Ovarian germ cell tumor medical therapy: Difference between revisions

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{{CMG}}{{AE}} {{Sahar}} {{MD}}
{{CMG}}{{AE}} {{Sahar}} {{MD}}
==Overview==
==Overview==
* Adjuvant Chemotherapy is recommended for all the patients with diagnosed malignant ovarian germ cell tumor, except those with stage 1a, stage 1a, 1b dysgerminoma, and grade 1 immature teratomas. The platinum-based regimen is currently the most effective management.
[[Adjuvant]] [[Chemotherapy]] is recommended for all the patients with [[Diagnosis|diagnosed]] [[malignant]] [[ovarian]] [[germ cell]] [[tumor]], except those with stage 1a, stage 1a, 1b [[dysgerminoma]], and grade 1 immature [[Teratoma|teratomas]]. The [[platinum]]-based regimen is currently the most effective management.
Among [[ovarian]] [[germ cell]] [[tumors]], only [[dysgerminoma]] is radiosensitive. [[Radiotherapy]] is not anymore the first option of treatment for [[dysgerminoma]] considering its association with [[ovarian failure]] development.


==Medical Therapy==
==Medical Therapy==
* Adjuvant Chemotherapy is recommended for all the patients with diagnosed malignant ovarian germ cell tumor, except those with stage 1a, stage 1a, 1b dysgerminoma, and grade 1 immature teratomas.<ref> "NCCN Clinical Practice Guidelines in Oncology: Ovarian Cancer. National comprehensive cancer network, 2011; http://www.nccn.org/professionals/physician_gls/pdf/ovarian.pdf."</ref><ref name="GershensonMorris1990">{{cite journal|last1=Gershenson|first1=D M|last2=Morris|first2=M|last3=Cangir|first3=A|last4=Kavanagh|first4=J J|last5=Stringer|first5=C A|last6=Edwards|first6=C L|last7=Silva|first7=E G|last8=Wharton|first8=J T|title=Treatment of malignant germ cell tumors of the ovary with bleomycin, etoposide, and cisplatin.|journal=Journal of Clinical Oncology|volume=8|issue=4|year=1990|pages=715–720|issn=0732-183X|doi=10.1200/JCO.1990.8.4.715}}</ref>
*There is no [[pharmacologic]] [[therapy]] for the [[Mature cystic teratoma|mature teratoma]].
* In those with stage 1a dysgerminoma and immature teratoma, surgery will be curative.   
* [[Adjuvant]] [[Chemotherapy]] is recommended for all the patients with [[Diagnose|diagnosed]] [[malignant]] [[ovarian]] [[germ cell]] [[tumor]], except those with stage 1a, stage 1a and 1b [[dysgerminoma]], and grade 1 immature [[Teratoma|teratomas]].<ref>"NCCN Clinical Practice Guidelines in Oncology: Ovarian Cancer. National comprehensive cancer network, 2011; http://www.nccn.org/professionals/physician_gls/pdf/ovarian.pdf."</ref><ref name="GershensonMorris1990">{{cite journal|last1=Gershenson|first1=D M|last2=Morris|first2=M|last3=Cangir|first3=A|last4=Kavanagh|first4=J J|last5=Stringer|first5=C A|last6=Edwards|first6=C L|last7=Silva|first7=E G|last8=Wharton|first8=J T|title=Treatment of malignant germ cell tumors of the ovary with bleomycin, etoposide, and cisplatin.|journal=Journal of Clinical Oncology|volume=8|issue=4|year=1990|pages=715–720|issn=0732-183X|doi=10.1200/JCO.1990.8.4.715}}</ref>
* In pregnant women, chemotherapy should be postponed at least until the end of the first trimester.
* In those with stage 1a [[dysgerminoma]] and immature [[teratoma]], [[surgery]] will be curative.   
* Platinum-based regimen is currently the most effective management.
* [[Platinum]]-based regimen is currently the most effective management.
** This regimen is as following:
** This regimen is as following:
*** [[Bleomycin]] 30 Unit IV per dose be given on day 1, 8, and 15 of the cycle  
*** [[Bleomycin]] 30 Unit [[Intravenous therapy|IV]] per [[dose]] be given on day 1, 8, and 15 of the cycle  
**** It must be diluted in  50 ml of normal saline (NS) and over 10 minutes.
**** It must be [[diluted]] in  50 ml of [[normal saline]] ([[Normal saline|NS]]) and over 10 minutes.
*** [[Etoposide]] 100 mg/m2 IV per day be given on days 1-5.
*** [[Etoposide]] 100 mg/m2 [[IV]] per day be given on days 1-5.
**** It must be diluted in 500 ml NS (concentration less than 0.4 mg/mL) and administered over one hour.
**** It must be [[diluted]] in 500 ml [[Normal saline|NS]] (concentration less than 0.4 mg/mL) and administered over one hour.
*** [[Cisplatin]] 20 mg/m2 IV per day be given on Days 1 through 5.
*** [[Cisplatin]] 20 mg/m2 [[Intravenous therapy|IV]] per day be given on Days 1 through 5.
**** It must be diluted in 250 mL NS and administer over two hours.
**** It must be [[diluted]] in 250 ml [[Normal saline|NS]] and administer over two hours.
**** No aluminum needles or intravenous sets be used for the administration.
**** No aluminum needles or [[intravenous]] sets be used for the administration.
** This regimen is given every 21 days for three cycles (or four cycles in the presence of bulky residual disease after surgery.
** This regimen is given every 21 days for three cycles (or four cycles in the presence of bulky residual [[disease]] after [[surgery]].
** Factors that should be monitored during the treatment:
** Factors that should be monitored during the treatment:
***Complete blood count (CBC) weekly during treatment
***[[Complete blood count]] ([[CBC]]) weekly during treatment
***Liver function test (LFT) before each treatment cycle
***[[Liver function test]] ([[LFT]]) before each treatment cycle
***Creatinin and electrolytes before each treatment cycle
***[[Creatinine|Creatinin]] and [[Electrolyte|electrolytes]] before each treatment cycle
***Pulmonary function test before starting bleomycin and at repeated intervals
***[[Pulmonary function test]] before starting [[bleomycin]] and at repeated intervals
** The overall [[survival rate]] for the patients treated with this regimen is 87% to 98%.<ref name="SegelovCampbell1994">{{cite journal|last1=Segelov|first1=E|last2=Campbell|first2=J|last3=Ng|first3=M|last4=Tattersall|first4=M|last5=Rome|first5=R|last6=Free|first6=K|last7=Hacker|first7=N|last8=Friedlander|first8=M L|title=Cisplatin-based chemotherapy for ovarian germ cell malignancies: the Australian experience.|journal=Journal of Clinical Oncology|volume=12|issue=2|year=1994|pages=378–384|issn=0732-183X|doi=10.1200/JCO.1994.12.2.378}}</ref><ref name="DimopoulosPapadimitriou2004">{{cite journal|last1=Dimopoulos|first1=Meletios A.|last2=Papadimitriou|first2=Christos|last3=Hamilos|first3=Georgios|last4=Efstathiou|first4=Eleni|last5=Vlahos|first5=Georgios|last6=Rodolakis|first6=Alexandros|last7=Aravantinos|first7=Gerassimos|last8=Kalofonos|first8=Haralambos|last9=Kouroussis|first9=Charalambos|last10=Gika|first10=Dimitra|last11=Skarlos|first11=Dimosthenis|last12=Bamias|first12=Aristotle|title=Treatment of ovarian germ cell tumors with a 3-day bleomycin, etoposide, and cisplatin regimen: a prospective multicenter study|journal=Gynecologic Oncology|volume=95|issue=3|year=2004|pages=695–700|issn=00908258|doi=10.1016/j.ygyno.2004.08.018}}</ref>
* Another regimen for the treatment of [[ovarian]] [[germ cell]] [[tumors]] is the combination of [[Vincristine]], [[dactinomycin]], and [[cyclophosphamide]] (VAC); however, [[Platinum]]-based regimen are now preferred because of a lower relapse rate and shorter treatment time.<ref name="WilliamsBlessing1994">{{cite journal|last1=Williams|first1=S|last2=Blessing|first2=J A|last3=Liao|first3=S Y|last4=Ball|first4=H|last5=Hanjani|first5=P|title=Adjuvant therapy of ovarian germ cell tumors with cisplatin, etoposide, and bleomycin: a trial of the Gynecologic Oncology Group.|journal=Journal of Clinical Oncology|volume=12|issue=4|year=1994|pages=701–706|issn=0732-183X|doi=10.1200/JCO.1994.12.4.701}}</ref>
===Treatment during pregnancy===
* In [[pregnant]] women, [[chemotherapy]] should be postponed at least until the end of the [[first trimester]].<ref name="HubalekSmekal-Schindelwig2007">{{cite journal|last1=Hubalek|first1=Michael|last2=Smekal-Schindelwig|first2=Caecilia|last3=Zeimet|first3=Alain G.|last4=Sergi|first4=Consolato|last5=Brezinka|first5=Christoph|last6=Mueller-Holzner|first6=Elisabeth|last7=Marth|first7=Christian|title=Chemotherapeutic treatment of a pregnant patient with ovarian dysgerminoma|journal=Archives of Gynecology and Obstetrics|volume=276|issue=2|year=2007|pages=179–183|issn=0932-0067|doi=10.1007/s00404-007-0328-2}}</ref>
* [[Etoposide]] use is associated with [[teratogenicity]] during the [[first trimester]] of the [[pregnancy]] and therefore should be avoided.<ref name="AmantHalaska2014">{{cite journal|last1=Amant|first1=Frédéric|last2=Halaska|first2=Michael J.|last3=Fumagalli|first3=Monica|last4=Dahl Steffensen|first4=Karina|last5=Lok|first5=Christianne|last6=Van Calsteren|first6=Kristel|last7=Han|first7=Sileny N.|last8=Mir|first8=Olivier|last9=Fruscio|first9=Robert|last10=Uzan|first10=Cathérine|last11=Maxwell|first11=Cynthia|last12=Dekrem|first12=Jana|last13=Strauven|first13=Goedele|last14=Mhallem Gziri|first14=Mina|last15=Kesic|first15=Vesna|last16=Berveiller|first16=Paul|last17=van den Heuvel|first17=Frank|last18=Ottevanger|first18=Petronella B.|last19=Vergote|first19=Ignace|last20=Lishner|first20=Michael|last21=Morice|first21=Philippe|last22=Nulman|first22=Irena|title=Gynecologic Cancers in Pregnancy: Guidelines of a Second International Consensus Meeting|journal=International Journal of Gynecologic Cancer|volume=24|issue=3|year=2014|pages=394–403|issn=1048-891X|doi=10.1097/IGC.0000000000000062}}</ref>
** Also its use is associated with neonatal delayed growth and [[bone marrow suppression]].<ref name="CardonickIacobucci2004">{{cite journal|last1=Cardonick|first1=Elyce|last2=Iacobucci|first2=Audrey|title=Use of chemotherapy during human pregnancy|journal=The Lancet Oncology|volume=5|issue=5|year=2004|pages=283–291|issn=14702045|doi=10.1016/S1470-2045(04)01466-4}}</ref>
* [[Paclitaxel]]-[[carboplatin]] or [[cisplatin]]-[[vinblastine]]-[[bleomycin]] is recommended to be used during the [[pregnancy]].<ref name="AmantHalaska2014">{{cite journal|last1=Amant|first1=Frédéric|last2=Halaska|first2=Michael J.|last3=Fumagalli|first3=Monica|last4=Dahl Steffensen|first4=Karina|last5=Lok|first5=Christianne|last6=Van Calsteren|first6=Kristel|last7=Han|first7=Sileny N.|last8=Mir|first8=Olivier|last9=Fruscio|first9=Robert|last10=Uzan|first10=Cathérine|last11=Maxwell|first11=Cynthia|last12=Dekrem|first12=Jana|last13=Strauven|first13=Goedele|last14=Mhallem Gziri|first14=Mina|last15=Kesic|first15=Vesna|last16=Berveiller|first16=Paul|last17=van den Heuvel|first17=Frank|last18=Ottevanger|first18=Petronella B.|last19=Vergote|first19=Ignace|last20=Lishner|first20=Michael|last21=Morice|first21=Philippe|last22=Nulman|first22=Irena|title=Gynecologic Cancers in Pregnancy: Guidelines of a Second International Consensus Meeting|journal=International Journal of Gynecologic Cancer|volume=24|issue=3|year=2014|pages=394–403|issn=1048-891X|doi=10.1097/IGC.0000000000000062}}</ref>
* [[Chemotherapy]] during the second and third [[trimester]] of [[pregnancy]] has not been observed to be associated with increased risk of [[fetal]] [[abnormalities]].<ref name="pmid12094965">{{cite journal |vauthors=Khi C, Low JJ, Tay EH, Chew SH, Ho TH |title=Malignant ovarian germ cell tumors: the KK Hospital experience |journal=Eur. J. Gynaecol. Oncol. |volume=23 |issue=3 |pages=251–6 |date=2002 |pmid=12094965 |doi= |url=}}</ref>
* [[Miscarriage]] rate following [[chemotherapeutic]] treatment has been reported to be the same as for general population.<ref name="ZanettaBonazzi2001">{{cite journal|last1=Zanetta|first1=Gerardo|last2=Bonazzi|first2=Cristina|last3=Cantù|first3=Maria Grazia|last4=Bini†|first4=Sergio|last5=Locatelli|first5=Anna|last6=Bratina|first6=Giorgio|last7=Mangioni|first7=Costantino|title=Survival and Reproductive Function After Treatment of Malignant Germ Cell Ovarian Tumors|journal=Journal of Clinical Oncology|volume=19|issue=4|year=2001|pages=1015–1020|issn=0732-183X|doi=10.1200/JCO.2001.19.4.1015}}</ref>
===Chemotherapy for malignant ovarian germ cell tumors and ovarian function===
The long term effects of [[chemotherapy]] on ability of [[ovary]] for future [[pregnancies]] has been studied and the results are as following:
* In one study, 83% of cases treated for these [[tumors]], resumed regular [[period]] during follow ups.<ref name="Gershenson1988">{{cite journal|last1=Gershenson|first1=D M|title=Menstrual and reproductive function after treatment with combination chemotherapy for malignant ovarian germ cell tumors.|journal=Journal of Clinical Oncology|volume=6|issue=2|year=1988|pages=270–275|issn=0732-183X|doi=10.1200/JCO.1988.6.2.270}}</ref>
* In another study, regular [[menses]] resumed in 100% of patients within 1 year of [[chemotherapy]] completion.<ref name="WeinbergLurain2011">{{cite journal|last1=Weinberg|first1=Lori E.|last2=Lurain|first2=John R.|last3=Singh|first3=Diljeet K.|last4=Schink|first4=Julian C.|title=Survival and reproductive outcomes in women treated for malignant ovarian germ cell tumors|journal=Gynecologic Oncology|volume=121|issue=2|year=2011|pages=285–289|issn=00908258|doi=10.1016/j.ygyno.2011.01.003}}</ref>
* [[Infertility]] rate for women who has been treated [[Chemotherapeutic|chemo-therapeutically]] for these [[tumors]] has been reported between 5% and 10%.<ref name="Gershenson1988">{{cite journal|last1=Gershenson|first1=D M|title=Menstrual and reproductive function after treatment with combination chemotherapy for malignant ovarian germ cell tumors.|journal=Journal of Clinical Oncology|volume=6|issue=2|year=1988|pages=270–275|issn=0732-183X|doi=10.1200/JCO.1988.6.2.270}}</ref><ref name="pmid10918171">{{cite journal |vauthors=Low JJ, Perrin LC, Crandon AJ, Hacker NF |title=Conservative surgery to preserve ovarian function in patients with malignant ovarian germ cell tumors. A review of 74 cases |journal=Cancer |volume=89 |issue=2 |pages=391–8 |date=July 2000 |pmid=10918171 |doi= |url=}}</ref>


==Medical Therapy==
==Raditherapy==
*The mainstay of therapy for ovarian germ cell tumor is [[chemotherapy]].<ref name= cba> Stage I Ovarian Germ Cell Tumors
* Not all the [[ovarian]] [[germ cell]] [[tumors]] are radiosensitive.<ref name="pmid12733128">{{cite journal |vauthors=Chen VW, Ruiz B, Killeen JL, Coté TR, Wu XC, Correa CN |title=Pathology and classification of ovarian tumors |journal=Cancer |volume=97 |issue=10 Suppl |pages=2631–42 |date=May 2003 |pmid=12733128 |doi=10.1002/cncr.11345 |url=}}</ref>
. http://www.cancer.gov/types/ovarian/hp/ovarian-germ-cell-treatment-pdq#section/_33. URL Accessed on Nov 5, 2015</ref><ref name= sss> Stage II Ovarian Germ Cell Tumors
* [[Dysgerminoma]] is a radiosensitive [[tumor]].  
. http://www.cancer.gov/types/ovarian/hp/ovarian-germ-cell-treatment-pdq#section/_43. URL Accessed on Nov 5, 2015</ref><ref name= www> Stage III Ovarian Germ Cell Tumors
* [[Radiotherapy]] is not the first option for treating [[dysgerminoma]] and it reserved for patients for whom [[chemotherapy]] is contraindicated for whatever reason.
. http://www.cancer.gov/types/ovarian/hp/ovarian-germ-cell-treatment-pdq#section/_54. URL Accessed on Nov 5, 2015</ref><ref name= rrr> Stage IV Ovarian Germ Cell Tumors
* Whole [[abdominal]] [[radiotherapy]] is used for the treatment of [[dysgerminoma]], however, it may be associated with [[ovarian failure]].<ref name="MitchellGershenson1991">{{cite journal|last1=Mitchell|first1=Michele Follen|last2=Gershenson|first2=David M.|last3=Soeters|first3=Robbert-Paul|last4=Eifel|first4=Patricia J.|last5=Delclos|first5=Luis|last6=Wharton|first6=J. Taylor|title=Long-term effects of radiation therapy on patients with ovarian dysgerminoma|journal=Cancer|volume=67|issue=4|year=1991|pages=1084–1090|issn=0008-543X|doi=10.1002/1097-0142(19910215)67:4<1084::AID-CNCR2820670436>3.0.CO;2-E}}</ref>
. http://www.cancer.gov/types/ovarian/hp/ovarian-germ-cell-treatment-pdq#section/_65. URL Accessed on Nov 5, 2015</ref>
*There is no pharmacologic therapy for the mature teratoma.
===Stage I ovarian germ cell tumors===
* Dysgerminomas
:* Unilateral [[salpingo-oophorectomy]] with adjuvant [[radiation]] therapy or chemotherapy
* Other germ cell tumors
:* Unilateral salpingo-oophorectomy with adjuvant [[chemotherapy]]
 
===Stage II ovarian germ cell tumors===
* Dysgerminomas
:* Total abdominal hysterectomy and bilateral salpingo-oophorectomy with adjuvant radiation therapy or chemotherapy
:* Unilateral salpingo-oophorectomy with adjuvant chemotherapy
* Other germ cell tumors
:* Unilateral salpingo-oophorectomy with adjuvant chemotherapy
 
===Stage III ovarian germ cell tumors===
* Dysgerminomas
:* Unilateral salpingo-oophorectomy with adjuvant chemotherapy
* Other germ cell tumors
:* Total abdominal hysterectomy and bilateral salpingo-oophorectomy with adjuvant chemotherapy, with or without neoadjuvant chemotherapy
:* Unilateral salpingo-oophorectomy with adjuvant chemotherapy, with or without neoadjuvant chemotherapy
 
===Stage IV ovarian germ cell tumors===
* Dysgerminomas
:* Total abdominal hysterectomy and bilateral salpingo-oophorectomy with adjuvant chemotherapy
:* Unilateral salpingo-oophorectomy with adjuvant chemotherapy
* Other germ cell tumors
:* Total abdominal hysterectomy and bilateral salpingo-oophorectomy with adjuvant chemotherapy with or without neoadjuvant chemotherapy
:* Unilateral salpingo-oophorectomy with adjuvant chemotherapy with or without neoadjuvant chemotherapy


==References==
==References==

Latest revision as of 14:01, 22 April 2019

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Associate Editor(s)-in-Chief: Sahar Memar Montazerin, M.D.[2] Monalisa Dmello, M.B,B.S., M.D. [3]

Overview

Adjuvant Chemotherapy is recommended for all the patients with diagnosed malignant ovarian germ cell tumor, except those with stage 1a, stage 1a, 1b dysgerminoma, and grade 1 immature teratomas. The platinum-based regimen is currently the most effective management. Among ovarian germ cell tumors, only dysgerminoma is radiosensitive. Radiotherapy is not anymore the first option of treatment for dysgerminoma considering its association with ovarian failure development.

Medical Therapy

Treatment during pregnancy

Chemotherapy for malignant ovarian germ cell tumors and ovarian function

The long term effects of chemotherapy on ability of ovary for future pregnancies has been studied and the results are as following:

Raditherapy

References

  1. ↑ "NCCN Clinical Practice Guidelines in Oncology: Ovarian Cancer. National comprehensive cancer network, 2011; http://www.nccn.org/professionals/physician_gls/pdf/ovarian.pdf."
  2. ↑ Gershenson, D M; Morris, M; Cangir, A; Kavanagh, J J; Stringer, C A; Edwards, C L; Silva, E G; Wharton, J T (1990). "Treatment of malignant germ cell tumors of the ovary with bleomycin, etoposide, and cisplatin". Journal of Clinical Oncology. 8 (4): 715–720. doi:10.1200/JCO.1990.8.4.715. ISSN 0732-183X.
  3. ↑ Segelov, E; Campbell, J; Ng, M; Tattersall, M; Rome, R; Free, K; Hacker, N; Friedlander, M L (1994). "Cisplatin-based chemotherapy for ovarian germ cell malignancies: the Australian experience". Journal of Clinical Oncology. 12 (2): 378–384. doi:10.1200/JCO.1994.12.2.378. ISSN 0732-183X.
  4. ↑ Dimopoulos, Meletios A.; Papadimitriou, Christos; Hamilos, Georgios; Efstathiou, Eleni; Vlahos, Georgios; Rodolakis, Alexandros; Aravantinos, Gerassimos; Kalofonos, Haralambos; Kouroussis, Charalambos; Gika, Dimitra; Skarlos, Dimosthenis; Bamias, Aristotle (2004). "Treatment of ovarian germ cell tumors with a 3-day bleomycin, etoposide, and cisplatin regimen: a prospective multicenter study". Gynecologic Oncology. 95 (3): 695–700. doi:10.1016/j.ygyno.2004.08.018. ISSN 0090-8258.
  5. ↑ Williams, S; Blessing, J A; Liao, S Y; Ball, H; Hanjani, P (1994). "Adjuvant therapy of ovarian germ cell tumors with cisplatin, etoposide, and bleomycin: a trial of the Gynecologic Oncology Group". Journal of Clinical Oncology. 12 (4): 701–706. doi:10.1200/JCO.1994.12.4.701. ISSN 0732-183X.
  6. ↑ Hubalek, Michael; Smekal-Schindelwig, Caecilia; Zeimet, Alain G.; Sergi, Consolato; Brezinka, Christoph; Mueller-Holzner, Elisabeth; Marth, Christian (2007). "Chemotherapeutic treatment of a pregnant patient with ovarian dysgerminoma". Archives of Gynecology and Obstetrics. 276 (2): 179–183. doi:10.1007/s00404-007-0328-2. ISSN 0932-0067.
  7. ↑ 7.0 7.1 Amant, Frédéric; Halaska, Michael J.; Fumagalli, Monica; Dahl Steffensen, Karina; Lok, Christianne; Van Calsteren, Kristel; Han, Sileny N.; Mir, Olivier; Fruscio, Robert; Uzan, Cathérine; Maxwell, Cynthia; Dekrem, Jana; Strauven, Goedele; Mhallem Gziri, Mina; Kesic, Vesna; Berveiller, Paul; van den Heuvel, Frank; Ottevanger, Petronella B.; Vergote, Ignace; Lishner, Michael; Morice, Philippe; Nulman, Irena (2014). "Gynecologic Cancers in Pregnancy: Guidelines of a Second International Consensus Meeting". International Journal of Gynecologic Cancer. 24 (3): 394–403. doi:10.1097/IGC.0000000000000062. ISSN 1048-891X.
  8. ↑ Cardonick, Elyce; Iacobucci, Audrey (2004). "Use of chemotherapy during human pregnancy". The Lancet Oncology. 5 (5): 283–291. doi:10.1016/S1470-2045(04)01466-4. ISSN 1470-2045.
  9. ↑ Khi C, Low JJ, Tay EH, Chew SH, Ho TH (2002). "Malignant ovarian germ cell tumors: the KK Hospital experience". Eur. J. Gynaecol. Oncol. 23 (3): 251–6. PMID 12094965.
  10. ↑ Zanetta, Gerardo; Bonazzi, Cristina; Cantù, Maria Grazia; Bini†, Sergio; Locatelli, Anna; Bratina, Giorgio; Mangioni, Costantino (2001). "Survival and Reproductive Function After Treatment of Malignant Germ Cell Ovarian Tumors". Journal of Clinical Oncology. 19 (4): 1015–1020. doi:10.1200/JCO.2001.19.4.1015. ISSN 0732-183X.
  11. ↑ 11.0 11.1 Gershenson, D M (1988). "Menstrual and reproductive function after treatment with combination chemotherapy for malignant ovarian germ cell tumors". Journal of Clinical Oncology. 6 (2): 270–275. doi:10.1200/JCO.1988.6.2.270. ISSN 0732-183X.
  12. ↑ Weinberg, Lori E.; Lurain, John R.; Singh, Diljeet K.; Schink, Julian C. (2011). "Survival and reproductive outcomes in women treated for malignant ovarian germ cell tumors". Gynecologic Oncology. 121 (2): 285–289. doi:10.1016/j.ygyno.2011.01.003. ISSN 0090-8258.
  13. ↑ Low JJ, Perrin LC, Crandon AJ, Hacker NF (July 2000). "Conservative surgery to preserve ovarian function in patients with malignant ovarian germ cell tumors. A review of 74 cases". Cancer. 89 (2): 391–8. PMID 10918171.
  14. ↑ Chen VW, Ruiz B, Killeen JL, Coté TR, Wu XC, Correa CN (May 2003). "Pathology and classification of ovarian tumors". Cancer. 97 (10 Suppl): 2631–42. doi:10.1002/cncr.11345. PMID 12733128.
  15. ↑ Mitchell, Michele Follen; Gershenson, David M.; Soeters, Robbert-Paul; Eifel, Patricia J.; Delclos, Luis; Wharton, J. Taylor (1991). "Long-term effects of radiation therapy on patients with ovarian dysgerminoma". Cancer. 67 (4): 1084–1090. doi:10.1002/1097-0142(19910215)67:4<1084::AID-CNCR2820670436>3.0.CO;2-E. ISSN 0008-543X.

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