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
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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 contraceptivesSlide5Slide6
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 carcinomasSlide12Slide13
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