1. Management of Malignant Ovarian Germ Cell Tumors
İbrahim Serdar Serin, MD
University of Erciyes, Medical School, Department Of Obstetrics and Gynecology, Division of Gynecological Oncology

2. Ovarian germ cell tumors (OGCTs) are derived from primordial germ cells of the ovary

3. Malignant ovarian germ cell tumours (MOGCTs)
(MOGCTs) are rare (% 2-3)
Early diagnosis and multiagent chemotherapy are associated with high cure rates of 85.6%
Relapse with this cancer have poorer outcomes
MOGCTs are managed by multidisciplinary teams

4. MOGCT Most commonly occur in the first two decades of life
can appear at any age
Immature teratomas50 yr↑(more common)
(A review of the Norwegian Cancer registry)

6. MOGCT-Presentation Pelvic pain (acute and subacute)
Menstrual disturbance
A pelvic or abdominal mass
Ascites

7. MOGCT- Diagnosis
A solid mass on USG examination in younger women may indicate a MOGCT
Imaging of the abdomen, pelvis and chest by CT
MRI may provide additional information
LDH, AFP, HCG etc (TUMOR MARKERS) provides a highly sensitive and specific indicator of the presence of certain histologic components

8. MOGCT-Diagnosis The tumor marker results may help surgical planning
preservation of fertility potential
Furthermore,
monitoring the response to chemotherapy
posttreatment follow-up

9. MOGCT-Management The staging is the same as for EOC
Fertility-sparing surgery should be performed when possible
Children and adeloscents with a germ cell tumor (GCT) differs from that for adult women

10. Staging Peritoneal cytology total extrafascial hysterectomy with BSO
pelvic and paraaortic lymph node dissection
omentectomy and cytology of the diaphragm
biopsy of any areas where metastases are suspected
Cytoreduction often is performed when metastases are evident
L/T is generally used

11. Lympadenectomy Nodal involvement is more common with malignant OGCTs
Lymph node metastasis
dysgerminoma→ 28 %
mixed germ cell tumors → 16 %
malignant teratoma → 8 %
Lymph node involvement was an independent predictor of poor survival with a hazard ratio of 2.9 (95% CI ).
(Kumar S et al. The prevalence and prognostic impact of lymph node metastasis in malignant germ cell tumors of the ovary. Gynecol Oncol 2008; 110:125.)

12. Cytoreduction
risks
benefits

13. Cytoreduction
TUMOR VOLUME is one of the most important prognostic factors for outcome
The likelihood of disease progression after postoperative VAC was higher in incompletely resected disease
(GOG:Slayton RE et al.Cancer 1985; 56:243)

14. Cytoreduction Upfront surgical debulking→ important
More critical for nondysgerminoma tumors
NAC should be administered in rare instances (extent of metastatic disease↑, effusions, comorbidities)

15. Adjuvat Treatment Most women undergo adjuvant CT after surgery EXCEPT
 Stage IA, Grade 1 immature teratoma
 Stage IA and IB dysgerminoma

16. Adjuvant Chemotherapy
Multiple platinum-based regimens have been used for OGCTs
Bleomycin, etoposide, and cisplatin (BEP)
Etoposide and carboplatin
Etoposide and cisplatin (EP).
carboplatin may be a reasonable alternative for women who cannot tolerate cisplatin
For most patients, the regimen of choice is BEP

17. Adjuvant Chemotherapy-Survival
Surgery +BEP  %
(early-stage nondysgerminomatous tumors)
75-80 %
(advanced disease at presentation )
More favorable for ovarian dysgerminomas regardless of stage at presentation

18. Adjuvant Chemotherapy -Toxicity
Acute- and later-onset pulmonary toxicity → bleomycin
Therapy-related myeloid neoplasms →etoposide
Long-term renal and neurotoxicity →cisplatin

19. Adjuvant Chemotherapy -Dysgerminomas
BEP
3 courses  completely resected stage I disease
4 courses  more advanced-stage disease

20. Adjuvant Chemotherapy -Dysgerminomas
Brewer M. J Clin Oncol 1999; 17:2670
n:26 (with pure ovarian dysgerminoma)
54 % stage IIIC or IV
96 % disease free after at least 3 courses of BEP

21. Adjuvant Chemotherapy- Nondysgerminomas
Data is limited
BEP for three cycles appears to prevent recurrences
Especially in well-staged patients

22. Adjuvant Chemotherapy- Nondysgerminomas
Williams S. J Clin Oncol 1994; 12:701
GOG study
n=93
Follow-up between 4 and 90 months  91 were alive and free of recurrence
2 pts developed a treatment-related hematologic secondary malignancy

23. Fertility Preservation
Preservation of a normal-appearing uterus and contralateral ovary is an option
Occult contralateral ovarian involvement appears to be greatest with dysgerminomas(5-10 %)
The ipsilateral fallopian tube is removed
80 % of women will resume normal menstrual function
No increase in pregnancy complications

24. Fertility Preservation
Gordon A et al.Dysgerminoma: a review of 158 cases from the Emil Novak Ovarian Tumor Registry. Obstet Gynecol 1981; 58:497.
N=98
Stage IA dysgerminoma
9 developed disease in the contralateral ovary
Routinely perform a wedge biopsy of a normal-appearing contralateral ovary ?
This practice is not universally accepted

25. Relapsed Disease First two years after completion of therapy
Recurrence is usually detected by a rise in serum tumor markers OR
The evolution of new disease on radiographic studies

26. Relapsed Disease Only treated with surgery surgery+BEP
Treated with CT(as adjuvant therapy or first-line treatment of stage IV disease)  repeat treatment with a platinum-based regimen
DATA is LIMITED!!!

27. Management in Children and adolescents
Differs from that for adult women
The optimal approach has not yet been characterized
The contemporary pediatric surgical approach
 peritoneal cytology,
 primary tumor removal,
 biopsy or excision of suspicious implants
or lymph nodes,
 with no further biopsies
(Children’s Oncology Group Rare Tumors Disease Committee )

28. Management in Children and adolescents
Surveillance for girls with stage IA malignant OGCTs appears to be reasonable
Adjuvant chemotherapy is routinely offered to patients with higher-stage disease
BEP recomended

29. Conclusion MOGCT typically occur in the first 2 decades of life.
Initial clinical work up should include USG, CT scans, or both, as well as tumour markers, including AFP, LDH, β-hCG, and Ca-125.
Fertility-sparing surgery with USO is the standard surgical approach for MOGCT, along with surgical staging in apparently early disease.

30. Conclusion
The role of aggressive surgical debulking is not well defined in chemo-sensitive tumours.
BEP chemotherapy is the regimen of choice in advanced MOGCT
After fertility-sparing surgery and BEP chemotherapy, most women will resume their previous baseline menstrual function.
Fertility rates approximate those of the normal population, with no significant increase in the risk of early pregnancy loss or teratogenicity

31. Teşekkürler
Kapuzbaşı Şelalesi
Yahyalı/Kayseri