Oncology and reproductive outcomes over 16 years of malignant ovarian germ cell tumors treated by fertility sparing surgery

Table 1 Clinical data (n = 62)

	n (%)
Median age (range; yr)	22.0 (4-34)
Parity before surgery
0	48 (77.4)
1	8 (12.9)
2	6 (9.7)
Presentation
Pelvic mass	24 (38.7)
Abdominal pain	18 (29.0)
Abdominal distension	15 (24.2)
Others1	5 (8.1)
Tumor side
Right	34 (54.8)
Left	26 (41.9)
Bilateral	2 (3.2)
Detail of FSS
Unilateral SO	49 (79.0)
Unilateral cystectomy	4 (6.5)
Unilateral SO & cystectomy	9 (14.5)
Frozen section	26 (41.9)
Cytology
Not done	23 (37.1)
Negative	29 (46.8)
Positive	10 (16.1)
Omentectomy
Not done	18 (29.0)
Negative	40 (64.5)
positive	4 (6.5)
Lymphadenectomy
Not done	32 (51.6)
Negative	26 (41.9)
Positive	4 (6.5)
Appendectomy	32 (51.6)
Surgical outcome
No residual	47 (75.8)
Optimal	5 (8.1)
Suboptimal (residual tumor > 1 cm)	10 (16.1)
Histology
Dysgerminoma	17 (27.4)
Immature teratoma	20 (32.3)
Yolk sac tumor	15 (24.2)
Mixed type	5 (8.1)
Others2	5 (8.1)
Stage
I	46 (74.2)
II	6 (9.7)
III	7 (11.3)
IV	3 (4.8)
Adjuvant chemotherapy
None	19 (30.6)
BEP	42 (67.7)
EMACO	1 (1.6)
Cycles of chemotherapy
1-3	6
4-6	33
> 6	4
Long-term side effect
None	46 (74.2)
Numbness	3 (4.8)
Lung fibrosis	2 (3.2)
High-frequency hearing loss	1 (1.6)
Tinnitus	1 (1.6)
Progression of disease	4 (9.5)
Death	5 (8.1)
Alive	55 (88.7)
Missing data	2 (3.2)

¹Others: Amenorrhea (2), anti-NMDAR (N-methyl D-aspartate receptors) encephalitis (1), incidental finding during cesarean section (1), and hyperthyroidism (1).

²Others: Struma ovarii (1), carcinoid (1), chorioCA (1), steroid cell tumor (1), and papillary thyroid CA arising in teratoma (1).

Death: SN 43, 52, 74, 108, and 110. SO: Salpingo-oophorectomy; BEP: Bleomycin etoposide cisplatin; EMACO: Etoposide methotrexate actinomycin D cyclophosphamide vincristine.

Table 2 Progression cases (n = 4)

SN	Year	Age	Stage	Histology	Chemotherapy	Cycle	Site	Primary surgery	Note
50	2013	17	IC1	Immature teratoma grade 2	None	-	Right	Right SO and appendectomy	PFS 3 mos →pelvic recurrence → debulking tumor and BEP × 6 cycles → alive without disease DFS 103 mos, overall survival 109 mo
52	2013	15	IV	Yolk sac tumor	BEP	8	Right	Right SO and left cystectomy and omentectomy	Progression after BEP × 8: Liver & lung metastasis → TIP x 2 → PT × 1 → ifosfamide × 1 → progression → death (overall survival 16 mo)
74	2010	18	IV	Choriocarcinoma	EMACO	6	Left	Left SO and omentectomy and appendectomy and PAN sampling	EMACO × 6 → progression (PFS 7 mos) → cisplatin and ifosfamide × 5 → paclitaxel × 1 → Act D and 5 FU × 1 → VAC × 1 → TAH and right SO (19/4/2011) → EMA/EP × 9 → TP/TE × 1 → BEP × 2 → palliative treatment → death 5/7/2012 overall survival 28 mo
110	2005	16	IV	Yolk sac tumor	BEP × 2 → EP × 11	12	Right	Right SO and appendectomy	Progression after EP × 11 → ifosfamide × 1 → EMA × 1 → single paclitaxel × 1 → palliative RT 25/1/2006 → VAC × 1 → Death 4/7/2007,OS 30 mo (lung fibrosis after BEP × 2)

PFS: Progression-free survival; DFS: Disease-free survival; SO: Salpingo-oophorectomy; PAN: Para-aortic lymph node; BEP: Bleomycin etoposide cisplatin; EMACO: Etoposide methotrexate actinomycin D cyclophosphamide vincristine; TIP: Paclitaxel ifosfamide cisplatin; PT: Paclitaxel carboplatin; Act D; actinomycin d; EMA/EP: Etoposide methotrexate actinomycin D etoposide cisplatin; 5FU: Fluorouracil; VAC: Vincristine dactinomycin and cyclophosphamide; TP/TE: Paclitaxel cisplatin/paclitaxel etoposide; TAH: Total abdominal hysterectomy; EP: Etoposide cisplatin, palliative; RT: Radiotherapy.

Table 3 Menstrual data of studied patients who received chemotherapy (n = 43)

	n (%)
No menstruation after treatment	8 (18.6)
No menarche1	1
Premature menopause	7
Resume menstruation2	17 (39.5)
1 mo	2
2 mo	2
3 mo	2
4 mo	3
5 mo	1
6 mo	6
Median 4 mo (1-6)
Menstruation during and post-treatment	18 (41.9)

¹SN 4, no menarche at age 12 years old.

²SN 64, menarche at age 12.

Table 4 Details of premature menopausal patients (n = 7)

SN	Year	Age	Stage	Histology	Chemotherapy	Cycle	Site	Primary surgery	Note
25	2017	29	IIA	Yolk sac tumor	BEP	6	Right	Right SO and omentectomy January 6, 2017	16/1/18 abdominal pain and pelvic mass size 10 cm × 15 cm, solid and cystic, movable AFP 2.2 → TAH and left SO 19/1/18 → endometrioid CA IA → carboplatin × 6 → complete response → DFS 61 mo, HRT
43	2014	16	III	Dysgerminoma	BEP	4	Bilateral	Left SO and omentectomy	Partial response during BEP, overall survival of 3 mo, death from sepsis (neutropenia)
52	2013	15	IV	Yolk sac tumor	BEP	8	Right	Right salpingo-oophorectomy with left ovarian cystectomy	PFS 15 mo → TIP × 2 cycles → PT × 1 → ifosfamide × 1 cycle → death OS 16 mo
87	2008	28	I	Dysgerminoma	BEP	3	Left	Left SO	HRT icycloprogynova lost to follow up since 2009, unknown status
108	2005	15	III	Yolk sac tumor	BEP	6	Right	Right SO	Febrile neutropenia → sepsis → death 2005 OS 9 mo
110	2005	16	IV	Yolk sac tumor	BEP × 2 → EP × 11	12	Right		Progression after EP × 11 → ifosfamide × 1 → EMA × 1 → single paclitaxel × 1 → palliative RT January 25, 2006 → VAC × 1 → Death July 4, 2007, OS 30 mo (lung fibrosis after BEP × 2)
114	2005	23	II	Dysgerminoma	BEP	6	Right	Right SO	Alive, loss after 12 mo since start treatment, no HRT

BEP: Bleomycin etoposide cisplatin; SO: Salpingo-oophorectomy; TAH: Total abdominal hysterectomy; AFP: Alpha-fetoprotein; DFS: Disease free survival; HRT: Hormonal replacement therapy; PFS: Progression free survival; TIP: Paclitaxel ifosfamide cisplatin; PT: Paclitaxel carboplatin; OS: Overall survival; EP: Etoposide cisplatin; EMA: Etoposide methotrexate + actinomycin D; palliative RT: Radiotherapy.

Table 5 Pregnancy outcomes

SN	Year	Age Dx	Age Preg	Stage	Histology	Site	Chemotherapy	Cycle	Parity1	Primary surgery	Pregnancy outcome
19	2018	30	31	IA	Carcinoid tumor neuroendocrine tumor grade 1 arising in mature cystic teratoma	Left	None	-	1001	Laparoscopic left ovarian cystectomy June 1, 2018	1 Term pregnancy, GA 39 wk, NL August 1, 2019, BW 3030 gm
53	2013	21	27	IC	Dysgerminoma	Right	BEP	4	-	Right SO and omentectomy and appendectomy June 15, 2013	1 Term pregnancy, C/S GA 38 wk April 23, 2019, BW 2780 gm, ompholocele 9 cm × 8 cm, and atrial septal defect → surgical correction
84	2008	19	21	IA	Steroid cell tumor	Right	None	-	-	Right SO and omentectomy and PNS and PAS December 18, 2008	1 spontaneous abortion 31/1/2010
92	2005	34	35	IA	Immature teratoma grade1	Left	None	-	1001	Left SO	1 Term pregnancy, GA 38 wk, NL 10/12/2006, BW 2700 gm
94	2007	24	26	IA	Dysgerminoma	Left	None	-	1001	Left SO and omentectomy October 9, 2007	1 Term pregnancy with no available data of birth date, GA, and BW

¹Parity before primary surgery.

NB: 14 of 30 patients who could be contacted for this information revealed an attempt to conceive. GA: Gestational age; BW: Birth weight; BEP: Bleomycin etoposide cisplatin; SO: Salpingo-oophorectomy; C/S: Cesarean section; PNS: Pelvic lymph node sampling; PAS: Para-aortic lymph node sampling.