Gestational trophoblastic disease Gestational trophoblastic disease (GTD)(GTD)

Gestational trophoblastic disease Gestational trophoblastic disease (GTD)(GTD)

Gestational trophoblastic disease (GTD)Gestational trophoblastic disease (GTD)

Group of diseasesGroup of diseases

Abnormal proliferation of trophoblastic Abnormal proliferation of trophoblastic cellscells

Following an antecedent pregnancyFollowing an antecedent pregnancy

Gestational trophoblastic disease (GTD)Gestational trophoblastic disease (GTD)

Molar pregnanciesMolar pregnancies

Invasive molesInvasive moles

Gestational choriocarcinomasGestational choriocarcinomas

Placental-site trophoblastic tumorsPlacental-site trophoblastic tumors

Molar pregnanciesMolar pregnanciesComplete moleComplete mole

Partial molePartial mole

Comparison of partial & complete moleComparison of partial & complete mole

CharacteristicsCharacteristics Complete moleComplete mole Partial molePartial mole

CytogeneticsCytogenetics 46,xx 46,xx (parternal)(parternal)

69,xxx triploid69,xxx triploid(2 parternal)(2 parternal)

pathologypathology Diffuse hydropic villi and Diffuse hydropic villi and trophoblastic proliferation trophoblastic proliferation

fetal absentfetal absent

Focal hydropic villi and Focal hydropic villi and trophoblastic proliferation trophoblastic proliferation fetal or fetal RBC presentfetal or fetal RBC present

ClinicalClinical USG Dx, large uterus, USG Dx, large uterus, thecalutein cysts, thecalutein cysts, pre-eclamsia, etcpre-eclamsia, etc

Abortion like, Abortion like, others rareothers rare

Malignant Malignant sequelaesequelae

20%20% < 5%< 5%

IncidenceIncidence

Rare diseaseRare disease

between 0.2-9.9 : 1000 pregnancies.between 0.2-9.9 : 1000 pregnancies.

Asia is 10 times higher than Europe and Asia is 10 times higher than Europe and North America.North America.

about 1.87:1000 pregnancies in Vajira about 1.87:1000 pregnancies in Vajira Hospital.Hospital.

Risk factorsRisk factors

AgeAge

Socioeconomic statusSocioeconomic status

Reproductive history (abortion, infertile)Reproductive history (abortion, infertile)

Race/ethnicRace/ethnic

Diet (carotene, fat)Diet (carotene, fat)

Previous molar pregnancyPrevious molar pregnancy

Signs & SymptomsSigns & Symptoms

PregnancyPregnancy

11stst Vaginal bleeding (97%) Vaginal bleeding (97%)

Passage of hydropic villi.Passage of hydropic villi.

Anemia Anemia

Excessive uterine size.Excessive uterine size.

Medical condition: Pre-eclampsia, Hyper-emesis Medical condition: Pre-eclampsia, Hyper-emesis hyperthyroidism, Resp. insufficiency.hyperthyroidism, Resp. insufficiency.

Present of theca lutein cyst.Present of theca lutein cyst.

DiagnosisDiagnosis

USGUSG– vesicular sonographic pattern, vesicular sonographic pattern,

(snow storm).(snow storm).

– Focal cystic change in placenta.Focal cystic change in placenta.

– A ratio of transverse and A-P A ratio of transverse and A-P dimension >1.5.dimension >1.5.

hCGhCG– Markedly elevated (>100,000 Markedly elevated (>100,000

mIU/ml in 40%).mIU/ml in 40%).

Differential DiagnosisDifferential Diagnosis

Abortion with hydropic degenerationAbortion with hydropic degeneration

Missed abortionMissed abortion

Incomplete abortionIncomplete abortion

Pregnancy with other complication: twins, Pregnancy with other complication: twins, wrong date, other ovarian tumor, etc.wrong date, other ovarian tumor, etc.

ChoriocarcinomaChoriocarcinoma

ManagementManagement

Evaluation & StabilizationEvaluation & Stabilization

Evacuation Evacuation

Follow up and Close monitoring of hCGFollow up and Close monitoring of hCG

Evaluation & StabilizationEvaluation & Stabilization

Complete history and physical examination.Complete history and physical examination.

Investigation:Investigation:– hCG, CBC, BUN, Cr, LFT, thyroid function hCG, CBC, BUN, Cr, LFT, thyroid function

tests tests – pelvic USG, CXRpelvic USG, CXR

Stabilized hemodynamic and complication.Stabilized hemodynamic and complication.

EvacuationEvacuation

Suction curettageSuction curettage

Dilatation & curettage (D/C)Dilatation & curettage (D/C)

HysterotomyHysterotomy

HysterectomyHysterectomy

ComplicationComplication

Theca lutein cysts: pain, torsion, rupture, Theca lutein cysts: pain, torsion, rupture, bleeding.bleeding.

Respiratory distress syndrome.Respiratory distress syndrome.

Hyperthyroidism.Hyperthyroidism.

Uterine perforation.Uterine perforation.

Follow upFollow up

Clinical-physical examination.Clinical-physical examination.

Serum hCGSerum hCG– 24-48 hr. after evacuation24-48 hr. after evacuation– q 1 wk. until normal for 3 times.q 1 wk. until normal for 3 times.– q 1 mo. until 6-12 mo.q 1 mo. until 6-12 mo.

Other investigations as indicated.Other investigations as indicated.

Contraception 6-12 mos. (OC, condom).Contraception 6-12 mos. (OC, condom).

Risk factors for GTTRisk factors for GTT

Age > 40 yrs.Age > 40 yrs.

Pre-evacuation hCG > 100,000 mIU/ml.Pre-evacuation hCG > 100,000 mIU/ml.

Uterine size greater than GA.Uterine size greater than GA.

Theca lutein cysts > 6 cm. or bilateral cysts.Theca lutein cysts > 6 cm. or bilateral cysts.

Medical complication.Medical complication.

RDS post evacuation.RDS post evacuation.

Subsequence pregnancySubsequence pregnancy

Recurrent rate 1-2% (15-30% after 2Recurrent rate 1-2% (15-30% after 2ndnd mole) mole)

Not increase in adverse pregnancy outcome.Not increase in adverse pregnancy outcome.

Recommend early ANC and 1Recommend early ANC and 1stst USG. USG.

Send placenta or conceptive products for Send placenta or conceptive products for histology.histology.

hCG 6 week post-partum.hCG 6 week post-partum.

Gestational trophoblastic neoplasia (GTN)Gestational trophoblastic neoplasia (GTN)

Synonyms: gestational trophoblastic Synonyms: gestational trophoblastic tumor (GTT), malignant GTD, persistent GTD, tumor (GTT), malignant GTD, persistent GTD, etc. etc.

Include invasive mole, choriocarcinoma, placental Include invasive mole, choriocarcinoma, placental site trophoblastic tumor.site trophoblastic tumor.

Histologic present is invasive trophoblastic Histologic present is invasive trophoblastic proliferation with or without villi.proliferation with or without villi.

Histologic Diagnosis is not necessary before Rx.Histologic Diagnosis is not necessary before Rx.

45% present with metastatic disease.45% present with metastatic disease.

Hormonal criteriaHormonal criteria

Four values or more of plateaued hCG Four values or more of plateaued hCG ((± 10%) over at least 3 wks.± 10%) over at least 3 wks.

Rising of hCG > 10% for 3 Values or more Rising of hCG > 10% for 3 Values or more over at least 2 wks.over at least 2 wks.

The histologic diagnosis of choriocarcinoma.The histologic diagnosis of choriocarcinoma.

Persistence of hCG beyond 6 mos. or more.Persistence of hCG beyond 6 mos. or more.

Pre-therapy evaluationPre-therapy evaluation

Assessment of clinical risk factors.Assessment of clinical risk factors.

Physical examination include PVPhysical examination include PV

Laboratory evaluation: hematologic Laboratory evaluation: hematologic test, basic chemistry test, hCGtest, basic chemistry test, hCG

Radiographic survey: CXR or CT Radiographic survey: CXR or CT chest, USG or CT Abdomen, chest, USG or CT Abdomen, CT or MRI brain.CT or MRI brain.

Clinical risk fartorsClinical risk fartors

AgeAge

Type of antecedent pregnancy Type of antecedent pregnancy

Interval from antecedent pregnancyInterval from antecedent pregnancy

Previous treatmentPrevious treatment

Common metastatic sitesCommon metastatic sites

Lung 80%Lung 80%

Vagina 30%Vagina 30%

Liver 10%Liver 10%

Brain 10%Brain 10%

Other : GI, kidney, Other : GI, kidney, lymph node, etc.lymph node, etc.

* Liver and brain metastasis are rarely if no lung or * Liver and brain metastasis are rarely if no lung or vaginal metastasis.*vaginal metastasis.*

FIGO stage (2000)FIGO stage (2000)

II Disease confined to the uterus.Disease confined to the uterus.

IIII Disease extend outside uterus, but limited to genital Disease extend outside uterus, but limited to genital structures.structures.

IIIIII Disease extend to lung with or without genital tract Disease extend to lung with or without genital tract involvement.involvement.

IVIV All other metastatic sites.All other metastatic sites.

Anatomical stage

FIGO stage (2000)FIGO stage (2000)Risk score (modified WHO)

scorescore 00 11 22 44Age (yrs)Age (yrs) <40<40 ≥≥4040 -- --

Antecedent pregnancyAntecedent pregnancy MoleMole AbortionAbortion TermTerm

Interval from index preg. Interval from index preg. (mos)(mos)

<4<4 4-<74-<7 7-<137-<13 ≥≥1313

Pre-treatment hCG (IU/l)Pre-treatment hCG (IU/l) <10<1033 101033-<10-<1044 101044-<10-<1055 ≥≥101055

Largest tumor size (cm)Largest tumor size (cm) <3<3 3-<53-<5 ≥≥55 --

Site of metastasisSite of metastasis LungLung Spleen, Spleen, kidneykidney

Gastro-Gastro-intestinalintestinal

Liver, Liver, brainbrain

Number of metastasisNumber of metastasis -- 1-41-4 5-85-8 >8>8

Previous failed chemotherapyPrevious failed chemotherapy -- -- SingleSingle Two or Two or moremore

FIGO stage (2000)FIGO stage (2000)

Write stage:score such as Write stage:score such as stage II:4, stage IV:9stage II:4, stage IV:9

Minimum score = 0, maximum score = 25Minimum score = 0, maximum score = 25

Low risk group score < 7 Low risk group score < 7 High risk group score ≥ 7High risk group score ≥ 7

Clinical classification for GTNClinical classification for GTN

Non-metastatic GTNNon-metastatic GTN

Metastatic GTNMetastatic GTN– Good prognosisGood prognosis– Poor prognosisPoor prognosis

Prognosis for metastatic GTNPrognosis for metastatic GTN

Good prognosis Good prognosis

Duration < 4 mos.Duration < 4 mos.

hCG < 40,000 mIU/mlhCG < 40,000 mIU/ml

No antecedent term preg.No antecedent term preg.

No brain or liver metastasis. No brain or liver metastasis.

No prior chemotherapy. No prior chemotherapy.

Poor prognosisPoor prognosis

Duration ≥ 4 mos.Duration ≥ 4 mos.

hCG ≥ 40,000 mIU/ml.hCG ≥ 40,000 mIU/ml.

Antecedent term preg.Antecedent term preg.

Brain or liver metastasis.Brain or liver metastasis.

Prior chemotherapy.Prior chemotherapy.

Management of GTNManagement of GTNManagement of GTNManagement of GTN

Low risk GTNLow risk GTN

Single agent chemotherapy most common Single agent chemotherapy most common MTX, actinomycin D. MTX, actinomycin D.

Hysterectomy if complete family.Hysterectomy if complete family.

One additional dose after negative hCG.One additional dose after negative hCG.

Resistant to one drug can shift to another Resistant to one drug can shift to another single agent.single agent.

2.5-4% recurrence, mostly in 18 mos.2.5-4% recurrence, mostly in 18 mos.

Single drug regimenSingle drug regimen

Drug Dose Duration(days)

MTX - 1 mg/kg day 1,3,5,7 with folinic acid 0.1 mg/kg day 2,4,6,8

- 20-25 mg (0.4 mg/kg) IM x 5 days

14

7-14

Actinomycin D -10 µg/kg IV x 5 days

-1.25 mg/m2 IV

14

5 FU 30 mg/kg/d continuous 10 30 mg/kg/d continuous 10 day infusion day infusion

-

Etoposide 200 mg/m200 mg/m22 oral x 5 days oral x 5 days 14

Criteria for drug resistanceCriteria for drug resistance

hCG plateaus with three weekly hCG plateaus with three weekly measurements.measurements.

hCG rising ≥ 10% in two consecutive hCG rising ≥ 10% in two consecutive measurements.measurements.

Evidence of new metastasis.Evidence of new metastasis.

High risk GTNHigh risk GTN

5 yrs. survival nearly 90%.5 yrs. survival nearly 90%.

Initial treatment is multi-drug regimen: Initial treatment is multi-drug regimen: EMA-CO, MAC, MAC III, CHAMOCA EMA-CO, MAC, MAC III, CHAMOCA

Treatment continued 2-3 cycle after Treatment continued 2-3 cycle after negative hCG for 3 wks.negative hCG for 3 wks.

Radiotherapy for brain or liver metastasis.Radiotherapy for brain or liver metastasis.

High risk GTNHigh risk GTN

Surgical resection if indicated (single lesion, Surgical resection if indicated (single lesion, resistant nodule).resistant nodule).

Salvage therapy: EMA-EP, ICE, BEP.Salvage therapy: EMA-EP, ICE, BEP.

Common causes of death are hemorrhage Common causes of death are hemorrhage and pulmonary insufficiency.and pulmonary insufficiency.

Follow up for GTNFollow up for GTN

Clinical evaluation.Clinical evaluation.

hCG measurementhCG measurement– weekly until normal x 3 wks.weekly until normal x 3 wks.

– Monthly until normal x 12-24 mos.Monthly until normal x 12-24 mos.

Investigation as indicated.Investigation as indicated.

Contraception if remain fertility.Contraception if remain fertility.