bluuebunny/crossref_metadata_2025_split huggingface dataset:
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.
Neoplasms in People Living with Human Immunodeficiency Virus
Authors: Wang Chia‐Ching J. , Chiao Elizabeth Y. 
Published: October 2022

AbstractPeople 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

OverviewCancers 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

OverviewEsophageal 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.
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

OverviewUrothelial 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.