Gestational Trophoblastic Disease - wesley ob/gyn Trophoblastic... · Hydatidiform Mole Chorionic...
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Transcript of Gestational Trophoblastic Disease - wesley ob/gyn Trophoblastic... · Hydatidiform Mole Chorionic...
JACQUELINE MORGAN JUNE 10 TH, 2011
Gestational Trophoblastic Disease
GTD
Hydatidiform Mole
Complete
Partial
Invasive Mole
Choriocarcinoma
Placental Site Trophoblastic Tumor
Epithelioid trophoblastic tumor
Hydatidiform Mole
Chorionic villi fluid filled and distended
Scant blood vessels
Proliferation of the cytotrophoblast and syncitiotrophoblast.
Variable degree of hyperplasia and anaplasia
Difficult pathologic interpretation in earlier gestations
P53
Hydatidiform Mole
Incidence 0.6 – 1.1 per 1,000 pregnancies
Increased risk at extremes of reproductive age
Recurrence risk of 0.5 – 2.6%
Higher risk of neoplasia following recurrent molar pregnancy
Hydatidiform Mole- Diagnosis
Classic presentation seen less and less
Vaginal bleeding
Uterine enlargement > dates
Hyperemesis
1st & 2nd trimester hypertension/Pre-eclampsia
Hyperthyroidism
CHF
Pulmonary edema
Bilateral ovarian masses
Hydatidiform Mole- Diagnosis
Much earlier diagnosis now
U/S Vesicular pattern (Snow-storm)
Absent or abnormal fetus
hCG assay Elevated above normal levels, often > 100,000
Often diagnosed after histological review after treatment for incomplete or missed abortion
Hydatidiform Mole
Complete Molar Pregnancy
46XX or 46XY
Chromosomal DNA paternal
Absent fetus or embryo
Early and total villi swelling
Hyperplastic trophoblast +/- atypia
10-20% risk of subsequent trophoblastic neoplasia
Complete Molar Pregnancy
Complete Molar Pregnancy
Partial Molar Pregnancy
69XXY or 69XXX
Slowly progressive hydatidiform change
Not all villi affected
Functional villous blood vessels
Focal hyperplasia, minimal atypia
Abnormal fetus or embryo of membranes present
5% risk of subsequent trophoblastic neoplasia
Phantom hCG
Heterophilic antibodies
Human antimouse antibodies
Mimic hCG by binding to tracer mouse IgG
If suspect false positive
Check urine hCG
Serial dilution of serum
Obtain testing at national hCG testing lab
Avoid treating healthy patients with unnecessary surgery or chemotherapy
Coexisting Twin Pregnancy and Molar Pregnancy
Increased with the introduction of reproductive technologies
Increased risk of multiple pregnancies
Normal pregnancy and a complete mole most common combination
Diagnosis suggested on U/S
Definitive diagnosis by fetal karyotype
Coexisting Twin Pregnancy and Molar Pregnancy
Increased risk of hemorrhage, hyper emesis, hyperthyroidism, preeclampsia
40 - 57% risk of persistent GTN requiring further treatment
Survival rate of 25 - 30% if able to reach viability
Hydatidiform Mole- Evaluation
Detailed history Physical exam CBC Coags Chemistry panel TFTs Type and Crossmatch Serum hCG level Pelvic U/S CXR
Hydatidiform Mole- Evacuation
Suction D&C U/S guidance can be of benefit
Larger uterus
Variable amount of intrauterine tissue
Uterine wall soft
Hysterectomy If fertility not desired
Hysterotomy and medical induction of labor not recommended
Surgical Evacuation Follow Up
Pathologic analysis of all specimens
Serial hCG follow up
Contraception for 6 months- if no hysterectomy
Future pregnancies 6 week postpartum hCG level
Histological analysis of placenta or POC
Hydatidiform Mole- Follow Up
80% cured by evacuation alone
Repeat curettage
If continued bleeding
If U/S evidence of retained products
Rarely curative on its own
Serial hCG measurements
Serial hCG Follow Up
Serum hCG levels every 2 weeks until 3 consecutive normal tests
Testing to be performed at same lab, using same assay kit
Then monthly serum hCG levels for 6 – 12 months
Avoidance of pregnancy for 6 months
Post Molar Contraception
OCPs commonly used
No effect on prognosis or recurrence risk
Added benefit of suppressing endogenous LH which can interfere with hCG monitoring
Need a reliable form of contraception
Must tailor to the individual patient
Risk Factors for Postmolar GTN
Large pre-evacuation uterine size
Theca lutein cysts > 6cm
Age > 40yo
Serum hCG > 100,000
Medical complications from molar pregnancy
Previous molar pregnancy
Prophylactic Chemotherapy
Single agent Methotrexate or Actinomycin D following molar evacuation
Reduced incidence of post molar GTN from 47% to 14% amoung a population of patients with very high risk complete moles (Kim et al.)
No benefit to those without multiple high risk factors
Potential role when no follow up is available
Generally not recommended
Gestational Trophoblastic Neoplasia
Invasive mole
Choriocarcinoma
Placental site trophoblastic tumor
Epithelioid trophoblastic tumor
Gestational Trophoblastic Neoplasia- Presentation
Highly Variable
Lab only if ongoing hCG surveillance
Dependant upon site of disease
Mass effect
Tumors have high propensity to bleed Hemoptysis
Hematemesis
Intracranial hemorrhage
Young female with multiple tumor masses- Check hCG level
Gestational Trophoblastic Neoplasia- Presentation
Gestational Trophoblastic Neoplasia
Diagnosed by
Plateauing or rising hCG following molar pregnancy evacuation
Histopathologic diagnosis
Persistent elevation of hCG following any pregnancy event
Gestational Trophoblastic Neoplasia- Staging
History and Physical Exam
hCG level
CBC
Chemistry panel
CXR
CT chest/abdo/pelvis
MRI brain
NCI Criteria for high risk disease
Greater than 4 months from antecedent pregnancy
Pretreatment hCG >100,000 on 24hr urine
>40,000 serum hCG
Metastasis to sites other than vagina and lung
Antecedent term gestation
Prior failed chemotherapy
GTN Staging System- FIGO
Anatomic staging system, 1982
Stage I- Disease confined to uterus
Stage II- Disease extends to other genital structures
Stage III- Disease extends to lungs +/- genital disease
Stage IV- Disease involves other metastatic sites
GTN Staging System
WHO, 1983
Prognostic scoring system
<7 - low risk disease
= or>7 - high risk disease
In 2000 FIGO included a modified WHO score into its anatomic staging system.
WHO GTN Staging System
Characteristic Score
0 1 2 4
Age < 40 = or > 40 - -
Months from pregnancy < 4 4 - 6 7 - 12 > 12
Pretreatment hCG < 1,000 1,000-10,000
10,000-100,000
>100,000
Largest tumor size < 3 cm 3 – 4 cm = or > 5 cm
-
Site of metastasis Lung Spleen, kidney
GI tract Liver, Brain
No of metastasis - 1 - 4 5 - 8 > 8
Antecedent pregnancy Mole Abortion Term -
Previous failed chemotherapy
- - Single drug Two or more drugs
Non Metastatic Disease
Single agent chemotherapy only
Methotrexate (MTX) or dactinomycin
85-90% cure with primary therapy
Further 10% remission with alternate single agent therapy
Rarely require multiagent therapy
<5% require hysterectomy for persistent refractory uterine disease
Case
19yo presents with N/V
6 wks by LNMP
hCG- 98,000
U/S- No viable IUP, Intrauterine mass with vesicular pattern
D&C- “Immature chorionic villi, no molar change”
Case
W2- hCG 1367
W3- hCG 2256
W4- hCG 3582
IM Methotrexate 50mg
W5- hCG 9134, 5737
IM Methotrexate 50mg
W6 hCG 4159, 4504
Case
Pelvic U/S- No uterine abnormality, ES 0.47cm, no adnexal mass
CT- Chest, Abdomen and Pelvis- No abnormality
CT Head- No abnormality
Case
Commenced on Methotrexate 0.4mg/kg IM days 1-5
Completed 2 cycles
hCG 54
Treatment ongoing
Non compliant with OCPs
Single Agent Regimens
Drug Regimen
MTX 0.4mg/kg/day IV or IM for 5 days in 14 day cycle
Act D 10-12mg/kg/day IV for 5 days of 14 day cycle
MTX 1.0-1.5 mg/kg IM day 1,3,5,7, alternating with folinic acid 0.1mg/kg day 2,4,6,8 in 18d cycle
MTX 100mg/m² IV push then 200mg/m² over 12h, then folinic acid 15mg q 12hr x 4 doses
Act D 1.25 mg/m² IM weekly
MTX 30 – 50 mg/m²IM weekly
Single Agent Regimens for Non-metatstatic GTN Patients (No.)
Primary Remission Rate (%)
Multiagent ChemoRx (%)
Secondary Surgery (%)
MTX 5-Day- Hammond 1980
122 87 --
MTX 5-Day- Lurain 1995
253 89 1.2 0.8
MTX-FA- Berkowitz 1986
163 90 4.9 2.2
MTX-FA-Bagshawe 1989
348 80 -- --
Weekly MTX- Homesley 1990
62* 74 4.8 3.2
Weekly MTX- Hoffman 1996
20 60 5.0 --
Act D 5 Day- Kohorn 1996
43 88
Act D Pulsed- Kohorn 1996
18 78
Single Agent Chemotherapy for Low Risk GTN
Patients (No.) Primary Remission Rate (%)
Weekly MTX 30mg/m2 107 53
Pulsed Act D 106 69
Osborne R et al., 2008
Low Risk Metastatic Disease
Stage II and III, WHO score < 7 5 day MTX or Act D protocol or 8 day MTX-FA
protocol 50 – 70% remission with primary therapy Sequential single agent therapy if remission not
achieved, or toxicity to drug (30-50% of pts) If second single agent fails- Multi-agent
chemotherapy (5-15% of those on 2nd agent therapy)
Hysterectomy can be used as adjunctive therapy if childbearing complete
Survival approaching 100%
High Risk Metastatic Disease
FIGO IV or WHO score 7 or more
Initial multiagent chemotherapy
EMA-CO
EMA
EMA-EP
Complete response 70 – 80 %
Survival 90%
EMA-CO
Day Drug Dosing
1 Etoposide
Act D
MTX
100mg/m² IV over 30min
0.5 mg IV push
100mg/m² IV push then 200mg/m² over 12 hours
2 Etoposide
Act D
Folinic acid
100mg/m² IV over 30min
0.5 mg IV push
15mg IM or PO q 12hr x 4
8 Cyclophosphamide
Vincristine
600mg/m² IV
1.0mg/m² IV push
Resistant Disease
EMA-EP
BEP
VIP
ICE
Paclitaxel doublets ( ET/PT)
+/- GCSF agents
CNS Disease
50 – 80% survival
Whole brain irradiation
3,000 cGy in 200cGy fractions
MTX in EMA-CO increased to 1gm/m² with 30mg folinic acid q12 hr x 3 days
Intrathecal & IV high dose MTX
Surgical Treatments
Surgical resection of isolated known foci of chemo resistant disease
Hysterectomy
Thoracotomy for isolated pulmonary disease
Also for symptom control
Hemorrhage
Infection
GTN Follow Up
Treatment to hCG normalization, then 1 – 2 subsequent cycles
Monthly hCG level for 12 months
Contraception during therapy and for 1 yr following
Early U/S in subsequent pregnancy
Post pregnancy histopath.
hCG level 6 weeks post subsequent pregnancy
Reproductive Impact of Chemotherapy
Aside from those requiring hysterectomy
Most return to normal ovulatory function and fertility post therapy
No change in rate of abortion, still birth, prematurity or congenital anomalies
Increased risk of future GTN related to subsequent pregnancies
Secondary Malignancies
Related to etoposide use
Risk increased for
Acute myelogenous leukemia
Colon cancer
Melanoma
Breast cancer
Placental Site Trophoblastic Tumor
Intermediate trophoblasts
Secretes human placental lactogen (hPL)
Low level hCG production
Less vascular invasion and distant metastasis
More lymphatic spread
Presents often remote to nonmolar gestation
Pelvic mass
Abnormal bleeding
Placental Site Trophoblastic Tumor
Chemoresistant
Hysterectomy is primary therapy
Metastatic disease
Multi-agent chemotherapy
EMA-EP
Surgical resection
Epithelioid trophoblastic tumor
Presents typically with abnormal uterine bleeding/mass
Intermediate and syncytiotrophoblastic cells
hCG elevated
Presents remote from antecedent pregnancy
Chemoresistant
Primary surgical therapy