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had a score of 13. Mortality rate was estimated with the use of the
Kaplan-Meier method.
RESULTS: The 5-year overall mortality rate, after the exclusion of
placental site trophoblastic tumors and epithelioid trophoblastic tumors,
was 2% for patients with gestational trophoblastic neoplasia (95% confidence interval, 1.25e3.13%). High-risk patients had a 5-year mortality
rate of 12% (95% confidence interval, 7.49e18.9%). Patients with
an International Federation of Gynecology and Obstetrics score of 13
had a higher 5-year mortality rate (38.4%; 95% confidence interval,
23.4e58.6%) and accounted for 52% of the deaths in the entire cohort.
Early deaths, defined as those that occur within 4 weeks after treatment
initiation, occurred in 8 patients of the entire cohort. Six of them had an
International Federation of Gynecology and Obstetrics score of 13 at
presentation, of whom 5 patients had brain and/or liver metastases.
CONCLUSION: Gestational trophoblastic diseases with an International Federation of Gynecology and Obstetrics score of 13 have an
increased risk of early death. We suggest that an International Federation
of Gynecology and Obstetrics score of 13 becomes a consensual criterion for prediction of patients with gestational trophoblastic neoplasia
with increased risk of death, particularly early death. These patients justify
treatment in highly specialized gestational trophoblastic disease centers
and may benefit from the use of induction low-dose etoposide and
cisplatin.
Key words: gestational trophoblastic neoplasia, FIGO score, high risk,
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Original Research
TABLE 1
International Federation of Gynecology and Obstetrics score and stage of patients with gestational trophoblastic
neoplasia
International Federation
of Gynecology and
Obstetrics
Total number
of patients
(n 974), n (%)
International Federation of
Gynecology and Obstetrics
score, n (%)
6 (n 794)
7 (n 140)
Spontaneous
regression
(n 7), n (%)
19 (70.4)
stage
I
743
663 (83.6)
II
39
31 (3.9)
III
140
97 (12.2)
39 (27.9)
4 (14.9)
IV
43
2 (0.25)
39 (27.9)
2 (7.4)
Unknown
56 (40)
6 (4.3)
2 (7.4)
NA
3 (60)
score
0-4
685 (73)
682 (86)
5-6
113 (12)
112 (14)
NA
1 (20)
7-12
112 (12)
111 (79)
NA
1 (20)
13
29 (3)
29 (21)
NA
35
NA
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TABLE 2
Clinical characteristic
Total patients
(n 941)
33 (12e58)
10,290
Rangea
4e4,022,380
Missing data, n
7 (n 140)
13 (n 29 )
32 (12e57)
37 (18e58)
32 (18e50)
6,723
205,450
203,500
4e1,916,972
107e4,022,380
107e3,228,579
23
10
Antecedent pregnancy, n
Mole
787
731
53
Abortion
77
39
37
11
Birth
72
19
50
17
761
681
76
101
88
13
41
21
18
38
33
11
750
682
61
137
101
36
18
10
36
35
24
903
792
104
Unknown
International Federation of Gynecology and Obstetrics, n
Interval from antecedent pregnancy, y
27
27
20
15/902 (1.7)
0/765
15/133 (11.3)
10/29 (34.5)
Liver metastasis
n/N (%)
Not evaluated, n
36
29
Brain metastasis
n/N (%)
Not evaluated, n
17/833 (2.0)
104
5 (0e15.1)
0/698
96
5.2 (0.6e15.1)
17/132 (12.9)
14/29 (48)
4.5 (0e15.1)
2.85 (0e12.8)
Total deaths, n
18
16
11
Early deaths, n
Note: Placental site trophoblastic tumors and epithelioid trophoblastic tumors were excluded.
a
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Results
FIGURE 1
The treatment of GTN patients with PSTT or ETT was not decided according to FIGO score. Patients
with spontaneous remission of GTN without chemotherapy were excluded from analysis.
ETT, epithelioid trophoblastic tumor; FIGO, International Federation of Gynecology and Obstetrics; GTN, gestational trophoblastic
neoplasia; NA, not applicable; PSTT, placental site trophoblastic tumor.
Bolze et al. Mortality rate of patients with GTN with a FIGO score of 13. Am J Obstet Gynecol 2016.
Original Research
resonance imaging. The latest investigation was considered as reference for tumor size assessment. Any suspicion of
liver metastasis was further explored by
abdomen magnetic resonance imaging.
FIGO score and stage were extracted
from our database with PARADOX 9
software (Corel, Ottawa, Canada),
except for patients who were registered
before 2002, whose cases subsequently
were rescored (n 49). Early death was
dened as that which occurred within 4
weeks after treatment initiation. Survival
was calculated from the rst day of
treatment to 1 year after data extraction
or to the date of death. Survival was
estimated according to the FIGO score
with the use of the Kaplan-Meier
method, and a Wilcoxon test was used
to compare survival curves among
groups. Statistical analysis was performed with SAS software (version 9.2;
SAS Institute, Cary, NC).
Among 974 patients with GTN, 140 patients (14.4%) had a high-risk FIGO
score, of whom 29 patients had a score of
13 (Figure 1). The histopathologic
diagnosis was inconsistent with the
FIGO score for 33 patients (3.4%; 10
ETT and 23 PSTT) who were excluded
from high-risk patient analysis. Serum
hCG levels normalized in 7 patients
(0.7%; 4 with choriocarcinoma
conrmed by histology and 3 with a
clinical diagnosis of choriocarcinoma)
without the requirement for chemotherapy. The Kaplan-Meier estimate of
the 5-year overall death rate of the GTN
cohort (excluding PSTT and ETT) was
2% (95% condence interval [CI],
1.25e3.13%), which represented 18
deaths (2 low risk, 16 high risk). For
PSTT and ETT, the 5-year specic death
rate was 7.6% (95% CI, 1.9e28.1),
which represented 3 deaths. The median
time interval from treatment initiation
to death was 6.6 months (range,
0.1e64.4). The estimates of the 5-year
death rates for low- and high-risk patients were 0.3% (95% CI, 0.07e1.06)
and 12% (95% CI, 7.49e18.9), respectively. Among the high-risk patients, the
5-year death rate estimate was 38.4%
(95% CI, 23.4e58.6) and 4.9% (95% CI,
2.04e11.3) for cases that had a FIGO
score of 13 and <13, respectively
(p < .0001; Figure 2). High-risk patients
with a FIGO score of 13 accounted for
3% (29/974) of the entire GTN cohort.
Annual 5-year death rate varied from
0-4.5% for patients who were registered
until 2010 with no signicant trend.
However, the number of patients with
GTN who were registered in our center
increased from 25 in 1999 to 119 in 2010.
Among the entire cohort, 52% of
patients (11/21) who died had a FIGO
score of 13, and 6 of them died early.
Two other early deaths were identied
in the cohort, 1 death from massive
pulmonary embolism in a high-risk
patient (FIGO score, 8) and a second
death from intraperitoneal carcinomatosis from ETT origin (Figure 1). Three
quarters of early deaths (6/8) affected
high-risk patients with a FIGO score of
13; no early death happened in lowrisk patients.
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OBSTETRICS
Comment
Data from the French GTN cohort
highlight that early initiation of suitable
treatment is associated with a 5-year
survival of 98%. This study corroborates the long-standing concept, recently
strengthened in a worldwide survey by
Kohorn,13 that centralized treatment of
patients with GTN is associated with the
lowest mortality rate.
The 5-year mortality rate (12%) of
high-risk patients with GTN (FIGO
FIGURE 2
Patients were stratified according to the International Federation of Gynecology and Obstetrics
prognostic score at presentation.
ETT, epithelioid trophoblastic tumor; PSTT, placental site trophoblastic tumor.
Bolze et al. Mortality rate of patients with GTN with a FIGO score of 13. Am J Obstet Gynecol 2016.
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TABLE 3
Characteristics of dead high-risk patients with gestational trophoblastic neoplasia with an International Federation of Gynecology and Obstetrics score of 13
Human
chorionic
gonadotropin
level, IU/L
International
Federation of
Gynecology and
Obstetrics,
stage:score
First-line
chemotherapy
Time from
treatment
initiation
to death,
mo
Metastatic
disease
at diagnosis
Year of
treatment
initiation
Age,
y
Antecedent
pregnancy
2008
20
Birth
282,790
IV:18
BEP
0.6
Lung, mediastinum,
liver, bone, muscle,
skin, spinal dura
Drug-resistant disease
2009
20
Abortion
191,361
III:13
EA-CO
9.5
Lung
Drug-resistant disease
2010
28
Birth
42,449
IV:13
Death before
treatment
Lung, brain
Subarachnoid
hemorrhage
2010
18
Birth
205,450
IV:17
EMA-CO (high-dose
methotrexate)
0.1
Lung, spleen,
kidney, brain
Subarachnoid
hemorrhage
2010
34
Birth
319,813
IV:16
EMA-CO
0.6
Lung, liver
Bilateral pulmonary
embolism
2011
36
Birth
327,090
IV:15
BEP
0.2
2011
26
Birth
867,450
IV:17
EMA-CO (high-dose
methotrexate)
29.9
Drug-resistant disease
2012
45
Abortion
661,284
IV:17
Low-dose etoposide
and cisplatin, then
EMA-CO (high dose
methotrexate)
5.5
Lung, brain
Multisystem organ
failure
2013
41
Birth
9,348
IV:17
EMA-CO
14.7
Lung, liver
Drug-resistant disease
10
2013
40
Abortion
120,957
III:13
Low-dose etoposide
and cisplatin, then
BEP
7.7
Lung
Drug-resistant disease
11
2014
28
Abortion
2,365,500
IV:15
Low-dose etoposide
and cisplatin
0.1
Lung, brain
Subarachnoid
hemorrhage
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Original Research
BEP, bleomycin, etoposide, and cisplatin; EMA-CO, etoposide, methotrexate, and dactinomycinecyclophosphamide and vincristine.
Bolze et al. Mortality rate of patients with GTN with a FIGO score of 13. Am J Obstet Gynecol 2016.
Cause of death
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Case
number
Original Research
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