Advances in Diagnosis and Management of Ovarian Cancer

Preface
Contents
Contributors
1: Ovarian Cancer Epidemiology
Incidence and Geographical Distribution of Ovarian Cancer
Types of Ovarian Cancer
Risk Factors of Ovarian Cancer
Age
Family History
Reproductive Factors
Exogenous Hormones
The Oral Contraceptive Pill
Hormone Replacement Therapy
Medical Conditions
Endometriosis
High BMI
Diabetes
Polycystic Ovarian Syndrome
Other Factors
Genital Powder (Talcum Powder)
Smoking
Survival
Conclusion
References
2: Ovarian Cancer Screening and Early Detection
Background
Development of a Screening Test
Ovarian Cancer Symptom Index
Biomarkers
Ultrasound
Multimodal
Current Screening
Detection of STIC Lesions in the Fallopian Tube
Triage of Pelvic Masses
The OVA1/OVERA Tests
Conclusion
References
3: Ovarian Cancer Biomarkers
Introduction
Current Approaches and Biomarkers in Ovarian Cancer
Ovarian Cancer Biomarkers
Proteomics and Biomarkers
Gene-Based Biomarkers
Metabolite-Based Biomarkers
Epigenetic-Based Biomarkers
Liquid Biopsy Biomarkers
Future Perspective in Ovarian Cancer Biomarkers
Conclusion
References
4: Hereditary Ovarian Cancer
Background
BRCA1 and BRCA2 Mutations
Prevalence
Cancer Risks
Screening and Risk-Reducing Surgery
Phenotype
Treatment
PARP Inhibitors
Resistance and Super-Responders
Survival
Lynch Syndrome
Prevalence and Phenotype
Risk
Second Cancer Risk
Ovarian Cancer Screening
Aspirin Use
Implications for Treatment
Other Homologous Recombination Genes
BRIP1
RAD51C
RAD51D
Non-epithelial Ovarian Cancer
DICER1
Small Cell Cancer of the Ovary, Hypercalcaemic Type (SCCOHT)
Conclusion
References
5: Ovarian Cancer Pathology
Introduction
Epithelial Tumours
Serous Tumours
High-Grade Serous Carcinoma (HGSC)
Immunophenotype and Genetic Profile
Low-Grade Serous Carcinoma (LGSC)
Serous Borderline Tumours
Serous Borderline Tumour: Micropapillary Variant
Immunophenotype and Genetic Profile of SBT and LGSC
Peritoneal Lesions Associated with SBT
Diagnostic Challenges in Serous Tumours
Tumour Typing
Assignment of Primary Site of Origin
Synchronous Endometrial and Ovarian Serous Carcinoma
Prediction of Behaviour of SBT
Mucinous Carcinoma
Mucinous Borderline Tumour (MBT)
Immunoprofile and Molecular Phenotype
Challenges with Mucinous Tumours
Sampling of Mucinous Tumours
Endometrioid Carcinoma
Genetic Profile
Endometrioid Borderline Tumour (EBT)
Challenges in Endometrioid Carcinoma
Synchronous Endometrial and Ovarian Endometrioid Carcinoma (SEOs)
Distinction Between Serous Carcinoma and High-Grade Endometrioid Carcinoma
Clear Cell Carcinoma (CCC)
Immunophenotype and Genetic Profile
Clear Cell Borderline Tumour (CCBT)
Challenges in Clear Cell Carcinoma
Seromucinous Borderline Tumour
Immunophenotype and Genetic Profile
Malignant Brenner Tumour
Borderline Brenner Tumour (BBT)
Immunophenotype
Mesonephric-Like Adenocarcinoma
Immunophenotype and Genetic Profile
Dedifferentiated and Undifferentiated Carcinoma
Carcinosarcoma
Mixed Carcinoma of the Ovary
Mesenchymal Tumours
Low-Grade Endometrioid Stromal Sarcoma
High-Grade Endometrioid Stromal Sarcoma
Mixed Epithelial Mesenchymal Tumours
Adenosarcoma
Sex Cord Stromal Tumours
Pure Stromal Tumours
Fibrosarcoma
Steroid Cell Tumour (Lipid Cell Tumour)
Immunophenotype
Pure Stromal Tumours
Adult Granulosa Cell Tumour (AGCT)
Immunophenotype and Genetic Profile
Juvenile Granulosa Cell Tumour (JGCT)
Immunophenotype and Genetic Profile
Sertoli Cell Tumour
Immunophenotype
Sex Cord Stromal Tumour with Annular Tubules
Immunophenotype and Genetic Profile
Mixed Sex Cord Stromal Tumours
Sertoli Leydig Cell Tumour
Immunophenotype and Genetic Profile
Sex Cord Stromal Tumour NOS
Germ Cell Tumours
Immature Teratoma
Dysgerminoma
Immunophenotype and Genetic Profile
Yolk Sac Tumour
Immunophenotype
Embryonal Carcinoma
Immunophenotype
Choriocarcinoma
Mixed Germ Cell Tumour
Somatic-Type Tumours Arising from a Dermoid Cyst
Neuroectodermal-Type Tumours
Somatic-Type Tumours Arising from a Dermoid Cyst
Miscellaneous Tumours
Tumours of Rete Ovarii
Wolffian Tumour
Immunophenotype
Solid Pseudopapillary Tumour of the Ovary
Small Cell Carcinoma of Hypercalcaemic Type (SSCOHT)
Immunophenotype and Genetic Profile
Wilms’ Tumour (Nephroblastoma)
Other Tumours Non-specific to the Ovary
Mesothelial Tumours
Mesothelioma
Soft Tissue Tumours
Lymphoid and Myeloid Tumours
Secondary Tumours
Synchronous Tumours of Different Histogenesis
Hereditary Syndromes
Prognostic Factors in Ovarian Cancer
Frozen Sections in Ovarian Cancer Management
Molecular Inter- and Intratumoral Heterogeneity in Ovarian Cancer
References
6: Current Management of Patients with Early-Stage Ovarian Cancer
Introduction
Screening for Ovarian Cancer
Detection of Ovarian Cancer
Diagnosis and Staging
Treatment Options for Early-Stage Ovarian Cancer
Borderline Ovarian Tumors
Platinum-Based Chemotherapy for Early-Stage Ovarian Cancer
Minimally Invasive Surgery for Patients with Early-Stage Ovarian Cancer
Laparoscopic Surgery for Ovarian Cancer
Robotic Surgery for Ovarian Cancer
Fertility-Sparing Surgery (FSS) in Young Women with Early-Stage Ovarian Cancer
Borderline Ovarian Tumors
Type of Surgery
Other Potential Options to Preserve Fertility
Oncologic Outcomes After FSS
Reproductive Outcomes After Fertility-Sparing Surgery
Chemotherapy-Induced Gonadotoxicity Following FSS
References
7: Treatment of Advanced-Stage Ovarian Cancer
Introduction
Diagnosis
Surgery in Ovarian Cancer
Cytoreductive Surgery
Evaluation of Women for Surgery
Selection of Women for Primary Cytoreductive Surgery
Operative and Perioperative Management
Bowel Preparation
Enhanced Recovery After Surgery (ERAS)
Surgery
Pathological Review
Chemotherapy
Targeted Agents
Neoadjuvant Chemotherapy and Delayed Primary Surgery
Laparoscopic and Robotically Assisted Surgery
Palliative Surgery
Recurrence
Intraperitoneal Chemotherapy Ports
Novel Surgical Techniques
Hereditary Susceptibility
Future Directions
References
Untitled
8: Management of Recurrent Ovarian Cancer
Introduction
Surgery in Recurrent Ovarian Cancer
DESKTOP Studies I–III
Parameters with Impact to Survival
Minimal Invasive Surgery (MIS) for Secondary Cytoreduction
The Role of Tertiary Cytoreduction in Recurrent Ovarian Cancer
Systemic Treatment for Recurrent Ovarian Cancer
Conclusions
References
9: Overview of Ovarian Cancer Chemotherapy
Principles of Cytotoxic Chemotherapy
Cell Cycle, Growth Kinetics, Log Cell Kill
Resistance Mechanisms
Routes of Administration
Intravenous
Vesicants and Antidotes
Hypersensitivity and Alternate Formulation: Nanoparticles and Liposomes
Intraperitoneal Chemotherapy
Hyperthermic Intraperitoneal Chemotherapy
Dosing in Obesity
Mechanisms and Toxicities of Commonly Employed Agents
Platinums
Cisplatin
Carboplatin
Oxaliplatin
Microtubule-Binding Agents
Taxanes
Epothilones
Topoisomerase Inhibitors
Etoposide
Topotecan and Irinotecan
Nucleoside Analogs
Gemcitabine
Capecitabine and 5-Fluorouracil
Folate Antimetabolites
Methotrexate
Pemetrexed
Antineoplastic Antibiotics
Doxorubicin
Bleomycin
Actinomycin D
Vinca Plant Alkaloids
Vinorelbine
Vinblastine
Vincristine
Alkylating and Alkylating-Like Agents
Cyclophosphamide
Ifosfamide
Mitomycin C
Therapeutic Principles for Advanced-Stage Epithelial Histologies
High-Grade Serous and Advanced Clear Cell
NCCN First-Line Agents: Adjuvant Therapy Following Primary Debulking Surgery
Intravenous Regimens
Carboplatin and Paclitaxel
Evolution of the 3-Weekly Regimen
Dose Density
Bevacizumab in the Front-Line Setting
Carboplatin and Docetaxel
Carboplatin and Pegylated Liposomal Doxorubicin
Intravenous and Intraperitoneal
Neoadjuvant Therapy and Interval Debulking
Therapeutic Considerations for Other Epithelial Histologies
Carcinosarcoma
Biology and Surgical Approach
Chemotherapy
Low-Grade Serous and Borderline Tumors with Invasive Implants
Biology and Surgical Approach
Adjuvant Treatment
Mucinous
Biology and Surgical Approach
Adjuvant Therapy
Therapeutic Principles for Germ Cell Tumors
Biology and Surgical Approach
Etoposide, Cisplatin, w/wo Bleomycin
Therapeutic Principles for Sex Cord Stromal Tumors
Biology and Surgical Approach
Chemotherapy
BE(P)
Carboplatin/Paclitaxel
References
10: Management of Epithelial Ovarian Cancer with Peritoneal Metastases
Introduction
Intraperitoneal Administration of Anticancer Drugs Showed the Potential for Control of Small Peritoneal Nodules
Complete Visible Removal of Cancer from the Abdomen and Pelvis as the Goal for Cytoreductive Surgery
Perioperative Chemotherapy Following Best Efforts at Surgery
Survey of HIPEC Regimens for Ovarian Cancer
Intraperitoneal Paclitaxel
Normothermic Intraperitoneal Chemotherapy Long-Term for Optimally Cytoreduced Ovarian Malignancy
Literature Support of Cytoreduction to Microscopic Disease Plus Long-Term Intraperitoneal Chemotherapy as a Strategy to Maximize Survival in Ovarian Cancer
Conclusion
References
11: Targeted Molecular Therapy for Ovarian Cancer Patients
Introduction
Antiangiogenic Therapy
Antiangiogenic Agents
Bevacizumab
Cediranib
Pazopanib
Classical Transgene Delivery
DNA Vectors
Enhancing Vector Infectivity
Achieving Selectivity with Tumor-Specific Promoters
Armed CRAds
Incorporating Imaging into CRAds
Cellular Delivery of CRAds
Immunotherapy for Ovarian Cancer
Cancer Vaccines
Adoptive T Cell Therapy
Antibody-Based Immunomodulation
Dendritic Cell Activation
Effector T Cell Activation
Treg Depletion
Epithelial Growth Factor Receptor Targeting Therapy
Epithelial Growth Factor Receptor (Her1)/ErbB2 (Her2) in Ovarian Cancer
ErbB3 (Her3) in Ovarian Cancer
ErbB4 (Her4) in Ovarian Cancer
Poly (Adenosine Diphosphate Ribose) Polymerase (PARP) Inhibition Therapy
PARP Family of Enzymes
PARP1 Role in DNA Repair
Structure of Common PARP Inhibitors
Use of PARP Inhibitors in BRCA1/2 Mutations
Efficacy of PARP Inhibition Therapy in BRCA-Deficient Tumors
PARP Inhibitors Resistance
References
12: Ovarian Cancer in the Pediatric Population
Introduction
Incidence
Epidemiological Aspects
Anatomic Aspects of Ovarian Masses
Ovarian Masses Associated with Torsion
Ovarian Cysts in a Changing Hormonal Milieu
Histopathologic Types of Tumors
Malignant Germ Cell Tumors
Teratomas
Germinomas
Yolk Sac Tumor (Endodermal Sinus Tumor)
Mixed Cell Tumors: Embryonal Carcinoma and Choriocarcinoma
Non-germ Cell Tumors
Sex Cord–Stromal Tumors
Epithelial Tumors
Metastatic Disease to the Ovary
Molecular Pathology of Ovarian Tumors
Mature Teratomas
Immature Teratomas
Malignant Ovarian Germ Cell Tumors
Clinical Presentation
Management Strategy
Evaluation
Tumor Markers
Operative Management
Operative Staging
Surgical Management
Fertility-Sparing Approaches
Chemotherapy
References
13: Quality of Life in Women with Ovarian Cancer
Introduction
Terminology and Definitions: HRQL and PROs
How Ovarian Cancer Affects HRQL
Proximal Versus Distal Effects on HRQL
Treatment-Specific HRQL: Symptoms and Side Effects of Treatment
Surgery
Chemotherapy
Targeted Therapy
Psychological Impact
Loss of Fertility and Early Menopause
Psychosexual/Sexual Function (Problems Preventing/Interfering with Ability to Have Sex)
Supportive Care Needs of Women with Ovarian Cancer
Impact on Partners/Caregivers
Why Assess HRQL in Patients with Ovarian Cancer?
How is the HRQL of Patients with Ovarian Cancer Assessed?
Choosing a PRO Instrument
What Makes a Good Instrument?
PRO Instruments for Ovarian Cancer Clinical Research: Core Cancer Instruments Versus Tumour Specific Modules
EORTC Instruments
FACIT Instruments
MOST: Measure of Ovarian Symptoms and Treatment concerns
On-Going Clinical Trials in Ovarian Cancer
Conclusions and Recommendations
References
Index