H. ALHusaini, H. Soudy, A. Darwish, M. Ahmed, H. Al-hashem, A. Omar, I. Madkhaly, W. Elghamry, W. Edesa, A. Eltigani, T. Elhassan, S. Alhayli.

A. Albadawi

Gestational trophoblastic neoplasia Proliferative process arising from aberrant fertilization

event that has potential to develop into invasive malignant neoplasm

Include: persistent/invasive mole, choriocarcinoma, placental site trophoblastic tumors and epitheloidtrophoblastic tumor

Highly sensitive to chemotherapy and most curable cancer (>90%)

Therapeutic decision is based on anatomic staging and prognostic score

Low-risk group can be treated with single agent chemotherapy while high-risk group require combination chemotherapy

Aim of study Review our clinical experience in the treatment of

malignant GTN over the past 30 years at King Faisal Specialist Hospital

To evaluate complete response rate to chemotherapy, and to analyze risk factors affecting patient’s response and overall survival

Methods Retrospective study 221 women were identified Diagnosed to have GTN post molar, abortion, or full-

term pregnancy (excluding placental site and epithelioid trophoblastic tumor)

Treated at KFSH, between 1979 and 2010

Patients characteristics

Variable Number=221

Median age (range)<40≥40

37 (14-55)135 (61%)86 (39%)

Antecedent pregnancyhydatidiform moleabortionterm pregnancyother

157 (71%)27 (12%)30 (14%)7 (3%)

Interval <4months4-6 months7-12 months>12 monthsunknown

130 (59%)39 (18%)14 (6%)31 (14%)7 (3%)

Pretreatment hCG<10001000- <1000010000-<100000≥100000unknown

29 (13%)43(20%)72 (33%)69 (31%)8 (4%)

Clinicopathologic typepersistent/invasive GTNchoriocarcinomaunknown

103 (46.6%)117 (53%)1 (0.4%)

Variable Number (%)

Previous chemotherapy outsideNOYes

175 (79%)46 (21%)

FIGO stageIIIIIIIV

91 (41%)17 (8%)86 (39%)27 (12%)

Prognostic score Low riskHigh riskunknown

131 (59%)88 (40%)2 (1%)

Radiation therapyYesNo

unknown

17 (8%)203 (92%)1(0.4%)

SurgeryNOYes

Uterine evacuation hysterectomy Metastatectomy

16 (7%)203 (92%)158 (71%)71 (32%)8 (4%)

Results Median follow-up was 39 months 5-year overall survival was 97%

overall survival rate of low-risk: 100% overall survival rate of high-risk: 92%

Disease category/ chemotherapy Patientsnumber

Complete remission (%)

Low risk 131 CR1: 91 (69.5%)

Single-agent methotrexate 73 39(53%)

Single-agent dactinomycin 23 20 (87%)

Combination chemotherapy(EMA-CO or BEP or MAC)

35 32 (91%)

Low risk: salvage chemotherapy

Single-agent dactinomycin 11 9 (82%)

Single-agent methotrexate 2 1 (50%)

EMA-CO 8 6 (75%)

MAC 3 1(33%)

BEP or EP 12 7(58%)

VeIP 2 2(100%)

VIP 2 1(50%)

Overall CR:118 (90%)

Disease category/ chemotherapy Patientsnumber

Complete remission (%)

High risk 88 CR1: 50 (57%)

EMA-CO 16 15 (94%)

BEP 19 10 (53%)

Etoposide/cisplatin/actinomycin 20 14 (70%)

MAC 7 2(28.5%)

High risk: salvage chemotherapy

EMA-CO 6 3 (50%)

EMA-EP 2 2(100%)

BEP or EP 7 5(71%)

MAC 8 1(12.5%)

VeIP 8 1(12.5%)

VIP 4 2 (50%)

Overall CR:64 (73%)

Recurrence after complete remission occurred in 6 (3%) patients

Median time to relapse was 4 months

Prognostic factors Number (%) OR for response to initial chemotherapy(95% CI)

P-value Overall survival

P-value

Type of pregnancymolarnon-molar

157 (71%)64 (29%)

0.9 (0.5-1.8)1.0

0.9 98%93%

0.04

Metastatic siteslung or vaginaother sites

91 (41%)35 (16%)

1.00.38 (0.87-1.74)

0.02 98%85%

0.002

Prognostic scoreLowHigh

131 (59%)88 (40%)

1.7 (0.9-3.0)1.0

0.05 100%92%

0.01

FIGO stageI-IIIII-IV

108 (49%)113 (51%)

1.00.4 (0.2-0.7)

0.005 100%94%

0.02

Age <40≥40

135 (61%)86 (39%)

1.00.9 (0.5-1.5)

0.8 96%97%

0.7

Pretreatment hCG<10001000- <1000010000-<100000≥100000

29 (13%)43 (20%)72 (33%)69 (31%)

1.01.1 (0.3-3.2)0.4 (0.1-1.08)0.67 (0.2-1.7)

0.080.80.070.4

100%97%98%95%

0.6

Interval <4months4-6 months7-12 months>12 months

130 (59%)39 (18%)14 (6%)31 (14%)

1.02 (0.8-4.6)0.6 (0.2-1.8)1.0 (0.48-2.4)

0.20.090.30.8

98%97%92%90%

0.3

Chemo-outsideNO

Yes175 (79%)46 (21%)

1.01.1 (0.5-2.1)

0.5 96.3%97.5%

0.75

Univariate Logistic regression analysis of prognostic factors for CR to initial chemotherapy and OS

Fertility outcome 38 (17%) patients became pregnant

13 of these pregnant were of high-risk group 24 (63%) delivered babies without congenital

malformations. Abnormal pregnancies occurred in 7 (18%) patients:

miscarriage (n=5) stillbirth (n=2) molar pregnancy (n=1)

Conclusion Patients with GTN have excellent prognosis if properly treated

at experienced centers Single-agent dactinomycin seems more effective than single

agent methotrexate with higher complete response rate at low-risk groups

EMACO is the preferred chemotherapy for high-risk groups Factors that significantly associated with resistant to initial

chemotherapy were advanced FIGO stage, presence of metastatic disease other than lung and vagina and high-risk prognostic score

Survival was also significantly influenced by type of antecedent pregnancy, FIGO stage, prognostic score and site of metastases

Patients can anticipate a normal future reproductive outcome