Multidisciplinary management of malignant ovarian germ cell tumours

Objectives

Malignant ovarian germ cell tumours (MOGCT) are rare cancers of young women. Limited prospective trials exist from which evidence-based management can be developed. This review summarizes the available literature concerning MOGT in order to provide the clinician with information relevant to their multidisciplinary management.

Methods

MEDLINE was searched between 1966 and 2010 for all publications in English where the studied population included women diagnosed with malignant ovarian germ cell tumours.

Results

The majority of patients can be cured with fertility-preserving surgery with or without combination chemotherapy. Long term survival approaches 100% in early stage disease and is approximately 75% in advanced stage disease. Most studies suggest that the treatment has little, if any, effect on future fertility and limited data suggest that there is no adverse effect on the future quality of life.

Conclusion

MOGCTs are rare tumours of young women the majority of which can be successfully treated with fertility-preserving surgery with or without chemotherapy with preservation of reproductive function. Minimisation of chemotherapy in good prognostic groups and improved treatment in resistant and relapsed MOGCT are important goals for the future. Further studies are needed to quantify the late adverse effects of treatment in long term survivors.     

Treatment of malignant ovarian germ cell tumors with preservation of fertility

Preservation of fertility was practiced in 28 young patients with malignant germ cell tumors from 1962 through 1987. The pathologic diagnosis was immature teratoma in 16, endodermal sinus tumor in 7, dysgerminoma in 2 and germ cell tumor of mixed type in 3. At laparotomy, 16 patients proved to have stage I disease, one stage II, 9 stage III and 2 stage IV disease. The tumor was confined to one ovary in all the 22 cases operated on for the first time and the preserved ovary and uterus were normal in all 6 referred cases for recurrent diseases. Postoperative chemotherapy was given to all patients except two with stage I immature teratoma. A persistent remission was achieved in 22 patients, while 5 patients died and one was out of contact. The duration of survival was more than one year for all patients, more than 3 years in 16 cases (72.7%) and more than 5 years in 13 cases (59.1%). The menstrual periods were normal in all cases except 3, of which 2 were below the age of 12 and one failed to menstruate at the age of 19 with a hypoplastic uterus and underdeveloped secondary sex characteristics. Among 12 married patients, 7 of 10 desirous of childbirth became pregnant during follow-ups. Of these, 6 had normal term-deliveries and one is currently pregnant. The preliminary conclusion is that preservation of fertility for young patients with malignant ovarian germ cell tumor is a safe and practicable procedure in the absence of involvement of the contralateral ovary and uterus.     

Primary treatment failure in patients with malignant ovarian germ cell neoplasms

Between 1970 and 1990, 160 patients with malignant non-dysgerminomatous ovarian germ cell tumors have been treated at our own institution. Primary therapy failed in 42 of these patients, who constitute the basis for this study. Seventeen patients had stage I disease, 5 stage II, 17 stage III, and 3 stage IV. Histologic type included 13 immature teratomas, 8 endodermal sinus tumors, and 21 mixed germ cell tumors. Primary therapy for 14 patients was surgery alone, for 23, surgery plus chemotherapy, for 2, surgery plus radiotherapy and for 3, all three modalities. Median progression-free survival from initial diagnosis lasted 6.8 months (range, 0.9–24 months). Thirty-four patients received chemotherapy as part of salvage; 5/11 (45%) who received VAC are disease-free, and 6/11 (55%) who received cisplatin combinations are disease-free. When primary VAC failed, 3/7 (43%) were salvaged with cisplatin combinations. When primary cisplatin combinations failed, 2/5 (40%) were salvaged. Twelve of the 42 patients (29%) are currently alive disease-free. Primary treatment failure was attributed to surgery alone for 14 patients (7 because of misdiagnosis), radiotherapy for 5, and toxicity for 1. Of the 22 patients who failed chemotherapy, 12 did so because of a suboptimal regimen, 3 because of possible dose-intensity problems, one because of non-compliance, and 6 for unexplained reasons. Patients with ovarian germ cell tumors have an excellent probability of cure with aggressive primary therapy, but successful salvage may be difficult when primary treatment fails.     

Survival and reproductive outcomes in women treated for malignant ovarian germ cell tumors

Objective

The objective of this study is to review all malignant germ-cell tumors (MOGCTs) treated at our institution, focusing on reproductive outcomes and menstrual function of patients treated with fertility-sparing surgery and adjuvant chemotherapy.

Methods

We performed a retrospective chart review of patients treated for MOGCTs between January 1, 1979 and March 31, 2008. Charts of identified patients were abstracted and data were collected. Patients who had fertility-sparing surgery were contacted and a telephone questionnaire was performed to gather reproductive and menstrual history.

Results

Forty patients were treated for MOGCTs at our institution. Mean age at the time of diagnosis was 26.5 years (range, 10-48 years). Histologic subtypes were: immature teratoma (52.5%), dysgerminoma (27.5%), yolk sac tumor (10.0%), mixed germ cell tumor (7.5%), and choriocarcinoma (2.5%). Thirty-five percent of tumors were FIGO stages II-IV. Twenty-seven patients (67.5%) were treated with chemotherapy postoperatively, 23 (85%) of whom received bleomycin, etoposide and cisplatin (BEP). There were three recurrences, but no deaths.Fertility-sparing surgery was performed in 22 patients (55%), 16 of whom received adjuvant chemotherapy. Fourteen of these patients were contacted. Of the 10 remaining patients desiring pregnancy, 8 (80%) had 11 successful spontaneous pregnancies, one required in-vitro fertilization, and the other required donor egg in-vitro fertilization, resulting in 14 live births. All 14 patients had normal menstrual cycles within one year of completing chemotherapy.

Conclusions

Overall survival was 100% among patients with both local and advanced MOGCTs, including those who underwent fertility-sparing surgery. Fertility-sparing surgery plus adjuvant chemotherapy appeared to have little or no effect on fertility or menstrual cycles.     

晚期与复发性卵巢恶性生殖细胞肿瘤129例治疗结果的分析

目的探讨改进晚期及复发性卵巢恶性生殖细胞肿瘤治疗的方法。方法回顾性分析１９５８～１９９３年我院收治的１２９例晚期与复发性卵巢恶性生殖细胞肿瘤的治疗结果。对１９８４～１９９３年间采用ＶＡＣ方案（长春新碱＋更生霉素＋环磷酰胺）、ＰＶＢ方案（顺铂＋长春花碱＋博莱霉素）及ＢＥＰ方案（博莱霉素＋足叶乙甙＋顺铂）治疗的患者生存情况,与１９５８～１９８３年间采用随意治疗方案的患者生存情况进行比较。结果１２９例晚期与复发性卵巢恶性生殖细胞肿瘤总的５年生存率为３０％（３９／１２９）,其中无性细胞瘤的５年生存率为６８％（１９／２８）,而非无性生殖细胞瘤为２０％（２０／１０１）。近１０年,卵巢非无性生殖细胞瘤患者的５年生存率已由３％提高到４２％。联合化疗对生存率的提高起着关键作用。３个联合方案,以ＢＥＰ方案疗效较好。结论卵巢内胚窦瘤的发生率在中国各类型卵巢恶性生殖细胞瘤中位居首位。为改善晚期与复发性卵巢恶性生殖细胞瘤患者的预后,应对所有患者尽早采用目前较有效的化疗方案——ＢＥＰ方案治疗。     

Management of malignant ovarian germ cell tumors

Malignant ovarian germ cell tumors are rare, highly curable cancers of young women. The majority of patients can be cured with either fertility-preserving surgery alone or a combination of surgery and chemotherapy. Relapses occur in 10% to 20% of patients, and the significant proportion of them can be salvaged with chemotherapy. There is no evidence that treatment for malignant ovarian germ cell tumors will adversely affect menstrual or reproductive functions, increase future pregnancy loss, or increase the risk of congenital malformations of the fetus. Late effects, such as secondary leukemia, from chemotherapy are reported but rare. TARGET AUDIENCE: Obstetricians & Gynecologists and Family Physicians. LEARNING OBJECTIVE: After completing this CME activity, physicians should be better able to diagnose ovarian germ cell tumors, outline management of malignant ovarian germ cell tumors, and understand the impact of treatment on fertility and late effects.     

Fertility after chemotherapy for ovarian germ cell tumours

Gonadal function was assessed in 17 women who successfully completed chemotherapy with the POMB/ACE regimen (cisplatin, vincristine [Oncovin], methotrexate, bleomycin/actinomycin D, cyclophosphamide, etoposide) for ovarian germ cell tumours, and had a remaining ovary and uterus. A 20-year-old girl has not yet recovered menstruation 5 months off chemotherapy. All the remaining women whose mean age at start of chemotherapy was 21 (9-38) are now menstruating with a median time of recovery of 41/2 months after completion of chemotherapy. Five women have so far conceived after chemotherapy resulting in three full term normal deliveries of healthy infants, one termination of pregnancy, two miscarriages and one continuing pregnancy. Gonadal function does not appear to be permanently impaired in the majority of patients receiving POMB/ACE chemotherapy for ovarian germ cell tumours.     

Outcomes and prognostic factors of patients with recurrent and persistent malignant ovarian germ cell tumors

Archives of Gynecology and Obstetrics - Due to the rarity of recurrent and persistent malignant ovarian germ cell tumors (MOGCTs), there is no standardized protocol for salvage therapy. This study...     

A case series of patients with gonadal dysgenesis-associated mixed malignant ovarian germ cell tumor

Abstract

Introduction: Malignant germ cell tumors (MGCT) can occur in both genders. In this study, we present eight cases of mixed ovarian MGCT in patients. Most patients reported in the current study are young women, among whom clinical characteristics of gonadal dysgenesis associated MGCT were rarely reported.

Methods: Comprehensive information of eight patients with mixed ovarian MGCTs, including patients’ age, clinical features, tumor markers, imaging findings, surgical records, pathology, karyotyping tests, chemotherapy and follow-up were collected. Surgical specimens were evaluated by two specialized gynecologic pathologists.

Results: All patients received surgery, while seven received chemotherapy. Among them, two received a second surgery and three patients received hormone replacement therapy (HRT) after gonadectomy. Four of five patients with amenorrhea were found to have 46, XY karyotype. All patients showed no sign of recurrence at the latest follow-up.

Discussion: Karyotyping or genetics testing in patients with amenorrhea is necessary, especially for patients with pelvic mass, which can help surgeons to evaluate the necessity of gonadectomy before surgery. The patients with gonadal dysgenesis associated mixed ovarian MGCT seem to have better prognosis and long survival time. Thus, HRT, an option that can improve life quality, is worth considering for these patients after gonadectomy.     

卵巢恶性生殖细胞肿瘤保守治疗探讨

目的 探讨卵巢恶性生殖细胞肿瘤（MOGCT）保守治疗对患者存活率、月经和生育功能的影响.方法 1987年1月至2004年10月对天津医科大学总医院妇科共收治MOGCT患者50例中的22例行保守手术,21例行广泛性切除手术,7例行姑息手术,比较3种术式患者的存活率.行保守手术和辅助化疗并存活的MOGCT患者17例（研究组）,随机抽取同期因成熟型畸胎瘤行单侧附件切除术的未绝经患者35例（对照组）与之对照,比较两组治疗后的月经和生育功能.结果 MOGCT占卵巢恶性肿瘤的9.35%,广泛手术和保守手术的存活率分别为74.97%和43.85%（P＞0.05）;研究组和对照组月经紊乱的发生率分别为26.32%和5.71%（P＜0.05）,两组妊娠率分别为83.33%和81.25%,分娩率分别为83.33%和81.25%,均无统计学意义（P＞0.05）.结论 保守手术和辅助化疗对有生育要求的MOGCT患者是安全、有效的,在不影响存活率的前提下,对月经和生育功能无影响.     

Clinicopathological study of malignant ovarian germ cell tumor

In treating malignant germ cell tumors clinicopathologically at Kurume University Hospital, for 18 years, the total number of patients was 112, including 25 yolk sac tumors (YST), 10 mixed form germ cell tumors (MF), 36 dysgerminomas (DYS), 26 immature teratomas (IT), 2 choriocarcinomas (CHO) and 13 dermoid cysts with malignant transformation (DCMT). The average age of patients in each group was 25.9 years for DCMT patients. When DCMT cases were excluded, ages was closely related to the age of menarche in each patient. The 5 year survival rate for each germ cell malignancy after the first operation was 31.6% for YST cases, 20.0% for MF, 76.7% for DYS, 60.0% for IT and 50.0% for DCMT cases. Despite currently used aggressive kinds of chemotherapy, the clinical stage still had a prognostic significance in all malignant germ cell tumors except dysgerminoma. Since histological maturation of the tumor tissue following treatment courses was observed in YST and IT cases, the possibility of a relationship between prognosis and the histogenetic process was shortly discussed.     

Menstrual function and childbearing potential after fertility-sparing surgery and platinum-based chemotherapy for malignant ovarian germ cell tumours

Malignant ovarian germ cell tumours (MOGCT) account for 5% of all ovarian malignancies. Their elevated chemosensitivity, the frequent unilaterality and the young age of patients have strongly supported the conservative surgery as the standard approach, often followed by adjuvant platinum-based chemotherapy. The risk for recurrence is not affected by the performance of conservative versus radical surgery. During chemotherapy 50% of patients become amenorrhoeic but more than 95% of them resume normal menses after treatment completion. Literature has reported several healthy babies born after fertility-sparing surgery with or without chemotherapy for MOGCT. The incidence of miscarriages is in the normal range, whereas malformation rate is slightly higher compared to general population, without any difference between chemotherapy-treated and -untreated patients. Therefore, young women with MOGCT must be reassured of their excellent chances of survival and fertility preservation following conservative surgery and adjuvant platinum-based chemotherapy.     

Molecular genetic analysis of malignant ovarian germ cell tumors

OBJECTIVE: Relatively little is known about the molecular mechanisms involved in the initiation and progression of ovarian germ cell tumors (OGCTs), in contrast to testicular germ cell tumors (TGCTs) which have been extensively investigated. Ovarian germ cell tumors share many pathological and biological features with TGCTs and it is likely that they share similar molecular genetic alterations, although this has not been studied in detail. The aim of this study was to compare and contrast loss of heterozygosity (LOH) in OGCTs at chromosomal regions that are commonly involved in TGCTs. METHODS: Universal amplification was performed on 35 paired specimens of malignant OGCT and constitutional DNA that had been microdissected from single paraffin-embedded tissue sections in 32 patients. Sixty-two microsatellite markers were used to assess LOH at chromosomal regions mapping to 3q, 5q, 9p, 11p, 11q, 12q, 17p, and 18q as these are commonly involved in testicular germ cell tumors. RESULTS: Assessment of these regions demonstrated common sites of deletion at 3q27-q28 (50%), 5q31 (33%), 5q34-q35 (46%), 9p22-p21 (32%) and 12q22 (53%) in all histological subtypes of OGCT. We and others have previously found these regions to be frequently deleted at early stages of tumor development in TGCTs. CONCLUSIONS: These chromosomal regions may contain tumor suppressor genes that are important in the initiation and progression of both malignant OGCTs and TGCTs.     

复发性耐药性卵巢恶性生殖细胞肿瘤的治疗

恶性生殖细胞肿瘤治疗关键是规范化,包括手术切除肿瘤、手术病理分期、术后规范化疗,强调及时、足量、正规,可争取90%以上甚至100%的持续缓解率。初次化疗不规范,病情可能持续不缓解或复发。对于复发性恶性生殖细胞肿瘤,再次肿瘤细胞减灭术有减轻瘤负荷的作用,为术后的化疗奠定基础。复发性卵巢恶性生殖细胞肿瘤术后的二线化疗也至关重要。化疗药物应个体化,化疗的疗程数也强调个体化,有阳性肿瘤标志物的患者治疗应持续至肿瘤标志物降至正常后2个疗程。无阳性的肿瘤标志物的患者治疗应持续4~6个疗程。无性生殖细胞瘤和未成熟畸胎瘤对再次化疗或手术仍有效,预后好。卵黄囊瘤则效果很差。卵巢胚胎癌及原发绒癌很少见,治疗经验少。     

Etoposide combination chemotherapy in refractory ovarian malignant germ cell tumor

Thirty-three patients with malignant germ cell tumor of the ovary received postoperative vincristine, dactinomycin, and cyclosphosphamide (VAC) treatment. Eight failed VAC treatment and received etoposide, bleomycin, and cisplatin (PEB) combination chemotherapy. Three were cured and remained disease free 24-79 months after completion of PEB therapy.     

Childhood malignant ovarian germ cell tumors: a monoinstitutional experience

OBJECTIVES: We reviewed our 23-year monoinstitutional exprience with childhood malignant ovarian germ cell tumors (MOGCT), with respect to survival and iatrogenic sequelae. METHODS: Twenty-nine patients (median age 12 years) with newly diagnosed MOGCT were treated: all girls but 2 underwent surgery as initial treatment. There were 9 pure dysgerminomas and 20 nondysgerminoma tumors (5 immature teratomas, 4 yolk sac tumors, and 11 mixed histology tumors). According to the FIGO classification, 9 girls were classified as stage I, 4 as II, 11 as III, and 3 as IV, and 2 were not evaluable because they were submitted to primary chemotherapy. Twenty-four received chemotherapy with VAC, PVB, or PEB regimens, according to the ongoing protocols through the years. Three stage I girls did not receive adjuvant chemotherapy because of their histology (2 dysgerminomas, 1 immature teratoma) and stage. In the early years, postoperative radiotherapy was given alone in advanced dysgerminoma stages. RESULTS: Five patients died of their disease: 2 dysgerminomas (stage IIIc and IV) and 3 nondysgerminomas (2 stage II and 1 stage IIIc). OS and EFS rates at a median of 112 months were 81.8%. Among 24 survivors, 4 experienced iatrogenic amenorrhea because of radiotherapy and/or bilateral oophorectomy. CONCLUSIONS: MOGCT are highly chemosensitive and curable, with preservation of reproductive function. The management of recurrent disease remains an open issue.     

Clinical review of 55 cases of malignant ovarian germ cell tumors

PURPOSE OF INVESTIGATION: A retrospective analysis of 55 cases of malignant germ cell tumors in a 20-year period was done to evaluate the impact of conservative surgery and adjuvant treatment on survival and fertility. METHODS: Fifty-five cases of malignant ovarian germ cell tumors (MOGCTs) were studied. Mean age was 22 years. Dysgerminoma was the most common histotype (45%). RESULTS: Thirty-nine patients (71%) presented with FIGO surgical Stage I disease. Fertility-sparing surgery was performed in 39 (71%) women. Postoperative systemic chemotherapy was administered to 40 women (73%), 27 (68%) had received conservative treatment. One woman developed renal failure after the first cycle of chemotherapy and died a few days thereafter and there was one case of bleomycin-induced death due to pulmonary fibrosis. There were eight (14.5%) clinical recurrences. Overall survival rate for relapsing women was 75% (6/8). The recurrence rate for women treated conservatively was 15%, and it was 13% for those treated radically. With a median follow-up of 129 months the overall survival rate for the entire study-population was 90.9%. Eleven pregnancies occurred in 36 women treated with fertility-sparing surgery who were of child-bearing age. CONCLUSION: The management of MOGCTs with fertility-sparing surgery is a safe, practicable treatment option. The majority of these patients can retain normal ovarian function and reproductive potential after chemotherapy treatment.