Ovarian tumors

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Ovarian tumors

• STAGING MANAGEMENT

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TREATMENT OF OVARIAN CYSTS AND BENIGN TUMORS

• Ovarian cysts lt 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.

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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.

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LAPAROSCOPY

• Ovarian cyst and benign tumors can also be
  resected by this technique

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Staging The Federation Internationale de
Gynecologie et d'Obstetrique (FIGO) and the
American Joint Committee on Cancer (AJCC) have
designated staging.
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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.

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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.

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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.

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Stage IV ovarian cancer

• tumours involving 1 or both ovaries with distant
  metastasis. Parenchymal liver metastasis equals
  stage IV.

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Management
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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,

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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

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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.

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SURGERY
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Treatment of Ovarian Epithelial Cancer
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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.

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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.

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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.

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Stage IV

• CYTOREDUCTIVE SURGERY/DEBULKING
• surgery to remove as much of the tumor as
  possible.
• Most researchers consider residual disease of lt1
  cm to be optimal debulking surgery. followed by
  combination chemotherapy

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Trial of 146 patients with stage III and IV
ovarian cancer treated with cisplatin at
Rosewell park Cancer Institute
SIZE OF RESIDUAL DISEASE SURVIVAL SURVIVAL
SIZE OF RESIDUAL DISEASE 5 YEARS 8 YEARS
lt1 CM 56 42
1-2 CMS 19 10
gt2 CMS 13 8.7
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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

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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.

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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

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• 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.

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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.

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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

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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.

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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.

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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.

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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.

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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.

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REGIMENS IN OVARIAN CANCER
REGIMEN DOSE
CP CISPLATIN PACLITAXEL 75 mg/sq.m 135-175mg/sq.m
CT CARBOPLATIN PACITAXEL AUC5 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
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REGIMEN FOR NON-EPITHELIAL TUMORS
VAC Vincistrene
VBC
BEP
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SIDE EFFECTS
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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

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• 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)

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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.

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• 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.

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Recurrent Ovarian Epithelial Cancer

• Detection of Recurrent Disease
• Second-Look Surgery

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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

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The findings of second-look surgery are

• microscopically positive (grossly negative, but
  microscopically positive)
• macroscopically positive (grossly and
  pathologically positive)

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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)

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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.

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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.

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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.

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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.

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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.

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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.

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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.

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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.

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