1. In The Name of God

2. Diagnosis and treatment of gestational trophoblastic disease

3. Gestational Trophoblastic Neoplasia
A spectrum of interrelated conditions originating from placenta:
Complete and partial moles
Invasive mole
Gestational choriocarcinoma
Placental Site Throphoblastic Tumor

5. 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

11. 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

12. 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

14. 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

16. Gestational choriocarcinoma
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

17. 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

18. 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

19. 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

21. 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

22. Poor-prognosis metastatic gestational trophoblastic disease(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

23. 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

24. FIGO Scoring System

25. 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

26. 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

27. Chemotherapy Single agent MTX therapy Nonmetastatic
Low risk metastatic
Multi agent regimens resistance to MTX initially high risk tumors

28. 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

29. Strategies for further courses
Regular administration every 7-14 days
Single systematic course, further courses depending on HCG decrease(if plateau or reelevatd

30. 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

31. Remission and Relapse
Remission :hCG level within normal range for at least three consecutive weeks
Relapse :Rising hCG after remission

32. Thanks

33. MTX Toxicity Hepatotoxicity GI disturbances Granulocytopenia
Thrombocytopeni
Mucositis

34. Demographic praperties of low risk GTN case vali. Ase Hospital TUMS
Age
Min
max
Mean
Gravid 1 11
3.2
Abortion 4
0.4

35. Staging of low risk GTN case vali. Ase Hospital TUMS

36. FIGO Score of low risk GTN case vali. Ase Hospital TUMS

37. Toxicity of MTX in low risk GTN case vali. Ase Hospital TUMS

38. Failure Frequency of low risk GTN case vali. Ase Hospital TUMS

39. Results Failure frequency :18 (28%) Initial resistance 11 (17%)
Relapse
Toxicity (11%)

40. 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

41. Results 66 low risk GTN cases(58 nonmetastatic and 8 metastatic)
97% following molar pregnancy and 3% following abortion

42. Toxicity %7.8 Hepatotoxicity %17.2 GI disturbances %2 Granulocytopenia
No Mucositis

43. Second Line of treatment
Pulse Actinomicin(1.25mg/m2)Biweekly
18 cases
%100 Response

44. Time to Negative Beta hCG
First line _3.5 weeks
Second line 21+-weeks

45. BhCG Level
Resistant Group :16937 mIu/ml
Response Group :8056 mIu/ml

46. 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

47. 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

48. 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

49. Discussion
Gleeson 1993,Hoffman1996,Homsely 1988(GOG) Weekly pulse MTX 73-89% complete response 30% GI disturbance ,20% lucopenia

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