DIAGNOSIS, TREATMENT AND FOLLOW-UP IN AREAS OF LIMITED RESOURCES

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DIAGNOSIS, TREATMENT AND FOLLOW-UP IN AREAS OF
LIMITED RESOURCES
Gestational Trophoblastic Lesions

• Virach Wootipoom, MD
• Prince of Songkla University
• Songkhla, Thailand

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Limited resources

• Gynecologic Oncologists
• Laboratory (hCG)
• Imaging
• Chemotherapy
• Radiotherapy
• Surgery

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Incidence of hydatidiform mole from selected
studies
Lancet Oncol 2003 4 67078
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Ratios of choriocarcinoma from selected studies
Lancet Oncol 2003 4 67078
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Age-standardised incidence rates of
choriocarcinoma per 100 000 women from
cancerregistry- based statistics in different
areas of the world.
Lancet Oncol 2003 4 67078
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GTD variation

• The reason for this variation is not understood
• women over 40 years having at least a fivefold
  increase in risk.
• previous molar is a predisposing factor

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GTD in South-East Asia

• GTD used to be a common gynecological problem in
  South-East Asian countries.
• The true incidence is unknown because of the lack
  of a tumor registry in many countries.

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DIAGNOSIS, TREATMENT AND FOLLOW-UP IN AREAS OF
LIMITED RESOURCES

• Gynecologic Oncologists
• Laboratory (hCG)
• Imaging
• Chemotherapy
• Radiotherapy
• Surgery

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Thailand

• Population (millions) . 63
• Provinces . 76
• Gynecologic Oncologists .. 110
• Fellowship training centers . 9
• Fellowship Training (years) . . 2
• Society . TGCS

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Hydatidiform mole
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Diagnosis of HM

• Ultrasound has replaced all other noninvasive
  means for diagnosis.
• Ultrasound hCG is suggestive.
• Today, US and hCG are available in nearly every
  areas of limited resources.

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Management of HM

• patients should be monitored with
• serum quantitative hCG values
• CBC
• chest X-ray
• coagulation tests
• renal and liver function tests
• Mole should be evacuated as soon as possible.

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Management of HM

• Suction curettage
• preferred method of evacuation.
• Hysterectomy
• an alternative treatment in selected cases.
• reduces malignant postmolar sequelae.
• risk of postmolar GTN remains 35
• these patients should be monitored
  postoperatively with serial hCG levels.

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Prophylactic chemotherapy

• May be appropriate for some specific
  circumstances in areas of limited resources
• High-risk cases

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Limpongsanurak S. Prophylactic actinomycin D for
high-risk complete hydatidiform mole. J
Reprod Med 2001461106

• High-risk criteria
• Initial hCG gt 100,000 mIU/mL
• Size gt date
• Theca lutein cysts gt 6 cm
• Maternal age gt 40
• Associated medical problems (toxemia,
  hyperthyroid, embolization, DIC)

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Limpongsanurak S. Prophylactic actinomycin D for
high-risk complete hydatidiform mole. J Reprod
Med 2001461106

• one course of Actinomycin-D given.
• Result 72 decrease in malignant sequelae (14
  VS 50)
• Prophylaxis may be beneficial in high-risk cases
  who cannot be followed closely.
• considered in selected patients or special
  situations (poor compliance).

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Surveillance After Evacuation

• Serial quantitative serum hCG
• 48 hours of evacuation
• baseline values (5 mIU/mL)
• every 12 weeks, then at 1-2 month intervals for
  612 months.
• Reliable contraception recommended during hCG
  surveillance.

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Rationale for monitoring

• Identifify patients at risk of postmolar
  malignant GTN.
• almost all malignant sequelae occur within 6
  months of evacuation.

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Role of general OB-GYN

• They should be able to manage HM
• diagnosis of postmolar GTN.
• evaluating patients risk for referral.
• Currently, suction curettage and hCG monitoring
  for postmolar GTN are available in nearly every
  areas of limited resources.

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PSU Management of HM(January 2002 - April 2006)

• 33 complete HM
• remission 16 (64)
• low-risk GTN 9 (36)

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Gestation Trophoblastic Neoplasia (GTN)
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GTN Staging/classification

• FIGO staging system of GTN
• 1982 anatomically based
• 1992 include two prognostic factors (Bagshawe
  1976, modified by WHO in 1983)
• 2000 FIGO revised GTN staging/ classification,
  adopted in 2000 and published in 2002 (ISSGTD,
  IGCS, FIGO)
• Anatomical staging into I-IV
• scoring system modified from WHO

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FIGO
Anatomical staging
UICC
ClinicalMorphological classn
FIGO
New anatomical substage
Hammond
Clinical classn
1967
1973
1976
1982
1983
1992
2000
Bagshawe
Revised FIGO
Prognostic scoring system
anatomical staging Modified-WHO-scoring
WHO
Modified Bagshawe
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4 major consensus statements

• The term GTN is recommended for abnormal
  gestational trophoblastic proliferation that
  required Rx for potential of malignancy.
• The diagnostic criteria of GTN following HM.
• The recommendation of investigative tools.
• The use of 2 risk groups instead of 3 as
  recommended by WHO
• low-risk group (score 6)
• High-risk group (score 7)

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Criteria for the diagnosis of postmolar GTN Criteria for the diagnosis of postmolar GTN
1 Plateau of hCG over a period of 3 weeks (day 1, 7, 14, 21)
2 Rising of hCG over a period of 2 weeks (days 1, 7, 14)
3 hCG remains elevated for 6 months
4 Histologic diagnosis of choriocarcinoma
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Diagnostic criteria

• Mostly based on
• History taking
• Serum ß-hCG
• Chest X-ray
• Ultrasound
• All are available in area of limited resources

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• Current FIGO guidelines for the diagnosis and
  staging of GTN allow uniformity for reporting
  results of treatment.
• It is important to individualize treatment of
  patients with malignant GTN based on risk factors
• Single agent therapy for low-risk.
• Multiagent therapy for high-risk.

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FIGO 2000 staging and classification of GTN FIGO 2000 staging and classification of GTN
FIGO Anatomical Staging FIGO Anatomical Staging
Stage I Disease confined to the uterus
Stage II GTN extends outside of uterus, but is limited to the genital structures (adnexa, vagina, broad ligament)
Stage III GTN extends to the lungs, with or without known genital tract involvement
Stage IV All other metastatic sites
Modified WHO Prognostic Scoring System as Adapted by FIGO Modified WHO Prognostic Scoring System as Adapted by FIGO Modified WHO Prognostic Scoring System as Adapted by FIGO Modified WHO Prognostic Scoring System as Adapted by FIGO Modified WHO Prognostic Scoring System as Adapted by FIGO
scores 0 1 2 4
Age lt40 40 - -
Antecedent pregnancy H-Mole Abortion term -
Interval (mo) from index pregnancy lt4 4 - 6 7 - 12 gt12
Pretreatment hCG (mIU/mL) lt103 103 - 104 gt104 - 105 gt105
Largest tumor size (including uterus) - 3 - 4 cm 5 cm -
Site of metastases - kidney, spleen GI tract brain, liver
Number of metastases - 1 - 4 5 8 gt8
Previous failed chemotherapy - - Single drug two or more drugs
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Tochareonvanich, Chichareon S, Wootipoom V, et
al. Correlation of risk categorization in
gestational trophoblastic tumor between old and
new combined staging and scoring system. J Obstet
Gynaecol Res 20032920-27

• Comparing the treatment pattern and the outcome
  among the different classifications, we found
  that all classifications were equivalent without
  compromising the outcome.

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FIGO 2000

• User friendly
• Feasible and practical in areas of limited
  resources, using only
• complete history taking
• serum ß-hCG
• chest X-ray
• ultrasound

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Investigative Tools to Diagnose Metastases

1. Chest X-rays are appropriate for lung metastases
   and for counting the number of metastases.
2. Liver metastases may be diagnosed by US or CT
   scan.
3. Brain metastases may be diagnosed by MRI or CT
   scan.

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The diagnostic problem in the areas of limited
resources may be only lacking of CT or MRI for
detection of brain matastasis
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• High-risk sites of metastases rarely occur
  without pulmonary metastases.
• (Hunter V, et al. Cancer 199065164750)
• Cerebral metastases are rare unless there are
  concurrent lung or vaginal metastases.
• Therefore CT or MRI brain scans may be omitted in
  those patients without vaginal or lung metastases
  on chest X-ray.
• (TY Ng, LC Wong. Best Practice Research
  Clinical Obstetrics and Gynaecology
  20031793903)

NOTE 40 postmolar GTN with negative chest
X-rays have pulmonary lesions detected by CT
scan, but small pulmonary metastases do not
affect survival.
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Treatment of GTN in the areas of limited resources

• Treatment should be limited to low-risk GTN
  (score 6).
• Patients with score 7 should be referred to
  specialized center.

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• Chemotherapy for low-risk nonmetastatic and
  low-risk metastatic GTN

1 Methotrexate 1 mg/kg intramuscular (IM) on days 1, 3, 5, and 7, with folinic acid 0.1 mg/kg IM on days 2, 4, 6, and 8 repeat every 7 days if possible (10 primary failure rate).
2 Methotrexate 0.4 mg/kg (2025 mg) intravenous (IV) or IM daily for 5 days repeat every 7 days if possible. If no response, increase dose to 0.6 mg/kg or switch to actinomycin D (20-25 primary failure rate).
3 Methotrexate 40 mg/M2 IM weekly (30 primary failure rate).
4 Actinomycin D 12 µg/kg IV daily for 5 days repeat every 7 days (8 primary failure rate).
5 Pulse actinomycin D 1.25 mg/M2 repeat every 2 weeks (20 primary failure rate).
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• At PSU, we treat low-risk GTN patients with
  weekly methotrexate regimen.
• 40 mg/m2 given intramuscularly every week.
• This is the most cost-effective regimens when
  feasibility, efficacy, toxicity, and cost are
  taken into consideration.
• Chemotherapy is continued until normal hCG is
  achieved, and one additional course is given.

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• If hCG values have not decreased by 10,
  treatment should be changed to alternative
  single-agent regimen.
• In case of failure, the patient should be
  referred to specialized center.
• Cure rate for low-risk disease 100, with
  recurrence rates less than 5.

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Conclusion
In areas of limited resources

• Management of Hydatidiform mole
• Appropriate treatment is avialable.
• Prophylactic chemotherapy may be considered in
  high-risk cases.

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Conclusion
In areas of limited resources

• Management of GTN
• Based on FIGO 2000
• Low-risk GTN (score 6) can be managed.
• Weekly methotrexate is a cost effective
  chemotherapy.

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Conclusion
In areas of limited resources

• Management of GTN
• Based on FIGO 2000
• High-risk GTN (score 7) should be referred to
  specialized center.

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GTD at PSU

• Hydatidiform Mole (HM)
• 2.8/1,000 deliveries
• Gestation trophoblastic neoplasia (GTN)
• 4.6/1,000 deliveries

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PSU CPG for the Management of GTN
GTN
Investigate, stage, risk-score (FIGO 2000)
hCG, CBC, BUN, Cr, LFT, TFT, Coagulogram, CXR,
US, CT/MRI in ve CXR
Stage I-III low-risk (6)
Stage IV any score or Stage I-III, high-risk (7)
Multi-agent chemoRx (EMA-CO)
Plateau or ? hCG
Single-agent chemoRx (weekly MTX)
Plateau or rising hCG
ve
Investigate
-ve hCG
-ve hCG
EMA-CE
-ve
Act-D
Investigate
Stage I
Stage II-III
Plateau or ? hCG
2 additional courses
-ve
Plateau or ? hCG
one addition course
Weekly hCG until ve X 3

• hCG q 1mo. x 12 mo., OCP, pregy if need
• CXR q 3 mo. (in lung metas)

• hCG q 1mo. X 24 mo., OCP, pregy if need
• CXR q 3 mo. (lung metas)

Salvage therapy
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Management of GTN at PSU (January 2002 - April
2006)

• 57 GTN
• Low-risk GTN (39 cases)
• Remission 100
• High-risk GTN (18 cases)
• Remission 77

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The most important factors to assure successful
therapy

• Experience with gestational trophoblastic
  lesions
• Reliable hCG assay
• Experience with chemotherapy
• Patients compliance

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welcome to the next IGCS 2008
Thank you for your attention