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Ovarian Cancer Epithelial Tumor postmenopausal women Germ cell younger women Sex cordstromal origin any age Approximately 90 of ovarian cancer is epithelial significant therapeutic challenges ID: 357059

patients ovarian disease cancer ovarian patients cancer disease stage chemotherapy platinum tumors epithelial tumor 125 therapy surgery relapse survival

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Slide1

Ovarian CancerSlide2

Ovarian Cancer

Epithelial Tumor,

postmenopausal women

Germ cell,

younger women

Sex cord-stromal origin,

any ageSlide3

Approximately 90% of ovarian cancer is epithelial

significant

therapeutic challenges

(Epithelial Tumor)

other types of ovarian cancer are

often localized

,more

amenable to surgical resection,

more

favorable

px

peritoneal

serous carcinoma and fallopian tube carcinoma

(their clinical

and management considerations are similar to those of epithelial ovarian

cancer)Slide4

Epidemiology

leading

cause of gynecologic cancer

mortality

The

lifetime risk

:1.7

%,

familial

predisposition

:of

10% to 40

%

The

median age at diagnosis for sporadic disease is 60 years,

improvement

in 5-year

survival

A

higher risk

for

nulliparous

women

lower

risk for those who have had children, who have breastfed, who have undergone tubal ligation, or who have taken oral contraceptivesSlide5
Slide6

Pathogenesis and Patterns of Metastases

arise

from the surface epithelium covering the ovary, which is contiguous with peritoneal

mesothelium

. It is thought that malignant transformation preferentially occurs within epithelium that becomes trapped within ovarian inclusion cysts during

ovulation, where it can develop into a variety of mullerian-type histologies. Thus

, ovarian serous carcinomas can resemble the fallopian tube, ovarian mucinous tumors may resemble the endocervix, and ovarian endometrioid carcinomas may resemble the endometrium. Slide7

Pathogenesis and Patterns of Metastases

Germ cell tumors

most likely originate in cells derived from the primitive streak that ultimately migrated to the gonads.

The ovarian stroma consists of granulosa cells, theca cells, and fibroblasts, which give rise to the

sex cord- stromal tumors

.Slide8

Several molecular abnormalities

in

patients with epithelial ovarian cancer,

Cytogenetic analysis may reveal complex

abnormalities

Mutation

in the p53 proto-oncogene occurs in over 50% of cases,

Mutations

in the K-ras proto-oncogene

are

more common in ovarian borderline tumors (which typically do not undergo p53 mutation

).

Amplification of the Her-2/neu gene

,

8%

Overexpression of proapoptotic genes such as

BAX(Px good)

Expression

of

(VEGF) (high serum :Px poor)Slide9

exfoliate

from the ovarian

surface

The tumor typically spreads to the omentum and to peritoneal surfaces

The

lymphatic drainage

para-aortic region,

pelvic

sidewall lymphatics,

(external

iliac, obturator, and hypogastric

chains)

inguinal

lymph nodes

.

10

% to 15%

appears

to be localized to the ovaries have metastases to para-aortic lymph

nodes

retroperitoneal

lymph node involvement is found in over 50% of patients with advanced disease.Slide10

The

most common site of

extra-abdominal spread

is the pleural space (thought to occur via transdiaphragmatic lymphatics), where it causes a malignant pleural effusion in some patients.

Hematogenous

metastases to the

liver,

spleen

, or

lung

Bone

or central nervous system

metastasesSlide11

Histologic Classification of Epithelial Tumors

The nomenclature for these tumors reflects the cell type, location of the tumor, and degree of malignancy, ranging from benign lesions to tumors of low malignant potential (LMP) to invasive carcinomasSlide12
Slide13

Tumors of LMP (borderline tumors)

epithelial papillae with atypical cell clusters

excellent

prognosis

increased mitotic

activity

lack stromal invasionSlide14

Epithelial carcinomas

characterized by histologic

cell type and

degree

of differentiation (tumor grade

)

The histologic cell type has limited prognostic significance

independent

of clinical

stage

High

tumor grade

,especially

in patients with early stage epithelial tumors.Slide15

papillary serous variety of epithelial ovarian cancer: psammoma bodies

clear

cell histology may also be associated with endometriosis,

hypercalcemia , relatively

resistant to

chemotherapy

mucinous

ovarian cancers are

chemoresistant

,

sometimes

associated with pseudomyxoma peritonei, and may not be associated with dramatic elevations of

(

CA 125

)Slide16

COMMON EPITHELIAL TUMORS

Malignant serous

tumor

Malignant mucinous

tumor

Malignant endometrioid

tumorSlide17

SEX

CORD - STROMAL

TUMORS

Granulosa - stromal

cell

tumor

Androblastoma: Sertoli-Leydig cell

tumor

Germ cell

tumorSlide18

DDx

Gastric, breast (especially

ILC),

mesothelioma, and colorectal cancers may occasionally present with diffuse peritoneal implants, ascites, and ovarian metastases that mimic primary ovarian cancer.

routine

light microscopic histologic evaluation,

IHC

cytokeratin

CK7

+and

CK20

- in

most cases of primary serous ovarian cancer,

Staining for

gross cystic disease fluid protein

(GCDFP) may be positive in up to 50% of patients with

breast

cancer, whereas this marker should be negative in patients with gastric, colorectal, or ovarian cancer. Slide19

Common Histologic Types of Epithelial Ovarian Cancer

Papillary

serous

Endometrioid

Mucinous

Clear cellSlide20

Papillary serous

The most common type of epithelial ovarian cancer

.

May contain psammoma bodies

often

associated with CA 125 elevation.

Identical

histology is observed for primary peritoneal serous cancer (PPSC).Slide21

Endometrioid

Sometimes

associated with endometriosis or an independent uterine cancer of similar histology. May occur with

early stage

disease in

younger

patients, although advanced disease is also possible.Slide22

Mucinous

May

rarely be associated with pseudomyxoma peritoneii. CA 125 levels may not be markedly elevated. Relatively chemoresistant. Differential diagnosis of a mucinous ovarian tumor includes metastatic disease from an appendiceal primary.Slide23

Clear cell

The

most chemoresistant type of ovarian cancer. Often contains

hobnail

cells with cleared out cytoplasm due to glycogen. Sometimes associated with endometriosis or humorally mediated hypercalcemia.Slide24

Diagnosis

asymptomatic

Symptomatic of spreads

to the upper

abdomen

Approximately

70%

with stage

III or

IV

whereas the majority of patients with borderline, germ cell, and sex

cord -stromal

tumors present with early stage disease limited to the

pelvis

mass

on routine pelvic examination or because of pelvic pain caused by ovarian torsion.

ovarian

germ cell malignancies tend to stretch and twist the infundibulopelvic ligament, causing severe

painSlide25

Abdominal discomfort, bloating, and early satiety

(ascites

and a pelvic mass on physical

examination)

(

Sister Mary Joseph's node) or a pleural

effusion

The

mass on pelvic examination is frequently firm and fixed, with multiple nodularities palpable in the cul-de-sac.Slide26

The CA 125 serum level is elevated in more than 80% of serous epithelial ovarian

cancers.

not

a reliable diagnostic test, since it can also be elevated in a variety of benign gynecologic conditions (such as

endometriosis,

pelvic inflammatory disease

, or

pregnancy

) and nongynecologic malignancies (such as

breast

,

lung

, and

GI

).

the

CA 125 level is elevated in

50

% of patients with early stage epithelial ovarian cancer,

CA

19-9, which is elevated in some mucinous ovarian carcinomas, and carcinoembryonic antigen (CEA) are less frequently useful. Slide27

It is typical for a patient with epithelial ovarian cancer to have a

normal CEA

level in the setting of a

significantly elevated CA 125

level.

Postoperatively, the CA 125 level provides a sensitive way to monitor treatment response and development of disease recurrence. Because relapsed epithelial ovarian cancer is usually incurable, however, there is

currently no evidence that early detection of recurrence through CA 125 levels confers a survival advantage in this disease.Slide28

International Federation of Gynecology and Obstetrics Staging System for Epithelial Ovarian CancerSlide29

STAGE

I

Tumor

limited to ovary or

ovaries

a

IA One

ovary, without ascites, positive peritoneal washings, surface involvement, or rupture.

IB Both

ovaries, without ascites, positive peritoneal

washings

, surface involvement, or rupture.

IC Ascites

, positive peritoneal washings, surface involvement, or rupture present.Slide30

STAGE II

Ovarian tumor with pelvic extension

a

IIA

Involvement of the uterus or fallopian tubes.

IIB

Involvement of other pelvic organs (e.g., bladder, rectum, or pelvic sidewall).

IIC

Pelvic extension, plus findings indicated for IC.Slide31

STAGE III

Tumor involving the

upper abdomen

or lymph nodes

IIIA

Microscopic

disease outside of the pelvis, typically involving the omentum.

IIIB

Gross deposits less

than or equal to 2 cm in diameter.

b

IIIC

Gross deposits

greater than 2

cm in diameter, or nodal involvement.

bSlide32

STAGE IV

Distant organ involvement, including pleural space

c

or hepatic/splenic parenchyma.Slide33

a

Patients

with disease that appears to be confined to the ovaries or pelvis require nodal biopsy for complete staging, in order to exclude the possibility of occult stage IIIC

.

b

Disease measurements for staging purposes are made before debulking has been attempted

.

c

Pleural effusion must be cytologically proven to be malignant if used to define stage IV disease.Slide34

TVU

diagnostic

tool

TVU

is more sensitive

(CTS)

The

classic sonographic finding of malignancy is a

complex‌

cyst, defined as containing both solid and cystic components, sometimes with septations and internal echogenicity

.

Finding a complex cyst on sonography, especially in the presence of signs and symptoms consistent with ovarian cancer, often requires surgery for further evaluation. It is best to avoid percutaneous biopsy during the initial

evaluation

, which can result in cyst rupture and spillage of malignant cells into the peritoneal cavity. Bilateral ovarian involvement and ascites are sometimes detected by sonography as well

.

Color Doppler

imagingSlide35

Simple cysts

Simple cysts in asymptomatic postmenopausal do

not always require surgical evaluation if they are associated with normal CA 125 levels,

Postmenopausal

women with simple cysts in association with

elevated serum CA 125

levels, simple cysts that

exceed 5 to 10 cm

in diameter, or simple cysts in association with

abnormal color Doppler flow

studies are often referred for surgery.Slide36

Simple cysts In premenopausal

may

be functional (i.e., a corpus luteum cyst)

a

benign process such as a serous cystadenoma.

simple

cysts that are persistent or enlarging, especially in the setting of a rising CA 125 level, are reasonable candidates for surgical evaluation to exclude

malignancy.

several

benign conditions in premenopausal women may also be associated with elevated CA 125 levels, such as pregnancy or endometriosis, and there is no absolute CA 125 cutoff to distinguish benign from malignant pathologiesSlide37

CT or

(

MRI)

in

defining the extent of peritoneal disease

However

, for the patient with a complex ovarian cyst and clinical signs and symptoms to suggest ovarian cancer, these studies generally do not obviate the need for surgical exploration.

CT may sometimes be helpful in distinguishing a gynecologic malignancy from a

metastatic pancreatic neoplasm

, for instance, for which an exploratory

laparotomy

may not be warranted. In selected patients, CT may also assist in

surgical planning

by locating the site of suspected bowel obstruction. Slide38

MRI has not been shown to have a clear advantage over CT in patients with an ovarian mass, except for pregnant patients when ultrasonography is inconclusive and there is a desire to avoid radiation exposure. Slide39

PET:there is currently no proven role for PET in the diagnosis or subsequent follow-up of patients with ovarian cancer.

CXR may sometimes be performed to evaluate the presence of pleural effusions, which occur in 10% of patients with epithelial ovarian cancer at diagnosis.Slide40

Screening and Early Detection

identifying the majority of patients with precancerous lesions or early disease

major surgery

Costs

mortality

the false-positive rate

positive predictive value (PPV)Slide41

screening procedure

serum tumor marker levels

ultrasonography

bothSlide42

CA 125 serum level

alone, is not a useful

not specific for ovarian cancer

cirrhosis, peritonitis, pleuritis, pancreatitis, endometriosis, uterine leiomyomata, benign ovarian cysts, and pelvic inflammatory disease

elevated in other malignancies

such as breast, lung, colorectal, pancreatic, and gastric cancers.

CA 125 level is elevated in the majority of patients with advanced epithelial ovarian cancer, it is abnormal in only 50 % of patients with early stage disease.Slide43

candidate markers

show promise for enhancing the accuracy of CA 125 levels,

HE4 (human epididymis 4)

osteopontin

mesothelin

osteoblast-stimulating factor-2.

OVX-1

Lysophosphatidic acidSlide44

these markers may be complementary to CA 125

None of these tests has been proven to have sufficient sensitivity and specificity for routine screening at the current time.Slide45

CA 125+ TVU

an attempt to improve screening.

TVU suggested a sensitivity of close to 100% but a specificity of 98%, which is insufficient to achieve a PPV of 10%.

color Doppler imaging improves the specificity of TVU ,PPV?

using a morphologic index? Slide46

Two randomized controlled trials

measurement of CA 125 level (single threshold elevation of more than 35 U/mL) and TVU together, performed annually, as a first-line screen

will require an average of 10 years of follow-upSlide47

The second randomized screening trial is currently being conducted in the United Kingdom and uses CA 125 levels (or rate of rise of CA 125) as a trigger for performing TVU. Slide48

Hereditary Ovarian Carcinoma

5% to 10% epithelial ovarian carcinoma carry a germline mutation

The breast -ovarian cancer syndrome 90% of hereditary ovarian cancer and is often suspected whenever the pedigree reveals

multiple

affected family members with

ovarian cancer

,

bilateral or early onset breast cance

r,

both breast and ovarian cancer in the same individual

, or

a male relative with breast cancer

.

Fallopian tube cancer

and

primary peritoneal serous cancer

(PPSC)Slide49

Breast and ovarian cancers

inherited germline mutations in the BRCA1 or BRCA2 genes,

transferred by either parent,

these genes act as tumor suppressors and play a critical role in the repair of double-stranded DNA breaks.

32Slide50

The lifetime risk of ovarian cancer is

20% to 60%

for patients with

BRCA1 mutations

, and 10% to 35% for BRCA2 mutation carriers.

Ovarian cancer with germline mutations of BRCA1 appears to present with distinct clinical and pathologic features compared with sporadic ovarian cancer.

The majority of BRCA1-associated cancers are

serous adenocarcinomas

, with an average age at diagnosis of

48

years, whereas the mean age for BRCA2-associated ovarian cancers is 60 years.Slide51

Furthermore,

BRCA-associated cancers may have a more favorable course than sporadic ovarian cancer.

chemosensitivity may be partly due to the inability of tumor cells to repair platinum-induced DNA damage in the setting of a BRCA1 or BRCA2 mutation.Slide52

The more favorable survival of patients with BRCA1 or BRCA2 mutations when compared to their sporadic counterparts is not necessarily related to a higher rate of cure, but may also be related to

a longer duration of responsiveness to chemotherapy

agents used in the relapsed setting. Slide53

Hereditary nonpolyposis colorectal cancer

5% to 10% of all hereditary ovarian cancer

autosomal dominant

right colon, as well as an increased risk of developing

endometrial,

ovarian, hepatobiliary

,

upper gastrointestinal

, and

Gyn cancers

.

Colorectal and uterine

cancers comprise the majority of tumors developing in affected families. Slide54

A germline mutation in one of five genes involved in DNA mismatch repair is responsible for the HNPCC phenotype:

hMSH2

(chromosome arm 2p), hMLH1 (chromosome arm 3p), hPMS1 (chromosome arm 2q), hPMS2 (chromosome arm 7p),

The majority of affected patients are found to have defects in either

hMSH2 or hMLH1Slide55

Patients with HNPCC due to germline mutation of

hMSH6

may be particularly predisposed to

uterine cancer

. In addition, HNPCC may account for approximately 7% of cases with

synchronous uterine and ovarian

cancers, which are

often low grade

and of endometrioid histologySlide56

Patients at high risk of having a hereditary cancer

genetic counseling

Multidisciplinary services available in such a setting often include pretest and posttest counseling, screening, treatment, and psychosocial counseling.Slide57

Test results

an identifiable mutation,

no identifiable mutation

a polymorphism of indeterminate clinical significance. Slide58

Management of patients with an inherited genetic predisposition to ovarian cancer

complex

variable penetrance of genetic alterations

lack of effective early detection methods for ovarian cancer

Although annual pelvic examinations, serum CA 125 determinations, and TVU are sometimes considered in affected individuals, there is currently

no conclusive evidence that ovarian cancer

mortality i

s reduced

as a result of these interventions

efficacy of prophylactic, risk reduction bilateral salpingo-oophorectomy (RRSO) for patients with the hereditary breast-ovarian cancer syndrome has been more convincingly demonstrated.Slide59

RRSO

Chemoprophylaxis

Other risk-reducing strategies

Management of patients with an inherited genetic predisposition to ovarian cancerSlide60

Even after RRSO, BRCA mutation carriers are still at small risk for developing primary peritoneal serous cancer, which is histologically and clinically similar to epithelial ovarian cancer. Such cancers represent malignant transformation of the peritoneal mesothelium, which is contiguous with ovarian surface epithelium.Slide61

RRSO

most effective preventative strategy

at high risk for developing ovarian cancer and who have completed childbearing, especially if they are at least 35 years of age

A laparoscopic approach Slide62

The surgical pathologist must perform a careful examination of the surgical specimens, as occult ovarian and tubal carcinoma have been found in 2% to 10% of RRSO specimens.

Some patients with occult disease discovered after careful pathological evaluation may require a second operation to complete surgical staging in order to determine the need for postoperative treatment .

Significant issues regarding RRSO remain unresolved, such as the physiologic adjustments to premature surgical menopause and the safety of hormone replacement therapy in this group, especially in those at high risk for breast cancer.Slide63

chemoprophylaxis with oral contraceptives for 5 years might decrease ovarian cancer risk by 50% in both the general population and in high-risk women.

Other risk-reducing strategies such as tubal ligation and hysterectomy have also been associated with a reduced incidence of ovarian cancer among high-risk women.Slide64

Staging

laparotomy permits histologic confirmation of disease,

Surgery is also necessary to determine the extent of disease (staging), post opTX ,Px

debulking

optimally cytoreduced (defined as having less than or equal to 1-cm diameter residual tumor)Slide65

midline incision

ascitic fluid

If intraperitoneal carcinomatosis is absent, first resect the ovarian tumor

The grossly normal, opposite ovary may undergo biopsy, or any visible benign-appearing cysts may be excised.

Pelvic and para-aortic retroperitoneal lymph nodes

Any enlarged pelvic retroperitoneal lymph nodes should be removedSlide66

The staging system for ovarian cancer is defined by FIGO based on the findings at exploratory laparotomy Slide67

Staging

fertility

endometrioid ovarian cancer Slide68

incomplete surgy

completing the surgical staging if the findings would alter postoperative management(stage IA, grade 1 or 2 )

( at least stage IC or stage II )or (tumor is grade 3),less importent

Laparoscopic techniques

CT scan?Slide69

Prognostic Factors for Epithelial Ovarian Cancer

FIGO stage,

volume of residual disease after cytoreductive surgery

histologic subtype,

histologic grade,

age,

malignant ascites.Slide70

5ys stage IA disease and grade 1 or 2

>90%

after surgery alone( or +stage IB, grade 1 or 2 )

relapse rate without postop adj treatment is

30% to 40%

for patients with stage IC , stage I, grade 3 , or stage II

a 5-ys 80% after postop adj therapy

Controversial: some investigators report that rupture alone does not appear to confer a worse prognosis if it occurred intraoperatively, as opposed to preoperatively.Slide71

advanced-stage disease

5ys 20% to 30%

After postoperative treatment stage III optimally debulked, and this decreases to less than 10% for patients with suboptimally debulked stage III disease or those with stage IV tumors.

stage IIIA disease survivals in the range of 50% after postoperative adjuvant therapy.

mucinous or clear cell histologic

have worse PxSlide72

CA 125

Preoperative serum CA 125 levels frequently reflect the volume of disease and do not appear to have an independent effect on survival, after correcting for stage and debulking status.

postoperative CA 125 levels, both

during and after completion of first-line chemotherapy,

have prognostic value.

normalization

of the serum CA 125 levels after three cycles of cht is associated with more favorable outcome, as well as achievement of a CA 125

nadir of less than or equal to 10 U/mL

upon completion of treatment. Although this information has prognostic significance, it has limited therapeutic value in the absence of effective salvage regimens with curative potential.Slide73

The prognostic significance

DNA ploidy and S-phase fraction

aneuploidy?

relationship between histologic grade and the degree of aneuploidy?Slide74

molecular prognostic factors

markers of proliferation

drug resistance

levels of serum cytokines

growth factor receptors

expression of genes associated with metastases.Slide75

Management of Early Stage Disease

Postoperative Chemotherapy

Postoperative Radiation TherapySlide76

Postoperative Chemotherapy

can improve both progression-free and overall survival in patients with

high-risk, early stage

ovarian cancer. Such patients include those with stage I, grade 3, stage IC, or any stage II disease.

six cycles of adjuvant carboplatin plus paclitaxel chemotherapy for high-risk, early stage patients, Slide77

Postoperative Radiation Therapy

different chemotherapy regimens

whole abdominal radiotherapy (WAR)

intraperitoneal (IP) administration of radioactive phosphorus (

32

P).Slide78

In summary

these randomized trials generally found WAR or IP

32

P was less effective or more toxic than platinum-containing regimens. Hence, adjuvant radiation therapy has fallen out of use as the primary treatment for patients with high-risk, early stage ovarian cancerSlide79

Management of Advanced-Stage Disease

Primary Cytoreductive Surgery

Postoperative Chemotherapy for Epithelial Ovarian Cancer

Intraperitoneal Chemotherapy

Interval Cytoreductive Surgery

Radiotherapy After First-Line Chemotherapy

Maintenance TherapySlide80

Primary Cytoreductive Surgery

The theoretical benefits of cytoreductive surgery include removal of large, necrotic tumors with poor blood supply that might lead to impaired chemotherapy delivery.

tumor debulking may permit residual tumor to proliferate more rapidly and thereby enhance sensitivity to postoperative chemotherapy.

Although neither of these mechanisms has been proven, the association between successful cytoreduction and more favorable outcome has been demonstrated in many surgical series.Slide81

optimal cytoreduction

residual disease of 1 cm or smaller in maximum individual diameter

Primery cytoreduction refers to performance of debulking surgery prior to administration of first-line chemotherapy and is the standard approach for managing most patients with suspected epithelial ovarian cancer.Slide82

neoadjuvant chemotherapy and an interval cytoreduction

patients with a poor performance status initiating neoadjuvant CHT →surgical cytoreduction in responding patients after

three cycles

of chemotherapy

stage IV diseaseSlide83

neoadjuvant chemotherapy

Potential advantages of neoadjuvant chemotherapy are

a more rapid improvement in quality of life

a technically more feasible operation

shorter hospitalization

less morbidity. Slide84

Postoperative Chemotherapy for Advanced-stage epithelial ovarian cancer

It is a chemoresponsive disease in the majority of cases, although relapse often occurs and resistance eventually develops to most forms of treatment.

The platinum compounds remain the single most active drugs in the treatment of this disease.

the use of carboplatin instead of cisplatin conferred an equivalent survival advantage, but with

less myelosuppression

,

neuropathy, nephropathy

, and

emesis Slide85

P base + a taxane such as paclitaxel

is now accepted as an appropriate first-line,

The response rate as high as 70% for patients with suboptimally debulked disease,

over 80% for patients who are optimally cytoreduced.

nonoverlapping mechanisms of action, Slide86

Combination or sequential single agents

For individuals who may have difficulty tolerating a combination regimen (e.g., those with marginal performance status or significant comorbid medical conditions), it is reasonable to

initiate treatment with intravenous single-agent carboplatin

and

later add intravenous paclitaxel to the regimen

or

deliver the drugs as sequential single agents.

For appropriate patients with stage III disease who are optimally cytoreduced,

intraperitoneal chemotherapy

is an important new optionSlide87

carboplatin (AUC = 5) plus paclitaxel (175 mg/m

2

)

icarboplatin (AUC = 5) and docetaxel (75 mg/m

2

)

has shown

equivalent response rates

,

progression-free

, and

overall survival

, although their toxicity profiles differed. More grade 4 neutropenia occurred with the docetaxel-containing regimen, and a greater incidence of grade 2 or 3 neuropathy was observed with the paclitaxel-containing program.

These data indicate that a carboplatin and docetaxel combination is an acceptable first-line regimen for patients with advanced ovarian cancer, especially in the setting of pre-existing neuropathy (where paclitaxel may be difficult to tolerate).Slide88

How many cycles

There appears to be no value in extending platinum-based first-line therapy beyond five or six cycles to ten or 12 cycles.

there is no convincing evidence to suggest a benefit to the addition of cytotoxic drugs such as

liposomal doxorubicin

,

epirubicin,

topotecan,

or

gemcitabine

to the platinum and taxane doubletSlide89

Bevacizumab ?Slide90

Intraperitoneal Chemotherapy

The rationale for this approach is based on the observation that many active drugs such as cisplatin and paclitaxel have favorable peritoneal to plasma concentrations, on the order of

20 to 1

and

1,000 to 1

, respectively.

generally acceptable systemic side effects,

limited penetrationSlide91

receive either a control arm of IV paclitaxel (135 mg/m

2

administered over 24 hours) and IV cisplatin (75 mg/m

2

) for six cycles,

IV paclitaxel on day 1 (135 mg/m

2

administered over 24 hours), IP cisplatin on day 2 (100 mg/m

2

), and IP paclitaxel on day 8 (60 mg/m

2

), for six cycles.

The median overall-survival was 65.6 months for the IP arm and 49.7 months for the IV arm (HR 0.75; 95% CI 0.58 to 0.97; P = .03).

This significant prolongation of median overall survival was associated with several toxicities, including a higher incidence of

neutropenia,

i

nfection

,

catheter blockage,

neuropathy

,

abdominal pain

,

renal dysfunction,

and

electrolyte abnormalitiesSlide92

Although some investigators still feel that IP chemotherapy should remain experimental, others feel that these data offer strong support for the IP approach.

Slide93

IP therapy

no superior to IV treatment in

stage IV disease,

suboptimally debulked residual disease

relapsed disease.

It should also be avoided in patients with comorbid conditions such as

renal insufficiency, significant baseline neuropathy, or extensive intra-abdominal adhesions

.Slide94

Improve the tolerability of IP therapy

reduction of the day-2 IP cisplatin dose,

administration of day-1 IV paclitaxel over 3 hours instead of 24 hours,

and/or omitting day-8 IP paclitaxel until patient tolerance to the first cycle of IP cisplatin can be assessed.

reduce toxicity while still preserve the benefits of the IP approach?

use of IP carboplatin instead of IP cisplatin

it is not yet known whether carboplatin is as effective as cisplatin when administered via the IP route.Slide95

Technical Aspects of Intraperitoneal Chemotherapy Administration

either cisplatin or paclitaxel

a catheter with a subcutaneous access port in the anterior chest wall region, just below the breast, which then tunnels subcutaneously downward to the midabdomen, where it enters the peritoneal cavity. IP catheter insertion can be performed at the time of primary cytoreductive surgery, or afterward by laparoscopy. Slide96

Based on the available data, colon resection with fecal contamination or left colon resection would appear to represent relative contraindications to placement of an IP catheter at the time of primary cytoreductionSlide97

Tenckhoff catheter

adhesion formation within the peritoneal catheter related to the development of a fibrous sheath surrounding the catheter fenestrations, and intestinal obstruction due to the Dacron sheath migrating into the peritoneal cavity

2. a single-lumen silicone catheter with an implantable port designed for IV injection may be preferable, Slide98

Catheter insertion typically involves the following steps

A separate 5 to 6 cm transverse incision is made two to three fingerbreadths above the left inferior costal margin in the midclavicular line and is carried down to the fascia.

A subcutaneous pocket is created to house the implantable port

The port is sutured to the fascia at the four corners

A tonsil clamp or similar instrument is tunneled subcutaneously above the fascia for approximately 10 cm from the port. At a point about 6 cm lateral to the umbilicus, a small aperture is made in the peritoneum.

The proximal end of the catheter is grasped with the clamp and brought through from the peritoneal cavity, through the subcutaneous tunnel, to the port.

The catheter is connected to the port, and it is trimmed to allow approximately 10 cm of catheter within the peritoneal cavity

The catheter is flushed with heparinized saline to check patency.

The transverse skin incision is closedSlide99

Intraperitoneal instillation

If the infusion rate is slow, repositioning the patient may be beneficial in an attempt to move the catheter tip away from bowel loops or a pocket caused by adhesions.

a second prewarmed liter of fluid

Standard premedicationsSlide100

Interval Cytoreductive Surgery

Interval cytoreduction is defined as a debulking procedure performed after several cycles of chemotherapy have been administered, typically in those patients who had a suboptimal cyto-reduction at the time of initial surgery.

a randomized trial : improvement in median overall survival (P = .01), suggesting a role for this strategy in suboptimally debulked patients who are

responding to first-line chemotherapy

.Slide101

the negative results of the

GOG study

than in the

EORTC trial

, are partly due to

definition of suboptimally debulked disease

performance of initial surgery by a gynecologic oncologist,

more effective paclitaxel and cisplatin regimen in the GOG trial (compared to cyclophosphamide and cisplatin in the EORTC trial)

may have negated any added value of interval cytoreduction

.Slide102

Thus, patients who are deemed to be suboptimally debulked after a cytoreductive effort performed by

a surgeon skilled

in this procedure, who then receive

first-line paclitaxel- and platinum-based

chemotherapy, are not likely to benefit from interval cytoreduction.

For those patients who did

not adequate attempt

at initial cytoreduction (due to being a poor operative candidate or due to lack of surgical expertise), the EORTC study suggests that an attempt at interval cytoreduction is reasonable if disease control can be achieved during the first three cycles of chemotherapy.Slide103

Radiotherapy After First-Line Chemotherapy

Cht+ :

WAR

Pelvis +para aort

IP

32

P

observeSlide104

In conclusion ?

the value of radiation therapy as consolidation therapy following chemotherapy for patients with ovarian cancer is uncertain.

Routine use of consolidation radiotherapy after chemotherapy is not generally recommended.Slide105

Maintenance Therapy

There is no evidence that continuing first-line platinum-based chemotherapy beyond five to six cycles confers added benefit for patients with advanced ovarian cancerSlide106

There is currently great interest in studying the value of

antiangiogenic agents

such as bevacizumab, which is a humanized monoclonal antibody that neutralizes vascular endothelial growth factor in the maintenance setting.Slide107

Surveillance After First-Line Chemotherapy

Over

50%

of newly diagnosed patients with advanced-stage epithelial ovarian cancer will achieve a clinical complete remission after platinum and taxane induction chemotherapy.

Clinical complete remission

is defined as no evidence of disease on

physical examination

, a normal

CA 125

level, and normal

radiographic

studies such as CT. Slide108

Patients with advanced-stage disease who achieve a clinical complete remission have

a high chance of relapse

follow

pelvic examinations

CA 125 determinationsSlide109

CTS

Routine performance of CT in the absence of symptoms, findings on physical examination, or an elevated CA 125 level has no proven value in the management of patients with this disease. This is partly due to the lack of sensitivity of CT compared to serologic testing with

CA 125, which is currently the most sensitive method for detection of early relapseSlide110

There is currently no proven benefit for routine surveillance with other radiographic tests such as PET scans in the posttreatment settingSlide111

second-look laparotomy

Although performance of a second-look laparotomy after completion of first-line therapy will reveal residual disease in over half of all patients with advanced ovarian cancer who have achieved a complete clinical remission, this procedure does not appear to confer a survival advantage. This is due to the current lack of curative treatment options for patients with disease that persists after platinum-based, first-line therapy.

In addition, a negative second-look laparotomy does not guarantee against the development of disease relapse, which occurs in 50% of patients with advanced stage disease who have a negative second-look procedure.

Slide112

For these reasons, second-look laparotomy is no longer considered a standard procedure in the assessment of patients after completion of first-line therapy, although it is sometimes used as an investigation tool in the context of clinical trials.Slide113

Management of Recurrent Disease

Hormonal Therapy

Chemotherapy

Surgery

Radiation TherapySlide114

Hormonal Therapy

(marker-only relapse)

Unfortunately, the majority of patients with recurrent ovarian cancer are destined to die of their tumors, regardless of the second-line treatment modality used. Patients who demonstrate marker-only evidence of relapse, are often initially managed with a drug like

tamoxifen

or

an aromatase inhibitor

. These drugs are potentially active in ovarian cancer and are generally well tolerated. Slide115

The response to hormonal agents is typically slow and may require approximately 2 to 3 months before a reduction in the CA 125 level is evidentSlide116

Chemotherapy

Chemotherapy for recurrent disease is usually indicated for the development of

tumor-related symptoms

,

objective evidence of significant disease on examination or CT,

or

failure of hormonal therapy

.

Platinum is the most active agent in the management of patients with epithelial ovarian cancer, and retreatment with this drug may produce valuable responses that translate into improvement in quality of life. Slide117

However, the likelihood of benefit depends on the interval between the last dose of platinum and the time of relapse (i.e., the platinum-free interval,

PFI

). Slide118

In patients with PFI:

less than 6 months are less likely to respond to second-line platinum and are often managed with an alternative agent, (platinum resistant)

between 6 and 24 months have an approximately

30%

chance of benefit from second-line platinum used at the time of relapse.

very prolonged PFI (e.g., greater than 2 years), the response rate with second-line platinum may be as high as

60% to 70%.Slide119

Patients with a PFI of greater than 6 months are referred to as potentially platinum sensitive and are often treated with either single-agent platinum or a combination of platinum with another agent such as

paclitaxel

or

gemcitabine

.Slide120

combination chemotherapy compared to single-agent platinum in the setting of potentially platinum-sensitive relapse (PFI greater than 6 months)?Slide121

combination second-line chemotherapy with regimens like

paclitaxel and carboplatin

or

gemcitabine and carboplatin

are a reasonable consideration in selected patients who are potentially platinum sensitive, based on their PFI.

since the primary goal of relapse management is palliation of symptoms, the decision to use combinations in this setting should be based on

patient age

,

amount of disease

,

kinetics of relapse

, and

patient preference

after a discussion of the issuesSlide122

For older patients

who require chemotherapy for asymptomatic, minimal volume, potentially platinum-sensitive relapse, it is reasonable to use

single-agent carboplatin

as a first step. Slide123

liposomal doxorubicin

is a generally well-tolerated alternative if there is a contraindication to the use of carboplatin, if carboplatin fails to induce a response, or if an allergic reaction develops to carboplatin that precludes further administration.

With either single-agent carboplatin or liposomal doxorubicin, patients have minimal problems with alopecia or myelosuppression, and their quality of life is generally well preserved. Slide124

For younger patients who wish to adopt an aggressive approach to the management of potentially platinum-sensitive relapse, combination chemotherapy with either

paclitaxel and carboplatin

or

gemcitabine and carboplatin

is reasonable.Slide125

aggressive approach

This is especially the case for the

symptomatic

patient with

kinetically brisk relapse

, or the patient who has undergone a

successful secondary cytoreduction after a very long PFI

.

Some physicians prefer the use of gemcitabine and carboplatin in this setting if there is persistent peripheral neuropathy related to first-line therapy.

Given concerns over

toxicity

, the decision to use combination chemotherapy for patients with potentially platinum-sensitive relapse should be individualized.Slide126

There are currently no data supporting a role for combination chemotherapy regimens in the management of patients with platinum-resistant relapse.Slide127

Patients who are

platinum resistant

, as defined by a short PFI of less than 6 months or progression during platinum-based chemotherapy, or those who tolerate second-line platinum poorly are typically treated with a variety of

single agents

. Potentially non “cross-resistant drugs with activity in the platinum-resistant setting include

liposomal doxorubicin

,

paclitaxel,

docetaxel

,

topotecan

,

gemcitabine

, or

oral etoposide

. Slide128

Liposomal doxorubicin

is often well tolerated in doses of 40 mg/m

2

given every 4 weeks, although the development of palmer-planar erythrodysesthesia (

hand-foot syndrome

) or

mucositis

may require dose reductions and treatment delays.

Topotecan

may cause significant

myelosuppression

and

fatigue

, although this agent is generally well tolerated through the use of weekly dosing schedulesSlide129

Unfortunately, the likelihood of obtaining a response to any of these agents in the platinum-resistant setting is less than 20%, responses are generally short lived (median

PFS in the range of 4 to 6 months

), and they tend to become progressively shorter with each subsequent regimen.Slide130

Bevacizumab

Randomized data in metastatic colorectal, breast, and lung cancers have shown a survival advantage for the use of this drug in combination with chemotherapy.

As a single agent, bevacizumab has been shown by the GOG to induce

responses in 18%

of patients with relapsed ovarian cancer (either platinum sensitive or platinum resistant, treated with less than or equal to two prior regimens), with 39% of patients progression-free at 6 months.

Slide131

the risk of bowel perforation with bevacizumab in the recurrent ovarian cancer setting might be related to a

higher number of prior treatment regimens,

radiographic evidence of

bowel wall involvement

, or

bowel obstruction

These and other possible risk factors for this complication will require further evaluation.Slide132

No approved

ET743 (trabectedin)

halichondrin B

pertuzumab

EpothilonesSlide133

Secondary cytoreductive surgery

an attempt at surgical debulking of disease at the time of relapse and is performed in selected patients prior to the administration of second-line chemotherapy.

a successful secondary cytoreduction: no gross residual disease greater than 1 cm in diameter,

However, it is possible that the ability to perform a successful secondary cytoreduction may simply identify those patients with

biologically less aggressive disease

or those with a

lower tumor burden

at the time of relapse. Slide134

Secondary cytoreductive surgery

relapse within 12 months after completion of first-line therapy, especially if they have ascites, are generally not candidates for this procedure.

late relapses (i.e., greater than 2 to 3 years after finishing chemotherapy)

apparently isolated relapses

may experience a prolonged disease-free interval after successful secondary cytoreduction followed by additional chemotherapy.Slide135

Combination Chemotherapy1519

cervix 4b

Most reports of combination chemotherapy for carcinoma of the cervix have described small, uncontrolled phase II trials of drug combinations

. However, the results of two phase III randomized trials, published in 2004 and 2005, have provided the first solid evidence that combination chemotherapy can improve both progression-free survival (cisplatin plus paclitaxel vs. single-agent cisplatin,

272

cisplatin plus topotecan vs. single-agent cisplatin

273

) and overall survival (cisplatin plus topotecan

273

) when it is administered as treatment for recurrent or metastatic carcinoma of the cervix

. In the cisplatin-topotecan trial, the combination regimen (cisplatin 50 mg/m

2

day 1 and topotecan 0.75 mg/m

2

days 1 to 3 every 3 weeks) was associated with a median overall survival of 9.4 months, compared with 6.5 months (P = .17) for single-agent cisplatin.

273

An ongoing GOG phase 3 trial is directly comparing several platinum-based combination chemotherapy regimens in this clinical setting.Slide136

Management of Recurrent Disease1582ovary relapse

 

Two randomized trials have investigated the value of combination chemotherapy compared to single-agent platinum in the setting of potentially platinum-sensitive relapse (PFI greater than 6 months). The

ICON-4 trial

compared combination chemotherapy with paclitaxel and platinum to single-agent platinum in patients with potentially platinum-sensitive disease, with most patients having a PFI of 12 months or greater.

111

This study demonstrated

a statistically significant improvement in overall survival

for the combination regimen, with an absolute difference at 2 years of 7% (P = .023). However, 58% of patients in the single-agent platinum arm never received a taxane as part of first-line therapy, and 69% of patients in the single-agent platinum arm never received a taxane as part of relapse management (i.e., after progression on single-agent platinum). Thus, 40% of patients in the single-agent platinum arm never received a taxane at any point during the course of their disease.

Given the proven survival benefit of taxanes in this disease, the imbalance in the use of taxanes between these two treatment arms makes the results of ICON-4 difficult to interpret.Slide137

Palliative surgery

colostomy

lysis of adhesions

management of small bowel

obstruction

surgery

gastrostomy

tubeSlide138

Surgery generally plays no role in management of patients with a

pseudo-obstructive pattern

due to intra-abdominal carcinomatosis, with infiltration of the myoenteric plexus of the small bowel.

TX :MetoclopramideSlide139

Radiation Therapy

A minority of patients with localized recurrences may experience prolonged survival after WAR or limited-field irradiation. Slide140

RT?

The small number of highly selected patients in these series and the use of multiple concurrent treatment modalities make it difficult to adequately assess whether radiation therapy truly improves long-term outcome in this setting.Slide141

palliation

Symptoms from a growing pelvic mass can cause

pain, bleeding

, and

rectal narrowing

.

Palliative pelvic radiotherapy can provide rapid relief and, in some cases, may prevent or delay the need for diverting colostomy. Doses of

8 to 10 Gy in a single

fraction,

20 Gy in five

fractions,

30 Gy in ten

fractions, or

higher total doses

given in smaller fractions have produced acceptable short-term results, with serious complications in 5% or fewer patients.

Finally, patients with epithelial ovarian cancer may rarely develop isolated cerebral or bone metastases that can sometimes be successfully palliated with radiotherapy.Slide142

Borderline Tumors

Definition and Clinical Features

absence of stromal invasion

low malignant potential (LMP

serosal implants

majority of patients present with early stage diseaseSlide143

The median age : 40 years, 20 years younger than the median age for women with epithelial ovarian cancer.

asymptomatic mass

pelvic pain

Nonspecific GI symptomsSlide144

serous feature:

more common

bilateral in 10% to 20%

mucinous feature

larger than their serous counterparts

infrequently bilateral,

pseudomyxoma peritoneiSlide145

pseudomyxoma peritonei

mucinous borderline ovarian tumor

mucinous ovarian carcinoma

gastrointestinal tumors such as appendiceal mucinous cystadenocarcinoma.

The

mainstay of treatment for pseudomyxoma peritonei is intermittent

surgerySlide146

careful examination of the tissue blocks

The presence of microinvasion

Mucinous borderline tumors are characterized by multiloculated cystic masses, with smooth outer surfaces and areas of papulations and solid thickening on the inner surfaceSlide147

Greater than 90% of patients with early stage borderline tumors are alive at 10 years

more than 50% of patients with advanced disease experience long-term survival.

survival does not appear to be improved by

postoperative adjuvant treatment

with either chemotherapy or radiation

borderline serous tumors may behave more aggressively if they are associated with micropapillary features, and/or invasive implants elsewhere in the peritoneal cavity.Slide148

Patients

with serous borderline tumors

without invasive implants

have expected 10-year survival rates of greater than 95%, whereas those with serous borderline tumors and

invasive implants

have survival rates of approximately 60% to 70% at 10 years

.

Thus, it is possible that micropapillary features portend a poorer prognosis because of their association with invasive implants, although this is still an area of controversy.Slide149

Surgical Management

TAH, BSO,

tumor debulking, and full

staging

Conservative surgery

An appendectomy is considered in patients with suspected mucinous borderline tumors because of its occasional association with a primary appendiceal carcinoma.Slide150

Conservative surgery

with preservation of the uterus, the contralateral ovary and fallopian tube, and in some cases the ipsilateral ovary (i.e., cystectomy)

One of the largest studies found a

12%

recurrence rate for patients treated conservatively compared to

2.5%

for

TAH, BSO.

Recurrences or progression to carcinoma (1.5%) were more common among patients with

invasive implants

or

advanced-stage disease

.Slide151

Borderline ovarian tumors during pregnancy. Slide152

Postoperative Management

Without adjuvant therapy, long-term survival is generally excellent

simple

observation

with

serial examinations

, with radiographic studies as needed to investigate new symptoms or findings on examination.

long-term follow-up

Surgery is the mainstay of treating recurrent disease

Tx multiple recurrences : HT(as tamoxifen

)

CHTSlide153

Germ Cell Tumors of the Ovary

Definition and Clinical Features

2% to 3% of all ovarian cancers

in younger women( early 20s)

It is often possible to cure these malignancies while preserving fertility, Slide154

WHO classification for germ cell tumors of the ovary

Dysgerminoma(

male seminoma

)

Nondysgerminoma

Endodermal sinus tumor (AFP)

Embryonal carcinoma(both AFP and HCG elevation)

Polyembryoma

Choriocarcinoma(HCG)

Immature teratoma

Mature dermoid cyst with malignant transformation

Monodermal and highly specialized

Struma ovarii

Carcinoid

Struma ovarii and carcinoid

Others

Mixed formsSlide155

Abdominal pain,

abdominal pain can be severe(hemorrhage, rupture, or ovarian torsion)

distension,

pelvic fullness,

urinary symptomsSlide156

rapid growth

palpable adnexal mass

TVU, which may show a complex cyst comprised of solid and cystic region

(AFP)

(HCG)Slide157

Pure immature teratoma : normal levels of AFP and HCG, although the AFP may be elevated in 30% of cases.

Mature cystic teratoma (dermoid cyst), a benign germ cell tumor, usually have normal levels of AFP and HCG. Slide158

choriocarcinoma

hyperthyroidism

mature cystic teratoma

hyperthyroidism

a Coomb's positive hemolytic anemiaSlide159

Germ cell tumors

60% to 70% are stage I at diagnosis

Stages II and IV tumors are relatively uncommon

stage III disease accounts for about 25% to 30% of tumors. Slide160

Bilateral ovarian involvement

dysgerminoma and mature cystic teratoma may be bilateral in 10% to 15% of cases

More advanced disease may involve

retroperitoneal lymph nodes

and

multiple peritoneal surfaces

, although ascites is infrequent.Slide161

Hematogenous spread to the liver, lung, and brain can be observed, especially with choriocarcinomaSlide162

Surgical Management

1.برداشت یک تخمدان

2.برداشت یک تخمدان و سیستکتومی یا بیوپسی تخمدان دیگر

3.درمان روتین

second-look

operations

In some patients whose tumor contains teratomatous elements, however, a second-look procedure may be beneficialSlide163

Postoperative Management of Dysgerminoma

stage IA disease can be observed without further postoperative

treatment

.

Approximately

15% to 25% of such patients will experience recurrence, although salvage chemotherapy is almost

always

successful

Dysgerminoma in patients with higher than stage IA disease is typically treated with

platinum-based

chemotherapy

PVB ,BEPSlide164

Postoperative Management of Nondysgerminoma

Tx:

Surgery followed by combination chemotherapy, as even patients with early stage nondysgerminomas have a significant risk of relapse that can be reduced by postoperative adjuvant therapySlide165

Current regimen of choice is BEP

Toxicities

bleomycin-induced pulmonary damage

etoposide-induced leukemia,

platinum-induced neuropathy and nephropathy.

Many patients will regain fertility after completion of treatment

However, patients are known to be at increased risk for development of premature menopause following chemotherapy.Slide166

In pure immature teratoma

with

stage IA, grade 1

(

5-ys :90%), there is no evidence to suggest that CHT improves outcome

Patients with stage IA, grade 2 and 3 immature teratoma have a higher relapse rate that generally warrants consideration of postoperative chemotherapySlide167

The Children's Oncology Group (COG) is currently studying the approach of surgery followed by surveillance in patients with stage I germ cell tumors of the ovary. Although this strategy appears to be potentially promising, further study, particularly in adult patients, is warranted to ensure its safety and efficacySlide168

Sex Cord-Stromal Tumors

Definition and Clinical Features

Patients often present with stage I disease

long-term follow-up

Granulosa cell tumors are the most common

typeSlide169

Sex cord-stromal tumors such as granulosa cell tumors may secrete:

Estradiol

inhibin

mullerian inhibitory substanceSlide170

The hormonal manifestations :

precocious puberty

amenorrhea or abnormal menses, intra-abdominal hemorrhage that mimics an ectopic pregnancy

postmenopausal bleeding due to endometrial hyperplasia (or a separate uterine carcinoma)Slide171

Surgical staging

of sex cord-stromal tumors is the same as that for epithelial ovarian cancer.

Surgical management

of sex cord-stromal tumors is based on the stage of the tumor as well as the age of the patient. Slide172

premenarchal women or patients presenting in the reproductive years with stage I disease

In women who have completed childbearing, Slide173

Postoperative Management

Stage is the most important prognostic factor,

10-year survivals of over 85% for stage I

50% to 65% for stage II disease

17% to 33% for stages III and IV.Slide174

Tx

stages II to IV sex cord-stromal tumors are reasonable candidates for additional therapy after initial surgery

,

although the survival benefit of such therapy has not been

proven

Approximately 30% to 50% of patients will respond to

platinum-based chemotherapy

, Slide175

cyclophosphamide, doxorubicin, and cisplatin (CAP)

PVB,

BEP

paclitaxel and carboplatin Slide176

BEP

bleomycin-induced lung damage,

etoposide-induced leukemia

, renal dysfunction, hypertension

Raynaud's phenomenonSlide177

in the older patient

EP (without bleomycin)

in the young patient

paclitaxel and carboplatin Slide178

(

S1)

Who

has higher risk?

large tumor size (greater than 10 to 15 cm in diameter)

high mitotic count (greater than 4 to 10 mitoses per 10 high-power fields).

Rupture

surface involvement

Age

Slide179

Relapse

may recur several years after the original diagnosis

abdominal or pelvic discomfort, a mass on pelvic examination, or an asymptomatic rise in serum tumor markers such as estradiol or inhibin

hematogenous spread to the liver, lung, or boneSlide180

Tx Relapse :

S-CHT or RT

surgical

resection

postoperative therapy such as

platinum-based

treatment ,resistant to platinum-based chemotherapy, in which case

single-agent paclitaxel

, or the use of

progestational agents or leuprolide

, may be considered.

radiotherapy.

In cases in which the recurrence is isolated and can be encompassed in a radiation field, older literature suggests that radiation therapy may be of value for granulosa cell histology. Slide181

Primary Peritoneal Serous Carcinoma

PPSC is a distinct clinical entity that resembles ovarian cancer histologically, clinically, and in its response to treatment

multifocal fashion

PPSC occurs at a higher incidence in patients with germline mutations in BRCA1 and BRCA2,Slide182

differential diagnosis

epithelial ovarian carcinoma

metastatic breast cancer(expression of GCDFP)

peritoneal mesothelioma

gastric or pancreatic cancers, and hepatobiliary tumors.Slide183

Dx

an exploratory laparotomy is usually necessary to establish the histologic diagnosis and to perform tumor cytoreduction.

almost all patients with PPSC present with stages III or IV disease.

Tx

are the same as those for epithelial ovarian cancer.

Px

is likely to be the same, as for epithelial ovarian cancer.Slide184

There is currently no effective screening procedure that enables early detection of PPSC in this clinical setting.Slide185

Fallopian Tube Cancer

papillary serous adenocarcinoma or other mullerian histologies such as endometrioid tumors

A minority are bilateral

the majority are confined to the tubes and pelvic structures.

a higher propensity for retroperitoneal lymph node spread

Advanced stage disease may occur with a pattern of intraperitoneal disseminationSlide186

Postmenopausal vaginal bleeding

colicky lower abdominal pain

intermittent abdominal pain and leucorrhea are common presentations

.

Occasionally, a Papanicolaou smear revealing abnormal glandular cells with negative cervical or endometrial findings Slide187

DDX

metastatic

ovarian carcinoma

the

main criterion used to establish the diagnosis of a primary fallopian tube carcinoma is histologic evidence of

a transition between in situ carcinoma and invasive malignancy within the fallopian tube epithelium.

tubo-ovarian

carcinoma.Slide188

Survival is partly dependent on the

depth of invasion

of the primary lesion.

For intramucosal lesions, the 5-year survival is 91%, compared with 53% for tumors that invade the muscular wall, and less than 25% for tumors that have penetrated the tubal serosa.

Histologic differentiation

and

lymphatic capillary space involvement

may also have prognostic significance.Slide189

surgical management

identical to that of patients with epithelial ovarian cancer.

Postoperatively :

paclitaxel and carboplatin

in patients with fallopian tube carcinoma that has spread beyond the tube.

reasonable candidates for postoperative adjuvant treatment, based on features :

muscle wall invasion,

serosal extension,

high-grade histology