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In The Name of God. Dr. F Behnamfar MD. Diagnosis and treatment of gestational trophoblastic disease. Gestational Trophoblastic Neoplasia. A spectrum of interrelated conditions originating from placenta: Complete and partial moles Invasive mole Gestational choriocarcinoma

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in the name of god
In The Name of God

Dr. F Behnamfar MD

gestational trophoblastic neoplasia
Gestational Trophoblastic Neoplasia

A spectrum of interrelated conditions originating from placenta:

  • Complete and partial moles
  • Invasive mole
  • Gestational choriocarcinoma
  • Placental Site Throphoblastic Tumor
hydatiform moles
Hydatiform Moles
  • 1 in 1500 pregnancy
  • 1 in 600 therapeutic

abortions

  • 20% will develop malignant sequelae requiring chemotherapy
  • Most will have non-metastatic molar proliferation or invasive moles
  • gestational choriocarcinomas and metastatic disease can develop
complete hydatiform moles
Complete Hydatiform Moles
  • Some diagnosed as missed abortions (early ultrasound without symptoms)
  • most patients have a clinical or ultrasonographic diagnosis of hydatidiform mole
  • Uterine enlargement beyond the expected

gestational age in up to 50%

  • may present with vaginal bleeding or expulsion of molar vesicles
complete hydatiform moles1
Complete Hydatiform Moles
  • complications of molar pregnancy, including pregnancy induced hypertension, hyperthyroidism, anemia, and hyperemesis gravidarum, are more frequently seen among patients with complete moles
  • 15–25% of patients will have theca lutein cysts with ovarian enlargement of more than 6 cm
diagnoses
Diagnoses

usually during the first trimester of pregnancy

  • most common symptom: abnormal bleeding
  • uterine enlargement greater than expected for gestational age
  • absent fetal heart tones
  • cystic enlargement of the ovaries
  • hyperemesis gravidarum
  • Abnormally high level of hCG for gestational age
gestational choriocarcinoma
Gestationalchoriocarcinoma

occurs in approximately 1 in 20,000–40,000 pregnancies

  • 50% after term pregnancies
  • 25% after molar pregnancies
  • remainder after other gestational events

Placental site trophoblastic tumors can develop after any type of pregnancy

molar pregnancy
Molar Pregnancy
  • Usually diagnosed during first trimester
  • Most common symptom abnormal bleeding
  • Ultrasonography has replaced all other diagnostic procedures
  • Findings may be subtle in cases of early complete or partial mole
  • Suction curettage is the best type of uterine evacuation
follow up
Follow up
  • Serial hCG values, as long as decreasing no role for chemotherapy
  • AUB more than 6weeks after any kind of pregnancy should be evaluated with hCG
diagnoses of malignant sequele
Diagnoses of Malignant Sequele
  • Increasing hCG levels (Increase of three values > 10% over 2 weeks ) or plateau (four values ± 10% over 3 weeks )
  • Histologic diagnoses of Choriocarcinoma or invasive mole from uterine currettage
  • Clinical or radiographic evidence of metastases
gestational trophoblastic neoplasia1
Gestational Trophoblastic Neoplasia
  • Staging

Nonmetastatic (I)

Metastatic(II-IV)

  • FIGO Scoring

Low risk (Total score<7)

High risk (Total score>7and =7)

  • Clinical classification of NCI
poor prognosis metastatic gestational trophoblastic disease nci
Poor-prognosis metastaticgestational trophoblasticdisease(NCI)
  • Any risk factor:
  • Long duration (z4 months

since last pregnancy)

  • Pretherapy hCG level z40,000 mIU/ml
  • Brain or liver metastases
  • Antecedent term pregnancy
  • Prior chemotherapy
figo scoring system
FIGO scoring system
  • Age(years)
  • Antecedent pregnancy
  • Interval from index pregnancy (months)
  • Pretreatment human chorionic gonadotropin level
  • Largest tumor size including uterus (cm)
  • Site of metastases
  • Number of metastases identified
  • Previous failed chemotherapy
treatment of low risk gtn
Treatment of low risk GTN
  • Variety of agent :MTX,Actinomycin D ,Etoposide,5FU and Cisplatinum
  • Early hysterectomy shortens the duration and amount of chemotherapy to produce remission
  • Alternative single agent if plateu or increasing hCG
  • Multiagent regimen if alternative single agent failes
  • 100% curable
methotrexate
Methotrexate
  • Li et al,1956,First treatment of metastatic GTN
  • 1964,Bagshawe,administration of folinic acid, reducing toxicity
  • 1976, Bagshawe, mutch better response to single agent MTX for nonmetastatic
  • Other drugs tested, more toxic
chemotherapy
Chemotherapy
  • Single agent MTX therapy

Nonmetastatic

Low risk metastatic

  • Multi agent regimens resistance to MTX initially high risk tumors
mtx single agent protocols
MTX single agent protocols
  • MTX alone, 5days,0.4mg/kg/day
  • MTX alone,one inj. weekly,30 -50mg/m2
  • MTX with folinic acid ,MTX 1mg/kg/day folinic acid 0.1mg/kg/day,every other day,8days regimen
  • MTX with folinic acid ,MTX100mg/m2 IV bolus,followed by 200mg/m2/12h and folinic acid
strategies for further courses
Strategies for further courses
  • Regular administration every 7-14 days
  • Single systematic course, further courses depending on HCG decrease(if plateau or reelevatd
change of chemotherapeutic agent
Change of chemotherapeutic agent
  • Stable hCG for three consecutive weeks
  • Re-elevated hCG
  • Not falling at least one log within 18 days of first treatment
remission and relapse
Remission and Relapse
  • Remission :hCG level within normal range for at least three consecutive weeks
  • Relapse :Rising hCG after remission
mtx toxicity
MTX Toxicity
  • Hepatotoxicity
  • GI disturbances
  • Granulocytopenia
  • Thrombocytopeni
  • Mucositis
results
Results

Failure frequency :18 (28%)

  • Initial resistance 11 (17%)
  • Relapse 0
  • Toxicity 7 (11%)
methods
Methods
  • Retrospective study,1996-2006 Valie-Asr
  • Low risk GTN(metastatic and nonmetastatic)
  • Single agent weekly pulse MTX 30-50mg/kg
  • Questionare from files and telephoning to patients
results1
Results
  • 66 low risk GTN cases(58 nonmetastatic and 8 metastatic)
  • 97% following molar pregnancy and 3% following abortion
toxicity
Toxicity
  • %7.8 Hepatotoxicity
  • %17.2 GI disturbances
  • %2 Granulocytopenia
  • No Mucositis
second line of treatment
Second Line of treatment
  • Pulse Actinomicin(1.25mg/m2)Biweekly
  • 18 cases
  • %100 Response
time to negative beta hcg
Time to Negative Beta hCG
  • First line 7.18+_3.5 weeks
  • Second line 21+-weeks
bhcg level
BhCG Level
  • Resistant Group :16937 mIu/ml
  • Response Group :8056 mIu/ml
slide41
Pulse MTX,72% remission rate with low toxicity
  • Actinomycin as second line,%100 cure of MTX resistant and toxic group
  • Prolonged regression of HCG in resistant

group

  • Higher HCG level in resistant group
discussion
Discussion

New England Center of Boston(1984)

(Only nonmetastatic)

  • 8 days regimen (MTX-FA)
  • 88% remission rate
  • 1.2 cycles in average
  • 14% Hepatotoxicity
  • 6% granulocytopenia
discussion1
Discussion

Jaice S. Kwon et al (2001)

  • Weekly IV Methotrexate 100mg/m2 with folinic acid (nonmetastatics)
  • 45.5% respnse rate (Folinic acid may be detrimental)
  • Low toxicity ( no change of treatment )
  • Only significant prognostic factor pretreatment hCG level
discussion2
Discussion

Gleeson 1993,Hoffman1996,Homsely 1988(GOG)

Weekly pulse MTX

73-89% complete response

30% GI disturbance ,20% lucopenia

advantages
Advantages
  • Outpatient administration
  • Patient convenience
  • Minimal systemic toxocity
  • Low cost
  • Comparable efficacy to other first-line treatments