Conservative surgery to preserve ovarian function in patients with malignant ovarian germ cell tumors. A review of 74 cases

BACKGROUND: Effective combination chemotherapy has improved the previously dismal prognosis for malignant ovarian germ cell tumors (MOGCT) dramatically. In young patients, conservative surgery with adjuvant chemotherapy has made the preservation of fertility possible, even in patients with advanced disease. The increase in cure rates has shifted the focus of recent studies to the long term menstrual, reproductive, and gynecologic outcomes in these patients. METHODS: The current study is a retrospective review of 74 patients with MOGCT treated by conservative surgery, retaining the uterus and contralateral ovary to preserve ovarian function, with or without chemotherapy. RESULTS: The mean age of the patients was 20.9 years (range, 10-35 years). The histologic subtypes included 31 dysgerminomas (41.9%), 16 immature teratomas (21.6%), 13 endodermal sinus tumors (17.6%), 11 mixed germ cell tumors (14.9%), and 3 embryonal cell tumors (4.1%). There were 56 International Federation of Gynecology and Obstetrics (FIGO) Stage I tumors (75.7%), 3 Stage II tumors, (4.1%), 11 Stage III tumors (14.9%), and 4 Stage IV tumors (5.4%). Adjuvant chemotherapy was administered in 47 patients (63.5%). The overall mean follow-up period was 52.1 months. There were 7 recurrences (9.5%) and 2 deaths (2.7%). Survival for patients with Stage I disease was 98.2% and that for patients with advanced disease stages was 94.4%. During chemotherapy 61.7% of patients developed amenorrhea but 91.5% of these women resumed normal menstrual function on completion of chemotherapy. Fourteen healthy live births were recorded in the chemotherapy group and there were no documented birth defects. There was 1 case of infertility (1.4%). CONCLUSIONS: The surgical approach in young patients with MOGCT confined to a single ovary should aim to preserve fertility. Advanced disease is not usually accompanied by contralateral ovarian disease and should not necessarily contraindicate conservative surgery. The majority of these patients who have received combination chemotherapy resume normal ovarian function and can expect a normal fertility rate and healthy offspring.     

Treatment of malignant ovarian germ cell tumors: response to vincristine, dactinomycin, and cyclophosphamide (preliminary report)

From November 1971 to November 1975, 27 patients with malignant germ cell tumors of the ovary (excluding pure dysgerminoma and tumors containing trophoblastic elements) were treated with vincristine, dactinomycin, and cyclophosphamide; 12 patients received other therapy. Fourteen tumors were pure endodermal sinus tumors, two were embryonal carcinomas, 11 were mixed germ cell tumors and 12 were immature teratomas. Of 23 patients with surgically resected disease (Stages I-IIA) only seven have failed. Median follow-up for 16 patients remaining free of disease is 24.5 months. Restaging (second-look) laparotomies were done in 15 patients. Eight were negative. Fifteen of the patients had tumors with endodermal sinus elements. Six of these have failed. Of 16 patients with advanced disease (Stage IIB, III and recurrent), eight have responded to chemotherapy, eight have failed. Median follow-up period for those remaining free of disease is 26.5 months. Six have had negative second-look surgery and one had mature teratoma. Four of eight cases which contained endodermal sinus elements responded to chemotherapy and remain disease-free. Grade 3 hematologic toxicity was seen in eight patients, dose-limiting gastrointestinal toxicity in five patients, dose-limiting neurotoxicity in five patients.     

Vincristine, dactinomycin, and cyclophosphamide in the treatment of malignant germ cell tumors of the ovary. A Gynecologic Oncology Group Study (a final report)

Seventy-six patients with malignant germ cell tumors of the ovary received vincristine, dactinomycin, and cyclophosphamide (VAC) postoperatively. Fifty-four were treated after removal of all gross disease. The majority of these remain disease-free. Indeed, only 15 (28%) have failed, including 11 of 24 with pure endodermal sinus tumor, 3 of 11 (27%) with mixed germ cell tumor containing endodermal sinus elements, and only 1 of 20 with immature teratoma grade 2 or 3, a patient seen initially with recurrent disease. Postoperative VAC therapy, however, did not appear to be effective in patients with unresectable or incompletely resected germ cell tumors of the ovary. Fifteen of 22 patients (68%) with incompletely resected germ cell tumors failed VAC therapy, including 4 of 7 with pure endodermal sinus tumor, 5 of 5 with mixed germ cell tumors containing endodermal sinus elements, 2 of 2 with embryonal carcinoma, and 4 of 8 with immature teratoma. In failing, patients' median time to progression was 8 months. Dose-limiting toxicity was seen in 30% of the entire group. Combined cisplatin, vinblastine and bleomycin therapy now is being tested in this group of tumors.     

Treatment of malignant germ cell tumors of the ovary with bleomycin, etoposide, and cisplatin.

Since 1984, we have treated 26 patients with malignant ovarian germ cell tumors with a combination of bleomycin, etoposide (VP-16), and cisplatin (BEP) at The University of Texas MD Anderson Cancer Center (UTMDACC). The median age of the patients was 19 years (range, 8 to 32). All patients underwent initial surgery (unilateral salpingo-oophorectomy in 14, unilateral salpingo-oophorectomy plus abdominal hysterectomy in one, and bilateral salpingo-oophorectomy with or without hysterectomy in 11 patients). Twenty patients had no residual disease, three had less than or equal to 2 cm (one each, dysgerminoma, mixed, and immature teratoma), and three had more than 2 cm lesions (two dysgerminomas, one endodermal sinus tumor). Fourteen patients had pure dysgerminoma (five, stage I; one, stage II; six, stage III; and two, recurrent), and 12 had nondysgerminomatous tumors (five, stage I; two, stage II; three, stage III; and two, recurrent). All four patients with clinically measurable disease had a complete response. All four patients who underwent second-look laparotomy had negative findings. Twenty-five patients (96%) remain in sustained remission 10.4 to 54.4 months from the start of chemotherapy. One patient died of progressive disease 14 months after beginning chemotherapy. We conclude that the BEP regimen has excellent activity and acceptable toxicity in patients with malignant ovarian germ cell tumors.     

Malignant Ovarian Germ Cell Tumours: A Survival and Prognostic Analysis

The medical records and histopathology of all ovarian germ cell tumours (OGCT) in a tertiary centre between 1980 and 1996 were reviewed. Response, overall survival (OS), relapse-free survival (RFS) and prognostic factors were analysed. Sixty-seven patients with OGCT were identified and treated, including 33 dysgerminomas, 18 immature teratomas, 10 endodermal sinus tumours, and 6 mixed tumours. Fifty-three patients (79%) received conservative surgery, 24 (36%) had residual disease post-primary surgery, and 43 (64%) had chemotherapy. Complete response was achieved in 62 patients (93%), 4 out of 5 patients who relapsed were successfully salvaged; OS and RFS at 5 years were 89% and 76%, respectively. Advancing stage of disease was the only significant adverse prognostic factor (p=0.0001 for OS, and 0.0003 for RFS at 5 years). Out of 44 women with the potential to conceive following treatment, there were 16 successful pregnancies. None of the children born subsequent to the chemotherapy were reported to have any congenital abnormalities. The review indicates a high cure rate in OGCT with combined surgery and chemotherapy and that conservative surgery and preservation of fertility are feasible.     

Retroperitoneal germ cell tumors in childhood. A clinical and pathologic study of 11 cases

During the last 54 years at the Children's Hospital 11 children (10 female, 1 male) had been treated for an extragonadal germ cell tumor arising in the retroperitoneum. There were eight teratomas (five mature, three immature), two endodermal sinus tumors and one tumor with a mixture of both components. Abdominal pain or discomfort was the usual presenting complaint, with the average age at diagnosis being 18 months. On physical examination, each child had a palpable abdominal mass usually localized in the upper quadrants. The finding of calcification, bone or teeth, on radiologic study was most helpful in establishing a preoperative diagnosis of teratoma. The preferred treatment for children with mature and immature teratomas is complete surgical resection; decisions regarding adjuvant therapy for patients with immature tumors must be evaluated on an individual basis. The prognosis remains guarded for children with unresectable primaries or those with endodermal sinus tumor. Of three tumor-related deaths, two were due to metastatic endodermal sinus tumor and one resulted from extensive local growth by immature teratoma. Successful management of children with endodermal sinus tumor requires surgery aimed at debulking or complete resection in combination with aggressive adjuvant chemotherapy.     

Treatment of nondysgerminomatous ovarian germ cell tumors: an analysis of 69 cases.

BACKGROUND: Combination chemotherapy has dramatically improved the prognosis of patients with nondysgerminomatous ovarian germ cell tumors (NDOGCT). However, guidelines are needed for the identification of patients at risk of relapse. METHODS: The authors performed a retrospective analysis of women with NDOGCT managed during the period 1970-1994 at the Royal Marsden Hospital and other hospitals of the London Gynaecological Oncology Group. RESULTS: Sixty-nine women were included; their median follow-up was 5.7 years (minimum, 12 months). The median age was 21 years (range, 4-44 years), with a histology of immature teratoma (IT) for 17 patients, endodermal sinus tumor (EST) for 20 patients, and mixed tumors for 32 patients. Thirty-five patients (51%) had Stage I disease. Nine patients with Stage I tumors were observed without further therapy (six with IT and three with mixed tumors), and one relapsed. Seven patients received non-platinum-based chemotherapy, and four relapsed. A total of 52 patients were treated with platinum-based chemotherapy, with relapse free and overall survival rates of 87% (95% confidence interval [CI], 73-93%) and 84% (95% CI, 70-91%), respectively. Of these patients, relapse was seen in 0 of 9 IT patients, 1 of 25 patients with mixed tumors, and 6 of 18 EST patients. With alpha-fetoprotein (AFP) > 1000 kU/L, relapse was seen in 6 of 18 patients compared with 1 of 33 relapses with lower AFP levels. In multivariate analysis, including all patients who received chemotherapy, AFP >1000 kU/L (P = 0.001) and non-platinum-based chemotherapy (P = 0.005) were associated with relapse. When only patients given platinum-based treatment were considered, EST histology (P = 0.003) and AFP >1000 kU/L (P = 0.003) were associated with relapse in univariate analysis; however, these factors were linked. No malignant tumor was found at second-look surgery performed on 24 patients. Of 26 women assessable for fertility, 24 subsequently recommenced regular menstrual function, and 11 patients had pregnancies. CONCLUSIONS: Platinum-based chemotherapy has been confirmed to be effective in the management of patients with NDOGCT. Relapses were principally seen among patients with AFP >1000 kU/L or pure EST histology. Efforts to improve outcome need to focus on patients with EST, whereas less intensive management strategies may be appropriate for some patients with IT.     

Prognostic factors in yolk sac tumors of the ovary. A clinicopathologic analysis of 29 cases.

Twenty-nine ovarian cancer patients with yolk sac tumors and germ cell tumors with yolk sac tissue as a component of their disease (16 endodermal sinus tumor, 11 mixed germ cell tumors, one embryonal carcinoma, and one polyembryoma) were treated with cytoreductive surgery and combination chemotherapy. Prognostic factors were investigated in this group. Patients with Stage I disease had a more favorable prognosis (P less than 0.003) than those with Stages II and IV disease. The difference in prognosis was significant in cases where residual tumor was absent (P less than 0.003) and in cases where ascites was either absent or less than 100 ml in volume (P less than 0.05). Endodermal sinus tumor with either an intestinal (P less than 0.05) or microcystic pattern (P less than 0.01) was more common in survivors than in those who died. The age, preoperative serum alpha-fetoprotein level, maximum tumor size, and tumor weight had no significant correlation with prognosis. In advanced cases, chemotherapy regimens including cisplatin gave better results than those containing vincristine, dactinomycin, and cyclophosphamide (P less than 0.05). The optimal treatment of yolk sac tumors or tumors with yolk sac tissue as a component of the ovary is discussed in light of these results.     

Sequential combination chemotherapy for malignant germ cell tumors of the ovary

Fourteen patients with malignant ovarian germ cell tumors were treated postoperatively with a short-term, sequential regimen combining cisplatin, vincristine, methotrexate, bleomycin, dactinomycin, cyclophosphamide, etoposide, Adriamycin (Adria Laboratories, Columbus, OH), and vinblastine (POMB/ACE/PAV). Two patients had Stage I disease, Five had Stage II, five had Stage III, and two had Stage IV. The histologic diagnosis was immature teratoma in five cases (two cases were Grade 2 and three cases were Grade 3) endodermal sinus tumor in two cases, dysgerminoma in three cases, and mixed germ cell tumors in four cases. The chemotherapy regimen appeared to be highly effective against all histologic types, including advanced stages, with 12 of 14 (86%) overall sustained remissions. The median duration of treatment was 5 months. The toxicity of the regimen, which contained low total doses of cisplatin and bleomycin, was only moderate. After a median follow-up of 53+ months, 13 patients were alive without evidence of disease. The results and toxicity obtained were compared with those from other currently used regimens. Also, some comments on initial surgery and second-look surgery are given.     

Conservative surgery for malignant ovarian tumor in women of childbearing age

Background. The traditional operative procedures for the treatment of ovarian cancer have been simple total hysterectomy, bilateral salpingo-oophorectomy, and omentectomy. However, young patients who want to preserve fertility are occasionally encountered. This study was designed to assess the results of conservative surgical management for young women with stage I epithelial ovarian carcinoma or malignant germ cell tumor and to explore the indications for such surgical treatment. Methods. Fifty-eight patients aged under 35 years were treated for malignant ovarian tumors (germ cell tumor, n = 20; epithelial tumors, n = 38) between 1971 and 1996. We studied all 20 patients with germ cell tumors and 22 pa-tients with stage I epithelial tumors; we excluded the 12 patients with stage II and more advanced disease and the 4 patients with stage I clear cell carcinoma, because these patients had poor prognoses. Eleven of the 22 patients with stage I epithelial tumors and 8 of the 20 patients with germ cell tumors received conservative surgery (conservative surgery group); the remaining 23 patients underwent radical surgery, including hysterectomy and bilateral salpingo-oophorectomy (radical surgery group). The overall survival rates of the two groups were compared, and ovarian function and pregnancy outcome were evaluated in the conservative surgery group. Results. Of the patients with malignant epithelial tumor who were treated with conservative surgery, 3 patients with stage Ic mucinous adenocarcinoma died 1 year and 8 months, 7 years and 6 months, and 8 years, respectively, after the initial surgery. The 10-year survival rate was 65% for the conservative surgery group and 91% for the radical surgery group. All patients with stage Ia epithelial tumors in both groups survived, and there were no differences in survival curves between the two groups among the patients with stage Ic epithelial tumors. All patients with germ cell tumors in the conservative surgery group survived. Their survival rate, however, was not significantly better than that in the radical surgery group. All patients with germ cell tumors who received platinum-based chemotherapy survived and had a significantly better survival rate than those who received non-platinum-based regimens (P < 0.05). All the patients in the conservative surgery group received postoperative chemotherapy; 10 of these patients had transient ovulation failure after the completion of chemotherapy, although a normal menstrual cycle was restored within 1 year. Of the 10 patients who wished to have babies, 6 became pregnant, and they have had a total of 11 children. Conclusion. Conservative surgery is feasible in patients with stage Ia epithelial carcinoma and germ cell tumor. Postoperative chemotherapy suppressed ovarian function in these patients, but only for a brief period. Received: January 5, 1999 / Accepted: October 27, 1999     

Outcomes of Malignant Ovarian Germ-Cell Tumors Treated in Chiang Mai University Hospital over a Nine Year Period

Malignant ovarian germ cell tumors (MOGCT) are rare neoplasms that most frequently occur in women at a young reproductive age. There have been limited data regarding this disease from Southeast Asian countries. We therefore conducted a retrospective study to analyze the clinical characteristics and the treatment outcomes of MOGCT treated at our institute between January, 2003 and December, 2012. Seventy-six patients were recruited from this period with the mean age of 21.6 years and 11.8% were pre-puberty. The two most commonsymptoms were pelvic mass and pelvic pain. Two-thirds of the studied patients presented at an early stage. The most common histology was immature teratoma (34.2%) followed by endodermal sinus tumor (28.9%), dysgerminoma (25%), mixed type (10.5%) and choriocarcinoma (1.3%). Over 80% of these patients received fertility sparing surgery and about 70% received adjuvant chemotherapy with the complete response rate at 73.3% and partial response at 11.1%. The most frequent chemotherapy was BEP regimen (bleomycin, etoposide, cisplatin). With the mean follow up time at 56.0 months, 12 patients (15.8%) developed recurrence and only an advanced stage was the independent prognostic factor. The ten year progression free survival (PFS) and overall survival rate of our study were 81.9% and 86.2%, respectively. In conclusion, MOGCT often occurs at a young age. Treatment with fertility sparing operations and adjuvant chemotherapy with a BEP regimen showed a good outcome. An advanced stage is a significant prognostic factor for recurrence.     

Chemotherapy of extragonadal germ cell tumors

Forty-nine patients with histologically proven germ cell tumors arising in extragonadal sites were retrospectively reviewed. Included in the review were an additional seven patients with undifferentiated tumors with a pathologic appearance compatible with that of a germ cell tumor and elevated levels of serum biomarkers (beta subunit of human chorionic gonadotropin [beta-HCG] +/- alpha-fetoprotein [AFP]. Nineteen patients had a pure seminoma arising in an extragonadal site, whereas 30 patients had nonseminomatous germ cell tumors. Seven patients had primary undifferentiated tumors with elevated levels of serum biomarkers. Sixteen (84%) of the 19 patients with pure extragonadal seminomas with normal levels of serum AFP are alive and free of disease. Eighteen of these 19 patients received platinum-containing regimens and four had received prior chemotherapy that failed. Of the patients with nonseminomatous germ cell tumors, 12 (40%) of the 30 are alive and free of disease with vinblastine/bleomycin +/- cisplatin (13 patients) or CISCAII (cisplatin, cyclophosphamide, and doxorubicin) (nine patients) alternating CISCAII/VBIV (eight patients) chemotherapy. None of the seven patients with undifferentiated germ cell tumors are alive and free of disease. Three of the five patients with pure anterior mediastinal endodermal sinus tumors treated with chemotherapy remain alive and free of disease. Of the seven patients with choriocarcinomas arising in extragonadal sites, three are alive and free of disease. A classification for patients with extragonadal germ cell tumors incorporating site of origin, histology, and likelihood of being truly extragonadal is proposed. The implications of this classification are discussed.     

Combination cisplatin, vinblastine, and bleomycin chemotherapy (PVB) for malignant germ-cell tumors of the ovary

Nine women with germ-cell tumors of the ovary (three endodermal sinus tumors, four immature teratomas, and two mixed germ-cell tumors) were treated with cisplatin, vinblastine, and bleomycin (PVB) chemotherapy after cytoreductive operations. Five patients were stage I, three were stage III, and one patient had recurrent disease. All nine women are alive and without evidence of disease with a median follow-up of 31 months from diagnosis and 27 months since completion of PVB. Treatment toxicity although occasionally severe was rapidly reversible.     

年轻卵巢恶性肿瘤患者保留生育功能手术总结

Objection： To evaluate the impact of fertility-preserving surgery and adjuvant chemotherapy on survival and fertility of young patients with ovarian malignant tumors. Methods： Retrospective analysis of 39 patients with ovarian malignant germ cell tumors, 23 patients with malignant epithelial tumors and 4 patients with sexual cord mesenchymal tumors receiving conservative treatments. Results： Two patients lost follow-up （we do not statistics them）. Fifty-nine among 64 patients were alive up to now （92.19%）. The overall survival rate for ovarian epithelial malignancies, malignant germ cell tumors and sexual cord mesenchymal tumors were 95.45%, 89.47% and 100% respectively. Fifteen patients received second operation and recurrence was found in 6 patients. Among the 59 surviving patients, 53 patients have normal menstruation. Thirteen patients among 20 patients who want to pregnant have 15 pregnancies and 9 successful deliveries. Conclusion： The management of fertility-preserving surgery on patients with ovarian malignant germ cell tumors, whatever the FIGO staging is, is a safe option. For patients with ovarian epithelial carcinomas, fertility-preserving surgery only confined to low-stage （stage Ⅰ）, low-grade （G1）, and patients who want keep fertility function seriously. Cisplatinum-based combination chemotherapy is necessary. Standardized chemotherapy has no affection on fertility function.     

Ovarian endodermal sinus tumor during pregnancy

We present the rare case of a 31-year-old pregnant woman who underwent resection of a FIGO stage Ia ovarian endodermal sinus tumor at 7 weeks of gestation, and who received no additional treatment, before or after giving birth. She was delivered of a healthy male infant at 40 weeks of gestation, and exhibited no signs of recurrence 28 months after the primary operation. There are 14 previous reports of endodermal sinus tumors during pregnancy. The present case represents the first patient who gave birth to a healthy infant without receiving any additional treatment following surgery, indicating that an early-stage endodermal sinus tumor does not necessarily require adjuvant chemotherapy. Received: August 7, 1998 / Accepted: April 21, 1999     

Serum alphafetoprotein (AFP) in patients with germ cell tumors of the gonads and extragonadal sites: correlation between endodermal sinus (yolk sac) tumor and raised serum AFP

During the last 6 1/2 years, serum AFP has been determined by radioimmunoassay in 387 patients with germ cell tumors of the gonads and extragonadal sites. The histological appearances of all these neoplasms were carefully reviewed. Highly elevated levels of serum AFP were noted in patients with tumors containing endodermal sinus (yolk sac) tumor elements irrespective of the location of the neoplasm or presence or absence of metastatic disease. There was good correlation between the presence and quantity of endodermal sinus (yolk sac) tumor elements within the primary tumor or its metastases and elevated levels of serum AFP. All patients with tumors composed of pure seminoma or dysgerminoma, and teratoma, had normal serum AFP levels. Slightly elevated levels of serum AFP up to 60 ng/mg (upper limit of normal 20 ng/ml) were noted in a few patients with testicular tumors composed of pure embryonal carcinoma, whereas patients with tumors composed of or containing endodermal sinus (yolk sac) tumor elements had serum AFP levels that could be measured in 100's or 1000's of ng/ml. Serum AFP was elevated only in patients with active disease. Serum AFP was determined in 81 patients with gonadal tumors of non germ cell origin and was normal in all these patients. Serum AFP is a very good tumor marker in patients with germ cell tumors composed of or containing endodermal sinus (yolk sac) tumor, irrespective of their location. Serial serum SFP determinations can be used for diagnostic purposes, for monitoring the results of treatment, and for early detection of metastases and recurrences. Serial serum AFP determination is a useful procedure in all patients with germ cell neoplasms and is highly recommended.     

Pregnancy Outcomes after Conservative Surgery for Early-Stage Ovarian Neoplasms

Objective: This retrospective, single institute study aimed to evaluate pregnancy and oncologic outcomes in reproductive-age Thai women with early-stage ovarian neoplasms undergoing conservative surgical treatment. Methods: Medical records of 84 women of reproductive age (15-45 years) with histologically confirmed early-stage (IA-IIC) borderline ovarian tumors or cancers who had undergone conservative surgery between January 2003 and December 2012 were retrospectively reviewed. Results: The mean age of patients at diagnosis was 28.0 years (SD 7.2). Histologically, 30 (35.7%) had borderline ovarian tumors, 28 (33.3%) epithelial cancers, 22 (26.2%) malignant germ cell tumors, and 4 (4.8%) sex cord stromal tumors. Thirty-five women (41.7%) had complete surgical staging performed, whereas 49 (58.3%) underwent an incomplete staging procedure. Thirty-four patients (40.5%) received postoperative chemotherapy. Among 29 patients subsequently attempting pregnancy, 15 conceived successfully (51.7%). Pregnancy outcomes were one spontaneous abortion and 14 viable births. There were no serious adverse obstetric and neonatal outcomes among women with documented live births and no reported fetal abnormalities. Pregnancy rates were not impacted by surgical staging (53.8% vs 50.0%, p=0.837) or adjuvant chemotherapy (55.6% vs 50.0%, p=0.782). The 5-year disease-free survival was 91.0% and pregnancy after conservative surgery did not affect progression-free survival (p=0.194). Conclusion: Conservative surgery with or without appropriate adjuvant chemotherapy can be offered to young women with early-stage ovarian neoplasms who wish to preserve their fertility potential.     

Treatment of childhood germ cell tumors. Review of the St. Jude experience from 1979 to 1988.

BACKGROUND. The outlook for patients with germ cell tumors was poor before the advent of effective chemotherapy. The authors assessed the outcome of treatment with multiagent chemotherapy (with or without radiation therapy) in children treated for germ cell tumors at St. Jude Children's Research Hospital (SJCRH). METHODS. Sixty children with germ cell tumors were treated between January 1979 and June 1988. Postsurgical treatment was based on tumor site, stage, and histology. Most patients received chemotherapy with vincristine, actinomycin-D, and cyclophosphamide (VAC), or a modified Einhorn regimen (cisplatin, bleomycin, and vinblastine [PVB]); in the absence of response to initial therapy, patients received alternating courses of VAC and PVB (VAC/PVB regimen). Exceptions were patients with Stage I testicular tumors (observation only) and ovarian germinomas (Stage I tumors measuring less than 10 cm, observation only; tumors larger than 10 cm or Stage II-III disease, radiation only; and Stage IV disease, VAC plus radiation). RESULTS. The estimated 5-year survival is 100% for patients with Stage I disease (n = 18), 87% for patients with Stage II (n = 8), 72% for Stage III (n = 25), and 56% for Stage IV (n = 9). Patients with testicular tumors of any stage or with Stage I-II ovarian tumors had 100% 5-year survival. Extragonadal tumors responded poorly to VAC alone with recurrent or progressive disease in eight of nine patients. Treatment for those tumors was changed to alternating courses of VAC and PVB, which failed in only one of seven patients. Nine of 19 patients with advanced ovarian tumors had disease recurrence with VAC; these patients then received PVB, which was effective in four cases. CONCLUSIONS. For patients with advanced germ cell cancers, intensification of therapy or the development of new approaches is necessary. In contrast, future trials in children with limited stage should focus on reducing acute and long-term toxicities.     

Management of primary intracranial germ cell tumors

Primary intracranial germ cell tumors are rare and usually localized in the pineal and the suprasellar regions. They are divided into the following histologic types: germinoma, teratoma (mature, immature, malignant), choriocarcinoma, embryonal carcinoma, endodermal sinus tumor (yolk sac tumor), and mixed tumors. Clinically, they are manifested with ocular signs or signs of obstructive hydrocephalus. Localized germinomas are treated with radiation therapy and exhibit a relatively good prognosis. Chemotherapy is reserved for disseminated germinomas. Mature teratomas are treated with surgery. The rest of germ cell tumors are managed with various combinations of surgery, chemotherapy, and radiotherapy depending on the tumor type. If the tumors secrete beta-human chorionic gonadotrophin (hCG) or alpha-fetoprotein (FP), these tumor markers can be used to accurately monitor response to treatment. Prognosis is best for germinomas and mature teratomas and worst for choriocarcinomas and embryonal carcinomas.     

Menstrual and reproductive function after treatment with combination chemotherapy for malignant ovarian germ cell tumors

Forty patients who had been treated for malignant ovarian germ cell tumors completed a questionnaire designed to evaluate their menstrual and reproductive function. All patients met the following eligibility criteria: (1) successful treatment with combination chemotherapy, and (2) retention of a normal contralateral ovary and uterus. Median age at diagnosis was 15 years (range, 6 to 29), and median age at the time of interview was 25.5 years (range, 14 to 40). Patients had received a variety of chemotherapeutic regimens, the most common of which was a combination of vincristine, dactinomycin, and cyclophosphamide (N = 28). Since discontinuation of chemotherapy, one patient remains premenarchal, and 27 patients have maintained regular menses. The other 12 patients have had menstrual difficulties, but in only three were the problems considered to be serious. Of the 16 patients who have attempted to become pregnant since completing chemotherapy, 11 have delivered 22 healthy infants, none of whom had major birth defects. Only one patient has had persistent problems with infertility. In summary, it appears that the majority of patients who receive combination chemotherapy for malignant ovarian germ cell tumors can anticipate normal menstrual function and a reasonable probability of having normal offspring.