bluuebunny/crossref_metadata_2025_split huggingface dataset:
Chemical Carcinogenesis
Authors: Hofseth Lorne J. , Weston Ainsley , Harris Curtis C. 
Published: August 2023

OverviewHuman exposure to chemical carcinogens can result in cancer. What dictates this outcome is relatively predictable but highly variable. Factors governing the outcome include type of exposure, amount of exposure, time of exposure, and genetic makeup of the host (i.e., humans). The latter is comprised of variations in single nucleotides within genes (e.g., single nucleotide polymorphisms in deoxyribonucleic acid–repair genes), as well as the metabolomic, proteomic, microbiomic, transcriptomic, and epigenomic background of the individual. It is becoming increasingly clear that these endpoints can be modified by chemical carcinogens and that inflammatory load influences outcome. To this end, the past decade has seen an explosion of extremely sensitive and highly accurate technology. Linking this technology to the rapid development of bioinformatics has enabled us to begin merging the totality of lifetime exposure (exposome) with the totality of metabolomic, proteomic, microbiomic, transcriptomic, epigenomic, and other “omic” profiles. We feel optimistic that the next decade will bring the development of tools to identify an individual's weighted risk signature as a biomarker for cancer risk and develop a personalized and precise approach to cancer chemoprevention and treatment.
Endocrine and Genetic Bases of Hormone‐Related Cancers
Authors: Bernstein Leslie , Pu Xia , Gu Jian 
Published: August 2023

OverviewNeoplasia of hormone‐responsive tissues currently accounts for more than 30% of all newly diagnosed male cancers and almost 40% of all newly diagnosed female cancers in the United States. Given that endogenous hormones apparently affect the risk of these cancers and their overall frequency, concern exists about the effects on cancer risk if the same or closely related hormones are administered for therapeutic purposes (e.g., as contraceptives, as menopausal hormone therapy, or for the prevention of miscarriage). Depending on the timing of hormone use and the tissue‐specific effects, some of these compounds will reduce risk while others increase risk of “hormone‐dependent” cancers. This chapter focuses on breast, endometrial, and ovarian cancers among women and prostate cancer among men and provides a review of the epidemiologic and endocrinologic evidence for the role of hormones in cancer development. It also reviews the current status of the relationship between exogenous hormones and risk of cancers of the breast, endometrium, and ovary. In addition, it summarizes our current knowledge of genetic susceptibility to breast, endometrial, ovarian, and prostate cancers. Other less common cancers (e.g., cervical cancer, clear cell vaginal adenocarcinoma, thyroid cancer, testicular cancer, and osteosarcoma) may have a hormonal basis as well, but are not reviewed in this chapter.
Inflammation and Cancer
Authors: Todoric Jelena , Umemura Atsushi , Taniguchi Koji , Karin Michael 
Published: August 2023

Overview
Epidemiological studies and experimental evidence have provided strong support to the long standing notion that chronic inflammation stimulates the development and progression of malignant neoplasms. It is now clear that pre‐existing inflammation caused by persistent viral and microbial infections, autoimmune diseases, environmental irritants, and even obesity promote tumor development and may account for up to 20% of all cancer deaths. Inflammation also appears subsequent to cancer development and such “tumor‐elicited inflammation” plays a key role in the malignant progression and metastatic dissemination of most cancers. Although some common anti‐inflammatory drugs, such as aspirin, substantially reduce cancer risk, there is still an unmet need for the clinical development of new therapeutics that target cancer‐associated inflammation.
Palliative Care and Pain Management
Authors: Smith Cardinale B. 
Published: August 2023

OverviewPalliative care is an essential component of comprehensive cancer care. Palliative care is given concurrently with other disease‐modifying, life‐prolonging, and curative therapy. Palliative medicine specialists focus on helping patients and their families with a variety of care needs including symptom control, psychosocial support, physician–patient communication, addressing care goals in relation to the patient's condition, prognosis, values, and preferences, as well as with transitions in care. Cancer patients often experience significant symptom distress either from the illness itself or from the associated treatments. The beneficial effects of palliative care have been well documented. When integrated into early oncologic care, palliative care is associated with a significant improvement in quality of life, depression, and survival. As such, palliative care should be given throughout the trajectory of cancer care whether during early stage disease in which the focus is on cure or in more advanced disease when the focus is on maximizing quality of life. Currently, national and international organizations have clinical guidelines that recommend palliative care be routinely integrated into comprehensive cancer care.
Personalized Medicine in Oncology Drug Development
Authors: Dracopoli Nicholas C. , Grewal Iqbal , Takimoto Chris H. , Lebowitz Peter F. 
Published: August 2023

OverviewThe concept of personalized medicine in oncology drug development is no longer an aspiration; it is now, in large measure, the accepted paradigm of how oncology drugs should be developed. In modern oncology drug development, determining which molecularly characterized tumors will benefit the most from a drug is a critical part of the development plan. In addition, another important personalized medicine approach is emerging whereby a therapeutic is specific to an individual patient. Examples of this individualized therapeutic approach include engineering of autologous immune cells with reinfusion into the patient or cancer vaccines that are specific to an individual tumor.A growing number of successful examples have demonstrated that the personalized medicine approach via biomarker selection can provide more benefit to patients and more rapid approval of drugs. The benefits of a personalized medicine strategy in oncology drug development are multiple and include an increased probability of overall success, smaller Phase 3 registration trials, and the potential for enhanced clinical benefits for patients. In a recent review, Falconi and colleagues examined the outcome of 676 Phase 1, 2, and 3 clinical trials of novel therapeutics for non‐small cell lung cancer conducted from 1998 to 2012.1Overall, the cumulative success rate, as defined by the advancement to the next stage of clinical testing or to approval, was only 11%. However, when a biomarker was utilized for patient selection, the cumulative success rate increased by nearly sixfold to 62%. Thus, there is strong objective evidence for predictive biomarkers to enhance the probability of success in drug development. Using specific genetic and/or protein markers, a number of important drugs have been developed and approved in specific populations. This approach represents a paradigm shift that has proved so powerful that it is now a standard.
Pharmacology
Authors: Sharma Manish R. , Ratain Mark J. 
Published: August 2023

OverviewThe biology and clinical indications relevant to systemic anticancer therapies are covered extensively in other chapters in this book. In this chapter, 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. The United States Food and Drug Administration (FDA) conducts a question‐based clinical pharmacology and biopharmaceutics review for each approved drug (http://www.fda.gov/downloads/AboutFDA/ReportsManualsForms/StaffPoliciesandProcedures/ucm073007.pdf). Their reviews are publicly available on the FDA website (http://www.accessdata.fda.gov/scripts/cder/drugsatfda/) by searching for the drug name, and often include details that are not included in the product label. We will use their standard questions to introduce the principles of clinical pharmacology and will highlight examples that illustrate these principles.
Carcinoma of the Stomach
Authors: Schmidt Carl , Murphy Mariela Blum , Yao James C. , Crane Christopher H. 
Published: August 2023

Overview

Gastric cancer is the second most common cause of cancer‐related death worldwide and risk factors include autoimmune gastritis, chronic
Helicobacter pylori
infection, 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 CDH1 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 has led to efficacious use of targeted biologic therapies with cytotoxic chemotherapy in the advanced setting, such as use of 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 and extent of lymphadenectomy are not consistent, and standards for best practice are needed. Chemotherapy and radiation play an important role in the adjuvant setting and, therefore, decisions regarding choice and timing of these therapies require accurate staging by thorough evaluation with endoscopy, cross‐sectional imaging and, in some cases, endoscopic ultrasound or positron emission tomography.
Palliative interventions and therapy are often important, both for patients with symptoms in the metastatic setting and after recurrence as cure is not achieved in either situation. Results of recent clinical trials are encouraging, and there have been multiple positive phase III trials in the adjuvant and metastatic setting during the past 10 years. Despite this, most people diagnosed with gastric cancer will die from it eventually, so much more research is needed.
Primary Neoplasms of the Liver
Authors: Shindoh Junichi , Brudvik Kristoffer W. , Vauthey Jean‐Nicolas 
Published: August 2023

Overview
Primary liver cancer is the second leading cause of cancer death in men and the sixth leading cause among women. Hepatocellular carcinoma (HCC) constitutes 70–85% 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 only a limited evidence of systemic therapy have been available, prevention, surveillance, early diagnosis, and multidisciplinary treatment approach are important factors to maximize treatment outcomes. In addition, most of the primary hepatic neoplasms are associated with chronic liver disease or cirrhosis, and the 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 balanced with acceptable results. Selection of treatment should be determined in a multidisciplinary approach with the local expertise. The most curative treatment options including surgical resection, radiofrequency ablation, and orthotopic liver transplantation (OLT) should be the first priority as long as such treatments are approved. For the other hepatic malignancies, only limited clinical evidence is available and surgical resection or OLT is considered as the first‐line treatment.
Gallbladder and Bile Duct Cancer
Authors: Kaseb Ahmed O. , Uemura Marc , Thomas Melanie B. , Curley Steven A. 
Published: August 2023

OverviewPrimary gallbladder and bile duct cancers are relatively rare tumors of the gastrointestinal tract. Both are mainly adenocarcinomas that start as abnormal growths within the mucous lining of the gallbladder and bile ducts. Bile duct tumors, or cholangiocarcinomas, are further differentiated by their location within the liver (intrahepatic) or outside the liver (extrahepatic). Both tumor types have distinct pathophysiologies and modes of hepatocarcinogenesis. Gallbladder cancers, for example, are associated with gallstones, chronic choleycystitis, and the porcelain gallbladder. They are commonly found incidentally on cholecystectomy specimens. On the other hand, cholangiocarcinomas have frequent associations with parasitic infections and other diseases causing chronic inflammation in the bile ducts (primary sclerosing cholangitis). While both gallbladder and cholangiocarcinomas can be cured if surgically resected, unresectable or advanced tumors have a poor prognosis and usually require systemic chemotherapy.
Neoplasms of the Anus
Authors: Minsky Bruce D. , Guillem Jose G. 
Published: August 2023

OverviewAlthough an uncommon tumor, the incidence of anal cancer has increased over the past few decades. This increase may be due to sexual transmission of human papillomavirus virus as well as the impact of human immunodeficiency virus. Chemoradiation therapy (CMT) involving pelvic radiation and concurrent chemotherapy (5‐FU combined with either mitomycin‐C or cisplatin) has resulted in 5‐year survival rates of approximately 80% while maintaining sphincter preservation for most patients. Surgery is reserved for selected patients with T1M0 disease who can undergo resection with acceptable functional outcomes or an abdominoperineal resection (APR) for salvage following CMT.
Urothelial cancer
Authors: Raghavan Derek , Cote Richard , Burgess Earle F. , Riggs Stephen B. , Haake Michael 
Published: August 2023

Overview
Urothelial malignancy is one of the most common cancers in Western society and involves the bladder, urethra, ureters, and renal calyces. It is predominantly associated with smoking, industrial dyes, schistomiasis, radiation exposure, and certain geographical locations. Well‐defined molecular prognosticators 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 cisplatin‐based chemoradiation. Patients with metastatic disease achieve response rates of up to 70% with MVAC (methotrexate, vinblastine, doxorubicin, and cisplatin) or GC combination chemotherapy but are infrequently cured. New approaches to the management of systemic disease are predicated on recent data reflecting the importance of unblocking checkpoints for immune function and correlate with expression of PD‐L1 (programmed death‐ligand 1).
Soft Tissue Sarcomas
Authors: Maki Robert G. , Raut Chandrajit P. , O'Sullivan Brian 
Published: August 2023

OverviewThe management of soft tissue sarcomas is driven by the anatomic site and histology of the primary and is increasingly affected by the specific genetics of the sarcoma. In this chapter, we focus on the principles of management of this group of over 50 cancer subtypes to highlight commonalities and differences from anatomical constraints of surgery to specifics of adjuvant radiation to identification of systemic therapeutics that are appropriate for each histology.We will discuss in this chapter the etiology, presentation, diagnosis, staging, and multidisciplinary management of patients with sarcomas of soft tissue. Surgery remains paramount to achieve cure for the vast majority of sarcomas. Radiation therapy is used for larger tumors in the appropriate clinical context. The evolution of increasingly sophisticated radiation techniques is highlighted in this chapter. As pertains to systemic therapy, this chapter is written at a time in which first‐line therapies for soft tissue sarcomas may change, raising anew some questions of adjuvant therapy that remain incompletely answered. Where appropriate, we attempt to link specific histologies or molecular changes to therapeutic suggestions, with the understanding and hope that novel agents will supplant the medications that are available but that have not materially affected outcomes for few diagnoses other than GIST in the past several years.
Myeloproliferative Neoplasms: Essential Thrombocythemia, Primary Myelofibrosis, and Polycythemia Vera
Authors: Tefferi Ayalew 
Published: August 2023

OverviewThe chronic myeloid neoplasms are a diverse group of malignant bone marrow conditions that originate in a transformed multipotential hematopoietic progenitor cell. This heterogeneous group of diseases shares an initially indolent clinical course with a variable degree of risk to evolve into overt acute leukemia. Even in the absence of leukemic transformation, the consequences of the cellular excesses or deficiencies characteristic of these disorders are troublesome for patients and all too frequently fatal; some of these disease complications include thrombosis, bleeding, marked hepatosplenomegaly, profound constitutional symptoms, and cachexia.
Neoplasms of Unknown Primary Site
Authors: Hainsworth John D. , Greco F. Anthony 
Published: August 2023

OverviewCancer of unknown primary site (CUP) is a clinical syndrome accounting for 2–3% of all cancer diagnoses. This heterogeneous group is comprised of patients who have no anatomic primary site identified after a standard clinical evaluation. Complete pathologic evaluation is essential. Accurate prediction of the tissue of origin, based on examination of a biopsy from a metastatic lesion, is now possible in most patients using improved immunoperoxidase stains and molecular gene expression profiling. After completion of clinical and pathologic diagnostic evaluation, approximately 20% of patients with carcinoma of unknown primary site are included in favorable prognosis subsets and require specific treatment as detailed in this chapter. Until recently, the remaining 80% of patients have been treated with empiric combination chemotherapy. However, as therapy for various solid tumors improves and becomes more site specific, empiric chemotherapy is less likely to provide optimal treatment. Site‐specific therapy directed by the tissue of origin predicted by molecular profiling or immunoperoxidase staining is now appropriate for these patients. New data supporting the use of site‐specific therapy are reviewed.
Anorexia and Cachexia
Authors: Ohnuma Takao 
Published: August 2023

OverviewCancer cachexia is a wasting syndrome with extensive loss of skeletal muscle mass with or without adipose tissue. It may be contrasted with simple starvation in which fat replaces glucose as the preferred fuel to spare lean body mass. It results from altered metabolism rather than just an energy deficit, and cannot be reversed by conventional nutritional support. The causes of cancer‐related cachexia are multifactorial including production of procachectic cytokines and metabolic derangements. European cancer community is credited in developing new definition and classification of cancer cachexia. Recent studies identified anamorelin, an oral ghrelin analogue, as a new agent for the treatment of cancer cachexia.
Neurologic Complications of Cancer
Authors: DeAngelis Lisa M. 
Published: August 2023

Overview
Neurologic complications of cancer are common and being seen with increased frequency as patients survive longer with better systemic disease control. Metastases can involve the brain, dura, subarachnoid space, spinal cord, roots, and nerve plexus. Chemotherapy can cause acute toxicities, such as encephalopathy from ifosfamide, which impede the delivery of a full course of effective anticancer treatment. In addition, the long‐term complications of radiotherapy such as radiation myelopathy, and chemotherapy such as peripheral neuropathy, can markedly impair quality of life. Early identification, treatment, and prevention strategies can reduce these toxicities in our growing population of survivors.
Dermatologic Complications of Cancer Chemotherapy
Authors: Patel Anisha B. , Duvic Madeleine M. 
Published: August 2023

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 chapter reviews the specific side effects associated with targeted therapies and the more classic side effects of cytotoxic chemotherapies and their associated drugs.
Gonadal Complications
Authors: Narayanan Vignesh , Klein Catherine E. 
Published: August 2023

OverviewImprovements in cancer therapy over the past 50 years have allowed survivors of pediatric sarcomas and leukemias, and young adults with high‐grade lymphomas, Hodgkin disease, and testicular tumors to reach adulthood but suffer the long‐term consequences of those therapies. Alterations in gonadal function are frequent and distressing side effects of modern cancer therapy. Women face symptoms of premature ovarian failure, including menopause, sterility, and presumably accelerated osteoporosis and possible early heart disease. Men experience oligo‐azoospermia and subclinical Leydig cell dysfunction, leading to infertility and long‐term effects of “andropause” including decreased bone density, lean muscle mass, decreased libido, and increased risk of coronary artery disease.With recognition has come better documentation of the frequency and severity of these complications, more effective patient counseling, and innovative approaches to attenuate gonadal toxicity. Options include hormonal manipulation, selection of alternative treatments, and pretreatment cryopreservation of embryos or germ cells, but these choices must be offered pretherapy, and patients remain uninformed of potential loss of fertility or options to preserve it. As cancer therapies improve and the number of cancer survivors increases, the practicing oncologist must address these issues in a timely and sensitive manner.
Sexual Dysfunction
Authors: Schover Leslie R. 
Published: August 2023

OverviewSexual problems related to cancer are usually caused by physiological damage from treatment, but are exacerbated by psychosocial issues such as poor communication, relationship conflict, or preexisting sexual dysfunction. Sexual dysfunction affects almost two‐thirds of the estimated 14 million cancer survivors in the United States, including over 50% of those treated for pelvic or breast cancers and at least 25% for other sites. Optimal treatment is multidisciplinary, addressing both physical damage and coping skills. If a committed relationship exists, it is best to include the partner in education and intervention.