R

Racial differences, in incidence of ovarian cancer, 3, 3t Radiation therapy for early carcinoma, 150, 150t for germ cell tumors, 215 for granulosa cell tumors, 205 for platinum-resistant ovarian cancer, 174 Radiofrequency ablation (RFA), for hepatic metastases, 118, 118f Rectosigmoid resection, for advanced-stage epithelial cancer, 114, 116-117 Recurrent ovarian cancer borderline, 199 central vs. pelvic sidewall, 80-81 chemotherapy for second-line combination vs. single-agent, 167-170, 167f,...

B

Cumulative risk of breast and ovarian cancer in BRCA1 (A) carriers and BRCA2 carriers (B). (From Antoniou A, Pharoah PD, Narod S, et al Average risks of breast and ovarian cancer associated with BRCA1 or BRCA2 mutations detected in case series unselected for family history a combined analysis of 22 studies. Am J Hum Genet 72 1117-1130, 2003 Figs. 3 and 4.) was not reported, and cases of ovarian cancer were not clearly identified as prevalent or incident. Therefore, although these...

Chemoprevention for Women with Increased Risk

In a similar fashion to studies in the general population, case-control investigations are used to determine the effect of oral contraceptive pills on women with an increased risk of ovarian cancer. Case-control studies face the same limitations with this group of subjects as those encountered in the general population. In addition, these investigations may be hampered by methods used to identify the subjects at risk for ovarian cancer. Some studies use family history, whereas others use formal...

Contributors

Associate Professor of Oncology, Gynecology, and Obstetrics, The Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins Medical Institutions, Baltimore, Maryland Research Associate, The Johns Hopkins University Genetic Counselor, The Johns Hopkins Hospital, Baltimore, Maryland Clinical Professor, Ohio State University Medical Director, Cancer Services, Riverside Methodist Hospital, Columbus, Ohio Professor and Director, The Kelly Gynecologic Oncology Service and Ovarian Cancer Center of...

Early Stage Epithelial Ovarian Cancer

At diagnosis, approximately one third of patients with epithelial ovarian cancer have early-stage disease that is confined to the ovary or pelvis. Although the 5-year survival for patients with early-stage ovarian cancer is much better than that for those with advanced disease, relapse rates ranging from 20 to 30 have been quoted for patients with poor prognostic factors. Classic clinical and pathologic prognostic factors, such as degree of differentiation, FIGO substage, histologic type, dense...

Key Points

Although there is no evidence for the curative potential of chemotherapy in recurrent or resistant ovarian cancer, improved survival associated with the delivery of several cytotoxic regimens has been documented. Treatment in the second-line setting must attempt to carefully balance the desired effects (e.g., improvement in symptoms, delay in subsequent progression) with potential serious adverse effects. Existing evidence supports the superiority of combination platinum-based chemotherapy,...

Liver Resection

When parenchymal liver disease is present, a partial liver resection can be attempted. Hepatic resection is considered safe, with a mortality rate of less than 5 , but it is not yet regarded as standard of care for the treatment of ovarian cancer. Bristow and associates22 identified a 50.1-month median survival in patients who were optimally cytoreduced of extrahepatic and parenchymal liver disease compared with 27.0 months in patients with optimal extrahepatic disease but suboptimal residual...

Lymph Node Resection

A bilateral pelvic and periaortic lymph node sampling must be done when the tumor nodules outside the pelvis are less than or equal to 2 cm (presumed stage IIIB) and in apparent stage I disease to exclude the possibility of microscopic nodal metastasis, which can occur in up to one third of patients with apparent early-stage disease. The role of lymph node resection has not been fully defined in advanced epithelial ovarian cancer. In their analysis of 93 patients who underwent lymph node...

Mechanisms of Action

Ovarian cancer is believed to result from incessant ovulation. Release of an oocyte results in damage to ovarian epithelium. Aberrant repair of this damaged epithelium may result in cell changes ultimately leading to ovarian cancer. Conditions that decrease exposure to ovulation such as parity and breastfeeding are associated with General population 1.4 (1 in 70) One first-degree relative with ovarian 4-5 Two first-degree relatives with ovarian 7 Deleterious BRCA1 mutation 30-40 Deleterious...

Molecular Alterations in Other Nonserous Types of Ovarian Carcinomas

The stepwise progression of borderline tumors (atypical proliferative tumor and noninvasive MPSC) to the low-grade serous carcinoma (invasive MPSC) closely approximates the adenoma-carcinoma sequence in colorectal carcinoma. This tumor progression model is also applicable to other type I carcinomas, specifically mucinous and endometrioid carcinoma. Accordingly, these mucinous and endome-trioid borderline tumors have been thought to represent an intermediate stage in the stepwise progression to...

Mutation of p53

The p53 tumor suppressor gene is the most commonly mutated gene in human cancer (Fig. 2-5). In contrast to low-grade serous carcinoma in which mutations in p53 are rare, mutations in p53 are common in high-grade serous carcinomas. Many studies have shown that 50 to 80 of advanced stage high-grade serous carcinomas have mutant p53.24-28 It has also been reported that mutant p53 is present in 37 of stage I and II presumably high-grade serous carcinomas.29 Overexpression ofp53 and mutation of p53...

Outcomes

Because most tumors are early stage at diagnosis and even advanced tumors are exquisitely sensitive to chemotherapy those with malignant ovarian germ cell tumors generally have an excellent prognosis.98,118 Several retrospective studies have demonstrated that with current platinum-based chemotherapy, 5-year survival rates are 95 to 97 , keeping in mind that the majority of patients are stage I at diagnosis.108,119 Even in disseminated cancer, Lai and associates103 noted an 88 5-year survival...

Preface

Worldwide, 204,449 new cases of ovarian cancer are diagnosed each year, with an estimated 124,860 disease-related deaths.1 In the United States, ovarian cancer is the leading cause of gynecologic cancer-related morbidity and mortality in large part due to the difficulty in detecting early-stage disease. One of the primary reasons that ovarian cancer is associated with such a significant burden of disease for the individual and for society is that it is a difficult disease to prevent, or at the...

References

Jemal A, Siegel R, Ward E, et al Cancer Statistics, 2009. CA Cancer J Clin 59 225-249, 2009. 2. Carlson KJ, Skates SJ, Singer DE Screening for ovarian cancer. Ann Intern Med 121 124-132, 1994. 3. Antoniou A, Pharoah PD, Narod S, et al Average risks of breast and ovarian cancer associated with BRCA1 or BRCA2 mutations detected in case series unselected for family history a combined analysis of 22 studies. Am J Hum Genet 72 1117-1130, 2003. 4. King MC, Marks JH, Mandell JB Breast and ovarian...

Robert E Bristow and Deborah K Armstrong

Ovarian cancer remains the leading cause of gynecologic cancer-related morbidity and mortality in developed countries. This volume contains contributions from many of the leading authorities in the clinical management of ovarian cancer as well as those at the cutting edge of basic research and translational science. Although the epidemiology of ovarian cancer has been relatively well defined, continued advances are being made with respect to understanding the molecular and genetic basis for...

Surgical Management

In general, as in malignant ovarian cancer, there should be a maximal surgical effort to remove as much tumor as possible from women with extraovarian tumors and to assess the extent and need for further staging procedures based on patient characteristics in women whose disease appears confined to the ovary. Most often the diagnosis of an ovarian borderline tumor is not known preoperatively, and a frozen section is obtained to establish a definitive diagnosis to guide the nature and extent of...

Surgical Staging

The importance of a thorough surgical staging was underscored by McGowan and colleagues57 when they reported in 1983 the stage distribution of 157 patients properly staged in comparison with data from the FIGO annual report of the same period showing a reduction in stage I figures from 28 to 16 , in stage II figures from 17 to 4 , and a reallocation to stage III from 55 to 80 when a thorough staging procedure was adopted. Similarly, Young and colleagues and subsequently Helewa and associates...

Clinical Characteristics

The peak incidence of ovarian germ cell tumors is between ages 15 and 19 years, and one third of these tumors are malignant.90 Ovarian germ cell tumors are generally rapid-growing and thus nearly 85 of patients present with abdominal and pelvic pain pressure and a palpable mass.94,96 Rupture, hemorrhage, and torsion are often seen and can mimic the picture of acute appendicitis. A few patients may present with signs of precocious puberty as a result of the production of hormones such as P-hCG...

Screening for Ovarian Cancer

Ovarian cancer is the fifth most common cancer in women and is the most common cause of gynecologic cancer mortality. Approximately 1 in 70 women will develop ovarian cancer in their lifetime. Many risk factors have been identified in the carci-nogenesis of ovarian cancer, and patients with varying levels of risk can be further stratified into different groups. Recommendations for ovarian cancer screening vary according to the patient's level of risk. Advancing age, infertility, endometriosis,...

Environmental Factors

Additional variables have been associated with an increased risk of ovarian cancer. An example is saturated fat consumption (OR 1.20 for each 10 g day of intake 95 CI 1.03 to 1.40 P .008).35 Clinical and epidemiologic studies have conflicting views on an association between ovarian carcinoma and talcum powder use.36,37 Coffee and tobacco consumption has not been found to be associated with an increased risk.38 Obesity is a risk factor for several hormone-related cancers, but evidence of an...

Sex Cord Stromal Tumors of the Ovary

Ovarian sex cord and stromal tumors represent a heterogeneous group of rare tumors arising from the ovarian stroma and cells that surround the oocytes. Their rarity precludes any definite recommendations regarding their management. Surgery is the cornerstone of therapy and is required for definitive diagnosis. The staging system is the same as that for epithelial ovarian cancer. Most malignant ovarian sex cord-stromal tumors, however, tend to present at an earlier age and stage and to follow an...

Clear Cell Carcinoma

Clear cell carcinoma is also frequently associated with endometriosis, clear cell ade-nofibromas, and clear cell atypical proliferative (borderline) tumors, but molecular evidence for the stepwise progression model is still lacking. Recently, hepatocyte nuclear factor-ip and glutathione peroxidase 3 have been reported as molecular markers for ovarian clear cell carcinoma because both genes are highly expressed in ovarian clear cell carcinomas but rarely in other ovarian carcinomas.55,56...

Endometrioid Carcinoma

Mutation of P-catenin has been reported in approximately one third of cases,45,46 and mutation of PTEN in 20 , rising to 46 in tumors with 10q23 loss of heterozygosity.47 These mutations are generally detected in well-differentiated stage I tumors with a favorable prognosis, suggesting that inactivation of these genes is an early event. Moreover, similar molecular genetic alterations, including loss of heterozygos-ity at 10q23 and mutations in PTEN, have been reported in endometriosis, atypical...

Maintenance Therapy

Another concept, maintenance therapy, has been studied and debated among investigators over the last 5 years. Maintenance therapies focus on extending the duration of frontline treatment. There have been several reports concerning cytotoxic chemotherapy, hormonal therapy, and immunotherapy used in this manner.68-70 In 2003, a GOG trial demonstrated that maintenance paclitaxel given every 4 weeks for 12 months to patients in complete remission following standard intravenous...

Introduction

Ovarian cancer is the leading cause of mortality from gynecologic cancers in the United States. In 2009, an estimated 21,550 women will be diagnosed with ovarian cancer and 14,600 will die of the disease.1 It is the fifth most common cancer in women in the United States, and the fourth most common cause of death from malignancy2 (Fig. 1-1). In the United States, an estimated 1 in 72 women will develop ovarian cancer in their lifetime (Table 1-1), and 1 in 100 will die from the disease.

Overexpression of Human Leukocyte Antigen G

Besides molecular genetic alterations, both low-grade and high-grade serous carcinomas are characterized by distinct gene expression profiles. For example, transcriptome-wide gene expression profiling has demonstrated that human leukocyte antigen-G (HLA-G) is overexpressed in many high-grade serous carcinomas but rarely in low-grade serous carcinomas. HLA-G immunoreactivity, ranging from focal to diffuse, was detected in most high-grade ovarian serous carcinomas but not in any low-grade serous...

Adjuvant Treatment

Since survival rate in stage I patients approaches 100 , few experts suggest any further therapy after surgical excision and simply advocate for long-term surveillance.35 Even with advanced-stage borderline tumors, long-term survival rate may be as high as 70 .3 As previously discussed, these tumors are often associated with adverse prognostic factors including extraovarian disease, microinvasion, and or micropapillary patterns. Several groups have analyzed whether postoperative adjuvant...

Hereditary Ovarian Cancer Syndromes Hereditary Breast and Ovarian Cancer

BRCA1 and BRCA2 are two genes initially discovered by studying families strongly suggestive of hereditary breast cancer. Thus, they are named breast cancer susceptibility gene 1 (BRCA1) and breast cancer susceptibility gene 2 (BRCA2). Several hundred mutations have been reported in BRCA1 and BRCA2 since their identification.3 The BRCA1 and BRCA2 genes are known to be involved, both separately and coor-dinately, in DNA double-strand break repair. These breaks can occur in response to ionizing...

Secondary Cytoreduction

As in most clinical situations in medicine, patient selection for a chosen treatment modality is a significant factor in the success of this treatment. In the setting of recurrent ovarian cancer, in which cure is rarely a reasonable outcome to hope for, the clinician's role is to choose among several treatment schemes meant to prolong survival with good quality of life and minimal morbidity. It is not always possible to predict the patient's response to chemotherapy or how much she will benefit...

Allelic Imbalance and Chromosomal Instability

A progressive increase in the degree of allelic imbalance (calculated as the number of SNP markers with allelic imbalance total SNP markers examined) of chromosomes 1p, 5q, 8p, 18q, 22q, and Xp was noted when comparing atypical proliferative tumors with noninvasive MPSCs and low-grade serous carcinomas (invasive MPSCs).4 In particular, allelic imbalance of chromosome 5q was more frequently observed in noninvasive MPSCs compared with atypical proliferative tumors. Moreover, allelic imbalance of...

A

No rupture 859 758 692 618 517 417 During surgery 122 109 89 66 54 35 Before No rupture 859 758 692 618 517 417 During surgery 122 109 89 66 54 35 Before Figure 7-23. Actuarial disease-free survival according to degree of differentiation (A) and timing of cyst rupture (B) in stage I invasive epithelial ovarian carcinoma. (From Vergote I, De Brabanter J, Fyles A, et al Prognostic importance of degree of differentiation and cyst rupture in stage I invasive epithelial ovarian carcinoma. Lancet,...

Genetic Predisposition

To contain the costs to the population, chemoprevention or prophylactic surgery for ovarian cancer may be directed at high-risk groups. In the United States, a woman on average has a 1.4 lifetime risk of developing ovarian cancer. In contrast, the risk increases to 4 to 5 with one first-degree relative with ovarian cancer. With two first-degree relatives, the lifetime risk further increases to 7 . Approximately 10 of ovarian malignancies appear to be hereditary. Genetic predisposition should be...

Conclusion

There are no data from prospective randomized studies to support ovarian cancer screening in women at general population risk. Two large prospective ovarian cancer screening studies of low-risk women are ongoing one in the United States (PLCO) and one in the United Kingdom (UKCTOCS). Results from these studies will be forthcoming in the next several years. For high-risk individuals, given the extremely high lifetime risk of ovarian cancer, consensus groups recommend ovarian cancer screening...

Background

Ovarian cancer is one of the most chemotherapy-sensitive malignancies, with 60 to 80 of women with newly diagnosed advanced disease anticipated to achieve both substantial objective and subjective responses to primary therapy.1 Despite this fact, most women who respond to this treatment ultimately experience a relapse of the disease process.2 Thus, the need to ultimately consider a second-line treatment strategy in ovarian cancer is the rule, rather than the exception. This chapter reviews the...

Series Preface

Seen on a graph, the survival rate for many cancers resembles a precipice. Discovered at an early stage, most cancers are quickly treatable, and the prognosis is excellent. In late stages, however, the typical treatment protocol becomes longer, more intense, and more harrowing for the patient, and the survival rate declines steeply. No wonder, then, that one of the most important means in fighting cancer is to prevent or screen for earlier stage tumors. Within each oncologic specialty, there is...

Clinical and Theoretical Background of Surgical Cytoreduction

The concept of cytoreductive surgery for ovarian cancer has evolved since Meigs1 first proposed in 1934 that as much tumor as possible should be removed to enhance the effects of postoperative radiation. Forty years after Meigs' initial proposition, Griffiths2 published the landmark study that first clearly delineated the inverse relationship between postoperative residual tumor size and ovarian cancer patient survival. More contemporary studies published by Hoskins and the Gynecologic Oncology...

Overview of the Roles of Imaging in Ovarian Cancer

Imaging is an integral part of ovarian cancer detection, diagnosis, management, and treatment follow-up. A number of imaging modalities are available, and a variety of new techniques, especially molecular imaging approaches, are being developed. Each imaging modality has its unique advantages and limitations therefore, evidence-based use of imaging is essential for achieving the greatest possible benefit without over- or underuse of specific modalities. Since imaging is a continuously advancing...

Splenectomy

In the presence of extensive omental involvement, metastatic implants occasionally involve the splenic hilum, capsule, or parenchyma and may necessitate the removal of the spleen en bloc with the omentum. Magtibay and colleagues24 described their center's experience with splenectomy as part of cytoreductive surgery in ovarian cancer and showed that splenectomy as part of primary or secondary cytoreductive surgery is associated with modest morbidity and mortality. Their data also confirmed that...

Prophylactic Surgery in the General Population

Prophylactic surgery for ovarian cancer encompasses several procedures. Bilateral salpingo-oophorectomy with removal of both the fallopian tubes and the ovaries is often advocated for the prevention of ovarian cancer. The procedure may be performed through an open or laparoscopic approach. All peritoneal surfaces should be examined. The procedure should result in the removal of the entire ovary and all but the intramural portion of the fallopian tube. The ovarian vessels should be clamped...

Type II Tumors

Type II ovarian tumors are clinically high grade at presentation and include the morphologically defined entities such as high-grade serous carcinoma (moderately and poorly differentiated), malignant mixed mesodermal tumors (carcinosarcomas), and undifferentiated carcinomas (see Table 2-2). In addition, it is likely that some rare high-grade endometrioid and clear cell carcinoma should also be included in this group. Although malignant mixed mesodermal tumors were once thought to be mixed...

Hereditary Nonpolyposis Colorectal Cancer

Hereditary nonpolyposis colorectal cancer (HNPCC), also known as Lynch syndrome, was first identified in families with a significant history of young-onset colorectal cancer. The lifetime risk of this malignancy ranges from 25 to 75 , with an average age at diagnosis of colorectal cancer of 44 years. Almost 75 of HNPCC-associated colorectal cancers present in the ascending (right) colon, and the risk of a metachronous colorectal cancer ranges from 1 to 4 per year. Although colorectal cancer is...

Jeffrey G Bell and Christopher V Lutman

Early ovarian cancer can be divided into low-risk and high-risk groups. Complete surgical staging impacts treatment decisions. Patients with low-risk early-stage ovarian cancer do not require adjuvant chemotherapy. Adjuvant chemotherapy definitely benefits incompletely staged patients. The need for adjuvant chemotherapy for completely staged patients with high-risk, stage I non-clear cell histology is controversial. Carboplatin with paclitaxel is the preferred adjuvant regimen by extrapolation...

Ovarian Tumors of Low Malignant Potential

Ovarian epithelial tumors of low malignant potential or borderline ovarian tumors account for approximately 15 of ovarian epithelial tumors.13 Borderline ovarian tumors with serous or mucinous histologies are the most commonly observed (65 and 32 , respectively). Patients with these lesions tend to be younger than those with invasive ovarian carcinoma (average age at diagnosis 49 years), and a large portion of these tumors occurs in the 15- to 29-year-old age group.79 Surgery is required for...

Genetic Factors

A family history of ovarian cancer is the most significant known risk factor. Approximately 10 of all ovarian cancers can be associated with a familial genetic predisposition. The risk depends on the number of first- and second-degree relatives with ovarian cancer and their age at diagnosis. A woman with a single family member affected by ovarian cancer has a 4 to 5 lifetime risk of developing the disease. This risk increases to about 7 if two family members are affected3 (Table 1-4)....

Ovarian Cancer Chemoprevention in the General Population

Many investigations have evaluated the effect of oral contraceptive pills on ovarian cancer risk. The evidence supporting a protective influence of birth control pills on ovarian cancer risk has been obtained primarily from case-control studies. These investigations identify patients (cases) who have been diagnosed with ovarian cancer and women (controls) who do not have the disease. The two groups are then compared with respect to their exposure to oral contraceptive pills (a suspected...

Clinical Presentation Symptoms

The symptoms of ovarian cancer are vague and commonly occur in benign conditions. Patients with ovarian cancer often present late and are diagnosed at an advanced stage. In early-stage disease, patients may present with common gynecologic symptoms such as vaginal bleeding or discharge. Urinary frequency or constipation may be the result of compression of the bladder or rectum. Patients at all stages may present with abdominal pain and distention. Gastrointestinal symptoms such as nausea,...

Procedures Complications and Outcome of Secondary Cytoreductive Surgery

Linear Regression

The benefit of secondary cytoreduction appears to be seen only when optimal cytoreduction is achieved. In the primary setting, optimal cytoreduction is commonly defined as the maximal size of residual tumor measuring 1 cm. Many authors, however, suggest that the greatest benefit is seen if all grossly visible recurrent tumor is resected.14'16'18,19'21,22 The exact size of residual disease that should be considered optimal is still debatable, but we seek to achieve a complete gross resection in...

Chemotherapy of Recurrent Potentially Platinum Sensitive Ovarian Cancer

As previously noted, there is very strong evidence to support delivery of a platinum-based chemotherapy regimen in the second-line setting in women who have previously experienced an objective response to therapy with this class of drugs.7-11 Unfortunately, there has been a rather profound absence of evidence-based studies that have directly compared a platinum-based regimen with a non-platinum program in the setting of recurrent ovarian cancer. However, the limited randomized experience does...

Clinical and Pathologic Observations Supporting the Dualistic Ovarian Carcinogenesis Model

Comprehensive efforts have been made in analyzing histopathologic and clinical features of a large number of noninvasive and invasive epithelial ovarian tumors to delineate their pathogenesis and behavior.1,9-11 One of the main conclusions from these studies is the recognition of a subset of low-grade serous tumors designated micropapillary serous carcinoma (MPSC), which displays characteristic histopatho-logic features, low proliferative activity, and an indolent behavior that contrasts...

Type I Tumors

Type I ovarian tumors (low-grade serous carcinoma, mucinous carcinoma, endome-trioid carcinoma, malignant Brenner tumor, and clear cell carcinoma) develop in a stepwise manner from well-accepted precursors, namely, borderline tumors that in turn develop from cystadenomas adenofibromas4 (see Table 2-1 and Fig. 2-1). Serous and mucinous tumors appear to develop from the surface inclusion cysts or cystade-nomas, whereas endometrioid and clear cell tumors develop from endometriosis or...

Ca125

Serum levels of CA-125 loosely correlate with the volume of disease. Although there is controversy regarding the value of CA-125 before surgery as a predictor of survival, its role in assessment of treatment response is well established. Looking at the usefulness of the preoperative value of CA-125 in predicting optimal cytoreduction, it has been shown that preoperative CA-125 values of less than 500 U mL had a positive predictive value for optimal cytoreduction of 82 , but a poor negative...

Residual Disease after Cytoreductive Surgery

The volume of residual disease after cytoreductive surgery has been strongly associated with survival. Optimal cytoreduction is defined as residual disease of less than 1 cm. The GOG reported 37- and 31-month median survival times for patients with residual disease less than 1 cm and 1 to 2 cm, respectively. In an analysis of patients presenting with stage IV disease median survival of optimally cytoreduced patients was 38.4 months compared with 10.3 months for patients with suboptimal residual...

Granulosa Stromal Cell Tumors

Water The Silk Granulosa Cell Tumor

Granulosa-stromal cell tumors account for 70 of tumors in the sex cord-stromal group, and 2 to 5 of all ovarian tumors.40 They encompass GCTs, thecomas, and fibromas. Although GCTs are considered malignant, they grow slowly and do not behave as aggressively as their epithelial counterparts. However, if not detected at an early stage they do have the potential to metastasize and recur. Unlike epithelial-type ovarian tumors, there is no racial or ethnic predilection of GCTs. There is also no...

Followup

A number of approaches are used to detect recurrent disease after initial surgery and chemotherapy for ovarian cancer. These approaches include physical examination, determination of serum CA-125 levels, and imaging. CT, MRI, and PET all have been used to evaluate ovarian cancer recurrence.55 Recurrent ovarian malignancy may manifest as pelvic masses, peritoneal seeding, malignant ascites, and nodal recurrence (Fig. 5-12). Occasionally recurrent disease may present as pleuropulmonary lesions...

Combination Platinum Based Chemotherapy versus Single Agent Platinum

Endocrine Based Therapies Breast Cancer

If a patient is to receive a platinum agent, the next question is Should the platinum drug be administered alone or in combination with a second non-platinum drug Figure 9-3. Up to 15 to 20 of women receiving a second-line platinum-based chemotherapy program will experience a toxic reaction. (Data from Markman M, Kennedy A, Webster K, et al Clinical features of hypersensitivity reactions to carboplatin. J Clin Oncol 17 1141, 1999, Table 1.) Figure 9-3. Up to 15 to 20 of women receiving a...

Mucinous Carcinoma

Morphologic transitions from mucinous cystadenoma to mucinous atypical proliferative tumor (borderline tumor), to mucinous intraepithelial carcinoma and invasive mucinous carcinoma have been recognized for some time, and an increasing frequency of KRAS mutations at codons 12 and 13 has been described in every stage of tumor progression.7,41-44 In addition, the same KRAS mutation has been detected in mucinous carcinoma and in the adjacent mucinous cystadenoma and borderline Table 2-5. Ovarian...

Definition of Recurrent versus Platinum Resistant Ovarian Cancer

It has long been recognized that ovarian cancer patients whose tumors exhibit objective evidence of a response to chemotherapy may respond a second time to the same (or a similar) treatment program.3,4 In fact, this observation is not unique to ovarian cancer, having been demonstrated relatively early in the development of modern chemotherapy in the management of hematologic malignancies.5 Because of the central role of the platinum agents in ovarian cancer,6 it should come as no surprise that...

Overexpression of Apolipoprotein E

Based on serial analysis of gene expression(SAGE), investigators have found apolip-rotein E (ApoE) overexpression in ovarian carcinoma. Besides the well-known role of ApoE in cholesterol transport and in the pathogenesis of atherosclerogenesis and Alzheimer's disease, ApoE may play a novel role in the development of human cancer. ApoE immunoreactivity has been detected in 66 of high-grade but only 12 of low-grade ovarian serous carcinomas, and not in normal ovarian surface epithelium, serous...

Diseasefree Interval

In many series, an important prognostic and therefore selection factor is the disease-free interval (DFI), defined as the interval from the completion of chemotherapy to the diagnosis of recurrence. The platinum-free interval is the interval of time between the last dose of platinum-based chemotherapy and the diagnosis of recurrence. Generally, the DFI and the platinum-free interval are the same, since almost all patients receive primary platinum-based chemotherapy. The importance of the DFI in...

Surgical Principles

A substantial number of patients with advanced-stage ovarian cancer present with bulky upper abdominal disease, malignant pleural effusions, or even intraparenchymal liver disease and may require diaphragmatic or intestinal procedures, splenectomy with or without a distal pancreatectomy, and peritoneal stripping to achieve an optimal cytoreduction. A survey of the Society of Gynecologic Oncologists (SGO) in 2000 revealed that up to 45 of patients deferred several procedures such as splenectomy...

Staging

Ovarian Cancer Staging

Traditionally, ovarian cancer was staged surgically, based on the International Federation of Obstetrics and Gynecology (FIGO) classification system. However, current state-of-the-art imaging modalities have been shown to play a potential role in non-invasive preoperative staging. Intraperitoneal dissemination is the most common route of ovarian cancer spread, rather than solid organ parenchymal metastases in many malignancies. Peritoneal implants usually occur on the surfaces of the viscera...

Sex Cord Tumor with Annular Tubules

Sex cord tumors with annular tubules (SCTATs) were initially grouped with SLCTs, and some have proposed grouping them with GCTs. Correspondingly, these tumors possess characteristics of both, but they are recognized as a unique entity. Distinctive features include an association with Peutz-Jeghers syndrome in one third of cases, the potential to produce progesterone, and a higher penchant for lymph node metastasis than other sex cord-stromal tumors.84 The presentation of SCTATs differs based on...

Features and Risks of BRCA1 and BRCA2Related Cancers

Compared with the general population, BRCA1 2 mutation carriers have an increased risk of ovarian cancer. The lifetime risk of ovarian cancer in the general population Figure 3-3. Factors affecting penetrance. (From ASCO Curriculum Cancer Genetics and Cancer Predisposition Testing, 2nd ed, 2004, Slide 1-36.) Figure 3-3. Factors affecting penetrance. (From ASCO Curriculum Cancer Genetics and Cancer Predisposition Testing, 2nd ed, 2004, Slide 1-36.) 1 1 1 cnzi BRC repeats 1-8 Based on data from...

Choice of Chemotherapy and Duration of Treatment

Generally, choice of adjuvant chemotherapeutic agents for early-stage disease has been extrapolated from management of advanced-stage ovarian cancer. See the section on Advanced Ovarian Carcinoma, later in this chapter. Many of the investi-gational trials in early-stage ovarian cancer compared cisplatin-based combination chemotherapy to radiation therapy 18-20 (Table 8-5). Meta-analyses of these types of trials have shown no significant difference between chemotherapy and radiation therapy for...

New Combinations and Dose Schedules

GOG 182 ICON-5 is a large multicenter randomized trial, which closed to accrual in 2005 (Fig. 8-10). The aim of this study was to determine whether adding a third drug (topotecan, liposomal doxorubicin, or gemcitabine) and adjusting schedules Randomization Optimal and Suboptimal Stages III and IV Doxil triplet Carboplatin AUC 5 IV day 1 Paclitaxel 175 mg m2 IV day 1 Doxil 30 mg m2 IV every other day 1 Doxil triplet Carboplatin AUC 5 IV day 1 Paclitaxel 175 mg m2 IV day 1 Doxil 30 mg m2 IV every...

Sex Cord Stromal Tumors

Sex cord-stromal tumors consist of a pathologically diverse group of ovarian tumors originating from the sex cords and stroma of the ovary. Their exact histogenesis remains unclear. Collectively, they account for 5 to 8 of all ovarian tumors and can occur in women of any age group, but they are most commonly diagnosed in women in the fifth decade of life. Sex cord-stromal tumors are classified into granulosa cell tumors (GCTs), Sertoli-Leydig tumors, sex cord-stromal tumors with annular...

Broad Ligament Cystadenomas

Peritoneal Tumors Mri

Common sex cord-stromal tumor of the ovary and is benign. It is composed of fibroblasts and collagen and is without estrogenic activity.71 It may be associated with ascites and Meigs syndrome. Ovarian fibromas are worth mentioning from an imaging standpoint because they have a relatively specific appearance on imaging that may suggest the diagnosis. The characteristic appearance of fibroma on ultrasound is a homogeneous hypoechoic mass with posterior acoustic shadowing.59 On CT, it has been...

Sertoli Leydig Cell Tumors Androblastomas

Sertoli Leydig Ovarian Tumor Ultrasound

Sertoli-Leydig cell tumors (SLCTs) are rare, accounting for 0.2 of all ovarian tumors. Unlike granulosa-stromal cell tumors, they occur principally in women in the reproductive years with 75 occurring before age 40 and occurring less commonly during menopause or childhood. Similar to theca cells, SLCTs are usually hormonally active and secrete testosterone, thus resulting in androgen excess and potential virilization. The cause of SLCTs remains largely unknown because they originate from the...

General Population Screening Transvaginal Ultrasound

Transvaginal ultrasound (TVUS) has been evaluated for use in ovarian cancer screening in the general population. Because of the close proximity of the probe to the ovaries, TVUS offers excellent resolution of ovarian morphology. Volume, outline, papillations, and complexity of ovarian masses can be used to raise suspicion of cancer. Benign ovarian lesions are common, however, resulting in false-positives that may necessitate invasive surgery for asymptomatic women. In addition, TVUS as an...

Prophylactic Surgery in the High Risk Population

Cholecystectomy

When considering prophylactic procedure in the high-risk population, the surgeon needs to be cognizant of the risk of an occult malignancy. The patient needs to have signed consent forms for additional procedures including hysterectomy and full surgical staging, since there is a 4 chance of detecting an occult malignancy at the time of the procedure.21,22 Prophylactic bilateral salpingo-oophorectomy can be performed by laparotomy or laparoscopy (minimally invasive surgery). A methodical survey...

Histology

Dysgerminoma Tumor Ovary

Ovarian germ cell tumors comprise a number of different histologic types (Table 11-5). In terms of incidence, dysgerminomas are the most common malignant ovarian germ cell tumors (Fig. 11-8), followed by immature teratomas (Fig. 11-9) and endodermal sinus tumors (Fig. 11-10), although mixed varieties containing disparate tumor components also exist. Other histologic types such as embryonal carcinomas, nongestational choriocarcinomas, struma ovarii, and so on, are more rare. Surveillance,...

Detection and Characterization of Ovarian Tumors Role of Ultrasound

Ovarian Cancer Ultrasound

Ultrasound is considered the modality of choice for initial evaluation of an ovarian mass.19 It has been reported that in a setting similar to day-to-day clinical practice, in which the readers were given a brief clinical history of the patients (i.e., age, menstrual status, family history of ovarian cancer, previous pelvic surgery, and presenting symptoms), the experienced readers reached a prospective diagnostic accuracy of 92 , with excellent interobserver agreement (k 0.85). The less...

Tumor Biology

Various biologic factors have been associated with prognostic significance in ovarian cancer. The role of ploidy in predicting outcome in ovarian cancer remains controversial. In many studies, diploid tumors have been associated with better survival rates. Recurrence-free survival of patients with DNA-diploid primary ovarian cancer was significantly better compared with that of patients with DNA-aneuploid tumors in univariate analysis (47 versus 18 P .01). The tumor-dependent overall survival...

Mutation of BRAF and KRAS

Braf Und Kras

Several unique molecular changes characterize low-grade and high-grade serous carcinomas (Table 2-4 and Fig. 2-4). Among them, the most significant molecular genetic alterations are mutations in BRAF and KRAS oncogenes. The RAS, RAF, MEK, ERK, and MAP cascade is important for the transmission of growth signals Table 2-3. Summary of Clinicopathologic Features of the Prototypic Type I and Type II Tumors Type I Low-Grade Serous Carcinoma Type II High-Grade Serous Carcinoma 25 of serous carcinomas*...

Advanced Stage Epithelial Ovarian Cancer Principles of Surgical Cytoreduction

Advanced epithelial ovarian cancer typically presents with widely disseminated intraabdominal disease. The standard treatment of advanced epithelial ovarian cancer (EOC) includes primary cytoreductive or debulking surgery followed by adjuvant systemic chemotherapy. The goal of primary surgery for advanced epithelial ovarian cancer is to accurately establish a diagnosis and leave little or no residual disease. There are several potential benefits to the surgical removal of bulky tumor masses1,2...

Natural History of Untreated Early Ovarian Carcinoma

Pictures Stages Ovarian Cancer

Knowing the natural history of untreated early ovarian cancer should identify the need for adjuvant chemotherapy. Assessing an observation arm in randomized controlled trials RCTs should be an accurate means of determining the true rate of recurrent cancer after surgical resection. Table 8-1 lists five prominent randomized controlled trials comparing observation with a treatment arm. The rate of cancer recurrence in the observation arm varies from 9 to 35 owing to differences in substages and...

En bloc Pelvic Resection

Bladder Tumour Resection

Locally advanced ovarian cancer frequently distorts the pelvic anatomy encasing the adnexae, pelvic peritoneum, cul-de-sac, and rectosigmoid Fig. 7-5 . A retroperitoneal approach to the hysterectomy and bilateral salpingo-oophorectomy allows en bloc removal of the ovarian tumor and surrounding structures affected by confluent disease, including portions of the rectosigmoid and bladder.17 The procedure involves extending the peritoneal incisions along the paracolic gutters caudally Figure 7-5....