bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical and Research Informatics Data Strategy for Precision Oncology
Authors: Hartman Douglas , Chandran Uma , Davis Michael , Dhir Rajiv , Shirey William E. , Silverstein Jonathan C. , Becich Michael J.
Published: October 2022

Overview

Oncology informatics in the era of precision oncology is challenging because no unified comprehensive system exists linking Health Information Technology (HIT) deployed in clinical settings to the translational needs of researchers. Many advanced informatics solutions have been developed for clinical trials, biobanking, cancer imaging, and high‐throughput‐omic technologies. These are fundamentally transforming the treatment and management of cancer patients. However, the lack of fully developed interoperable cancer research informatics and HIT technologies to move between the bench and the bedside remains a significant challenge. Oncologists and translational cancer investigators require knowledge of informatics, data science, and advanced machine learning (artificial intelligence) as these are the major change agents influencing the development of new therapies, especially in the era of Precision Medicine and Learning Health Systems for oncology. In addition, cancer care delivery is very dependent on new developments in clinical practice and requires a thorough, systematic reevaluation of the electronic health records (EHRs) in use today. The ability (through mobile computing) to have information “on demand” during daily oncology practice is reshaping our thinking of how we record, document, and share data toward the common purpose of improving cancer outcomes for the patients we serve. This article looks at HIT and clinical, translational, and research informatics for oncologists and cancer researchers and begins to paint a picture of what an “ideal” environment for cancer care delivery would look like to support Precision Oncology and Learning Health Systems.
Chemical Carcinogenesis
Authors: Hofseth Lorne J. , Weston Ainsley , Harris Curtis C.
Published: October 2022

Overview

Human 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 human host. The latter is comprised of variations in single nucleotides within genes (e.g., single nucleotide polymorphisms in DNA repair genes), as well as the metabolomic, proteomic, microbiomic, transcriptomic, and epigenomic background of the individual. It is becoming increasingly clear that these endpoints and signatures can be modified by chemical carcinogens and that the inflammatory load influences outcome. To this end, the past decade has seen an explosion of extremely sensitive and highly accurate technology for measuring the impact of carcinogens. 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.
Inflammation and Cancer
Authors: Todoric Jelena , Umemura Atsushi , Taniguchi Koji , Karin Michael
Published: October 2022

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 preexisting 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.
Papillomaviruses and Cervical Neoplasia
Authors: Herfs Michael F. , Crum Christopher P. , Munger Karl
Published: October 2022

Overview

Even after the 2008 Nobel prize awarded to Prof. Harald zur Hausen, the field of HPV continues to advance rapidly with new insights into pathogenesis, the discovery of novel genotypes/variants, refined screening approaches using HPV testing, and the recent commercialization of vaccines covering several carcinogenic HPV types. The squamocolumnar junction, which is involved in approximately 90% of (pre)neoplastic lesions, has been more precisely characterized, and its potential as a target for prevention in women beyond optimal age for vaccination is being discussed. HPV testing is assuming a major role in screening women over the age of 30, at the expense of the Papanicolaou smear, which will be largely limited to women between age 20 and 30, with a reduction or the elimination of cervical screening for women under the age of 20. For prevention of cervical neoplasia, new broader spectrum vaccines (such as a 9‐valent vaccine) were introduced allowing for targeting of extended range of high‐risk HPVs.
Parasites
Authors: Azzouni Mervat El , Matar Charbel F. , Galal Radwa , Jabra Elio , Shamseddine Ali
Published: October 2022

Overview

Several parasites were investigated for a possible role in oncogenesis. Among the well‐known parasitic infections,Schistosoma haematobiumwas proved to play an important role in developing urinary bladder cancer. Moreover,Schistosoma japonicumis classified as a colorectal carcinogen especially in the Far East. Other class of parasites, such as helminthsClonorchisandOpisthorchisare proved to induce hepatobiliary cancer. In Africa, a strong correlation between Ebstein‐Barr virus infection and Burkitt lymphoma is present, with an evident enhancing role forPlasmodium falciparum. Chronic inflammation was incriminated to be the most accepted mechanism for parasite‐induced cancer; however, the roles of certain carcinogens, oncogenes, DNA mutations, and others were all approved as mechanisms enhancing carcinogenesis in parasitic infections. Strikingly, despite the above‐mentioned data, it seemed that certain parasites could modulate the host immune response in a manner that would lead to cancer regression or prevention. This is in the prospect of revaluation of the clinical importance of infectious agents; an issue that requires future concern.
Chemoprevention of Cancer
Authors: Hawk Ernest , Maresso Karen C. , Brown Powel , Savage Michelle I. , Lippman Scott M.
Published: October 2022

Overview

The field of cancer chemoprevention is underpinned by two phenomena of neoplasia: field carcinogenesis and multistep carcinogenesis. Accurate cancer risk models are critical to chemoprevention, and may accelerate drug development in this setting. The Food and Drug Administration has approved several chemoprevention agents. This article describes cancer risk modeling and phase II/III chemoprevention clinical trials focused on the four major cancer sites in Western populations (lung, colon and rectum, prostate, and breast), as well as broader, site‐agnostic chemoprevention studies. Immunoprevention strategies, including vaccines, are highlighted.
Principles of Radiation Oncology
Authors: Floyd Scott R. , Adamson Justus , Connell Philip P. , Weichselbaum Ralph R. , Willett Christopher G.
Published: October 2022

Overview

Ionizing radiation can halt the growth of cells, mainly through the induction of damage in DNA. Cancerous cells differ from normal cells in their response to this radiation‐induced DNA damage, creating a therapeutic window that is exploited in the clinical practice of radiation oncology to stop cancer cells while protecting normal tissues. This article will introduce the basic concepts behind the physics of radiation interaction with tissues, radiation treatment modalities and the radiation biology of treatment responses. Current concepts from the forefront of radiation physics and biology that may shape the future of radiation oncology are also presented.
Integrative Oncology in Cancer Care
Authors: Lopez Gabriel , Liu Wenli , Narayanan Santhosshi , Cohen Lorenzo
Published: October 2022

Overview

Integrative medicine seeks to merge conventional medicine and complementary therapies in a manner that is comprehensive, personalized, evidence‐based, and safe. Integrative oncology is the term used to describe the application of integrative medicine to cancer care. The field of integrative oncology is a constantly evolving set of disciplines. This article reviews the role of integrative medicine in cancer care with an emphasis on effective communication, an overview of the evidence, integrative‐based resources to guide health care providers and patients, and presents a model of how to effectively incorporate integrative medicine within cancer care. Existing research suggests that the majority of cancer patients desire communication with their doctors about integrative medicine. It is the health care professional's responsibility to ask patients about their use of complementary medicines and to provide evidence‐based advice to guide patients in this evolving area. Key findings in the areas of mind‐body practices, massage, and acupuncture are presented. Mind‐body practices help to improve mood, sleep quality, physical functioning, and overall well‐being. Massage is helpful at relieving pain, anxiety, and increasing relaxation. Acupuncture has the greatest evidence to support its use in managing symptoms such as chemotherapy‐induced nausea, vomiting, and pain; additional research suggests benefit in providing relief for radiation‐induced xerostomia, hot flashes, arthralgias, and other symptoms. Many authoritative resources now exist to help guide patients' appropriate use of complementary therapies, allowing the medical team to follow evidence‐based guidelines.
Health Services Research
Authors: Dinan Michaela A. , Check Devon K.
Published: October 2022

Overview

Health services research (HSR) describes a diverse group of research strategies and fields that seek to evaluate the impact of health care on patients and populations and has been a critical component of understanding the use, outcomes, and costs associated with oncology care since its inception over 100 years ago. In modern times, physicians and researchers often tout “bench to bedside” innovations as the goal of biomedical research. However, patients, physicians, and health care systems in the real world are subjected to a host of factors that impact patient care before, during, and after an intervention occurs at the bedside. Although HSR is a complex and evolving concept, a basic understanding of the key principles of HSR is needed to accurately assess, quantify, and optimize the real‐world impact of progress in oncology today and in the future.
Precision Medicine in Oncology Drug Development
Authors: Tsimberidou Apostolia M. , Fountzilas Elena , Kurzrock Razelle
Published: October 2022

Overview

In recent years, advances in technology have led to identification of complex and unique biologic mechanisms of tumorigenesis. Precision medicine uses tumor and cell‐free DNA profiling, immune markers, RNA and proteomic analyses, and other biomarkers in combination with patients' unique characteristics and comorbidities to individualize anticancer therapy. The focus of selected clinical trials has shifted from tumor type‐centered to gene‐directed, and in some cases, histology‐agnostic approaches. Innovative trial designs tailored to biomarker profiling aim to improve treatment outcomes. These designs enable the dynamic evolution of the studies, allow the elimination of treatment arms with inferior outcomes and modification of patient randomization, and optimize biomarker selection based on real‐time study outcomes. They also accelerate regulatory approval of novel drugs by empowering seamless transition from phase I to phase II and III clinical trials. Companion diagnostic biomarkers provide essential information for the safe and effective use of the corresponding targeted or immune treatments and lead to improved clinical outcomes of patients with molecular alterations treated with matched targeted treatments. However, the complex interaction between tumors, immune cells, and the tumor microenvironment complicates the identification of robust biomarkers. To overcome biologic complexity and tumor heterogeneity, clinical trials evaluate combinations of gene‐targeted therapy with immune‐targeted approaches (e.g., checkpoint blockade, personalized vaccines, oncolytic viruses, and/or adoptive cell therapy), hormonal therapy, chemotherapy, and/or novel agents, customized to individuals in an N‐of‐1 fashion. In this article, we discuss the rapid evolution of precision medicine in oncology and the challenges and opportunities associated with its implementation into daily clinical practice.
Drug Development of Small Molecule Cancer Therapeutics in an Academic Cancer Center
Authors: Coss Christopher C. , Patrick Jeffrey T. , Gerald Damien , Hilinski Gerard , Shakya Reena , Byrd John C.
Published: October 2022

Overview

Drug development of small molecules in the context of an academic cancer center is a challenging but imminently achievable process. The process involves stage‐gated, strategic decision‐making informed by the best experimental data that can be obtained. In addition to validating and comprehensively testing the drug molecule in all of the ways suggested, one of the most vital components in drug development aimed at achieving commercialization is intellectual property (IP). Most academic cancer centers are likely going to have access to an internal or external partner who establishes and maintains intellectual property. Intellectual property is in fact what a commercial partner will license with regard to a drug development program. Whether the IP is related to novelty of molecule structure, a synthesis process, an unanticipated (nonobvious) effect or a specific utility against a disease or in combination with another agent, the IP suite established for a drug development asset is the key value attribution that will garner interest from commercial entities.

A robust preclinical development data package depicting clarity of mechanism of action, a tolerable or acceptable toxicity profile along with comparative data to similar programs and finally a robust intellectual property position strongly enhances the likelihood of obtaining a commercial partner as well as enabling full clinical development and commercialization. In addition to advancing basic research to enable translation to clinical research, cancer drug development can also provide a commercial resource support mechanism that can help fuel future research at the developing center based on the financial returns to the academic center from the commercialization process. With all of the available resources, with the right team and vision in place, drug development can be a rewarding process that also aligns to the academic research goals and needs.
DNA
Topoisomerase Targeting Drugs
Authors: Thomas Anish , Bates Susan , Figg William D. , Pommier Yves
Published: October 2022

Overview

Topoisomerases are an important class of enzymes that are ubiquitously expressed across all organisms, and function to resolve deoxyribonucleic acid (DNA) supercoiling and prevent and resolve ribonucleic acid (RNA) entanglements. These biochemically distinct enzymes play a critical role in DNA replication, transcription, and cellular division. Inhibitors that target specific topoisomerases, therefore, represent a major component of the anticancer chemotherapeutic armamentarium. In this chapter, we provide an overview of topoisomerase biology and topoisomerase inhibitors. We review the common and specific mechanisms of action and the molecular pharmacology of the drugs that target the topoisomerase cleavage complexes by interfacial inhibition. Molecular pathways for cancer cell death and DNA repair associated with each specific topoisomerase inhibitor are discussed. Other mechanisms of anticancer activity of selected topoisomerase inhibitors that include DNA intercalation and/or generation of oxygen radicals destabilizing and damaging chromatin structure are described. We summarize the clinical use, toxicity profile, and the molecular basis of sensitivity and resistance to topoisomerase inhibitors. We also discuss the pharmacogenomics focusing on genetic variants in drug‐metabolizing enzymes, transporters, and other proteins associated with topoisomerase inhibitors. Evolving data demonstrate the important role of molecular profiling and analysis of genetic variants in individuals that enable personalized dosing and enhance therapeutic efficacy, minimizing toxicity. Ongoing efforts focus on optimization of treatment selection, identification of novel combination therapies, elucidation of the molecular basis of response and resistance, and development of strategies for tumor‐targeted delivery based on tumor molecular signatures.
Vaccines and Immunomodulators
Authors: Schlom Jeffrey , Gameiro Sofia R. , Palena Claudia , Gulley James L.
Published: October 2022

Overview

This article provides an overview of vaccine trials for a range of human cancers. It is not meant to be a compendium of all completed and ongoing trials. The vast majority of ongoing trials involve combination therapies with checkpoint inhibitor monoclonal antibodies and/or other immunomodulators. This article also deals with two concepts that are emerging as important to consider in cancer vaccine trials: tumor cell plasticity and epigenetic modulation of tumor cells and immune cells.
Hematopoietic Cell Transplantation
Authors: Bashir Qaiser , Shpall Elizabeth J. , Champlin Richard E.
Published: October 2022

Overview

Hematopoietic cell transplantation (HCT) is an essential component of therapy for various malignant and nonmalignant conditions and provides the only curative modality for several high‐risk disorders. While HCT can be associated with significant morbidity, meaningful progress has been made to reduce treatment‐related toxicities and improve patient outcomes following HCT. Together with the development of international donor registries and the feasibility of alternative donor transplants, these advances have broadened the indications of HCT in recent years.
Cancer and Aging
Authors: Rosko Ashley E. , Presley Carolyn J. , Williams Grant R. , Olin Rebecca L.
Published: October 2022

Overview

Cancer is a disease of older adults; with over half of cancers diagnosed in adults 65 years and older. Older adults are also comprising a larger portion of cancer survivors, accounting for 62%. The therapeutic landscape and treatment approaches are highly variable as is the health of older adults. The unique factors that older adults face must be considered when developing treatment strategies for maximum care and quality of life.
Disparities in Cancer Care
Authors: Brawley Otis W.
Published: October 2022

Overview

With the tremendous progress in cancer over the past half‐century, increased emphasis has been placed on the study of outcomes. One glaring finding is that some populations have done better than others. This has led to the academic discipline of the study of disparities in health. The causes of cancer are both genetic and environmental; a few of the differences are due to differences in population biology. Most of the disparities are due to population differences in the practice and receipt of prevention and risk‐reduction activities. Population differences also occur in receipt of quality treatment. It is estimated that at least one in five cancer deaths in the US is avoidable. The study of health disparities focuses on how to get adequate care to those who often do not receive it.
Neoplasms of the Endocrine Glands and Pituitary Neoplasms
Authors: Feng Rui , Gandhi Chirag D. , Pain Margaret , Post Kalmon D.
Published: October 2022

Overview

Pituitary neoplasms represent a phenotypically and pathologically diverse family of tumors. Symptoms may derive from abnormal hormone production, compression of adjacent nervous system structures, and in rare cases, metastases. New cell lineage classification based on transcription factors brings new insights into pathogenesis and treatment. Transsphenoidal surgery represents a command well‐tolerated treatment for most pituitary adenomas; however, advances in radiation and chemotherapy have increased treatment options enhancing treatment efficacy and eligibility.
Neoplasms of the Head and Neck
Authors: Ferris Robert L. , Garden Adam S. , Saba Nabil F.
Published: October 2022

Overview

Head and neck cancers (HNCs) comprise a diverse group of malignancies affecting the upper aerodigestive tract. The most common tumor type is squamous cell carcinoma. While the main risk factors for HNC remain tobacco and alcohol abuse, oncogenic viruses such as human papilloma virus and Epstein–Barr virus play a major carcinogenic role in tumors of the oropharynx and nasopharynx respectively. The management of head and neck malignancies is site and histology specific and requires a multidisciplinary team approach. Immunotherapy has become the standard of care in the treatment of advanced metastatic squamous cell cancers. In this article, we will review the current knowledge of HNC, with focus on squamous and salivary cancers, and discuss ongoing and future research aiming to improve the management and outcomes of patients with these malignancies.
Tumors of the Heart and Great Vessels
Authors: Wyler von Ballmoos Moritz C. , Reardon Michael J.
Published: October 2022

Overview

The most common neoplasms of the heart and great vessels are metastatic from other primary tumors, followed by benign primary cardiac tumors and then malignant primary tumors of the heart and great vessels. Cardiac‐specific symptoms are due to mass effect, disruption of normal conduction, and embolic events. Echocardiography is the most commonly used and widely available imaging modality, while cardiac MRI provides more detailed resolution, tissue characteristics, and functional assessment that help with differential diagnosis, staging, and surgical planning. Most benign and malignant tumor benefit from surgical resection, when amenable, but overall prognosis for malignant neoplasm is poor with limited or no other options for treatment.
Primary Germ Cell Tumors of the Thorax
Authors: Hainsworth John D. , Greco Frank A.
Published: October 2022

Overview

Primary germ cell tumors (GCT) of the thorax are rare but potentially curable. Benign teratomas, which account for approximately 60–70% and usually appear in young adults, are curable with surgical resection. Malignant mediastinal GCT usually occur in young men and can be divided histologically into pure seminoma (about 52% of cases) and various nonseminoma histologies. Pure seminomas are highly sensitive to chemotherapy; treatment with three cycles of a standard cisplatin‐based testicular GCT regimen is curative in more than 80%. Selected patients with small (<6 cm) localized seminomas have high cure rates with radiation therapy alone. Nonseminomatous mediastinal GCT are associated with Klinefelter syndrome (5–10% of cases) and are also associated with various acute leukemias. Optimal treatment includes four cycles of a standard cisplatin‐based testicular GCT regimen, followed by resection of residual mediastinal masses. Since most patients require surgical resection following chemotherapy, use of a bleomycin‐containing first‐line regimen should be avoided if possible. The cure rate for these relatively poor prognosis GCT is approximately 45%.
Gallbladder and Bile Duct Cancer
Authors: Eskander Mariam F. , Aquina Christopher T. , Pawlik Timothy M.
Published: October 2022

Overview

Biliary tract malignancy, which includes gallbladder cancer and cholangiocarcinoma, is an aggressive disease that is often advanced at the time of diagnosis and thus associated with a poor prognosis. In this article, we will review the epidemiology, risk factors, pathology, clinical presentation, diagnostic imaging modalities, and current treatment recommendations for gallbladder adenocarcinoma and cholangiocarcinoma.
Endometrial Cancer
Authors: Westin Shannon N. , Lu Karen H. , Rahaman Jamal
Published: October 2022

Overview

Endometrial carcinoma is the most frequent gynecologic cancer in the United States with over 65,000 new cases diagnosed per year. Over 80% have the classic estrogen‐dependent endometrioid histology with a favorable prognosis. Nonendometrioid histology types, including uterine serous carcinomas (USC), carcinosarcomas, and clear cell carcinomas, have a different molecular profile associated with more virulent disease and diminished survival. The Cancer Genome Atlas (TCGA) has defined four molecular subtypes of endometrial cancer, based on somatic mutations, copy number alterations, and microsatellite instability status. Over 75% of patients present with irregular or post‐menopausal bleeding. Surgical staging includes a hysterectomy, bilateral salpingo‐oophorectomy, with or without pelvic and para‐aortic lymph node sampling done via a laparotomy, laparoscopy, or robotic surgery. Surgery, where possible, constitutes the definitive primary treatment for most patients with endometrial carcinoma. Primary radiation therapy and primary hormonal therapy are alternatives for inoperable patients. Adjuvant therapy for stage I disease is determined by age, depth of myometrial invasion, lymph‐vascular space invasion, and tumor grade. For patients with advanced and recurrent disease radiation therapy, chemotherapy, and hormonal therapy are utilized. The combination of paclitaxel and carboplatin is the most effective and tolerable chemotherapy combination and currently serves as the backbone for a number of investigational strategies. Immune check‐point inhibitors are FDA approved for the treatment of metastatic endometrial cancer, including pembrolizumab alone for microsatellite instability‐high (MSI‐H) cancers and pembrolizumab and lenvatinib for microsatellite stable (MSS) disease. The growing understanding of the molecular aberrations common in endometrial cancer has led to exploration of a number of therapies, targeting angiogenesis and the PI3K/AKT, HER2, RAS/RAF, and DNA damage repair pathways.
Nonepithelial Ovarian Malignancies
Authors: Berek Jonathan S. , Renz Malte , Friedlander Michael L. , Bast Robert C.
Published: October 2022

Overview

Compared with epithelial ovarian cancers, nonepithelial ovarian tumors are uncommon, constituting <10% of all ovarian malignancies. They include germ cell malignancies, sex cord‐stromal tumors, and a variety of extremely rare ovarian cancers, including sarcomas and lipoid cell tumors. Although there are many similarities in presentation, evaluation, and management of the patients, these tumors also have unique features that require special approaches to management.1–5Germ cell malignancies are derived from primordial germ cells of the ovary and can be distinguished by histotype and expression of the biomarkers α‐fetoprotein (AFP) and/or human chorionic gonadotropin (hCG). They include dysgerminomas (AFP− hCG−), embryonal carcinomas (AFP+ hCG+), immature teratomas (AFP− hCG−), endodermal sinus (yolk sac) tumors (AFP+ hCG−), and ovarian choriocarcinomas (AFP− hCG+). Germ cell tumors occur in premenarchal girls and young women, grow rapidly, and can present with a symptomatic pelvic mass. As preservation of fertility is almost always an important priority, unilateral salpingo‐oophorectomy should be performed often followed by adjuvant platinum‐based therapy. Of note, dysgerminomas can be bilateral in 10–15% and are associated with gonadal dysgenesis in 5% of cases. Metastatic germ cell cancers are very sensitive to chemotherapy and the long‐term survival rate is high, even in advanced stages. At some institutions, young patients with stage IA germ cell tumors are followed carefully after resection with excellent outcomes and chemotherapy given only if there is recurrence with excellent outcomes. Sex cord‐stromal tumors include granulosa‐stromal tumors, juvenile granulosa tumors, and Sertoli–Leydig cell tumors. Granulosa‐stromal tumors can occur at all ages and produce estrogen resulting in pseudo‐precocious puberty in a small fraction of girls, amenorrhea in premenopausal women, and endometrial hyperplasia in postmenopausal adults. Granulosa‐stromal tumors are indolent and often confined to one ovary where surgery can cure stage I disease in more than 75% of cases. Adjuvant chemotherapy is generally not given after complete resection. Late recurrence has, however, been observed. Persistent or recurrent disease has responded to platinum‐based and hormonal therapy, including progestational agents, GnRH agonists, and aromatase inhibitors. Inhibin B has been a useful biomarker. Sertoli–Leydig cell tumors generally present in the third or fourth decade, produce androgens, and induce virilization in more than 70% of patients. As many Sertoli–Leydig cell tumors are in early‐stage and rarely bilateral, unilateral salpingo‐oophorectomy is often performed with 70–90% 5‐year survival.
Molar Pregnancy and Gestational Trophoblastic Neoplasia
Authors: Horowitz Neil S. , Goldstein Donald P. , Berkowitz Ross S.
Published: October 2022

Overview

Molar pregnancy and
gestational trophoblastic neoplasia
(
GTN
) comprise a group of interrelated diseases that includes
complete hydatidiform mole
(
CHM
) and
partial hydatidiform mole
(
PHM
), invasive mole,
choriocarcinoma
(
CCA
),
placental site trophoblastic tumor
(
PSTT
), and
epithelioid trophoblastic tumor
(
ETT
). Molar pregnancy and GTN produce a distinct tumor marker,
human chorionic gonadotropin
(
hCG
), which can be used for diagnosis, monitoring the effects of therapy, and follow‐up to detect relapse. Complete and partial moles are noninvasive, localized tumors that develop as a result of an aberrant fertilization event that leads to a proliferative process. The other trophoblastic tumors which as a group are referred to as GTN represent malignant disease because of their local invasion and metastases. GTN most commonly develops from a molar pregnancy but can arise
de novo
after any gestation. Although these tumors are rare, it is important for medical oncologists to understand their natural history and management because of their life‐threatening potential in reproductive‐age females and their high degree of curability with preservation of reproductive function if treated early and appropriately.
1,2
Despite the advances made in the management of GTN over the past six decades, patients with protracted delays in diagnosis, particularly after nonmolar pregnancies, still present with extensive tumor burdens and are at substantial risk for treatment failure and death.
Gynecologic Sarcomas
Authors: Rahaman Jamal , Cohen Carmel J.
Published: October 2022

Overview

Sarcomas are extremely rare and account for less than 1.5% of gynecologic cancers. Carcinosarcoma and leiomyosarcoma each account for 35–40% of uterine sarcomas, with endometrial stromal sarcoma (ESS) accounting for 10–15% and other sarcomas including adenosarcomas comprising 5–10 %. Uterine carcinosarcoma should be classified as a metaplastic carcinoma of the uterus. Most adenosarcomas and ESSs have good prognosis and respond to hormonal therapy. Undifferentiated endometrial sarcoma (UES) and adenosarcomas with sarcomatous overgrowth are rare and have poor prognosis and require chemotherapy. ESS are histologically and clinically distinct from UES and each have distinct gene rearrangements. More than 50% of stage I leiomyosarcomas and carcinosarcomas patients will recur. Chemotherapy is required for advanced or recurrent disease. In leiomyosarcomas, the active drugs are doxorubicin, ifosfamide, gemcitabine, and docetaxel. For uterine carcinosarcomas, the drugs of choice are ifosfamide, cisplatin/carboplatin, and paclitaxel. Adjuvant radiation therapy may provide locoregional control in select cases of uterine carcinosarcomas. Hormonal therapy, including progestational agents, GnRH analogs, and aromatase inhibitors, has a role in the treatment of advanced or recurrent low‐grade ESSs and adenosarcomas.
Neoplasms of the Breast
Authors: Tripathy Debu , Makhnoon Sukh , Arun Banu , Sahin Aysegul , Kettner Nicole M. , Damodaran Senthil , Keyomarsi Khandan , Yang Wei , Hunt Kelly K. , Clemens Mark , Woodward Wendy A. , Mitchell Melissa P. , Layman Rachel , Hobbs Evthokia A. , Lim Bora , Dupuis Megan , Murthy Rashmi , Alhalabi Omar , Ibrahim Nuhad , Subbiah Ishwaria M. , Barcenas Carlos
Published: October 2022

Overview

Breast cancer is the most common cancer among women in the United States and growing in incidence worldwide, while mortality due to breast cancer is slowly decreasing. The last two decades have witnessed many changes in the diagnostic landscape both in terms of imaging studies and laboratory tests, most notably next‐generation sequencing both on tumor and blood. Our understanding of breast oncogenesis, tumor heterogeneity, and metastasis has deepened. Segmental mastectomy and sentinel lymph node (SLN) biopsy have been used in the majority of cases coupled with radiation therapy. In cases managed with mastectomy, radiation of one to three positive nodes has been utilized more often. Gene expression profiling has been used to identify women with hormone receptor‐positive (HR+) breast cancer who would benefit from adjuvant chemotherapy. Targeted therapy has been developed for HR+, HER2 amplified, and triple‐negative breast cancer. Immune checkpoint inhibitors have improved the management of triple‐negative disease. poly(adenosine diphosphate [ADP]–ribose) (PARP) inhibitors have improved outcomes for breast cancer patients with BRCA1/2 mutations. Combinations of targeted therapies and hormonal therapies have proved effective for adjuvant therapy and in recurrent disease.
Other Skin Cancers
Authors: McMurray Stacy L. , Stebbins William G. , Millican Eric A. , Neel Victor A.
Published: October 2022

Overview

Nonmelanoma skin cancer (NMSC) includes squamous cell carcinoma (SCC), basal cell carcinoma (BCC), Merkel cell carcinoma (MCC), and other premalignant and malignant tumor types. The incidence of NMSC has increased significantly in recent years. These cancers are diverse in their clinical presentation, biology, and capacity to metastasize. Our understanding of the molecular biology of NMSC has grown considerably in recent years, leading to the development of new treatment options. In addition to malignant NMSC, this article will discuss several benign skin tumors that arise due to underlying internal malignancies.
Bone Tumors
Authors: Damron Timothy A.
Published: October 2022

Overview

As a group, bone tumors are uncommon lesions arising from a wide array of cells, affecting all ages of patients, and involving any bone in the body. Benign bone lesions are quite common and range from inactive to active and aggressive tumors. Treatment of inactive bone lesions is most often observation. Active benign bone lesions are frequently treated surgically by curettage. Benign aggressive tumors often require extended intralesional curettage with adjuncts. Among malignant bone lesions, the most common bone malignancy is metastatic carcinoma, and the most common primary bone malignancy is myeloma. The focus on bone involvement in these tumors is fixation of pathologic fractures and prediction of impending fractures. Primary bone sarcomas are rare tumors with characteristic clinical, radiographic, and pathologic features. Treatment of bone sarcomas most often requires wide surgical resection with or without chemotherapy and/or radiotherapy. Although often numerous specialties may contribute to their evaluation and care, orthopedic oncology is the only subspecialty focused specifically on all aspects of bone tumors.
Soft Tissue Sarcomas
Authors: Thornton Katherine A. , Baldini Elizabeth H. , Maki Robert G. , O'Sullivan Brian , Leyfman Yan , Raut Chandrajit P.
Published: October 2022

Overview

The management of soft tissue sarcomas is driven by the anatomic site as well as the histologic subtype of the primary disease. In this chapter, we focus on the importance of a multidisciplinary approach to this diverse group of over 75 different tumor types.

We will discuss in this chapter the etiology, clinical presentation, staging, histopathologic classification and prognostic factors for patients with soft tissue sarcoma. Surgery remains paramount to achieving cure for the vast majority of sarcomas. We will discuss how adjunctive therapies, like radiation and chemotherapy can improve overall outcome, as well as highlight the limitations and unanswered questions, both with respect to local recurrence and distant metastases. Where appropriate, we attempt to link specific histologies or molecular changes to the therapeutic approach to disease. We hope to draw attention to the fact that in a field that has traditionally had stagnation in the development of new therapeutic strategies, there has been a renaissance of new molecularly and mechanistically targeted therapies helping to improve outcomes for soft tissue sarcoma patients.
Myelodysplastic Syndromes
Authors: Borate Uma M.
Published: October 2022

Overview

Primary, secondary, and familial myelodysplastic syndromes (MDS) became a reportable group of malignancies in 2001. Over the past 20 years, there have been tremendous strides in genetic and translational research, which has influenced the pathological diagnosis and classification, risk stratification scoring systems, and genomic characterization of MDS. In certain cases, this has led to more personalized therapy options such as Luspatercept in RARS patients with SF3B1 mutations. In this chapter, we discuss the history behind the various MDS prognostic risk stratification and classifications. We also examine our current understanding of MDS pathophysiology, the complexities with establishing an MDS diagnosis including the evolving diagnostic criteria, and the use of next‐generation sequencing analyses. Then, we outline both the standard of care therapeutic options including hypomethylating agents, and their impact over the past decade, as well as multiple clinical trials and treatment options being investigated for MDS patients. Finally, we discuss what personalized treatments and possible preventative strategies we may expect to see – in the next decade – for MDS development in high‐risk patient populations.
Non‐Hodgkin's Lymphoma
Authors: Freedman Arnold S. , LaCasce Ann S.
Published: October 2022

Overview

The malignant lymphomas are neoplastic transformations of cells that reside predominantly within lymphoid tissues. Although Hodgkin and non‐Hodgkin lymphomas (NHLs) both infiltrate lymphohematopoietic tissues, their biologic and clinical behaviors are distinct. They differ with neoplastic cells of origin, sites of disease, presence of specific symptoms, and response to treatment. Although both are among the most sensitive malignancies to radiation and cytotoxic therapy, their cure rates markedly differ. Hodgkin lymphomas are cured in nearly 80% of all patients employing both conventional and salvage treatment strategies whereas NHLs are cured in fewer than 50% of patients.
Mycosis Fungoides and Sézary Syndrome
Authors: Hanel Walter , Chung Catherine , Reneau John C.
Published: October 2022

Overview

Mycosis fungoides (MF) and its leukemic variant, Sézary syndrome (SS), are the most common cutaneous T‐cell lymphomas. MF/SS originates in the skin and presentation may vary from limited patches to erythroderma and/or widespread cutaneous tumors. Although patients with limited patch‐plaque disease generally have an indolent course with favorable prognosis and survival similar to age‐matched control populations, patients who present with cutaneous tumors or extracutaneous disease have a relentless progressive course of disease. Treatments for patients with limited disease are primarily skin‐directed and include various topical therapies including steroids, chemotherapy (nitrogen mustard), retinoids (bexarotene), immunomodulators (imiquimod), radiation therapy, and phototherapy. When the disease is advanced, skin‐directed therapies are still often needed, but systemic treatment becomes essential. Conventional chemotherapy (single agent or combination) is frequently not effective. However, nonchemotherapeutic systemic agents such as retinoids, extracorporeal photopheresis, histone deacetylase inhibitors, the interferons, mogamulizumab, brentuximab vedotin, alemtuzumab, and checkpoint inhibitors may achieve responses. Durable responses are not normally observed and patients will typically require multiple sequential therapies with different mechanisms of action to maintain adequate disease control. Allogeneic hematopoietic cell transplant can be curative in select cases.
Antiemetic Therapy
Authors: Berger Michael J. , Ettinger David S.
Published: October 2022

Overview

Dramatic progress has been made in the prevention and treatment of chemotherapy‐induced nausea and vomiting (CINV), especially since the introduction of the 5‐HT3 receptor antagonists (5HT3 RAs) in the early 1990s and the 2003 introduction of the NK‐1 receptor antagonist (NK1 RA), aprepitant. Recent surveys indicate the need for heightened awareness of the frequency and severity of acute and especially delayed CINV. Fortunately, new agents have been added to the antiemetic arsenal to further enhance the efficacy of antiemetic prophylaxis. Complementary therapies such as acupuncture, and mind–body interventions appear promising in controlling nausea, and are being explored further. Appropriate implementation of guidelines for prophylaxis based on patient risk factors and the specific chemotherapy agents used will ensure that fewer patients experience these most distressing of side effects.
Neurologic Complications of Cancer
Authors: Castro Luis Nicolas Gonzalez , Batchelor Tracy T. , DeAngelis Lisa M.
Published: October 2022

Overview

Neurologic complications of cancer and its therapy are common and being seeing with increasing frequency as many patients survive longer with better systemic disease control. Cancer‐related complications can be metastatic or nonmetastatic. Metastases in the nervous system can involve multiple anatomical sites (brain, meninges, spinal cord, nerve roots, and nerves), leading to a variety of clinical presentations, including focal weakness, sensory changes, and seizures. Nonmetastatic complications include metabolic derailments, hypercoagulability, and paraneoplastic syndromes, as well as complications due to cancer therapy, such as chemotherapy‐induced neuropathy, radiation toxicity, and immunotherapy‐related neurologic syndromes.
Gastrointestinal and Hepatic Complications in Cancer Patients
Authors: Bresalier Robert S. , Coronel Emmanuel S. , Zhang Hao Chi
Published: October 2022

Overview

Gastrointestinal and hepatic complications represent some of the most common and potentially life‐threatening disorders associated with treatment of cancer patients. The expansion of therapeutic options for these patients has been accompanied by a growing number of direct and indirect consequences which affect the rapidly dividing cells of the GI tract. Cytotoxic, immunologic, and infectious insults often act synergistically to augment toxicity. Recognition of these complications, together with proper evaluation and management are key to the well‐being of these patients.
Endocrine Complications and Paraneoplastic Syndromes
Authors: Yeung Sai‐Ching J. , Gagel Robert F.
Published: October 2022

Overview

Transformation of normal cells results in activation and/or suppression of a number of hormonally active genes, resulting in ectopic humoral paraneoplastic syndromes. Treatment of cancer also results in a number of endocrine or metabolic abnormalities, most of which are related to hormone deficiency or drug‐related toxicity. Targeted therapy may disrupt signaling pathways involved in endocrine function, and immunotherapy has led to autoimmune endocrine dysfunctions. This article will outline ectopic endocrine paraneoplastic syndromes and the major endocrine toxicities of antineoplastic therapy.
Carcinoma of the Colon and Rectum
Authors: Suzuki Yota , Tyler Douglas S. , Phatak Uma R.
Published: October 2022

Overview

Colorectal cancer is the third most common malignant tumor and the second most common cause of cancer death worldwide. Improvements in education and performance of screening have led to a decrease in mortality and improvements in outcomes. Comprehensive management of colorectal cancer requires a multidisciplinary approach involving specialists in genetics, gastroenterology, radiology, radiation oncology, surgery, pathology, and medical oncology. New developments in cancer biology, medical therapeutics, and surgical techniques have also led to improvements in outcomes. Emerging concepts, such as total neoadjuvant therapy and watch‐and‐wait strategy for rectal cancer, are also changing treatment paradigms. This article will provide a comprehensive review of the current management and treatment of colorectal cancer.
Magnetically Assisted Rotationally Multistable Metamaterials for Tunable Energy Trapping–Dissipation
Authors: Seyedkanani Alireza , Akbarzadeh Abdolhamid
Published: October 2022

A motif for rotational multistability is developed by arranging permanent magnets in a circular pattern and creating magnet pairs with magnetically induced negative incremental torsional stiffness. Through a set of experimental and numerical studies, different means to tailor the torsional response of a rotational magnet pair are demonstrated. A magnet pair in tandem with tilted elastic arms is harnessed to form an energy‐trapping rotational unit cell. By stacking several of these unit cells upon each other, a 1D rotationally multistable metamaterial capable of storing the input energy and releasing it in the form of rotational waves is developed. The periodic stable equilibrium states in rotational magnet pairs invoke the notion of cyclic multistability, which is employed here to realize, for the first time, a tunable fluid‐free rotary metadamper with energy dissipation induced by repeating snap‐back instabilities. High tunability of magnetic interactions offers a new design paradigm for developing reusable energy dissipative and energy trapping rotary metamaterials, the properties of which can be easily tailored in situ and even at the post‐fabrication stage.
Anion Additive‐Induced Size, Morphology, and Local Structure Tuning of Lanthanide‐Doped Upconversion Nanoparticles
Authors: Yuan Ze , Lin Chen , Wang Yilin , Niu Yangyang , Yan Jiaxu , Lu Min , Li Xiaona , Huang Ling , Xie Xiaoji
Published: October 2022

Introducing additives during the preparation can effectively modulate characteristics of lanthanide‐doped upconversion nanoparticles (UCNPs) that are pivotal to applications of the nanoparticles, ranging from bioimaging to super‐resolution microscopy. Unfortunately, anion additive‐caused changes in the characteristics of lanthanide‐doped UCNPs are almost unexplored, even though anionic species are ubiquitous. Herein, Na(CCl3COO), as a representative anion additive, is used to demonstrate that anion additives can tune characteristics of cubic NaYF4:Yb/Er UCNPs, including size, morphology, and local structure. Experimental studies, together with theoretical calculations, reveal that Cl− ions released from the anion additive can affect the growth kinetics and selectively cap on planes of crystals during the formation of the UCNPs. Consequently, tuning of characteristics can be achieved, which also enables the modulation of upconversion properties of resulting nanoparticles. Furthermore, the anion additive‐based modulation can facilitate the fabrication of ultrasmall UCNPs with bright luminescence and advance the upconversion‐based information encryption when other techniques are integrated. These results reveal that anionic species should be considered during the preparation of UCNPs, and these findings should shed light on new avenues to fabricate UCNPs with desired properties.