Potential for cure in metastatic ovarian teratomas and dysgerminomas

Summary. Between 1977 and 1981 21 patients with metastatic ovarian germ cell tumours received sequential combination chemotherapy; 18 had malignant teratomas and three dysgerminomas. Thirteen patients with malignant teratoma have had no treatment for up to 45 months (mean 27.5 months) and one patient is still having treatment. Life table estimate of survival on 1 July 1981 projects a survival of 71% in those with malignant ovarian teratomas. Four patients with malignant teratoma have died. Two of these had received extensive treatment before referral and a third achieved complete remission but relapsed and did not subsequently respond fully to further treatment. A fourth patient had an undifferentiated tumour compatible with an embryonal carcinoma which proved refractory to all treatment. The three patients with advanced dysgerminomas are all in remission and have had no treatment for 5, 14 and 33 months respectively. The majority of metastatic germ cell tumours of the ovary now appear to be curable provided that effective treatment is begun early.     

Alpha-fetoprotein in malignant germ cell tumors of the ovary.

To investigate the clinical significance of alpha-Fetoprotein (AFP) in malignant germ cell tumors of the ovary, we studied 46 patients who were treated by the Tokai Ovarian Tumor Study Group. The 46 patients had the following tumors: immature teratoma (IT), 17 cases; endodermal sinus tumor (EST), 16 cases; mixed germ cell tumor containing EST, 11 cases; embryonal carcinoma, 1 case; polyembryoma, 1 case. In all 29 non-IT cases, AFP was positive, and in 27 cases (93%) the level was above 1000 ng/ml. In 11 of 17 cases of IT (64.7%), AFP levels were elevated and in 1 case the level was above 1000 ng/ml. Elevation of the AFP level above 1000 ng/ml suggested the presence of EST. AFP levels were monitored in 27 of 29 cases without IT during treatment and follow-up. It was found that AFP levels should be monitored closely for at least 1 year after induction of remission. No recurrence was observed when AFP continued to be negative longer than 1 year. The mean interval to clinical recurrence from the reelevation of AFP was 4 months (1.4-9 months). An increase in the AFP to a positive level, even without clinical signs of recurrence, should be regarded as a recurrence. AFP was found to be a useful tumor marker for the diagnosis and management of malignant germ cell tumors of the ovary.     

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。     

Serum lactate dehydrogenase levels in malignant germ cell tumors of ovary

Serum lactate dehydrogenase (LDH) levels were examined in 24 patients with germ cell tumors of the ovary to evaluate the usefulness of the enzyme as a tumor maker. Lactate dehydrogenase levels were found to be significantly elevated ( P < 0.001) in these patients at the time of diagnosis as compared to the controls. Lactate dehydrogenase levels in patients with benign ovarian tumors and controls were comparable. The positive rate of LDH for malignant germ cell tumors of the ovary was 94.5%. The LDH values significantly declined in the patients who responded to treatment. Metastatic or recurrent disease resulted in increased LDH levels. The results indicate that LDH is a useful tumor marker for malignant germ cell tumors of the ovary.     

Endodermal sinus tumor treated with high dose cisplatin

A woman with an endodermal sinus tumor of the ovary stage IV obtained a short but complete remission after treatment with vinblastine, bleomycin and standard dose cisplatin. A second complete remission for 42+ months was obtained with a regimen of vinblastine, bleomycin, etoposide, and high dose cisplatin. This result suggests a dose-response relationship for cisplatin in ovarian germ cell tumors.     

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.     

卵巢卵黄囊瘤手术和化疗后自然周期体外受精-胚胎移植成功分娩一例并文献复习

卵巢卵黄囊瘤属卵巢恶性生殖细胞肿瘤,占卵巢恶性肿瘤的1%。由于卵巢恶性生殖细胞肿瘤多见于儿童及年轻女性,故保存生育能力是关键。卵巢卵黄囊瘤对化疗药物敏感,手术联合术后辅助化疗是标准治疗方案。对于对侧卵巢和子宫未受肿瘤累及,并且有生育需求的患者均应行保留生育功能的手术。但肿瘤本身、手术和放化疗均可能造成患者不孕,术后可能需要借助辅助生殖技术助孕,本文通过1例卵巢卵黄囊瘤患者手术和术后化疗后行自然周期-体外受精-胚胎移植(NC-IVF-ET)的个案报道和文献复习,探讨卵巢卵黄囊瘤患者的生育助孕策略。     

Nondysgerminomatous tumors of the ovary treated with cisplatin, vinblastine, and bleomycin: long-term results.

Twenty-four consecutive patients with nondysgerminomatous germ cell tumor of the ovary were treated after surgery with cisplatin, vinblastine, and bleomycin (PVB regimen). The cycle was repeated every 3 weeks for three to five courses. Fourteen patients had endodermal sinus tumor, and 10 had mixed germ cell tumors. Stage of disease (FIGO, 1986) was as follows: stage I, 6; stage IIc-IV, 17; and recurrence, 1 patient. All patients were monitored by alpha-fetoprotein and human chorionic gonadotropin. Only 1 patient had received previous chemotherapy. All 5 patients without residual disease and with negative marker levels in which PVB was used as adjuvant treatment were free of disease for a median duration of 59 months from the start of PVB. Of the 19 patients with measurable disease (evident disease or positive marker levels), complete remission was obtained in 16 (84%), but 5 of these relapsed. Therefore, treatment with PVB failed in 8 out of 19 patients (42%) with measurable disease. Toxicity was evident, but no patient died of it. Menses were regular in 11 patients whose initial surgery was conservative. PVB regimen is an effective but not a satisfactory treatment. The considerable failure rate of PVB treatment suggests the investigation of other regimens.     

Reproductive function after conservative surgery and chemotherapy for malignant germ cell tumors of the ovary

OBJECTIVE: To analyze the long-term effects on reproductive function of fertility-preserving treatment for malignant germ cell tumors of the ovary. METHODS: A case series analysis was performed on patients with malignant germ cell tumors of the ovary seen or consulted on at our institution between 1975 and 1995. Follow-up information regarding reproductive function was obtained by a mailed or telephone questionnaire. RESULTS: A total of 106 patients with malignant germ cell tumors of the ovary were included in the study. Twenty patients were excluded because of loss of follow-up or death. For the remaining 86 patients, the median follow-up was 122 months (24-384 months). Fertility-preserving surgery was performed in 64 patients. Thirty-eight have attempted conception and 29 have achieved at least one pregnancy (76%). Among the patients who conceived, 20 were International Federation of Gynecology and Obstetrics (FIGO) stage I, one was stage II, and eight were stage III. Sixteen received vincristine, actinomycin D, and cyclophosphamide; three received cisplatin, vinblastine, and bleomycin; three received bleomycin, etoposide, and cisplatin; one received etoposide and cisplatin; four did not receive any chemotherapy; and two were treated with other combinations. Among the nine patients who could not conceive, seven were FIGO stage I and two were stage III. Four of these patients received vincristine, actinomycin D, and cyclophosphamide; three received etoposide and cisplatin; one received cisplatin, vinblastine, and bleomycin; and one patient received no chemotherapy. A total of 38 children were born to these women. Follow-up was available for 16 of these children, who have no evidence of congenital anomalies. CONCLUSION: Fertility-preserving surgery followed by chemotherapy, even in advanced-stage malignant germ cell tumors of the ovary, is effective in conserving the reproductive function of women with malignant germ cell tumors of the ovary.     

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.     

卵巢恶性生殖细胞肿瘤合并肺转移15例临床分析

目的 探讨卵巢恶性生殖细胞肿瘤(MOGCT)合并肺转移的临床特点、诊断、出现肺转移时间、治疗及预后.方法 对北京协和医院1982年1月至2010年12月收治的15例MOGCT合并有肺转移患者的临床资料进行回顾性分析.结果(1)临床特点:患者平均发病年龄为(23±11)岁(6 ～48岁).首发临床表现以腹部疼痛和不规则阴道流血为主,分别为8、4例.原发灶位于卵巢左、右侧者分别为8、6例,双侧者1例.转移灶仅为肺者12例,其他3例为多部位转移.(2)诊断:15例患者中,单纯性卵巢非妊娠性绒毛膜癌(绒癌;NGOC)9例,含有绒癌成分的卵巢混合性生殖细胞肿瘤3例(包括卵巢成熟性畸胎瘤合并绒癌1例、卵黄瘤为主伴绒癌及胚胎癌成分1例、绒癌伴无性细胞瘤1例),不含绒癌成分的卵巢恶性生殖细胞肿瘤3例(包括内胚窦瘤2例、未成熟性畸胎瘤1例).其中,仅1例于术前明确诊断.(3)出现肺转移时间:12例NGOC或含绒癌成分的混合性生殖细胞肿瘤患者中,11例在初始治疗的过程中即出现肺转移,1例为肿瘤复发后出现肺转移;3例不含绒癌成分的卵巢恶性生殖细胞肿瘤患者,均为肿瘤复发后在疾病晚期出现肺转移.(4)治疗:15例MOGCT合并有肺转移患者均采用手术联合化疗的综合治疗,平均化疗疗程数为16个(5 ～ 43个).(5)预后:10例(10/15)完全缓解,其病理类型均为NGOC或含绒癌成分的混合性生殖细胞肿瘤;3例患者在治疗过程中病情进展死亡(1例NGOC,1例内胚窦瘤,1例未成熟性畸胎瘤),2例肿瘤进展(1例NGOC,1例内胚窦瘤)放弃治疗后失访.结论 MOGCT发生肺转移以含绒癌成分者多见.MOGCT合并肺转移患者给予手术联合化疗的结合治疗,多数可获完全缓解,病理类型为NGOC或是含绒癌成分的混合生殖细胞肿瘤肺转移患者的预后远较其他类型的恶性生殖细胞肿瘤合并肺转移者为好.     

Second-look laparotomy in the management of malignant germ cell tumors of the ovary

From 1970 to 1985, 53 patients with malignant nondysgerminomatous germ cell tumors of the ovary underwent second-look laparotomy after initial surgery and combination chemotherapy. Twenty-two patients had immature teratoma, 15 had endodermal sinus tumor, 15 had mixed germ cell tumor, and one patient had embryonal carcinoma. Thirty-one of the neoplasms were stage I, four were stage II, 17 were stage III, and one was stage IV. Two patients received a combination of actinomycin-D, 5-fluorouracil, and cyclophosphamide; four patients received vinblastine, bleomycin, and cisplatin; 44 patients received vincristine, actinomycin-D, and cyclophosphamide; and three patients received a combination of the last two regimens. Second-look findings were negative in 52 patients and positive in one patient who was subsequently salvaged with further chemotherapy. One patient with stage I endodermal sinus tumor relapsed nine months after a negative second-look laparotomy and died. Two patients with negative findings subsequently died of leukemia. Of 53 patients undergoing second-look laparotomy, three are dead (one of cancer and two of leukemia), and 50 patients are surviving without disease. Although the precise role of second-look laparotomy in patients with malignant germ cell tumors is yet to be established, possible indications are discussed.     

Bleomycin, vinblastine, and cis-platinum in the treatment of advanced endodermal sinus tumor

The endodermal sinus tumor has traditionally been associated with an exceedingly poor prognosis. Three women with advanced pure endodermal sinus tumors were treated with a combination of bleomycin, vinblastine, and cis-platinum (VBC). Serum alpha-fetoprotein levels were monitored for all patients during and after therapy, and in each case the alpha-fetoprotein returned to normal range, correlating with complete clinical remission. Second-look laparotomy was negative for tumor in each case. Two patients have had no overt sign of recurrence 12 months after cessation of therapy. The third patient had post-treatment elevation of alpha-fetoprotein levels, and eventually was found to have recurrent tumor 6 months after chemotherapy was stopped. The VBC combination, previously found effective in testicular germ cell tumors, is also effective in ovarian germ cell tumors.     

Alpha-fetoprotein production by a malignant mixed Müllerian tumor of the ovary

Elevated levels of alpha-fetoprotein (AFP), a fetal serum protein, usually signal the development of hepatoma or germ cell tumors, including endodermal sinus tumors. We report the case of a 52-year-old woman with an alpha-fetoprotein-producing malignant mixed Müllerian tumor (MMMT) of the ovary. Serum AFP was 5348 ng/ml at diagnosis. Immunohistochemistry confirmed that the carcinomatous component of this biphasic tumor was the seat of AFP production. After three cycles of combination chemotherapy, the patient achieved a complete remission. Serum AFP was strongly correlated with response to treatment. This is the first report of AFP production by a MMMT of the ovary without a yolk sac component.     

Malignant germ cell tumors of the ovary. Pregnancy considerations

OBJECTIVE: To study the pregnancy association and malignant germ cell tumors of the ovary with regard to its effects on tumor prognosis. STUDY DESIGN:: Seventy-five patients with malignant germ cell tumors of the ovary treated at the King Faisal Specialist Hospital-Research Center (KFSH-RC) Riyadh, Kingdom of Saudi Arabia between January 1976 and December 1992, were reviewed. Data was retrieved from the medical records and the database of ovarian tumor pathology. Patients with tumor/pregnancy association were identified and correlation with obstetrical outcome and tumor prognosis analyzed. Patients who conceived after treatment were identified and their reproductive outcome described. RESULTS: Malignant germ cell tumor was associated with pregnancy in a group of ten patients. Possible tumor effects upon pregnancy in this group included operative delivery by caesarean section (n=3), mid-trimester termination (n=2), spontaneous abortion (n=1). Four patients had normal vaginal birth with no apparent tumor effects upon pregnancy. Pregnancy did not seem to influence the tumor prognosis of pure dysgerminoma (n=6), however, two patients with non-dysgerminomatous germ cell tumor (one endodermal sinus tumor and one immature teratoma) died of rapidly progressive disease during the second trimester. Two patients with advanced (stage IIIC) disease concurrent with pregnancy (one pure dysgerminoma and one mixed germ cell tumor), had normal fetal outcomes and achieved long-term survival. Amongst the 22 patients who planned to conceive after conservative surgery, with or without post-operative adjuvant chemotherapy, 12 conceived (12/22) and achieved a total of 20 pregnancies. Their outcomes included normal births (n=18) including one set of twins and hydatidiform moles (n=2). CONCLUSIONS: Our findings suggest that, (1) The association of pure dysgerminoma and pregnancy did not adversely affect the tumor prognosis or fetal outcome. However, the question remains as to whether pregnancy worsened the prognosis of non-dysgerminomatous germ cell tumors. (2) Recent platinum-based regimens of multiagent chemotherapy for germ cell tumors did not seem to affect fertility potential.     

Primary chemotherapy and the role of second-look laparotomy in non-dysgerminomatous germ cell malignancies of the ovary

In view of the rarity of germ cell tumors of the ovary, it is not surprising that little information exists about the indications for and significance of findings at second-look laparotomy in patients with these tumors. For this reason, we have reviewed 16 patients who received primary chemotherapy for malignant germ cell tumors of the ovary at Memorial Sloan-Kettering Cancer Center (MSKCC) between 1976 and 1983. Eleven of them underwent a second-look laparotomy after completion of their therapy. Primary therapy consisted of surgery, usually unilateral oophorectomy, and cis-platinum-based VAB chemotherapy. The histologic diagnoses were six immature teratomas, five endodermal sinus tumors, four mixed germ cell tumors, and one nongestational choriocarcinoma. Stage distribution was as follows: Stage IA, eight patients; Stage IC, one patient; Stage IIA, one patient; Stage III, four patients, and unstaged, two patients. The ages ranged from 15 to 56 years, with the mean of 29 years. All of the 11 patients undergoing second-look laparotomy were found to be free of disease. They are alive and have been continuously free of disease from 9 to 77 months (mean 39 months). This paper discusses primary chemotherapy and the role of the second-look laparotomy and suggests its value in modifying treatment, predicting cure, and safely stopping therapy in patients with germ cell malignancies of the ovary.     

The value of cancer antigen-125 as a tumor marker in malignant germ cell tumors of the ovary

The value of cancer antigen-125 (CA-125) as a tumor marker for malignant germ cell tumors (MGCT) of the ovary was investigated and compared with the other recognized tumor markers (human chorionic gonadotrophin (hCG), alpha-fetoprotein (AFP), carcinoembryonic antigen (CEA) and lactate dehydrogenase (LDH) isoenzymes. In the 10 months following June 1984, 4 new cases with MGCT and 1 patient with active disease on treatment were evaluated. In all cases prior to planned surgery the levels of CA-125 were significantly elevated. The serum values ranged from 154 to 617 U/ml (normal less than 20 U/ml). In 1 case (pure dysgerminoma) CA-125 was the only tumor marker. In 3 patients (2 mixed germ cell tumors and 1 immature teratoma) serum LDH (LD 1, 2, and 3) was elevated, and AFP was elevated in 1 of these. In the fifth case (mixed germ cell tumor), on treatment, serum AFP was used to monitor the disease. Four patients underwent cytoreductive surgery followed by combination chemotherapy. The changes in the serum levels of CA-125 paralleled those of the other tumor markers while on therapy. In our experience CA-125 is an invaluable indicator of the clinical status of the patient and could be a new tumor marker in patients with MGCT.     

Germ cell tumors of the ovary: Is there a role for aggressive cytoreductive surgery for nondysgerminomatous tumors?

Abstract. Bafna UD, Umadevi K, Kumaran C, Nagarathna DS, Shashikala P, Tanseem R. Germ cell tumors of the ovary: Is there a role for aggressive cytoreductive surgery for nondysgerminomatous tumors?
Thirty-three patients with germ cell tumor of the ovary were seen at Kidwai Memorial Institute of Oncology (KMIO), Bangalore, between 1996 and 1999. Twelve patients had endodermal sinus tumor (EST), 11 dysgerminoma, seven mixed germ cell tumor, and three immature teratoma. Thirteen patients had bulky residual disease of>10 cm after the primary surgery. All but one patient received a combination of bleomycin, etoposide, and cisplatin (BEP) either as neoadjuvant (NACT, 3 cases) or as adjuvant therapy (28 cases). In the present study, all 11 patients with dysgerminoma achieved sustained complete remission (CR), irrespective of the size of residual disease at the time of chemotherapy. Four out of six cases (66.6%) with bulky nondysgerminomatous tumor achieved CR, which was sustained in three cases and one recurred. Fifteen of the remaining 16 (93.7%) nonbulky, nondysgerminomatous tumors achieved CR, which was sustained in 14 cases and recurred in one. This study indicates that there may be a role for aggressive cytoreductive surgery, either primary/interval or at the time of second-look laparotomy, in selected patients with nondysgerminomatous germ cell tumor of the ovary.     

Serum ribonuclease in patients with malignant tumor of the ovary

The clinical significance of serum ribonuclease (RNase) was studied in patients with malignant tumor of the ovary, and the result was compared with serum sialic acid (SA). Serum RNase and SA level were determined in 190 women consisting of 35 normal women, 34 patients with ovarian cancer, 39 patients with other malignant gynecological tumors, 38 ovarian cancer patients with clinical remission after treatment and 44 patients with benign gynecological tumor. The sensitivity of serum RNase was 82.4% in the diagnosis of malignant tumor of the ovary. Serum RNase was positive in 42.9% of patients with minimal residual tumor and 88.9% those with residual tumors greater than 2 cm in diameter. Serum RNase assay is a simple, rapid and reliable method useful in monitoring the course of disease.     

Growing teratoma syndrome after chemotherapy for a mixed germ cell tumor of the ovary

A retroperitoneal enlarging mass was detected and resected in a 24-year-old nulliparous woman after fertility-preserving surgery and adjuvant chemotherapy for a malignant germ cell tumor (MGCT) of the right ovary. This enlarging mass contained only a mature teratoma component. Alpha-fetoprotein, which was elevated to 21236.6 ng/mL before the initial surgery, persisted within normal after the completion of adjuvant platinum-based chemotherapy. The patient was diagnosed with growing teratoma syndrome. Growing teratoma syndrome originating from ovarian germ cell tumor is very rare. Only 15 cases have been reported. Surgical resection and histological confirmation of growing mass after MGCT treatment is essential before conducting salvage chemotherapy.