bluuebunny/crossref_metadata_2025 huggingface dataset:
Cancer Bioinformatics
Authors: Weinstein John N.
Published: October 2022

Overview

Bioinformatics is a rapidly advancing interdisciplinary field in which computational methods are applied to the analysis, interpretation, and visualization of biological and/or medical data, most often at the cell or molecular level and usually in the form of large, multivariate datasets. PubMed citations for “bioinformatics” have risen sharply, increasing 24‐fold since the year 2000. Massively parallel sequencing and imaging technologies are now generating a data deluge—many trillions of numbers in all—that strain the capacity of our hardware, software, and personnel infrastructures for bioinformatics; hence, the computational aspect of a sequencing project is often more expensive and time‐consuming than the laboratory work. The field of bioinformatics includes “data scientists,” for whom useful innovative algorithms, software, and data structures are publishable ends in themselves, and “computational biologists,” for whom algorithms, software, and computers are just tools of the trade for answering biological or medical questions. Bioinformatic analysis can be hypothesis‐generating or hypothesis‐testing, and a large number of statistical and artificial intelligence algorithms, scripts, and software packages are now available for each type of analysis. In fact, the rapidly increasing number of options is almost paralyzing. Computational consortia formed around large‐scale, public, molecular profiling projects like The Cancer Genome Atlas project have served as incubators for rapid computational advance, particularly driving major innovations in single‐cell informatics, artificial intelligence, and computational immunology. One attractive working arrangement is a stable “dyad” in which the bioinformatician focuses primarily on database management, statistical analysis, and data visualization, whereas the biologist/clinical researcher focuses primarily on interpretation and biomedical application.
Biomarker Based Clinical Trial Design in the Era of Genomic Medicine
Authors: Harvey R. Donald , Liu Yuan , Owonikoko Taofeek K. , Ramalingam Suresh S.
Published: October 2022

Overview

The expansion of understanding in genomics and molecular biology of cancer development and progression has led to greater subtyping of tumor types beyond histology alone. Along with improved drug development and medicinal chemistry approaches, this understanding has led to a need for an evolution in clinical trial design and analysis. Multiple groups of smaller populations treated with targeted agents have been employed to improve speed and efficiency of efficacy signals. We review these novel trial designs for the development of biomarker‐driven therapeutics and diagnostics to inform their use.
Ionizing Radiation
Authors: Grdina David J.
Published: October 2022

Overview

Many experimental and epidemiologic studies have since confirmed the oncogenic effects of radiation. This chapter reviews briefly the effects of ionizing radiation on biological systems, adaptive and bystander effects, cellular and molecular mechanisms for radiation carcinogenesis, and pharmacologic countermeasures that can mitigate against these processes.
Herpesviruses
Authors: Cohen Jeffrey I.
Published: October 2022

Overview

Eight herpesviruses have been isolated from humans: two of these, Epstein–Barr virus (EBV), and Kaposi sarcoma‐associated herpesvirus (KSHV), are associated with human tumors. EBV has been detected in lesions from patients with posttransplant lymphoproliferative disease, nasopharyngeal and some types of gastric carcinoma, Burkitt lymphoma, Hodgkin lymphoma, and certain other lymphoid tumors. KSHV is associated with Kaposi sarcoma, primary effusion lymphoma, and Castleman disease. Each of these viruses encodes proteins important for establishment of latency, transforming cells, and evading the immune system.
Cancer Epidemiology
Authors: Fedirko Veronika , Nead Kevin T. , Daniel Carrie , Scheet Paul
Published: October 2022

Overview

This article gives a straightforward introduction to cancer epidemiology and is organized as follows. We first provide US data on cancer cases, deaths, and survival. These data, typically derived from national registries and surveys from scientific organizations devoted to the cause, for example, surveillance by the National Cancer Institute's Surveillance, Epidemiology, and End Results Program (SEER) and the International Agency for Research on Cancer (IARC), form the basis for policies centered around cancer control. We then discuss epidemiological methods the practicing oncologist may encounter in research or literature, followed by a tour of common (e.g., tobacco) and emerging (e.g., energy balance) causes of cancer. We follow this by describing molecular epidemiology, a subfield rejuvenated by molecular technologies to inform components of environmental factors and risks associated with the host, such as genetics, transcriptomics, metabolomics, and the microbiome. Finally, we discuss future directions, the potential and current importance of epidemiology.
Diet and Nutrition in the Etiology and Prevention of Cancer
Authors: Clinton Steven K. , Giovannucci Edward L. , Tabung Fred K. , Grainger Elizabeth M.
Published: October 2022

Overview

Over the last two centuries, improvements in food production, processing, storage, and distribution have led to major changes in diet composition throughout the world. During this period, life expectancy also dramatically increased within economically developed nations because of a combination of factors, including public health measures, improved occupational safety, and major reductions in nutrient deficiency syndromes. As the population has aged, there has been a shift in the major causes of morbidity and mortality toward chronic diseases, such as cancer and cardiovascular disease. In the United States, recent decades are characterized by an increasingly sedentary population with an epidemic of obesity, a trend that is emerging worldwide. Although nutritional deficiencies still plague subpopulations in developed nations amongst the poor, aged, chronically ill, and alcoholics, we now recognize that the affluent dietary pattern contributes to the pathogenesis of many chronic diseases, including cancer, that afflict the vast majority of the population. Efforts to understand the often complex etiologies of various cancers have led to laboratory, clinical, and epidemiologic studies that strongly implicate specific nutrients and certain dietary patterns in human carcinogenesis. The objective of this article is to provide an overview of efforts to define public health guidelines that impact policy for global health organizations and nations, while also providing a foundation for individuals seeking to consume healthy dietary patterns.
Cancer Screening and Early Detection
Authors: Brawley Otis W.
Published: October 2022

Overview

Cancer screening is a means of early detection of malignancy in an asymptomatic individual at risk for the disease. A positive screening test calls for additional diagnostic tests. The purpose of screening is to find a small, localized tumor that is destined to grow, metastasize, and kill before it spreads. Effective treatment can then lead to prevention of death. Simply finding disease is not adequate proof of benefit. Proper evaluation of a screening
test
involves demonstration that it leads to reduced risk of death. Screening is a population‐based intervention; appropriate individuals should be in a program of routine screening. Screening and treatment involve interventions which are often invasive. Proper evaluation of a screening
program
involves assessment of outcomes and a comparison of the benefits and risks.
Psycho‐Oncology
Authors: Banerjee Diya , Roth Andrew J.
Published: October 2022

Overview

Cancer increasingly is a disease of aging adults, given better diagnostic tools and improved and innovative treatments. This once uniformly deadly experience has been transformed into one that if not cured, can be lived with for longer periods of times as a chronic illness. Thus, the emotional needs of patients, family members and society has also morphed into more hope for potential and realized cures and therapies. However, dealing with a life‐threatening disease and the existential reality of mortality still brings on various emotions from sadness to depression, worry to anxiety to panic, to traumatic stress. Harsh treatments can cause delirium as well as changes in cognition., and the biology of cancer itself, with an impact on hormonal axes and generation of inflammatory responses, can engender psychiatric sequelae. These emotional, medical and psychiatric sequelae of cancer and cancer treatment are important to recognize and address in order to enhance adherence with complicated cancer treatment regimens, potentially improving success of these treatments, and, if needed, coping better with adverse outcomes. This article outlines basic information oncology treatment providers need for assessment and management of the most common psychiatric complications.
Principles of Cancer Rehabilitation Medicine
Authors: Stubblefield Michael D. , Escalon Miguel , Barchuk Sofia A. , Vyas Krina , Thomas David C.
Published: October 2022

Overview

Cancer is the abnormal and unchecked growth of cells in the body. There are many types of cancer and all of them have the potential to inflict a multitude of physical, cognitive, and psychological impairments that reduce functional capacity and quality of life. Aside from the direct physiologic impact of cancer on the human body, oncologic treatment can also have negative consequences. Cancer rehabilitation is the process of restoring function and quality of life (QOL) to cancer survivors by helping them achieve and maintain maximal physical, social, psychological, and vocational functioning within limits created by cancer and its treatments. Persons with cancer and undergoing treatment for cancer can have varied impairments including pain, weakness, sensory deficits and more, so a comprehensive team approach is crucial to ensure effective rehabilitation. Common secondary complications faced by those with cancer include fatigue, pain, neuropathy, lymphedema, and radiation fibrosis syndrome. This review aims to focus on delivering the most up to date information on cancer rehabilitation in brain, spinal cord, head and neck, as well as breast cancer with an emphasis on presenting new therapeutic techniques in the field.
Pharmacology of Small‐Molecule Anticancer Agents
Authors: Talebi Zahra , Baker Sharyn D. , Sparreboom Alex
Published: October 2022

Overview

The biology and clinical indications relevant to systemic anticancer therapies are covered extensively in other articles in this encyclopedia. In this article, we will focus on the principles of clinical pharmacology as they apply to systemic anticancer therapies and will attempt to illustrate how an understanding of clinical pharmacokinetics and pharmacodynamics can optimize the therapeutic index of these agents.
Pyrimidine and Purine Antimetabolites
Authors: Diasio Robert B. , Offer Steven M.
Published: October 2022

Overview

Antimetabolites based on pyrimidine and purine bases are some of the most widely used anti‐cancer drugs globally. Nucleotides, which consist of purine or pyrimidine bases covalently linked to five‐carbon carbohydrate group and one or more phosphate groups, are the “building blocks” of DNA and RNA that underlie fundamental cellular processes such as cellular proliferation and protein synthesis. The development of pyrimidine and purine antimetabolite drugs has been based on the rationale that nucleic acids are essential for these critical functions. Purine and pyrimidine antimetabolites have been shown to be highly effective against solid tumors such as colon and breast cancers, as well in certain hematological malignancies. Effectiveness has also been shown against primary tumors and against select advanced metastatic cancers. The mechanism of action and toxicity profiles associated with each drug vary, depending on biochemical structure, predominant mechanism(s) of action, metabolism, dose, and treatment schedule. The development of prodrugs has allowed for various administration routes, including orally bio‐available compounds. Combination therapies in which antimetabolites are co‐administered with other drugs have generally improved the efficacy of treatments without dramatic increases in toxicity compared to monotherapy. Healthcare providers should be aware of potentially serious drug–drug interactions, particularly when co‐administered drugs are metabolized by the same or linked enzymatic pathways. Furthermore, for many antimetabolites, genetic and nongenetic biomarkers have been demonstrated to be associated with varying degrees of risk for severe drug‐related adverse events, which in severe cases can result in death. Genotyping and DNA sequencing are increasingly being used to identify carriers of risk genotypes. The resulting pharmacogenomic data have shown strong potential for informing optimized treatment approaches and individualized dose‐adjustment to reduce the risk for developing severe drug‐related toxicity. Even with pharmacogenetically guided dosing, patients receiving this class of chemotherapeutics should be monitored closely for the development of adverse events. Ongoing research in this clinical area focuses on identifying biomarkers of response and/or toxicity, optimizing bioavailability and efficacy, and evaluating combination regimens containing multiple classes of anti‐cancer therapies. In this chapter, we review the various antimetabolite drugs that are analogs of uracil/thymine, cytidine/deoxycytidine, hypoxanthine/guanine, and adenosine that are used in cancer treatment. The focus is on metabolism, mechanism of action, clinical pharmacology, clinical activity, and toxicity.
Cancer Gene Therapy
Authors: Tashiro Haruko , Scherer Lauren , Brenner Malcolm
Published: October 2022

Overview

The encouraging results of cancer gene therapies have increased their entry into mainstream oncological practice. Gene transfer or gene editing can modify the cellular phenotype and behavior of malignant cells or of host cells, thereby modulating tumor responses. In this article, we discuss both of the above approaches and describe the vector systems that are able to produce the intended genetic modifications. We describe current clinical successes of gene therapy and outline the challenges it has yet to overcome. The success of any gene therapy for cancer requires efficient, safe gene transfer with vectors that can either integrate into the human genome (e.g., retroviral, lentiviral, adeno‐associated viral, or nonviral transposons) or remain largely or completely episomal (e.g., adenoviral, herpesviral, or nonviral plasmids). To date, genetic “correction” of consequential numbers of cancer cells has not proven feasible, but infectious cytolytic viral therapy, used with accompanying immunomodulatory genes within the oncolytic virus, is beginning to demonstrate an impact in the clinic. Enhancement of active cancer immunotherapy with forced expression of antigens and cytokines or the enhancement of adoptive immunotherapy by engineering T lymphocytes with specific T‐cell receptors and/or chimeric antigen receptors shows greatest immediate promise, although ultimately a combination of multiple approaches will prove optimal.
Cancer Nanotechnology
Authors: Jiang Xingya , Liu Yanlan , Liu Danny , Shi Jinjun , Langer Robert
Published: October 2022

Overview

The advances in state‐of‐the‐art nanotechnologies have offered enormous opportunities to overcome many obstacles in cancer therapy, such as suboptimal pharmacokinetics and therapeutic efficacy of anticancer drugs, their severe adverse effects, and the development of drug resistance. Here, we highlight clinical‐stage nanoparticle technologies applied in conventional cancer therapies and the development of novel classes of anticancer therapeutics. We also discuss recent cutting‐edge research efforts in this exciting field, which could lead to the development of novel and more effective cancer nanomedicines.
Cancer and Pregnancy
Authors: Litton Jennifer K.
Published: October 2022

Overview

The diagnosis of cancer during pregnancy is a clinical and emotional challenge for both the patient and the caregivers. A multidisciplinary approach including medical oncologists, surgeons, radiation oncologists, and obstetrics is vital to coordinate the treatment of the mother and the monitoring of the fetus. The available data regarding the treatment of cancer during pregnancy, including staging, surgery, radiation, and systemic therapy as well as outcomes for the patients and the children exposed to chemotherapy
in utero
is reviewed.
Neoplasms in People Living with Human Immunodeficiency Virus
Authors: Wang Chia‐Ching J. , Chiao Elizabeth Y.
Published: October 2022

People living with human immunodeficiency viruses (PLWH) are at increased risk for developing malignancies, particularly virally mediated cancers such as Kaposi sarcoma (KS), some types of lymphoma, and HPV‐related cancers, such as cervical cancer and anal cancer. PLWH also have higher rates of alcohol and tobacco use, which increases their risk of non‐virally mediated cancers, such as lung cancer and both oropharyngeal and non‐oropharyngeal head and neck cancers. KS and lymphomas tend to occur at lower CD4 counts, and the incidences of these cancers have decreased since the advent of effective combination antiretroviral therapy (ART). However, the incidence for virally mediated cancers (such as anal cancer) other non‐virally‐mediated non‐acquired immunodeficiency syndrome‐defining cancers (such as lung cancer) have risen in the past decade in part because PLWH are living longer with wide‐spread access to ART. In the past, PLWH with cancers often had lower survival and poorer outcomes due to severe immunodeficiency and poor performance status. In the modern ART era, survival and outcomes for individuals with human immunodeficiency virus (HIV)‐associated lymphomas are generally similar to the HIV‐negative population using standard rituximab‐based multi‐agent chemotherapy. For PLWH with other solid tumors, standard of care treatment is also currently recommended. Active areas of research for cancers in PLWH includes cancer prevention, immunotherapy, and continued development of new therapeutics to improve outcomes.
Cancer Survivorship
Authors: Foxhall Lewis
Published: October 2022

Overview

Continued advances in early detection and treatment as well as an increased proportion of older individuals in the United States have supported an ever‐expanding population of cancer survivors. Many live decades after completing treatment but with relatively frequent occurrence of persistent or late‐occurring side effects of treatment that may impinge on quality of life. The occurrence of second cancers and an increasing prevalence of comorbid conditions with aging, psychosocial problems, and opportunities for general health improvement warrant careful attention by clinicians. This article examines the growing awareness of the common challenges faced by survivors and highlights recommended strategies for management of these conditions. Consideration of health‐system‐related barriers to optimum care will focus on potential improvements in practice, potentially offering improvements in quality of care for cancer survivors.
Neoplasms of the Eye and Orbit
Authors: Alvarez Erica R. , Prospero Ponce Claudia M. , Chevez‐Barrios Patricia , Gombos Dan S.
Published: October 2022

Overview

Cancers of the eye and orbit are associated with diverse pathological conditions, disease prognosis, and significant mortality. The survival rates vary among patients from different countries and have been reported to be significantly lower in those from developing countries compared to those noted in the United States owing mainly to delay in diagnosis associated with advanced‐stage disease and unavailability of treatments. In this article, we provide an overview of the most common and rare ophthalmic malignancies that include ocular surface, external and adnexal diseases, and orbital and intraocular malignancies. We summarize the incidence, histopathology, risk factors, molecular alterations, clinical presentation, diagnostic evaluation, and therapeutic approaches for these diseases. We also describe the first‐line and salvage treatments and their complications. These treatments depend on disease stage at presentation and include pathology‐guided excision, Mohs microsurgery, chemo‐reduction, chemoprophylaxis, adjuvant chemotherapy after enucleation, and/or neoadjuvant chemotherapy. Complications include symblepharon, scarring, and limbal stem cell deficiency while incomplete excision of eyelid tumors may result in recurrence of larger and more aggressive tumors. Currently, identification of genetic abnormalities identified in genomic profiling of patient tumors improves treatment selection. Early diagnosis and involvement of an ocular oncologist at the time of diagnosis will optimize the therapeutic management of patients with these diseases.
Malignant Tumors of the Adrenal Gland
Authors: Lee Jeffrey E. , Habra Mouhammed A. , Campbell Matthew T.
Published: October 2022

Overview

Optimal evaluation and treatment of malignant or potentially malignant adrenal tumors including pheochromocytoma/paraganglioma and adrenal cortical carcinoma can be complex. It requires appropriate diagnostic imaging and endocrine hormone evaluation, and benefits from expert multidisciplinary coordination, by medical oncologists, endocrinologists, and surgeons, as well as additional specialists, for example genetic counselors. Recent advances in diagnostic imaging, including functional imaging such as PET, have facilitated early detection and diagnosis, enhanced the accuracy of staging, and improved treatment planning. Good‐risk patients with resectable localized, recurrent, or limited metastatic disease are usually recommended to undergo either minimally invasive or open surgery. Advances in minimally invasive and open surgical techniques have improved surgical outcomes. There is no defined role for adjuvant therapy following resection of pheochromocytoma/paraganglioma. Adjuvant therapy for patients with adrenal cortical carcinoma, most commonly single‐agent mitotane, is considered selectively. Systemic treatment options for patients with locally recurrent, unresectable, or metastatic malignant adrenal carcinoma include targeted treatments for patients with metastatic pheochromocytoma/paraganglioma, and combination chemotherapy with or without mitotane for patients with adrenal cortical carcinoma. Radiation therapy for patients with malignant adrenal tumors of either histology is also employed selectively. Emerging genetic and molecular data, as well as clinical trials, increasingly inform treatment strategies and choice of systemic therapy.
Tumors of the Diffuse Neuroendocrine and Gastroenteropancreatic System
Authors: Vosburgh Evan
Published: October 2022

Overview

The diffuse neuroendocrine system (DES) is represented by a small number of cells spread through the body, and the tumors that derive from these cells present a wide spectrum of epidemiologic, pathologic, biologic, genetic, and clinical features. Clinical and scientific investigation of the inherited multiple endocrine neoplasia (MEN) syndromes, and the various unique clinical syndromes secondary to secretion of specific peptides (e.g., insulinomas, glucagonomas, VIPomas) are challenging. Clinical presentation can be dramatic, nonspecific, or incidentally noted in absence of symptoms. Tumors might be small, difficult to detect tumors (<1 cm in size), or bulky hepatic metastases in a well patient. Cancer registry data show 5‐year survivals for tumors of the neuroendocrine system that have not improved in the past several decades, and that remain about 30–60%. The same registry data documents a rising and unexplained incidence of these tumors, particularly the neuroendocrine tumors of the gastroenteropancreatic system (GEP‐NETs), that when coupled with the long average survival results in prevalence figures similar to cancers such as testicular, ovarian, and multiple myeloma and pancreatic adenocarcinoma.

Recent advances in understanding of the genetics, biology, clinical features, and response to therapy are better defining subtypes of neuroendocrine tumors once clustered and studied as “carcinoids.” Revised histologic grouping and staging are informing ongoing clinical trials and are providing more informed clinical care of these diverse tumors. Surgery remains the best opportunity for cure at presentation and experience suggests a major role in local control of hepatic metastases. Recent trials of somatostatin analogs have better defined their utility. Results of a series of randomized trials of peptide receptor radiotherapy (PRRT) as well as chemotherapy and targeted therapies have expanded the therapeutic options for patients. Despite advances, the choice and sequencing of specific therapies remains poorly supported by clinical data.
Neoplasms of the Esophagus
Authors: Sung Max W. , Litle Virginia R.
Published: October 2022

Overview

Esophageal cancer, the sixth leading cause of cancer deaths worldwide, has benefitted from advances in therapeutic interventions, including noninvasive endoscopic mucosal resection for early‐stage disease, and minimally invasive robotic‐assisted surgical techniques for resection. For intermediate stage disease, multi‐modality approaches with the addition of neoadjuvant chemoradiation to resection are the standard of care. For advanced disease, the addition of hormonal, targeted, and immunomodulatory approaches have extended the benefits from systemic chemotherapy. The increased incidence in esophagogastric adenocarcinoma compared esophageal squamous cell carcinoma, particularly in North America and in Europe, in the past three decades has led to changes in classification and therapeutic modalities for esophageal neoplasms.
Carcinoma of the Stomach
Authors: Schmidt Carl , Daboul Nour , Likar Carly , Weir Joshua
Published: October 2022

Overview

Gastric cancer is the fifth most common cancer and third most common cause of cancer‐related death worldwide. Risk factors include chronic
Helicobacter pylori
infection, smoking, autoimmune gastritis, obesity, and other causes. Some countries with higher incidence have established screening programs but methodology and eligibility remain controversial. Despite knowledge of risk factors and screening for high‐risk populations, identification of earlier stage potentially curable disease remains a challenge.

Multiple genetic mutations are involved in gastric cancer pathogenesis, and mutations in the cellular adhesion protein E‐cadherin result in familial diffuse gastric cancer. Certain patterns of metastatic disease have been associated with particular molecular alterations. Increasing understanding of molecular pathways involved in gastric cancer allows efficacious use of targeted biologic therapies with cytotoxic chemotherapy in the advanced setting, such as trastuzumab in patients with gastric cancer and
HER2
/
neu
overexpression.

Surgical resection is the primary potentially curative therapy in those without metastatic disease. Type of resection, extent of lymphadenectomy, and use of laparoscopic or robotic surgery are variable emphasizing the need for best practice standards. Chemotherapy and radiation play an important role in the adjuvant setting. Choice and timing of these therapies require accurate staging by thorough evaluation with endoscopy, cross‐sectional imaging, and in some cases
endoscopic ultrasound
(
EUS
) or positron emission tomography.

Palliative therapy is important for patients with symptoms in the metastatic setting and after recurrence since cure is not possible in either situation. Results of recent clinical trials are encouraging including hope that immunotherapy will add to the collective therapies available. Ultimately, most people diagnosed with gastric cancer in the world will die. Research is ongoing in all areas from epidemiology to screening to diagnosis to staging and therapy.
Primary Neoplasms of the Liver
Authors: Cao Hop S. Tran , Shindoh Junichi , Vauthey Jean‐Nicolas
Published: October 2022

Overview

Primary liver cancer is the second leading cause of cancer death in men and the sixth leading cause among women worldwide. Its incidence in the United States has more than tripled since 1980. Hepatocellular carcinoma (HCC) constitutes three‐fourths of primary hepatic neoplasms, followed by intrahepatic cholangiocarcinoma (ICC) (10–15%) and other less common hepatic malignancies (5%) such as hepatic angiosarcoma, epithelioid hemangioendothelioma, or hepatic lymphoma. Primary hepatic malignancies are generally associated with poor survival, and limited systemic therapy options are available. As such, prevention, screening (in the case of HCC), early diagnosis, and multidisciplinary management are key to maximizing outcomes. In addition, most primary hepatic neoplasms are associated with chronic liver disease or cirrhosis, such that the resultant decreased hepatic functional reserve often precludes aggressive treatment for tumors. Therefore, for treatment selection, one should consider two intrinsic conflicting factors: curability and safety of treatment. Currently, several clinical staging systems and treatment algorithms are available to adequately select therapeutic options for HCC. The choice of therapy is individualized based on the tumor burden, degree of underlying liver disease, patient performance status, and the overall possibility of side effects or complications, and must be balanced with the anticipated benefits. Selection of treatment should be determined in a multidisciplinary fashion with the available local expertise. For patients with HCC or ICC, treatment options with curative intent including surgical resection, ablation, and orthotopic liver transplantation (OLT) should be the first priority as long as these treatments are approved.
Neoplasms of the Anus
Authors: Jácome Alexandre A. A. , Eng Cathy
Published: October 2022

Overview

Squamous cell carcinoma of the anal canal (SCCA) is a rare human papillomavirus (HPV)‐related malignancy, but with rising incidence in the last decade. Chemoradiotherapy (CRT) remains the cornerstone of the treatment of non‐metastatic disease, characterized by remarkable response rates of 90% and 5‐year overall survival (OS) of 80%. Nevertheless, despite the high efficacy observed with combined modality treatment, almost half of the patients with locally advanced disease have high‐risk features (T3, T4, or node‐positive disease) for treatment failure. The management of unresectable recurrences or metastatic disease is an unmet clinical need, marked by poor clinical outcomes. Immune checkpoint inhibitors and immunotherapeutic approaches have been demonstrating promising results in the management of advanced disease in the past few years, but big steps forward will only be taken when the underutilized HPV vaccination becomes more widely accepted for use.
Renal Cell Carcinoma
Authors: Grigg Claude M. , Burgess Earle F. , Riggs Stephen B. , Zhu Jason , Raghavan Derek
Published: October 2022

Overview

Renal cell carcinoma occurs in 73,000 patients each year in the United States and results in almost 15,000 deaths. For localized disease, cure is achieved by nephrectomy. Meticulous surgical staging is crucial. With improved imaging techniques, active surveillance has become an option for small, asymptomatic renal masses. Modifications in surgical technique, including laparoscopic and robotic approaches, have contributed to reduced morbidity. In advanced clear cell carcinoma, cytotoxic chemotherapy has negligible activity but targeted therapies, such as tyrosine kinase and mammalian target of rapamycin inhibitors, can cause dramatic regressions. Immune checkpoint inhibitors, which stimulate the immune system to eradicate cancer cells, can also achieve substantial and durable tumor reductions. Other cancers of the kidney are rare, and optimal management beyond aggressive surgical resection has not been defined.
Urothelial Cancer
Authors: Raghavan Derek , Cote Richard , Burgess Earle F. , McHaffie Derek , Clark Peter E.
Published: October 2022

Overview

Urothelial malignancy is one of the commonest cancers in Western society and involves the bladder, urethra, ureters, and renal calyces. It is associated with smoking, industrial dyes, schistosomiasis, radiation exposure, and certain geographical locations. Well‐defined molecular prognosticators and predictors have been identified, and in combination with improved staging techniques, have led to improved outcomes. Patients with nonmuscle invasive urothelial malignancy are best managed by surgical resection, often in combination with intravesical immunotherapy or chemotherapy. Muscle invasive disease is best managed by neoadjuvant cisplatin‐based chemotherapy followed by cystectomy; less robust patients are often effectively treated by chemoradiation. Patients with metastatic disease achieve response rates of up to 70% with MVAC or GC combination chemotherapy but are infrequently cured. The major innovation in the past decade has been the introduction of targeted therapies, in particular directed to the PD1/PD‐L1 interface, which have shown substantial activity in first‐line and salvage treatment of early‐stage and metastatic disease, but with a new spectrum of side effects.
Neoplasms of the Prostate
Authors: Aparicio Ana , Pilie Patrick , Surasi Devaki S. , Choi Seungtaek , Chapin Brian F. , Logothetis Christopher J. , Corn Paul G.
Published: October 2022

Overview

Cancer of the prostate is the most commonly diagnosed nonskin neoplasm and the second leading cause of cancer‐related mortality in men in the United States. Considerable advances have been made in screening, diagnosis, and therapy options, particularly in advanced disease, but controversies about the diagnosis and management of prostate cancer, especially in the areas of screening and choice of therapy, continue to evolve. Research initiatives in advanced disease have shifted from prognostication to prediction, and current treatment considerations are focused on optimization of therapy sequence, development of rational combinations, biomarker‐driven patient selection, determining the role of local disease control in patients with metastases, and bone targeting therapies. Despite progress, prostate cancer survival has not improved at the same pace as other cancer subtypes. It is anticipated that addressing knowledge gaps will lead to the development of novel agents with unique mechanisms of action and optimization of integrated strategies (surgical, radiation, and medical) to improve overall survival.

Prostate cancer awareness, clinical application of improved biopsy schemes, and advances in imaging combined with the widespread use of prostate‐specific antigen (PSA) have resulted in increased detection of early prostate cancer. The question of whether PSA screening would reduce mortality from prostate cancer has now been tested in the European Randomized Study of Screening for Prostate Cancer (ERSPC) and the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial first published in 2009. Though many of the apparent discrepancies between these trials can be accounted for by trial design and patient cross‐contamination, they brought to the forefront the dilemma of overdiagnosis and overtreatment, as well as the heterogeneous nature of prostate cancer and the urgent need to improve the accuracy of identifying clinically significant early disease with lethal potential. It is hoped that enhancing the current morphologic and anatomic classification of prostate cancer with a better understanding of the molecular underpinnings of diverse disease states will lead to a more refined taxonomy of prostate cancer and ultimately improve outcomes while minimizing treatment‐related morbidity.

Salient features that distinguish prostate cancer from other malignancies and frame the dilemmas surrounding it are its striking age‐dependent incidence, with progressively increasing frequency with increasing age, a strong familial and hereditary component, the variable lethality of morphologically identical cancers, the central role of androgen signaling, the preponderance of bone‐forming metastases, and metabolic derangements contributing to lethal progression. Important advances made in each of these areas will modify the approaches currently used to prevent, prognosticate, predict, and treat prostate cancer.
Tumors of the Penis and the Urethra
Authors: Chahoud Jad , Necchi Andrea , Spiess Philippe E.
Published: October 2022

Overview

Penile cancer is predominantly of squamous histology, a proportion of those are related to human papillomavirus (HPV). Penile squamous cell carcinoma (PSCC) is rare in the developed world and among circumcised men. For patients with localized PSCC, early potentially less debilitating surgery can be curative. Other modalities are less robust. Metastasis presents initially with lymphatic local regional disease progression, also the lymph node metastatic extent remains the strongest prognostic indicator of clinical outcomes. Patients with bulky locally advanced disease may benefit from multimodal approach with neoadjuvant cisplatin‐based chemotherapy followed by consolidative inguinal lymph node dissection.

Urethral cancer is a rare and histologically heterogenous carcinoma but can be aggressive depending on tumor histology. The prognosis and treatment approach depend on the gender, histology, location of the tumor within the urethra, and extent of disease.
Chronic Myeloid Leukemia
Authors: Cortes Jorge , Silver Richard T. , Kantarjian Hagop
Published: October 2022

Overview

Chronic myeloid leukemia (CML) was the first malignancy where a unique chromosomal abnormality, the Philadelphia chromosome (Ph), was directly linked to it. The unraveling of the molecular and physiologic consequences of this abnormality, with a fusion gene (
BCR‐ABL1
) translating into a chimeric protein with increased tyrosine kinase activity, led to the development of specific tyrosine kinase inhibitors (TKIs). The use of such agents as initial therapy has resulted in a dramatic change in the natural history of CML where patients properly managed can have a normal life expectancy. Several treatment options are also available for patients who may not have optimal response to their initial therapy. Current research goals are to improve the safety, efficacy, and wide availability of TKIs and to achieve a response such that patients can eventually discontinue therapy. With these approaches and ongoing research, the goal of eradication of chronic myeloid leukemia is ever closer.
Acute Lymphoblastic Leukemia
Authors: Jabbour Elias , Jain Nitin , Kantarjian Hagop , O'Brien Susan
Published: October 2022

Overview

Acute lymphoblastic leukemia (ALL) is characterized by clonal proliferation of lymphoid progenitors. In the last decade, significant advances in understanding the disease pathogenesis, refining prognostic groups, and developing novel therapies that target specific subsets, have improved our treatment strategies and patient outcomes. Therapies targeting either specific transcripts (e.g., BCR‐ABL1 tyrosine kinase inhibitors) or specific leukemic cell surface antigens (e.g., CD20, CD22, and CD19 monoclonal antibodies, chimeric antigen receptor T‐cell therapies) produced major therapeutic breakthroughs. These novel therapies and combinations are transforming our strategies for adults with ALL and are resulting in significant improvements in survival. Many of these approaches focus on decreasing or eliminating the role of chemotherapy, with the goal of making these regimens more tolerable in older adults and decreasing the morbidity and mortality associated with myelosuppression‐related infections and other complications of intensive chemotherapy.
Plasma Cell Disorders
Authors: Yee Andrew J. , Hideshima Teru , Raje Noopur , Anderson Kenneth C.
Published: October 2022

Overview

Plasma cell disorders have in common a proliferation of monoclonal plasma cells associated with the production of a monoclonal protein. These disorders range from the common, indolent condition of monoclonal gammopathy of undetermined significance to malignancies such as multiple myeloma characterized by the presence of hypercalcemia, anemia, renal dysfunction, and/or lytic bone lesions. Progress in the understanding of the molecular underpinnings of myeloma has led to remarkable advances in its treatment. High‐dose melphalan and autologous stem cell transplant have been a mainstay of treatment. Now, highly effective and well‐tolerated drug classes such as the proteasome inhibitors (e.g., bortezomib, carfilzomib), immunomodulatory drugs (e.g., lenalidomide, pomalidomide), and anti‐CD38 monoclonal antibodies (e.g., daratumumab, isatuximab) have rapidly transformed treatment and significantly improved overall survival. Newer therapies targeting B‐cell maturation antigen (BCMA) have the potential to further improve outcomes.
Neoplasms of Unknown Primary Site
Authors: Hainsworth John D. , Greco Frank A.
Published: October 2022

Overview

Cancer of unknown primary site (CUP) is a clinical syndrome accounting for 2–3% of all cancer diagnoses. This heterogeneous group is comprised of patients with metastatic cancer who have no anatomic primary site identified after a standard clinical evaluation. Using specialized pathologic techniques, including immunoperoxidase staining and molecular cancer classifier assays, identification of the tissue of origin is possible in most patients, even when an anatomic primary site cannot be located. For treatment planning, patients are divided into two groups. The first group includes a number of favorable subsets, identified by clinical and/or pathologic findings. Recently, new subsets have been identified, so that now approximately 40% of all CUP patients belong to a favorable subset. These various subsets require specific treatments, as detailed in the chapter. The remaining 60% of CUP patients do not fit into any of the favorable subsets; however, a tissue of origin can be predicted in most. These patients have traditionally received empiric chemotherapy, with modest efficacy. Increasing evidence suggests that site‐specific treatment, based on the predicted tissue of origin, improves treatment results, particularly in patients predicted to have responsive tumor types. Current studies are also addressing the use of comprehensive tumor molecular profiling to identify actionable molecular alterations in CUP patients.
Cancer Cachexia
Authors: Eid Assaad A. , Njeim Rachel , Khuri Fadlo R. , Thomas David K.
Published: October 2022

Overview

Cachexia is a systemic wasting syndrome of progressive muscle and, usually, adipose loss, multi‐organ dysfunction, and wide metabolic derangement, often exacerbated by anorexia and diminished nutritional intake. More than half of all cancer patients develop cachexia, which directly causes profound morbidity and substantially reduced survival. New large‐scale high‐dimensional clinical and experimental studies are revealing unexpected ground truths that cachexia frequently occurs in early stages of many cancers; has several distinct clinical phenotypes; increases complications of and reduces response to cancer‐directed therapies. More precise tools for early assessment, diagnosis, and multi‐modal interventions, including quantitative image‐based body composition analysis, molecular biomarkers, and new targeted therapeutics are in advanced development. These advances, with rapidly expanding basic research into causal molecular mechanisms, are transforming our fundamental understanding of this complex disease as being integral with cancer biology, treatment response, and patient outcomes.
Dermatologic Complications of Cancer Chemotherapy
Authors: Patel Anisha B. , Karri Padmavathi V. , Duvic Madeleine
Published: October 2022

Overview

Dermatologic complications of cancer chemotherapy have become increasingly significant, especially with the continued development of new targeted antineoplastic agents. The frequency of mucocutaneous complications in cancer chemotherapy is often a reflection of the increased proliferative nature of affected tissues, such as the mucous membranes, skin, hair, and nails, which renders them particularly susceptible to the actions of chemotherapeutic drugs. This article reviews the specific side effects associated with newer targeted and immune therapies as well as the more classic side effects of cytotoxic chemotherapies and their associated drugs.
Skeletal Complications
Authors: Via Michael A. , Iofin Ilya , Liu Jerry , Mechanick Jeffrey I.
Published: October 2022

Overview

The skeletal complications of cancer are highly prevalent. Bone metastases are present in approximately 70% of patients with cancer‐related deaths. Skeletal complications can present clinically as pain associated with bone metastases, pathologic fractures, or hypercalcemia. Additionally, several therapies for cancers may have deleterious effect on bone health such as aromatase inhibition in patients with breast cancer. The presence of skeletal metastases often indicates that cure from cancer unlikely. Goals of therapy may shift to palliation and to systemic control with possible prolonged survival. Surgical treatments, medical therapies, including antiresorptive agents, and/or radiation therapy should each be considered to achieve optimal care in patients with skeletal complications of cancer.
Coagulation Complications of Cancer Patients
Authors: Wang Tzu‐Fei , Sanfilippo Kristin
Published: October 2022

Overview

Patients with cancer have increased risks of coagulation complications including bleeding and/or thrombotic problems, which can be a result of malignancy itself and/or related to cancer therapies. These complications can lead to increased morbidity and mortality, as well as delays or alterations in cancer treatment. Therefore, identification of risk factors, preventation, and treatment strategies are important priorities in the care of cancer patients. In this chapter, we discussed and summarized relevant literature in common bleeding and thrombotic complications, their presentations, risk factors, prevention and management strategies.
Cardiac Complications
Authors: Ewer Michael S. , Ewer Steven M. , M. Suter Thomas
Published: October 2022

Overview

Patients with malignant diseases often have coexisting cardiovascular disorders or may face serious cardiovascular complications in the course of their disease.1The disorders may result from underlying conditions such as atherosclerosis, hypertension, or valvular abnormalities, or they may result directly from cancer or its treatment (Table 1). In addition, cardiovascular disorders that are unusual in patients not afflicted with cancer may be more common in the cancer patient, and sometimes are unsuspected. Furthermore, cardiovascular diseases common in the general population must not be overlooked in patients with cancer; the presentation of such entities may be unusual, and the diagnosis often is more complex. Increased clinical scrutiny is therefore necessary in this vulnerable population. Multiple clinical problems may also coexist and defy a simple illumination because of the complex interactions between the malignancy, consequences of its treatment, and the status of the cardiovascular system; what affects one of these variables often alters the presentation and course of the others. This article will look at some of the more common cardiovascular complications of cancer and its treatment and will also address some of the dilemmas encountered in cancer patients with concomitant cardiac conditions.