DiSaia and Creasman Clinical Gynecologic Oncology

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Front matter
	DiSaia and Creasman Clinical Gynecologic Oncology
Preface
Contents
1 Preinvasive disease of the cervix
	Key points
	Introduction
	Human papillomavirus natural history
	Epidemiology
	Human papillomavirus vaccination
	Screening
	Management of abnormal screening results
		Colposcopy
		Screening and treatment in immunocompromised women
		Management of abnormal screening results
		Managing abnormal results in young women
		Managing unsatisfactory cytology
		Cytology-negative, human papillomavirus-positive women
		Management of high-grade squamous intraepithelial lesion
		Atypical glandular cells
		Management of endometrial cells in older women
	Management of post-colposcopic results
		Management of women with no lesion or CIN1 at colposcopy
		Management of women with CIN2+
		Treatment of cervical disease
	Management of abnormal screening results in pregnancy
	Future directions
2 Preinvasive disease and dystrophies of the vagina and vulva and related disorders
	Key points
	Embryology and diethylstilbestrol exposure
	Treatment of women exposed to diethylstilbestrol
	Nonneoplastic epithelial disorders of the vulva and vagina
		Lichen simplex chronicus
		Lichen sclerosus
		Lichen planus
		Pigmented lesions
		Diagnosis and treatment
			Lichen simplex chronicus
			Lichen sclerosus
			Lichen planus
	Vulvar intraepithelial neoplasia
		Terminology
		Progression to cancer
		Human papilloma virus and vaccination
		Diagnosis
		Management
			Excision
			Laser
			Alternative ablative techniques
			Non-surgical treatment
				Imiquimod.
				Cidofovir.
				Photodynamic therapy.
			Surveillance
	High-grade squamous intraepithelial lesion of the vagina
		Clinical profile
		Diagnosis
		Management
3 Invasive cervical cancer
	Key points
	General observations
		Anatomy
		Epidemiologic studies
			Clinical profile
	Clinical profile of invasive cancer
		Symptoms
		Gross appearance
		Routes of spread
			Primary group
			Secondary group
	Glandular tumors of the cervix
	Staging
		International federation of gynecology and obstetrics
		Positron emission tomography
		Surgical staging
	Treatment of early-stage disease
	Superficial carcinoma of the cervix
		Stage IA1
		Stage IA2
	Adenocarcinoma
		Based on current data radical treatment is not justified in patients with adenocarcinoma stage IA
		Radical abdominal hysterectomy with lymphadenectomy
			Complications
		Indications for postoperative adjuvant therapy
		Sexual function
		Nerve-sparing radical hysterectomy
		Sentinel lymph node identification
		Minimally invasive radical hysterectomy with lymphadenectomy
		Fertility-preserving surgery for early-stage tumors
		Cervical conization for adenocarcinoma in situ and microinvasive carcinoma
		Vaginal radical trachelectomy with laparoscopic lymphadenectomy
		Lateral ovarian transposition
	Treatment of locally advanced disease
		Radiotherapy
			Intensity-modulated whole pelvic radiotherapy
			Radium and cesium therapy
			Interstitial therapy
			Extended-field irradiation therapy
		Radiation and chemotherapy
		Neoadjuvant chemotherapy and other novel treatment approaches
		Suboptimal treatment situations
	Neuroendocrine and other uncommon tumors of the cervix
	Glassy cell carcinoma, carcinosarcoma, lymphoma, and melanoma
	Survival results and prognostic factors for early-stage and locally advanced disease
	Recurrent and advanced carcinoma of the cervix
		Management and prognosis
		Surgical therapy: Radical hysterectomy
			Pelvic exenteration
			Patient selection
			Morbidity and mortality
			Survival results
		Radiation
		Chemotherapy
		Immunotherapy for advanced cervical cancer
		Pembrolizumab—the first US FDA approved immunotherapy for cervical cancer
		Anti-PD-1 and anti-CTLA-4 combinations
		Adoptive T cell therapy
		Tissue factor as a target
		Anti-HER strategies
4 Endometrial hyperplasia, estrogen therapy, and the prevention of endometrial cancer
	Introduction
	Endometrial hyperplasia: Pathologic diagnostic criteria
		Traditional endometrial hyperplasia
		Endometrial intraepithelial neoplasia
		Endometrial intraepithelial carcinoma
	Clinical presentation
	Management decisions for endometrial intraepithelial neoplasia
	Management of endometrial hyperplasia without atypia
	Prevention of endometrial cancer
	Benefits and risks of menopausal hormone therapy
		Hot flashes
		Critical assessment of risk/benefit ratio of hormone therapy: The women’s health initiative data
		Cardiovascular disease and stroke
		Cardiovascular disease and cancer risk
		Osteoporosis
			Osteoporosis prevention
			Pharmacologic therapies and osteoporosis: Hormones
			Pharmacologic therapies and osteoporosis: Selective estrogen-receptor modulators
			Bone specific pharmacologic therapies for treatment of osteoporosis
		Genitourinary syndrome of menopause
		Special populations
			Early menopause
			Elevated risk of breast cancer
	Risk modification with hormone therapy: Options and opportunities
		Use of lower doses and different formulations
		Discontinuation of hormone therapy
	Nonhormone therapies for menopausal symptoms
	Menopausal hormone therapy for endometrial and breast cancer survivors
		Hormone therapy for endometrial cancer survivors
		Hormonal therapy for women with or at risk for breast cancer
		Hormone therapy in women with hereditary cancer syndromes
			BRCA1 or BRCA2 gene
			Lynch syndrome
5 Adenocarcinoma of the uterine corpus and sarcomas of the uterus
	Key points
	Incidence
	Epidemiology
	Diagnosis
		Pathology
		Tumor grade
	Prognostic factors
		Stage of disease: Depth of invasion, cervical involvement, adnexal involvement, and nodal metastasis
			Tumor grade
			Lymphovascular space involvement
			Tumor size
			Peritoneal cytology
			Molecular indices
				Hormone receptors.
			Correlation of multiple prognostic factors
	Treatment
		Surgical management of endometrial cancer
		Radiation therapy
			Chemotherapy
		Drug development
			Advanced disease
			Adjuvant therapy: High-risk disease
			Hormones
	Antiangiogenic therapy in endometrial cancer
		Immunotherapy
		Special circumstances
			Multiple malignant neoplasms
			Uterine serous carcinoma
			Uterine clear cell carcinoma
			Carcinosarcoma
				Clinical profile.
				Surgical management.
		Adjuvant therapy
		Management of advanced stage or recurrent disease
	Uterine sarcoma
		Classification
	Incidence and epidemiology
	Leiomyosarcoma
		Clinical profile
		Surgical management
		Adjuvant therapy
		Management of recurrent disease
	Endometrial stromal sarcoma
		Clinical profile
		Surgical management
		Adjuvant therapy
		Management of recurrent disease
	Other sarcomas
		Follow-up for patients with endometrial cancer
6 Invasive cancer of the vulva
	Key points
	Invasive squamous cell carcinoma
		Histology
		Clinical presentation and diagnosis
		Location and spread pattern
		Staging
		Molecular markers and tumor etiology
			Sentinel lymph node biopsy
	Technique of inguinofemoral lymphadenectomy
		Management
		Technique of radical vulvectomy
		Morbidity associated with treatment of vulvar carcinoma
		Survival results
		Tolerance of the elderly patients to therapy
		Recurrent disease
		Immunotherapy in vulvar cancer treatment
	Very early vulvar carcinoma
	Paget disease
		Clinical and histologic features
		Clinical course and management
	Melanoma
	Sarcoma
	Bartholin gland carcinoma
	Basal cell carcinoma
7 Gestational trophoblastic disease
	Epidemiology
	Hydatidiform mole
		Cytogenetics and pathology
		Presentation and symptoms
		Diagnosis
		Evacuation
		Risk factors for postmolar gestational trophoblastic neoplasia
		Postmolar surveillance
		Prophylactic chemotherapy after molar evacuation
		Coexistent molar pregnancy with a normal fetus
	Gestational trophoblastic neoplasia
		Diagnosis
		Abnormal human chorionic gonadotropin assays
			“phantom” human chorionic gonadotropin
			The “hook effect”
		Pretherapy evaluation
		Classification and staging
		Treatment of nonmetastatic and low-risk metastatic gestational trophoblastic neoplasia
		High-risk metastatic gestational trophoblastic neoplasia
		Surgery
		Radiation therapy
		Placental site trophoblastic tumor
		Epithelioid trophoblastic tumor
	Other considerations
		Future childbearing
		Coexistence of normal pregnancy and gestational trophoblastic neoplasia
		Transplacental fetal metastases
		Survivorship issues after successful treatment of gestational trophoblastic neoplasia
8 Adnexal masses
	Key points
	Adnexal masses
		Evaluative approach
		Classifying the mass
			OVA1 test
			Human epididymis protein 4
			Multimodality approach
		Differential diagnosis
	Extraovarian adnexal masses
		Uterine masses
		Tubal masses
		Adnexal masses of nongynecologic origin
			Bowel
	Ovarian masses
		Functional cysts
		Endometriotic cysts
		Benign ovarian neoplasms
		Serous cystadenoma
		Mucinous cystadenoma
		Dermoid cyst (benign cystic teratoma)
		Fibroma
		Brenner tumor
	Management of adnexal masses
		Observation versus surgery
		Minimally invasive surgery for adnexal masses
	Special circumstances
		Adnexal masses in childhood
		Postmenopausal ovary
		Borderline malignant epithelial ovarian neoplasms
		Fertility preservation
		Cyst rupture or spill of tumor
		Prophylactic versus risk-reducing oophorectomy
9 Epithelial ovarian cancer
	Key points
	Classification
	Incidence, epidemiology, and etiology
		Familial ovarian cancer
	Signs and symptoms
		Diagnostic techniques
		Attempts at early detection (screening)
	Staging
		Therapeutic options for primary treatment
			Stages IA, IB, and IC
			Stages IIA and IIB
			Stage III
			Stage IV
		Surgery
			Maximal surgical effort
		Role of minimally invasive surgery
		Neoadjuvant chemotherapy and interval cytoreductive surgery
		Systemic therapy/chemotherapy
		Conventional (dose-intense platinum chemotherapy)
		Dose-dense paclitaxel
		Intraperitoneal chemotherapy
		Bevacizumab
		Treatment for rare epithelial histologies
		Frontline maintenance therapy
	Other considerations
		Extraovarian peritoneal serous papillary carcinoma
		Small cell carcinoma of the ovary
			Borderline epithelial neoplasms of the ovary
	Surveillance and follow-up techniques
		Use of CA 125 levels and other tumor markers
		Radiographic imaging
		Treatment for recurrent disease and targeted therapies
			Platinum-sensitive disease
			Platinum-resistant disease
		Targeted therapy
		Immunotherapy
		Surgery for recurrent disease
		Radiation
	Palliative/end of life support
	Conclusions on management
	Current areas of research
10 Germ cell, stromal, and other ovarian tumors
	Key points
	Germ cell tumors
		Classification
		Clinical profile
		Staging
		Treatment options
			Surveillance for stage I tumors
			Second-look laparotomy
			Radiation therapy
			Chemotherapy
			Neoadjuvant chemotherapy
		Recurrences in germ cell cancer
		Treatment toxicity
		Dysgerminoma
		Endodermal sinus tumor (yolk sac tumor)
		Embryonal carcinoma
		Polyembryoma
		Choriocarcinoma
		Mixed germ cell tumors
		Teratoma
			Mature cystic teratoma
			Mature solid teratoma
			Immature teratoma
			Monodermal or highly specialized teratomas
				Struma ovarii.
				Carcinoid tumors.
	Tumors of germ cell and sex cord derivation
		Gonadoblastoma
		Mixed germ cell–sex cord stromal tumors
	Tumors derived from special gonadal stroma
		Classification, clinical profile, and staging
		Treatment
		Granulosa–stromal cell tumors
		Thecomas
		Fibromas and sclerosing stromal cell tumors
		Sertoli-leydig cell tumors
		Sex cord tumor with annular tubules
		Gynandroblastoma
			Steroid cell neoplasms
	Tumors derived from nonspecific mesenchyme
	Small cell carcinoma of the ovary, hypercalcemic type
	Malignant lymphoma
	Metastatic tumors to the ovary
	Malignant ovarian tumors in children
11 Breast diseases
	Key points
	Introduction
	Anatomy of the breast
	Embryology and development of the breast
	Pregnancy and breast feeding
	Benign breast conditions
		Fibrocystic change
		Proliferative changes
		Complex sclerosing lesions
		Fibroadenoma
		Phyllodes tumor
		Adenoma
		Superficial thrombophlebitis
		Mastitis
		Duct ectasia
		Fat necrosis
		Nipple discharge
	History and physical examination
	Breast imaging
		Mammography
		Screening interval
		Breast imaging reporting and data system
		Diagnostic mammography
		Mammographic lesions
		Microcalcifications
		Digital mammography
	Breast ultrasound and magnetic resonance imaging
	Diagnostic evaluation
		Palpable mass
		Fine-needle aspiration or biopsy
		Image-guided percutaneous breast biopsy
		Ultrasound-guided biopsy
		Tissue-acquisition devices
		Excisional biopsy
		Surgical excision/breast biopsy
	Epidemiology of breast cancer
	Risk factors and assessment
		Age
		Family history and hereditary risk
		Personal history
		Reproductive history
		Exogenous hormone use
		Prior exposure to radiation therapy
		Other factors
		Relative risk and risk-assessment models
		Natural history
	Pathology
		Ductal carcinoma in situ
		Paget’s disease
		Lobular carcinoma in situ
		Invasive ductal carcinoma
		Infiltrating lobular carcinoma
		Inflammatory carcinoma
	Metastases from extramammary tumors
	Biologic markers and prognostic factors
		Axillary lymph node status
		Tumor size
		Histologic grade
		Hormone receptors
		HER2
		Ki-67
		Molecular profiling
	Staging of breast cancer using the tumor–node–metastasis system
	Treatment of breast cancer
		Surgery
			Mastectomy
			Breast-conservation therapy
			Patient selection
			Management of the axilla
			Sentinel lymph node biopsy
		Adjuvant therapy
			Neoadjuvant chemotherapy
			Estrogen receptor-positive breast cancer
			Gene expression assays
			HER2 positive breast cancer
			Triple negative breast cancer
		Endocrine therapy
			Ovarian ablation
			Tamoxifen
			Aromatase inhibitors
		Radiation therapy
		Breast reconstruction
	Special issues
		Breast cancer in the elderly woman
		Pregnancy and fertility
		BRCA1 and BRCA2
			Pathologic features and stage
			Treatment
			Chemoprevention
		Metastatic disease
	Conclusions
12 Cancer in pregnancy
	Key points
	Background and epidemiology of cancer
		Report from the european society of gynecological oncology cancer in pregnancy task force
	The more common solid tumors
		Cervical cancer
			Human papillomavirus in pregnancy
			Evaluation of cervical cytology in pregnancy
			The performance of colposcopy in pregnancy
			The natural history of cervical intraepithelial neoplasia in pregnancy
			Conization and related procedures in pregnancy
			Management of cervical intraepithelial neoplasia in pregnancy
			Management of squamous cell abnormalities
			Management of glandular cell abnormalities
			Intrapartum hysterectomy
			Invasive cervical cancer
			Microinvasive disease
			Cesarean–radical hysterectomy with pelvic lymphadenectomies
			Radical trachelectomy with lymphadenectomy
			Whole-pelvis radiotherapy with intracavitary brachytherapy
			Episiotomy site recurrence
			Planned delay of therapy
			Neoadjuvant chemotherapy in pregnancy
			Prognosis for patients with cervical cancer in pregnancy
			Obstetric outcomes
		Ovarian cancer
			Asymptomatic adnexal masses
			Surgical management of the ovarian mass
			Robotic-assisted laparoscopic management of adnexal masses during pregnancy
			Ovarian masses specific to pregnancy
			Histologic types of ovarian tumors
			Borderline ovarian tumors
			Frankly malignant ovarian tumors
			Malignant germ cell tumors in pregnancy
			Dysgerminoma in pregnancy
			Sex cord–stromal tumors in pregnancy
			Chemotherapy for nonepithelial ovarian cancer during pregnancy
			Epithelial ovarian cancer in pregnancy
			Chemotherapy for epithelial ovarian cancer during pregnancy
				Targeted (biologic) therapy for ovarian cancer in pregnancy
					Vascular endothelial growth factor inhibitors.
					PARP inhibitors.
			Other types of malignant ovarian tumors
			Summary of the adnexal mass and ovarian cancer in pregnancy
		Breast cancer
			Prognosis
			Presentation
			Evaluation
			Surgical management
			Sentinel lymph node identification
			Breast reconstruction
			Adjuvant therapy
			Neoadjuvant and adjuvant chemotherapy for pregnancy-associated breast cancer
			Chemotherapy for metastatic breast cancer
			HER2/neu–targeted agents in pregnancy
			Hormonal treatments for pregnancy-associated breast cancer
			Prognosis of pregnancy-associated breast cancer
			Lactation
			Hormonal considerations: Pregnancy preceding breast cancer
				Protective effect of human chorionic gonadotropin.
				Recent antecedent pregnancy.
				Breastfeeding.
			Hormonal considerations: Pregnancy coincident with breast cancer
			Estrogen-receptor and progesterone-receptor status
			Pregnancy termination
			Tamoxifen
			Hormonal considerations: Pregnancy after breast cancer
			Prophylactic oophorectomy
			Survival among patients with pregnancy-associated breast cancer
	Evaluation and therapeutic modalities
		Anesthesia and surgery in pregnant patients
			Anesthesia
			Surgery
			Laparotomy
			Laparoscopy
		Diagnostic and therapeutic radiation in pregnancy
			Radiobiology
			Radiation-induced anomalies
			Diagnostic radiology
			Ionizing radiation
			Nonionizing radiation
			Radionuclides
			Radiation therapy
			Radiation-induced carcinogenesis
			Genetic damage and infertility
		Chemotherapy
			Teratology and embryology
			Transplacental studies
			Classes of antineoplastic agents
				Antimetabolites.
				Alkylators.
			Anthracycline and antitumor antibiotics
			Plant alkaloids
			Taxanes
			Platinum analogs
				Targeted therapeutic pathways and placental development.
			Pharmacokinetics, sublethal fetal effects, and maternal risks
			Estimating the stillbirth rate
			Occupational exposure
			Recommendations on the use of chemotherapy during pregnancy
			Timing of delivery
			Breastfeeding
			Long-term neonatal follow-up
			Supportive therapy
		Serum tumor markers in pregnancy
			Obstetric considerations and antepartum management
				Reproductive options and counseling.
				Periviability.
				Anticoagulation.
				Antepartum monitoring and surveillance.
				Antenatal corticosteroids.
				Peripartum considerations.
				Postpartum care.
			Highlighted maternal-fetal medicine points
	Hematologic malignancies
		Leukemia
			Leukemia in pregnancy
			Chemotherapy for acute leukemia in pregnancy
			Acute myelogenous leukemia
			Acute lymphoblastic leukemia
			Acute promyelocytic leukemia
			Management of chronic leukemia
			Chronic myelocytic leukemia
			Hairy cell leukemia, multiple myeloma, and chronic lymphocytic leukemia
		Hodgkin disease
			Hodgkin disease in pregnancy
			Management of Hodgkin disease in pregnancy
			Non-Hodgkin lymphoma
			Non-Hodgkin lymphoma in pregnancy
	Other tumors
		Melanoma
			Staging of melanoma
			Melanoma in pregnancy
			Historical series of melanoma in pregnancy
			Contemporary studies of melanoma in pregnancy
			Management of melanoma in pregnancy
			Melanoma metastatic to the products of conception
		Thyroid cancer
			Thyroid cancer in pregnancy
			Undifferentiated lesions
			Prognosis among pregnant women with thyroid cancer
		Rare gynecologic malignancies in pregnancy
			Vulvar cancer
				Historical series of vulvar cancer in pregnancy.
				Management of vulvar cancer in pregnancy.
			Primary invasive vaginal tumors
			Endometrial cancer
			Fallopian tube cancer
			Trophoblastic tumors of the fallopian tube: “ectopic” pregnancy
		Placental and fetal tumors
			Complete hydatidiform mole with coexistent fetus
			Placental and fetal metastases
			Primary fetal tumors
13 Complications of disease and therapy
	Key points
	Disease–oriented complications
		Hemorrhage
		Urinary tract complications
			Ureteral obstruction
			Urinary tract fistulas
		Gastrointestinal complications
			Gastrointestinal obstruction
			Gastrointestinal fistulas
		Biliary obstruction
	Treatment-related complications
		Surgical
			Intraoperative and postoperative hemorrhage
				Intraoperative management of vascular complications.
				Hypogastric (internal iliac) artery ligation.
			Intraoperative and postoperative genitourinary tract injuries
				Intraoperative genitourinary injuries.
				Postoperative genitourinary injuries.
		Bladder dysfunction after radical surgery
		Intraoperative and postoperative gastrointestinal tract injuries
		Venous thromboembolic complications
			Risk factors
			Prophylactic methods
				Pharmacologic venous thromboembolism prophylaxis.
				Oral agents.
			Mechanical methods
			Extended postoperative prophylaxis
			Management of deep vein thrombosis and pulmonary embolism
				Diagnosis of deep vein thrombosis.
				Diagnosis of pulmonary embolism.
				Treatment of deep vein thrombosis.
					Low-molecular-weight heparin.
					Unfractionated heparin.
					Doacs and warfarin.
					Long-term anticoagulation.
					Inferior vena cava filter.
					Pulmonary embolism.
				Superior vena cava syndrome.
			Lymphedema
			Lymphocysts
			Postoperative infections
				Urinary tract infections.
				Pulmonary infections.
				Wound infections.
				Intraabdominal and pelvic abscesses.
				Necrotizing fasciitis.
			Special populations
				Obesity
					Incidence and definition.
					Postoperative complications and management.
				Elderly patients.
		Radiation therapy
			Gastrointestinal complications
				Acute complications.
				Chronic complications.
			Urologic complications
			Sexual function and vaginal stenosis
14 Basic principles of chemotherapy and other systemic therapies
	Key points
	Historical overview
	General principles
	Cell cycle control and growth kinetics
	Dynamics of chemotherapy
	Pharmacologic principles
		Drug interactions
		Drug resistance
		Calculation of dosage
			Jelliffe method
			Cockroft–Gault method
			Calvert formula
	Categories of drugs in current use (Table 14.7)
		Alkylating agents
		Antimetabolites
		Antitumor antibiotics
		Agents derived from plants
		Hormonal agents
		Targeted therapies and immunotherapy
	Drug toxicity
		Hematologic toxicity
			Growth factor therapy
				Granulocyte-stimulating therapy.
				Erythrocyte-stimulating therapy.
				Platelet-stimulating therapy.
		Gastrointestinal toxicity
		Skin reactions
		Hypersensitivity
		Hepatic toxicity
		Pulmonary toxicity
		Cardiac toxicity
		Renal toxicity
		Genitourinary toxicity
		Neurologic toxicity
		Gonadal dysfunction
		Immune-related adverse events
		Supportive care
	Evaluation of new agents
		Phase I
		Phase II
		Phase III
		Phase IV
15 Targeted therapy and molecular genetics
	Key points
	Targeted therapy
	Foundation of targeted therapy
	Targeted agents
	Angiogenesis
	Vascular endothelial growth factors and vascular endothelial growth factor receptors
		Agents targeting the vascular endothelial growth factor pathway
			Bevacizumab
				Ovarian cancer.
				Uterine cancer.
				Cervical cancer.
			Vascular endothelial growth factor-trap (aflibercept)
		Agents targeting vascular endothelial growth factor receptors
			AZD2171 (cediranib)
		Agents targeting multiple vascular endothelial growth factor–related molecules
			Sunitinib
			Pazopanib
			Nintedanib
			Lenvatinib
		Vascular disrupting agents
			Vadimezan (ASA404/DMXAA)
			Fosbretabulin (combretastatin A4); ombrabulin (AVE8062)
	Ofranergene obadenovec (VB-111)
	Phosphatidylinositol-3-kinase/AKT pathway
		Agents targeting mammalian target of rapamycin
			Temsirolimus (CC1-779)
			Everolimus (RAD001)
			Ridaforolimus (AP23573; MK-8669)
		Agents targeting AKT
		Agents targeting PI3K
		Combination agents
	Ras/Raf pathway
		Agents targeting MEK
	Poly (ADP-ribose) polymerase pathway
		Olaparib
		Rucaparib
		Niraparib
		Veliparib
	Epidermal growth factor receptor pathway
		Small molecule inhibitors targeting epidermal growth factor receptor
			Gefitinib
			Erlotinib
		Monoclonal antibodies targeting epidermal growth factor receptor
			Cetuximab
			Trastuzumab
			Pertuzumab
			Seribantumab
		Combination agents
			Lapatinib
	Multipathway targeted agents
		Sorafenib
		Vandetanib
		Imatinib
		Dasatinib
		Cabozantinib (XL-184)
	Other targets of interest
		Angiopoietin (Ang)/Tie-2
		Aurora kinase
		Delta-like 4 (DII4)/Notch
		Folate receptor α
		Antimesothelin antibodies
		Tissue factor
		Histone acetyltransferases and histone deacetylases
		Platelet-derived growth factor
		P53
		Immune therapy
	Unique toxicities of targeted therapy
		Hypertension
		Reverse protein leukoencephalopathy
		Cardiotoxicity
		Renal toxicity
		Thromboembolic events
		Gastrointestinal perforation and fistula
		Cutaneous complications
		Metabolic abnormalities
	Special considerations for targeted therapies
	Conclusions
	Acknowledgments
16 Molecular hallmarks of cancer
	Key points
	Biology of gynecologic cancers
	Molecular changes in gynecologic malignancies
	Cell cycle
	Agents
		Mechanism of targeted agents
	Targets
		Angiogenesis
		Vascular endothelial growth factors and receptors
		Poly-adenosine diphosphate-ribose polymerase pathway
			Olaparib
		Rucaparib
			Niraparib
			Veliparib
		The immunologic cascade
		Immune checkpoint inhibitors
			PD-1/PD-L1 pathway
			Pembrolizumab
			Nivolumab
			Other PD-1/PD-L1 inhibitors
			Cytotoxic T-lymphocyte-associated antigen 4 inhibitors
			Therapeutic vaccines
			Antibody drug conjugates
		Ras/Raf/mitogen-activated protein kinase pathway
			Agents targeting mitogen-activated protein kinase
		Epidermal growth factor receptor pathway
		Epigenetic considerations
			Histone acetyltransferases and deacetylases
		Special considerations with targeted therapies
			Hypertension
			Cardiotoxicity
			Gastrointestinal toxicities
			Dermatologic events
			Endocrine and metabolic abnormalities
			Secondary malignancies
		Assessing therapy response
	Conclusions
17 Immunotherapy in gynecologic malignancies
	Cytokines
		Interleukin-2
		Interleukin-12
		Interferons
	Monoclonal antibodies
		Oregovomab
		Human Milk Fat Globule 1
		Catumaxomab
		Farletuzumab (MORab003)
		Antibody-drug conjugate
		Mirvetuximab soravtansine (IMGN853)
	Clinical use of antibody drug conjugates
		Ovarian cancer
		Cervical cancer
	Immune checkpoint inhibitors
		Anti-cytotoxic T lymphocyte-associated protein 4 antibodies
			Ipilimumab
			Tremelimumab
			Zalifrelimab
	Clinical use of anti-CTLA-4 antibodies
		Ovarian cancer, cervical cancer
		Anti-programmed cell death receptor-1 antibodies
			Pembrolizumab (MK-3475)
			Nivolumab
			Dostarlimab
			Balstilimab
			Cemiplimab
		Anti-PD-L1 (programmed cell death receptor ligand-1) antibodies
			Durvalumab
			Avelumab
			Atezolizumab
	Clinical use of anti-PD-(L)1 antibodies
		Endometrial cancer
		Ovarian cancer
		Cervical cancer
		Gestational trophoblastic neoplasia
	Clinical use of combined immune checkpoint inhibition
		Endometrial cancer
		Ovarian cancer
		Cervical cancer
	Resistance mechanisms to immune checkpoint inhibition
	Therapeutic cancer vaccines
		Peptide/protein-based vaccines
			Ovarian cancer
			New york esophageal squamous cell carcinoma 1
				Ovarian cancer.
			DPX-survivac
				Ovarian cancer.
		Cell-based vaccines
			Ovarian cancer
		DNA/RNA-based vaccines
			Recombinant vaccinia and fowlpox vectors
				Ovarian cancer.
			Engineered listeria monocytogenes
				Cervical cancer, ovarian cancer.
		Glycan-based vaccines
			Lewis(y)
	Adoptive cell therapy
		Tumor-infiltrating lymphocytes therapy
			Ovarian cancer
			Cervical cancer
		Engineered T cell receptor therapy
			Ovarian cancer
		Engineered T cell chimeric antigen receptor therapy
			Ovarian cancer
		Natural killer cell therapy
	Immune-related adverse events
	Therapy of immune-related adverse events
	Special patient populations
	Obstacles to immunotherapy
	Summary
18 Genes and cancer: Genetic counselling and clinical management
	Key points
	Introduction
	Genetic alterations in cancer
	Mechanisms of human gene mutation
		Single base pair substitutions and point mutations
		Larger deletions
		Insertions
		Duplications
		Inversions
		Translocations
	Cancer epigenetics
	Genomic imprinting and cancer
	Genetic alterations that cause cancer
		Oncogenes
		Tumor suppressor genes
		Apoptosis
		Mismatch repair defects
		Telomerase
	Hereditary cancer risk assessment: Genetic counseling and genetic testing
		Clinically relevant hereditary syndromes
		Pre-test counseling
		Ordering genetic tests
		Post-test counseling
		Hereditary breast and ovarian cancer (BRCA1 and BRCA2; other DNA repair pathway genes)
			Management guidelines for hereditary breast and ovarian cancer (BRCA1 and BRCA2)
		Lynch syndrome (hereditary nonpolyposis colon cancer)
			Genetic testing for lynch syndrome
			Management guidelines for lynch syndrome
		Less common inherited cancer syndromes relevant to gynecologic oncology
			Peutz-jeghers syndrome
				Management guidelines for Peutz-Jeghers syndrome.
			Cowden syndrome
			Li-fraumeni syndrome
			Moderate risk and preliminary evidence genes
	Genetic counseling and genetic testing for hereditary cancers
	Referral of gynecologic cancer patients for hereditary cancer risk assessment
		Ovarian cancer
			Timing of referral for patients with ovarian cancer
		Endometrial cancer
		Referral of the patient for genetic counseling based on personal history of breast cancer or family history of cancer
	Genetic testing
		General guidelines for genetic testing for hereditary cancer risk
		Informed consent
		Ordering genetic testing
		Interpreting the test results
	Legal aspects of genetic testing
	Long-term contact for patients and families with hereditary risk for cancer
	DNA banking
	Conclusion
	Glossary
		A
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		D
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		W
19 Palliative care and quality of life
	Key points
	Evolution of palliative care
	Quality of life in gynecologic cancers
		Quality of life in ovarian cancer
		Quality of life in cervical cancer
		Quality of life in endometrial cancer
	Management of common physical symptoms
		Fatigue
		Pain
		Nausea and vomiting
		Diarrhea and constipation
			Cachexia and malnutrition
	Psychosocial and spiritual needs of patients and families
		Strategies for breaking bad news and preserving hope
	Management of psychosocial and spiritual distress
	Quality of life issues in advanced and recurrent ovarian cancer
		Pleural effusions
		Small bowel obstruction
		Ascites
		Role of palliative surgical procedures
	Quality of life issues in advanced and recurrent uterine and cervical cancer
		Ureteral obstruction
		Fistula
		Sexual dysfunction
		Anxiety and depression
	End-of-life decision making
		Patient benefit
		Patient self-determination
		Legal developments that have a bearing on end-of-life decision making
		Surrogate decision making
		Futility
		Hospice
20 Role of minimally invasive surgery in gynecologic malignancies
	Key points
	Laparoscopic surgery in gynecologic oncology
	Laparoscopic surgical staging of gynecologic malignancies
	Robotic surgery in gynecologic malignancies
	Length of stay
	Minimally invasive surgery learning curve
	Minimally invasive surgical technique
		Positioning of the patient
		Port sites and setup
	Surgery in the overweight and underweight patient
		Surgical procedure and technique
	Applications of minimally invasive surgery in gynecologic oncology
		Cervical cancer
			Early-stage cervical cancer: Radical hysterectomy
			Early-stage cervical cancer: Fertility-sparing surgery
			Advanced-stage cervical cancer: Surgical staging
		Endometrial cancer
			Laparoscopy
			Robotics
			Single-site surgery
			Minimally invasive sentinel lymph node assessment
			Removal of a large uterus
			Uterine manipulation for minimally invasive surgery
		Adnexal mass
			Minimally invasive surgery management
		Ovarian cancer
			Diagnosis of ovarian cancer
			Ovarian cyst rupture
			Early-stage ovarian cancer
			Advanced ovarian cancer
	Complications of laparoscopic surgery
		Port-site recurrences
	Conclusions
21 Epidemiology of commonly used statistical terms, and analysis of clinical studies
	Key points
	Epidemiology
	Evidence-based medicine
	Measures in epidemiology
	Analysis of clinical trials
	Graphical displays of complex statistical data
		Forest plot
		Swimmers plot
		Waterfall plot
	Types of clinical trials
	Evaluation of clinical trials
		Placebo treatment groups
		Controls used in clinical trials
		Studies of therapy
		Master protocols
		Blinding
		When to stop a clinical trial
22 Basic principles in gynecologic radiotherapy
	Key points
	Introduction to electromagnetic radiation
	Radiation units
	Radiation physics
		Energy deposition
		Sources of radiation
		Photon interactions
		Radioactive decay
		Inverse square law
		Depth dose characteristics of radiation
	Radiobiology
		Structural changes
		Radiosensitivity
			Radiobiology of ablative radiotherapy
	Radiosensitizers, hypoxic cell sensitizers, and radioprotectors
		Genetic effects
		Fetal effects
	Principles of clinical radiation therapy
		External-beam radiation (teletherapy)
		Local radiation (brachytherapy)
		Normal tissue tolerance
		Pelvic organ tolerance
		Long-term effects
	New radiation modalities
		Protons
		Electrons
		Fast neutrons
		Negative pi mesons and other heavy ions
	New radiation delivery technology
		Intraoperative radiation
		Hyperthermia
		Three-dimensional conformal radiation therapy
		Intensity-modulated radiation therapy
		Stereotactic radiotherapy
		Immunotherapy and radiation therapy
	Glossary
		A
		B
		D
		E
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		H
		I
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		R
		S
		X
APPENDIX A Staging
APPENDIX B Modified from common terminology criteria for adverse events (Common Terminology Criteria for Adverse Events)
	Quick reference
	Components and organization
		System organ class
		CTCAE terms
		Grades
APPENDIX C Blood component therapy
APPENDIX D Suggested recommendations for routine cancer screening
	Cervical cancer
	Breast cancer
	Endometrial cancer
	Ovarian cancer
	Colorectal cancer
	Lung cancer
	Skin cancer
APPENDIX E Normal nutrition
	Malnutrition and malignancy
	Diagnosis of malnutrition
	Nutritional supplementation
	Additional therapies
Index
	A
	B
	C
	D
	E
	F
	G
	H
	I
	J
	K
	L
	M
	N
	O
	P
	Q
	R
	S
	T
	U
	V
	W
	Y
	Z