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Ovarian tumors

STAGING & MANAGEMENT



TREATMENT OF OVARIAN CYSTS AND
BENIGN TUMORS

Ovarian cysts < 6 cms usually regress by absorption or spontaneous
rupture and the patient may be managed conservatively over 2
menstrual cycles with monthly rectovaginal examination.

If regression fails to occur, assessment is indicated

Diagnostic tests include laboratory blood studies and pelvic
examination. Usually, ultrasound studies with and without blood
flow measurements to the involved ovary are used for diagnosis and
to help determine the best therapy.

Some tumors require surgery to diagnose accurately, ruling out
malignancy, or to treat. If one ovary must be removed, normal
conception and childbirth is possible as long as a normal ovary
remains on the other side.
Medication


Female hormones or clomiphene may be prescribed.
These help shrink or destroy some tumors. Oral
contraceptives are often used as the first step in
treatment.
LAPAROSCOPY



Ovarian cyst and benign tumors can also be resected by
this technique
Staging The Federation Internationale
de Gynecologie et d'Obstetrique
(FIGO) and the American Joint
Committee on Cancer (AJCC) have
designated staging.
Stage I ovarian cancer
limited to the ovaries.
Stage IA: tumour limited to 1 ovary, the
capsule is intact, no tumour on ovarian surface
and no malignant cells in ascites or peritoneal
washings.
Stage IB: tumour limited to both ovaries,
capsules intact, no tumour on ovarian surface
and no malignant cells in ascites or peritoneal
washings.
Stage IC: tumour is limited to 1 or both ovaries
with any of the following: capsule ruptured,
tumour on ovarian surface, malignant cells in
ascites or peritoneal washings.
Stage II ovarian cancer
tumors involving 1 or both ovaries with pelvic
extension and/or implants.
Stage IIA: extension and/or implants on the
uterus and/or fallopian tubes. No malignant
cells in ascites or peritoneal washings.
Stage IIB: extension to and/or implants on
other pelvic tissues. No malignant cells in
ascites or peritoneal washings.
Stage IIC: Pelvic extension and/or implants
(stage IIA or stage IIB) with malignant cells in
ascites or peritoneal washings.
Stage III ovarian cancer
tumours involving 1 or both ovaries with microscopically
confirmed peritoneal implants outside the pelvis. Superficial
liver metastasis equals stage III.

Stage IIIA: microscopic peritoneal metastasis beyond
pelvis (no macroscopic tumour).
Stage IIIB: macroscopic peritoneal metastasis beyond
pelvis less than 2 cm in greatest dimension.
Stage IIIC: peritoneal metastasis beyond pelvis greater
than 2 cm in greatest dimension and/or regional lymph
node metastasis.
Stage IV ovarian cancer



tumours involving 1 or both ovaries with distant
metastasis. Parenchymal liver metastasis equals
stage IV.
Management
Treatment Options
The treatment of ovarian cancers based on the
stage of the disease which is a reflection of the
extent or spread of the cancer to other parts of
the body.
It also depends on histologic cell type,
and the patient's age and overall
condition.
There are basically three forms of treatment of
ovarian cancer:
surgery
Chemotherapy
radiation treatment,
GENERAL GUIDELINES:

Standard treatment is surgery (staging and optimal
debulking) followed by adjuvant chemotherapy in most
cases. Even if optimal surgery is not possible, removing
as much tumor as possible will provide significant
palliation of symptoms.

Borderline lesions may be treated with conservative
surgery
GENERAL GUIDELINES:

Germ cell tumors are treated with surgery and multi-
agent chemotherapy in most cases

Advanced epithelial ovarian cancer is very sensitive to
chemotherapy with responses in the range of 70-80% to
first-line chemotherapy. The majority, however, relapse
and ultimately die of chemotherapy-resistant disease.
Second-line chemotherapy to date is disappointing in all
forms of epithelial ovarian cancer with virtually no
chance of successful second-line treatment following
failure of initial regime.
SURGERY
Treatment of Ovarian
Epithelial Cancer
Stage I

Generally a total abdominal hysterectomy, removal of
both ovaries and fallopian tubes, omentectomy, biopsy
of lymph nodes and other tissues in the pelvis and
abdomen,is done. Young women whose disease is
confined to one ovary are often treated by a unilateral
salpingo-oophorectomy without a hysterectomy and
removal of the opposite ovary being performed

Depending on the pathologist's interpretation of the
tissue removed, there may be no further treatment if the
cancer is low grade, or if the tumor is high grade the
patient may receive combination chemotherapy.
Stage II


Treatment is almost always hysterectomy and bilateral
salpingo-oophorectomy as well as debulking of as much
of the tumor as possible and sampling of lymph nodes
and other tissues in the pelvis and abdomen that are
suspected of harboring cancer. After the surgical
procedure, treatment may be one of the following: 1)
combination chemotherapy with or without radiation
therapy or 2) combination chemotherapy.
Stage III



Treatment is the same as for Stage II ovarian cancer.
Following the surgical procedure, the patient may either
receive combination chemotherapy possibly followed by
additional surgery to find and remove any remaining
cancer.
Stage IV
CYTOREDUCTIVE SURGERY/DEBULKING:

surgery to remove as much of the tumor as
possible.

Most researchers consider residual disease of
<1 cm to be optimal debulking surgery.
followed by combination chemotherapy
Trial of 146 patients with stage III and IV ovarian
cancer treated with cisplatin at Rosewell park
Cancer Institute:
SIZE OF RESIDUAL DISEASE
SURVIVAL

5 YEARS 8 YEARS
<1 CM 56% 42%
1-2 CMS 19% 10%
>2 CMS 13% 8.7%
CHEMOTHERAPY

Prolongs remission and survival

Also used for palliative treatment in advanced n
recurrent disease

Administered in all cases beyond stage Ia

Earlier single agents were used, nowadays combination
therapy is favoured
CHEMOTHERAPY
No chemotherapeutic agent kills all cancer cells in one
treatment ,Tf treatment needs to be repeated several
times

All agents used should be active against that particular
tumor

should have different modes of action to avoid drug
resistance n should have differenr mechanisms of
toxicity.
CHEMOTHERAPY

This allows each of them to be used as nearv to the full
dose as possible.

Drugs are given at 3 weeks intervals

Intraperitoneal chemotherapy is also done


The initial treatment of ovarian cancer is called first-
line therapy.

If the cancer continues to grow with first-line therapy or
returns after first-line therapy, additional treatment,
called second-line therapy, may be administered.

If the tumor continues to grow after second-line
therapy, the next therapy is called third-line therapy,
and so on.
First-Line Chemotherapy

First-line chemotherapy for ovarian cancer typically
consists of two drugs given together. The combination
=paclitaxel + platinum drugeither carboplatin or
cisplatin.

Select women may benefit from administration of
chemotherapy directly into the abdomencalled
intraperitoneal therapyin addition to conventional
intravenous administration.


Second-Line Chemotherapy

The choice of drugs for second-line therapy depends
largely on which drugs were administered for first-line
therapy and how long it has been since the first-line
therapy was stopped.

chemotherapy drugs) for the treatment of ovarian
cancer that has returned:
GEMZAR (gemcitabine HCl for injection) plus another
chemotherapy, carboplatin, is indicated ,6 months after
their first-line therapy;
Second-Line Chemotherapy


Hycamtin (topotecan HCl for injection) is indicated as a
single agent (one drug) for the treatment of ovarian
cancer upon failure of first-line therapy;

and Doxil (doxorubicin HCl liposome injection) is
approved for use to treat women whose cancer has
returned following first-line therapy.



NICE guidelines for the use of
chemotherapy
It is recommended that paclitaxel in combination with
a platinum-based compound or platinum-based
therapy alone (cisplatin or carboplatin) are offered as
alternatives for first-line chemotherapy (usually
following surgery) in the treatment of ovarian cancer.

When relapse occurs after an initial (or subsequent)
course of first-line chemotherapy, additional courses
of treatment should be considered, using different
treatment options.
NICE guidelines for the use of
chemotherapy (contd..)
The following definitions are used by NICE:
Platinum-sensitive ovarian cancer: disease that responds to first-line
platinum-based therapy but relapses 12 months or more after
completion of initial platinum-based chemotherapy.

Partially platinum-sensitive ovarian cancer: disease that responds to
first-line platinum-based therapy but relapses between 6 and 12
months after completion of initial platinum-based chemotherapy.

Platinum-resistant ovarian cancer: disease that relapses within 6
months of completion of initial platinum-based
chemotherapy.Platinum-refractory ovarian cancer: disease that does
not respond to initial platinum-based chemotherapy.
NICE guidelines for the use of
chemotherapy (contd)
Paclitaxel in combination with a platinum-based compound
(carboplatin or cisplatin) is recommended as an option for the
second-line (or subsequent) treatment of women with platinum-
sensitive or partially platinum-sensitive advanced ovarian cancer,
except in women who are allergic to platinum-based
compounds.
Single-agent paclitaxel is recommended as an option for the
second-line (or subsequent) treatment of women with platinum-
refractory or platinum-resistant advanced ovarian cancer, and
for women who are allergic to platinum-based compounds.
PLDH (pegylated liposomal doxorubicin hydrochloride) is
recommended as an option for the second-line (or subsequent)
treatment of women with partially platinum-sensitive, platinum-
resistant or platinum-refractory advanced ovarian cancer, and
for women who are allergic to platinum-based compounds.
NICE guidelines for the use of
chemotherapy (contd.)


Topotecan is recommended as an option for second-line
(or subsequent) treatment only for those women
with platinum-refractory or platinum-resistant
advanced ovarian cancer, or those who are allergic
to platinum-based compounds, for whom PLDH and
single-agent paclitaxel are considered inappropriate.
REGIMENS IN OVARIAN CANCER
REGIMEN DOSE
CP CISPLATIN
PACLITAXEL
75 mg/sq.m
135-175mg/sq.m
CT CARBOPLATIN
PACITAXEL
AUC=5
135-175mg/sq.m
DC CISPLATIN
CYCLOPHOSPHAMIDE
75mg/sq.m
750mg/sq.m
CAP CYCLOPHOSPHAMIDE
DOXORUBICIN
CISPLATIN
600mg/sq.m
50mg/sq.m
75mg/sq.m
BEP BLEOMYCIN
ETOPOSIDE
CISPLATIN
10mg/sq.m x 3 days
20mg/sq.m x 5days
100mg/sq.m
REGIMEN FOR NON-EPITHELIAL TUMORS
VAC Vincistrene


VBC
BEP
SIDE EFFECTS
While chemotherapy drugs kill cancer cells, they also
damage some normal cells, causing side effects. These side
effects will depend on the type of drugs given, the amount
taken, and how long treatment lasts. Temporary side
effects might include the following:
nausea and vomiting
loss of appetite
hair loss
hand and foot rashes
kidney or nerve damage
mouth sores

an increased chance of infection (from a shortage of
white blood cells)

bleeding or bruising after minor cuts (from a shortage of
platelets)

tiredness (from low red blood cell counts)

RADIOTHERAPY:

Now, has a very small role since platinum based
protocols and paclitaxel have improved the median
survival.


-However it can be used as a palliative treatment for
metastatic bone or brain lesions or of localized
recurrence to alleviate the pain.
Also used in recurrent germ cell tumors especially
dysgerminomas which is very radiosensitive.

Radioactive isotopes of gold-Au198 and phosphorus-P32
have been used intraperitoneally along with external
radiotherapy.

However theres no improvement in survival rate.

High incidence of bowel complications have been noted.
Recurrent Ovarian Epithelial
Cancer


Detection of Recurrent Disease

Second-Look Surgery
Second-Look Surgery
The use of second-look surgery can help diagnose and
manage ovarian cancer.

evidence of enhanced survival after this procedure is
lacking.

It is defined as re-exploration n patients with advanced
stage III and stage IV ovarian cancer after a standard
course of chemotherapy have no clinical, biochemical, ro
radiologic evidence of disease
The findings of second-look surgery are:

microscopically positive (grossly negative, but
microscopically positive)


macroscopically positive (grossly and pathologically
positive)
Treatment of Recurrent Cancer


Patients who develop recurrent cancer despite surgery
and primary chemotherapy, and will be given salvage
chemotherapy, may be placed into one of three
groups (A-C):
GROUP A


are patients resistant to primary therapy and have
shown tumor growth during treatment. This persisting
tumor is considered to be refractory i.e. have absolute
platinum-resistance. Secondary non-cross resistant
chemotherapies or biological therapies should be
considered.
GROUP B


are patients who respond well to initial chemotherapy,
but develop recurrent cancer within months after the
end of primary care. This group with relatively platinum
resistant tumor has an intermediate prognosis.
GROUP C


are patients who showed a good response to primary
chemotherapy, and did not develop recurrent cancer for
more than 6 months after the end of primary treatment.
This group with platinum-sensitive tumor shows the best
responses to re-treatment with a platinum-containing
regimen.


prognosis
Overall 5-year survival in ovarian epithelial carcinoma is low because
of the preponderance of late-stage disease at diagnosis.
Stage I and II: 80-100%
Stage III: 15-20%
Stage IV: 5%
Patients under 50 in all stages have considerably better 5-year
survival than older patients (40% compared to 15%)
Dysgerminomas treated by surgery and radiation have an excellent
cure rate in both early and late-stage disease
Endodermal sinus tumour has poor prognosis.

prevention
Diet: a high-fat diet may play a role in the
aetiology of ovarian cancer.
Oral contraceptives appear to reduce the risk of
ovarian cancer for up to 10 years following
cessation of use. This protective effect appears
to apply to patients with BRCA mutations as
well.
Patients who have used fertility drugs should be
counselled as to their possible increase in risk of
ovarian cancer.

TREATMENT OF BENIGN
TUMORS
Diagnostic tests include laboratory blood studies and pelvic
examination. Usually, ultrasound studies with and without blood
flow measurements to the involved ovary are used for diagnosis and
to help determine the best therapy. Laparoscopy is required in some
cases, and rarely, a CT scan or MRI may be recommended.

Treatment may not be necessary, except to have regular pelvic
examinations so the tumor's growth can be monitored.

Some tumors require surgery to diagnose accurately, ruling out
malignancy, or to treat. If one ovary must be removed, normal
conception and childbirth is possible as long as a normal ovary
remains on the other side.

TREATMENT OF BENIGN
TUMORS


Germ cell tumors are treated with surgery and multi-
agent chemotherapy in most cases

Advanced epithelial ovarian cancer is very sensitive to
chemotherapy with responses in the range of 70-80% to
first-line chemotherapy. The majority, however, relapse
and ultimately die of chemotherapy-resistant disease.
Treatment of Sensitive Cancer
Patients with recurrent chemotherapy-sensitive disease are usually
treated again with primary chemotherapy usually
carboplatin/paclitaxel, but toxicity must also be taken into
consideration.

If carboplatin or cisplatin was used alone for primary therapy, taxol
should be considered for salvage chemotherapy.

For low-volume disease, intraperitoneal chemo- or radiotherapy can
be considered. These patients are also candidates for trials of high
dose chemotherapy with autologous bone marrow support.