies has dramatically altered outcomes for these patients, especially for persons with early disease. However, despite these achievements, metastatic disease is still not curable. This review summarizes the current treatment approach for patients in the preoperative and adjuvant setting, including data regarding selecting the optimal chemotherapy partner as well as determining the duration and type of anti-HER–directed therapy. This article also reviews how to approach patients with advanced HER2-positive disease and discusses promising new therapies that are in development.
mHealth: Mobile Technologies to Virtually Bring the Patient Into an Oncology Practice
Authors: Pennell Nathan A. , Dicker Adam P. , Tran Christine , Jim Heather S. L. , Schwartz David L. , Stepanski Edward J.
Published: October 2018

Accompanied by the change in the traditional medical landscape, advances in wireless technology have led to the development of telehealth or mobile health (mHealth), which offers an unparalleled opportunity for health care providers to continually deliver high-quality care. This revolutionary shift makes the patient the consumer of health care and empowers patients to be the driving force of management of their own health through mobile devices and wearable technology. This article presents an overview of technology as it pertains to clinical practice considerations. Telemedicine is changing the way clinical care is delivered without regard for proximity to the patient, whereas nonclinical telehealth applications affect distance education for consumers or clinicians, meetings, research, continuing medical education, and health care management. Technology has the potential to reduce administrative burdens and improve both efficiency and quality of care delivery in the clinic. Finally, the potential for telehealth approaches as cost-effective ways to improve adherence to treatment is explored. As telehealth advances, health care providers must understand the fundamental framework for applying telehealth strategies to incorporate into successful clinical practice.
Caring for the Older Population With Advanced Lung Cancer
Authors: Presley Carolyn J. , Reynolds Craig H. , Langer Corey J.
Published: October 2018

The management of advanced lung cancer is changing rapidly, with new drug approvals occurring almost monthly. The average age of a newly diagnosed patient with advanced lung cancer remains around age 70. Caring for the older adult with advanced cancer differs from the care of younger adults. Chronologic age often does not accurately reflect the physiologic and functional status of older adults. Selecting treatment based on age alone results in undertreatment and overtreatment of many older adults. Addressing issues such as multiple chronic conditions, polypharmacy, geriatric syndromes, and heterogeneity in functional status among an expanding menu of treatment options for advanced disease is increasingly difficult, particularly among older adults historically underrepresented in clinical trials. In this article, we highlight key issues in caring for the older adult with advanced non–small cell lung cancer and the continued need for data supporting current and emerging treatment options. Key issues include the unique challenges of managing advanced lung cancer and a summary of the current treatment evidence as they apply to the elderly lung cancer population including supportive care strategies, risk stratification, and patient-reported outcomes.
Adoptive T-Cell Therapy for Solid Tumors
Authors: Yeku Oladapo , Li Xinghuo , Brentjens Renier J.
Published: October 2018

Chimeric antigen receptor (CAR) T-cell therapy is an innovative form of immunotherapy wherein autologous T cells are genetically modified to express chimeric receptors encoding an antigen-specific single-chain variable fragment and various costimulatory molecules. Upon administration, these modified T cells traffic to, and recognize, cancer cells in an HLA-independent manner. CAR T-cell therapy has shown remarkable success in the treatment of CD-19–expressing B-cell acute lymphocytic leukemia. However, clinical gains to the same magnitude have not been reported in solid tumors. Several known obstacles to CAR T-cell therapy for solid tumors include target antigen identification, effective trafficking to the tumor, robust activation, proliferation, and in vivo cytotoxicity. Beyond these T-cell intrinsic properties, a complex and dynamic immunosuppressive tumor microenvironment in solid tumors hinders T-cell efficacy. Notable advancements in CAR design to include multiple costimulatory molecules, ligands, and soluble cytokines have shown promise in preclinical models, and some of these are currently in early-phase clinical trials. In this review, we discuss selected solid tumor malignancies and relevant preclinical data and highlight clinical trial results that are available. Furthermore, we outline some obstacles to CAR T-cell therapy for each tumor and propose strategies to overcome some of these limitations.
European/U.S. Comparison and Contrasts in Ovarian Cancer Screening and Prevention in a High-Risk Population
Authors: Mourits Marian J. , de Bock G. H.
Published: October 2018

The history of screening and prevention of ovarian cancer among high-risk women in the United States and Europe is one of mutual inspiration, with researchers learning from each others’ findings and insights and collaborating with investigators from both sides of the Atlantic ocean. Examples of simultaneous and joint development of knowledge and scientific points of view include the paradigm shift from ovarian to fallopian tube high-grade serous cancer and the cessation of simultaneous adoption of ovarian cancer screening by clinicians in both the United States and Europe. Examples of joint efforts with fruitful results include international collaboration in large population-based, genome-wide association studies and in epidemiologic database studies. Research in the field of hereditary ovarian cancer is a great example of mutual inspiration and joint efforts for the purpose of improving knowledge and health care for women with hereditary ovarian cancer.
Surgical Management of Advanced Kidney Cancer: The Role of Cytoreductive Nephrectomy and Lymphadenectomy
Authors: Patel Hiten D. , Karam Jose A. , Allaf Mohamad E.
Published: October 2018

Despite the evolution of systemic therapy from the immunotherapy to targeted therapy eras, surgical management remains a mainstay of treatment of patients with locally advanced, lymph node–positive, and distant metastatic renal cell carcinoma. Balancing patient and disease characteristics with the potential morbidity of surgery has gained increasing attention to better define the role of cytoreductive nephrectomy and lymphadenectomy. In this review, we critically evaluate the literature for the potential therapeutic role of cytoreductive nephrectomy and lymphadenectomy in advanced kidney cancer, highlighting current evidence, limitations, and best-management practices. Although retrospective data supported a similar survival benefit for cytoreductive nephrectomy in the targeted therapy era as it did for the initial immunotherapy era (1992 to 2006), level 1 evidence from the randomized Clinical Trial to Assess the Importance of Nephrectomy (CARMENA) demonstrated no benefit for intermediate- and poor-risk patients in the setting of sunitinib therapy. Level 1 evidence among a favorable-risk subset is still awaited from the trial Targeted Therapy With or Without Nephrectomy in Metastatic Renal Cell Carcinoma: Liquid Biopsy for Biomarkers Discovery (TARIBO). Another trial, Immediate Surgery or Surgery After Sunitinib Malate in Treating Patients With Metastatic Kidney Cancer (SURTIME), has compared upfront cytoreductive nephrectomy prior to targeted therapy with the initial initiation of targeted therapy followed by deferred cytoreductive nephrectomy. Lymphadenectomy is yet another controversial but less well-defined management option for patients with kidney cancer. The role of lymphadenectomy has been studied in both the localized and advanced settings over the past few decades, with a strong suggestion of no therapeutic benefit for patients with cT1-2N0M0 and cM1 disease, and with uncertain benefit in patients with high-risk disease (ie, locally advanced or cN1M0), leading to weak statements among clinical guidelines.
Imaging Advances in the Management of Kidney Cancer
Authors: Krajewski Katherine M. , Pedrosa Ivan
Published: October 2018

New developments in cross-sectional imaging, including contrast-enhanced ultrasound, dual-energy computed tomography, multiparametric magnetic resonance imaging, single-photon emission computed tomography, and positron emission tomography, together with novel application of existing and novel radiotracers, have changed the landscape of renal mass characterization (ie, virtual biopsy) as well as the detection of metastatic disease, prognostication, and response assessment in patients with advanced kidney cancer. A host of imaging response criteria have been developed to characterize the response to targeted and immune therapies and correlate with patient outcomes, each with strengths and limitations. Recent efforts to advance the field are aimed at increasing objectivity with quantitative techniques and the use of banks of imaging data to match the vast genomic data that are becoming available. The emerging field of radiogenomics has the potential to transform further the role of imaging in kidney cancer management through eventual noninvasive characterization of the tumor histology and genetic microenvironment in single renal masses and/or metastatic disease. We review of the effect of currently available imaging techniques in the management of patients with kidney cancer, including localized, locally advanced, and metastatic disease.
Non–Clear Cell Renal Cell Carcinomas: From Shadow to Light
Authors: Albiges Laurence , Flippot Ronan , Rioux-Leclercq Nathalie , Choueiri Toni K.
Published: October 2018

Non–clear cell renal cell carcinomas (RCCs) account for up to 25% of kidney cancers and encompass distinct diseases with distinct pathologic features, different molecular alterations, and various patterns of response to systemic therapies. Recent advances in molecular biology and large collaborative efforts helped to better define the oncogenic mechanisms at play in papillary, chromophobe, collecting duct, medullary, translocation, and sarcomatoid RCCs. Papillary RCCs are divided into several subsets of tumors characterized by distinct gene expression profiles, chromatin remodeling genes, cell cycle changes, and alterations of the MET pathway. Chromophobe RCC genomic analysis revealed mostly metabolic pathway alterations with mitochondrial dysfunctions. Translocation RCCs are characterized by MITF fusions and wide genomic reprogramming. Collecting duct carcinomas are distinct entities from upper tract urothelial carcinomas associated with high T-cell infiltration and metabolic alterations. Medullary RCCs present alterations of the INI1 gene and rhabdoid features at pathologic analysis. Finally, sarcomatoid RCCs represent sarcomatoid differentiation for any subsets of RCCs with specific alterations associated with mesenchymal dedifferentiation. From the standpoint of systemic therapy, more than a decade of using VEGF and mTOR inhibitors showed that they generally had limited efficacy in non–clear cell RCCs compared with clear cell RCCs. MET inhibitors are actively being developed for papillary RCC with a specific focus on MET-driven tumors. Other strategies under investigation include CDK4/6 inhibitors in tumors with cell cycle alterations and EZH2 inhibitors in RCCs with INI1 loss. The emergence of immune checkpoint inhibitors and combination strategies enlarges the spectrum of investigational treatments. Better understanding of driver and passenger alterations and better patient stratification along with dedicated clinical networks will be key to improving the management of these rare tumors.
Chromosome 3p Loss–Orchestrated VHL, HIF, and Epigenetic Deregulation in Clear Cell Renal Cell Carcinoma
Authors: Hsieh James J. , Le Valerie H. , Oyama Toshinao , Ricketts Christopher J. , Ho Thai Huu , Cheng Emily H.
Published: October 2018

Clear cell renal cell carcinoma (ccRCC) is the most common renal cell carcinoma subtype, and metastatic ccRCC is associated with 5-year survival rates of 10% to 20%. Genetically, ccRCC originates from sequential losses of multiple tumor suppressor genes. Remarkably, chromosome 3p loss occurs in more than 90% of sporadic ccRCCs. This results in concurrent one-copy loss of four tumor suppressor genes that are also mutated individually at high frequency in ccRCC (ie, VHL, 80%; PBRM1, 29% to 46%; BAP1, 6% to 19%; and SETD2, 8% to 30%). Pathogenically, 3p loss probably represents the first genetic event that occurs in sporadic ccRCC and the second genetic event in VHL-mutated hereditary ccRCC. VHL constitutes the substrate recognition module of the VCB-Cul2 E3 ligase that degrades HIF1/2α, whereas PBRM1, BAP1, and SETD2 are epigenetic modulators that regulate gene transcription. Because 3p loss and VHL inactivation are nearly universal truncal events in ccRCC, the resulting HIF1/2 signaling overdrive and accompanied tumor hypervascularization probably underlie the therapeutic benefits observed with vascular endothelial growth factor receptor inhibitors, including sorafenib, sunitinib, pazopanib, axitinib, bevacizumab, cabozantinib, and lenvatinib. Furthermore, recent marked advances in ccRCC genomics, transcriptomics, proteomics, metabolomics, molecular mechanisms, mouse models, prognostic and predictive biomarkers, and clinical trials have rendered invaluable translational insights concerning precision kidney cancer therapeutics. With an armamentarium encompassing 13 drugs that exploit seven unique therapeutic mechanisms (ie, cytokines, vascular endothelial growth factor receptor, mTORC1, cMET/AXL, fibroblast growth factor receptor, programmed cell death-1 and programmed death-ligand 1, and cytotoxic T-cell lymphocyte associated-4) to treat metastatic renal cell carcinoma, one of the imminent clinical questions concerning care of patients with metastatic ccRCC is how a personalized treatment strategy, through rationally combining and sequencing different therapeutic modalities, can be formulated to offer the best clinical outcome for individual patients. Here, we attempt to integrate recent discoveries of immediate translational impacts and discuss future translational challenges and opportunities.
The Immunobiology of Kidney Cancer
Authors: Drake Charles G. , Stein Mark N.
Published: October 2018

Although kidney cancer (renal cell carcinoma [RCC]) is susceptible to immunotherapy, the immunologic aspects of the tumor microenvironment (TME) in RCC are relatively unique among tumor types. In RCC, baseline CD8 T-cell infiltration is associated with a worse prognosis. In addition, kidney cancer responds to programmed death-1/programmed death-ligand 1 blockade, despite a relatively low tumor mutation burden. Recent clinical data highlight the efficacy of combined immune checkpoint blockade and demonstrate that combining antiangiogenic agents with programmed death-1/programmed death-ligand 1 blockade has additive activity. Yet an important unanswered question in RCC is the nature of the antigens that are targeted by the immune system when immunotherapy is successful. Ongoing clinical studies are interrogating the multiple suppressive mechanisms in the RCC TME, including metabolic pathways such as those mediated by adenosine and tryptophan as well as cytokine-based therapies. Future regimens are likely to be combinatorial and may eventually be based on a broader understanding of the RCC TME and how it is modulated by both conventional and immune-based therapy.
Novel Agents and Drug Development Needs in Advanced Clear Cell Renal Cancer
Authors: Powles Thomas , Rini Brian
Published: October 2018

The treatment of metastatic clear cell renal cancer is changing rapidly, with the focus switching from vascular endothelial growth factor–targeted therapies to immune checkpoint inhibitors and novel combinations. Specifically, recent data with programmed death ligand inhibitors is revolutionizing the standard approach to metastatic renal cell carcinoma. However, there is speculation around a number of newer potentially therapeutic targets, such as indoleamine 2,3-dioxygenase, transforming growth factor-β, interleukin-10, and adenosine. In this article, we review novel treatments, promising combinations, and consideration in both trial design and clinical application of therapeutics that will influence practice in the future.
Efficacy of an Intensive, Ultrasound-Guided Fine-Needle Aspiration Biopsy Training Workshop in Tanzania
Authors: Ng Dianna L. , Vuhahula Edda , Zhang Li , Waterhouse Emily G. , White Kristie L. , Mushi Beatrice Paul , Nyeriga Msiba Selekwa , Philipo Godfrey Sama , Mmbaga Elia J. , Sheth Sujay , Van Loon Katherine , Lee Amie Y. , Balassanian Ronald
Published: October 2018

Background

Fine-needle aspiration biopsy (FNAB) is a minimally invasive, cost-effective diagnostic tool that can be used in low-resource settings. However, adequacy and accuracy of FNAB is highly dependent on the skills of the operator and requires specialized training. Poor technique can preclude definitive diagnoses because of insufficient quality or quantity of FNAB samples. We evaluated the efficacy of an intensive training experience in Tanzania on improving ultrasound-guided FNAB techniques.

Methods

A 2-day workshop offered didactic lectures, demonstrations, and hands-on practicum on fundamentals of ultrasound imaging and FNAB technique. A prospective interventional study design was used with pre- and postintervention surveys and assessments to measure the effect of the workshop on specific skills related to slide smearing and ultrasound-guidance among participants.

Results

Twenty-six pathologists and radiologists, including trainees in each specialty, participated in the workshop. Pre- and postworkshop assessments demonstrated that most participants improved significantly in nearly all technical skills for slide smearing and ultrasound-guided FNAB. After the workshop, most participants demonstrated substantial improvements in ability to prepare the ultrasound equipment, measure the lesion in three dimensions by ultrasound, target lesions in one pass using both parallel and perpendicular approaches, and prepare high-quality aspirate smears.

Conclusion

An in-country 2-day workshop in Tanzania was efficacious in transferring basic skills in FNAB smear preparation and ultrasound-guided FNAB, resulting in skills enhancement among participating pathologists and radiologists. Although mastery of skills was not the goal of this short workshop, participants demonstrated proficiency in most technical elements after workshop completion, and the workshop generated interest among select participants to pursue additional intensive training in cytopathology.