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Objectives: To provide clinical guidance for early diagnosis and effective management of primary cesarean scar choriocarcinoma, which is an extremely rare but highly malignant trophoblastic tumor., Methods: This retrospective case series summarized the clinical courses of seven patients diagnosed with cesarean scar choriocarcinoma., Results: We identified two patients in our institution with cesarean scar choriocarcinoma. In addition, details of the previous five patients were extracted from databases and analyzed to provide more clinical information. The seven patients had an average age of 31.14 years, their tumor sizes ranged from 2.0 to 6.5 cm, and their pretreatment serum β-human chorionic gonadotropin (β-hCG) levels ranged from 3664 to 312 468 mIU/mL. All the patients were categorized as having FIGO Stage I disease, with four patients at low risk and three at high risk. Six of the seven were misdiagnosed with ectopic pregnancy before pathologic examination., Conclusions: Clinicians should pay attention to masses in cesarean scar and to continuous elevation of serum β-hCG levels after treatment. When cesarean scar choriocarcinoma is suspected, diagnostic surgery can be chosen for tentative treatment and pathologic sampling. Salvage EMA-CO chemotherapy (etoposide, actinomycin D, methotrexate, cyclophosphamide and vincristine) should be performed as early as possible to prevent metastasis and recurrence after pathologic diagnosis., (© 2023 International Federation of Gynecology and Obstetrics.)

Schisandrin A (SchA) has been reported as a multidrug resistance-reversing agent; however, its antitumor effects have been rarely reported. Consequently, we attempted to explore whether SchA per se possesses an antitumor property in choriocarcinoma JEG-3 and BeWo cells and its potential mechanisms. JEG-3, BeWo, and HTR-8/SVneo cells were stimulated with SchA at different concentrations (10-100 μM), and cellular viability was evaluated with Cell Counting Kit-8. After stimulation with SchA, proliferation, apoptosis, migration, and invasion were detected by bromodeoxyuridine assay, Annexin V-fluorescein isothiocyanate/propidium iodide (Annexin V-FITC/PI) method, and a Transwell system, in JEG-3 cells transfected with short hairpin-RNA for maternally expressed 3. Western blot was performed to quantify protein. MEG3 was examined by a quantitative reverse transcription-polymerase chain reaction. MEG3 was downregulated in choriocarcinoma tissues. SchA diminished cellular viability, decreased proliferative activity, inhibited migratory and invasive behaviors, and repressed phosphorylation of regulators of phosphatidylinositol 3 kinase/protein kinase B/nuclear factor κB (PI3K/AKT/NF-κB) signaling cascade in gestational choriocarcinoma cells. MEG3 was upregulated by SchA in JEG-3 and BeWo cells. SchA exhibited little suppressive effects in JEG-3 cells lacking MEG3. Besides, the phosphorylation of transducers was evoked in MEG3-silenced JEG-3 cells despite stimulation with SchA. SchA administration repressed the growth of JEG-3 and BeWo cells by upregulating MEG3. Besides, SchA blocked PI3K/AKT/NF-κB signal cascade by elevating MEG3., (© 2020 Wiley Periodicals, Inc.)

A 19-year-old man suffering from testicular choriocarcinoma presented to the dermatology department with a cutaneous metastasis on his head. This metastasis was the first sign of disease that led to medical consultation. Histopathology revealed cytotrophoblasts and syncytiotrophoblasts, the later expressing human chorionic gonadotropin antigen. Whole body computed tomography showed multiple metastases of the brain, lung, liver, bone, paraaortic lymph nodes and left uvea; the primary was found in the left testicle. Despite neurosurgical intervention and chemotherapy the patient died 9 days after the biopsy of the cutaneous metastasis. Cutaneous metastases of testicular choriocarcinoma are exceptionally rare, with fewer than a dozen cases reported in the English-language literature. The present case highlights that testicular choriocarcinoma metastatic to the skin should be included in the differential of cutaneous scalp tumors., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

A 40-year-old woman presented with subcutaneous masses on her chest wall, abnormal vaginal bleeding and an enlarged uterus. Chest X-ray and liver ultrasound revealed metastatic disease to these sites, respectively. A urine human chorionic gonadotrophin assay was positive. A biopsy of the chest wall lesion and endometrium revealed choriocarcinoma. Treatment with methotrexate, actinomycin-D and cyclophosphamide led to complete resolution of the disease on examination, X-ray and ultrasound scans. The urinary pregnancy test became negative.

Background: Human chorionic gonadotropin (hCG)-producing large or giant cell carcinoma of the lung is not uncommon, but primary pulmonary choriocarcinoma is an extremely rare entity. Even rarer are cases occurring in males; to date the authors have found only 12 reported cases in the English literature., Methods: The clinical record of a 61-year-old man who presented with hemoptysis is described. A review of the literature regarding patients with primary pulmonary choriocarcinoma also is reported., Results: Computed tomography scan of the chest demonstrated an expanding thickness of the bullous wall within areas of emphysematous change in the lower lobe of the right lung. Moreover, a new, round tumor near the thickness appeared and rapidly expanded evenly into the surrounding lung tissue. Exploratory thoracotomy revealed the previous tumor to be adenocarcinoma with a small foci of choriocarcinoma, and the new tumor to be a hemorrhage with choriocarcinoma. Because of the pleural dissemination, the patient was treated with chemotherapy. At last follow-up he was alive and well with a gradually increasing serum hCG-beta level in spite of chemotherapy., Conclusions: Primary pulmonary choriocarcinoma occurring in men is an extremely rare entity with a fatal prognosis. Of the 12 cases reported to date in the English literature, 3 cases of choriocarcinoma with the coexistence of another type of pulmonary carcinoma were reported. To the authors' knowledge the clinical relation between these two types of carcinoma are unknown because all cases to date have been detected at the time of autopsy. Only in the current study case could the clinical course of the disease be followed and pathologic confirmation achieved, although the pathogenesis of the two types of carcinoma could not be determined., (Copyright 2001 American Cancer Society.)

Our work was begun in 1949. through many yera's effort, several chemicals (such as 6 MP, 5 FU and others) were found to be effective for the treatment of choriocarcinoma (C.C.) and invasive mole (I.M.). From 1959 through 1985, 1500 patients were consecutively treated. The mortality rate of CC was reduced from > 90% to < 20%. No more death occurred in IM. All Survivors followed up for 10-38 years showed no evidence of residual disease. 80% of the young patients treated with chemotherapy alone conceived after recovery. The pregnancy outcome showed no deviation from that of the general population. All children are growing up normally many married and gave birth to normal third generations. The results indicated that chemotherapy with 5 FU achieves not only a complete remission, but also a cure, even with wide-spread metastases. The results of choriocarcinoma and invasive mole treated with mainly 5 FU were reported. The clinical experience in the management of metastases at different sites were also summarized.

The author engaged in the registration work and the clinical studies of trophoblastic disease over 20 years at Niigata University in Niigata prefecture, before transferring to University of the Ryukyus in Okinawa prefecture in 1992. In this paper, the following four topics are reviewed and discussed. 1) the registration data of trophoblastic disease in Niigata prefecture, 2) the treatment results of gestational chorio-carcinoma at the Niigata University Hospital, 3) a trial administration of Gn-RH analogue in patients with gestational choriocarcinoma to suppress secretion of hCG-like substance (hLS) which might cross-react anti-hCG antibodies in hCG immunoassay system, 4) the two rare cases of extrauterine gestational choriocarcinoma who were presented to the Ryukyus University Hospital.

Choriocarcinoma presenting in an infant or neonate is a rare entity that in the past has been uniformly fatal. The authors present the first reported case of choriocarcinoma successfully treated in a 3-week-old infant. Choriocarcinoma was not suspected in this case until pathologic examination revealed the diagnosis. In retrospect, however, the case fits well into the classic "infantile choriocarcinoma syndrome" initially described by Witzleben in 1968. Review of additional cases reported since the initial description validates Witzleben's initial observations and also indicates that the original definition should be broadened to include other significant presentations of the disease not initially appreciated, specifically anemic infants with central nervous system symptoms as well as newborns and older children. The importance of making a correct and rapid diagnosis is emphasized by the successful outcome in this case where aggressive surgery and subsequent chemotherapy have been curative. Serum beta-human chorionic gonadotropin (beta-HCG) levels have been uniformly positive, providing easy confirmation of the diagnosis. Because the mother can also be affected, an appropriate diagnosis of the infant may also lead to more rapid diagnosis and treatment of the mother.

A case is reported of a 38-year-old woman with metastatic choriocarcinoma which followed four recurrent consecutive hydatidiform moles occurring within the preceding 5-year period. She conceived while having pulmonary metastasis, had a coexistent normal pregnancy and delivered a normal infant at term. Surgical resection of the lung lesion together with chemotherapy accomplished a sustained remission, with no evidence of disease after 20 months' follow-up.

A case is reported of a metastatic gestational choriocarcinoma in a 25-year old woman. Extensive pelvic, pulmonary and brain metastases were associated with clinically manifest thyrotoxicosis. Multiagent chemotherapy alone was successful in achieving a durable remission and euthyroid state. The chemotherapy regimen consisted of cis-platinum, etoposide, actinomycin-D, and intrathecal methotrexate (PEA-M). The Patient conceived 2 years after completing therapy and gave birth at term to a normal infant.

Choriocarcinoma is a rare malignancy in Scandinavia. We present a case of a young primigravida who experienced an uneventful pregnancy and gave birth to a healthy baby. Six days after delivery she underwent neurosurgery for intracranial hemorrhage. Pathological examination of the evacuated hematoma revealed metastatic choriocarcinoma. Further work-up exposed additional metastases in the lungs and liver. The initial serum level of human chorionic gonadotropin (beta-HCG) was 350,000 IU/I. Chemotherapy was given both intravenously and intrathecally. At 10 weeks, beta-HCG had returned to normal. Treatment was continued for another 10 weeks. Two years after cessation of therapy the patient is still in complete remission. In the discussion we review a scoring system to be used in selecting the mode of treatment, and briefly mention diagnosis and prognosis.

In a period of a little over 20 years, chemotherapy of cancer has evolved from a period of empiricism with little impact on the cancer problem to become part of a sound medical discipline with firm scientific underpinning playing an increasingly important role in the control of cancer. This progress has come from an increasing knowledge of cancer biology and pharmacology and the application of this knowledge to improved design of clinical trials, with due consideration to the intricacies of the natural history of each disease in question. Now that the chemotherapeutic tools are sharpened, their use in combinations with other modalities in the previously unfamiliar setting of the patient with early stages of the disease promises to lead to an even more exciting chapter in clinical cancer research in the next decade.

Sixty patients who developed persistent or metastatic gestational trophoblastic disease (GTD) received primary oral etoposide therapy (VP 16-213). Twelve patients had metastatic GTD. Fifty-nine patients achieved biochemical remission. One patient had marked nausea and vomiting and the therapy was switched to a methotrexate/folinic acid regimen. Three patients developed relapse of GTD, giving a relapse rate of 5.1%. Etoposide is an active drug against choriocarcinoma. Its use should not be restricted to drug-resistant GTD.

Choriocarcinoma is a potentially curable neoplasm. Although the presence of intracranial metastases worsens the ultimate prognosis, several reports have shown successful response to therapy. This clinical report outlines a method by which the appropriate therapy may be initiated in a patient with intracranial metastases, who otherwise may not have survived the interval necessary for the induction of successful therapy.

The malignant germinal tumors found in the testis (seminoma, teratocarcinoma, embryonal carcinoma, choriocarcinoma, and mixtures of these) can originate in the anterior mediastinum. An occult testicular tumor must be sought, but primary mediastinal germinal tumors constitute a true entity. The details of 24 such patients treated at Walter Reed General Hospital are presented. Of 19 patients who died, 2 were women; postmortem examination of the testes of 13 men failed to reveal a primary tumor. Five patients are alive and well with no testicular abnormality. It is important to distinguish the histopathologic types. Seminomas are readily controlled with modest doses of irradiation. Embryonal carcinomas are also radiocurable with somewhat higher doses; 2 long-term disease-free survivors are reported. Teratocarcinomas are highly malignant and require higher doses for control. Choriocarcinomas progress so rapidly that chemotherapy is necessary.

The excretion pattern of human chorionic gonadotropin (hCG) or luteinizing hormone (LH) was observed in the urine of 77 patients with trophoblastic neoplasia, 109 with complete remission from trophoblastic neoplasia, and 94 with no trophoblastic neoplasia, when the anti-beta-subunit hCG system radioimmunoassay (anti-beta-subunit RIA), which specifically measured hCG was used. The sensitivity of anti-beta-subunit RIA was limited to urinary hCG 16 mIL/ml from the specificity of the anti-beta-subunit serum. Luteinizing hormone in the urine of patients with complete remission and in normal menstrual, postmenopausal, and castrated women was less than 16 mIU/ml in most cases. The excretion pattern of urinary hCG in the patients undergoing treatment for trophoblastic neoplasia was more clearly comprehended with the anti-beta-subunit RIA as compared with the anti-hCH RIA. The criteria for judgment of complete remission were that the hCG value dropped to less than 16 mIU/ml and that cellular response was not observed at least in the last two courses.

We studied 31 autopsied cases of gestational choriocarcinoma encountered at the Northwestern University Trophoblastic Disease Center in the past two decades to learn if the clinical and morphologic aspects of these cases have been altered by therapy. These cases were analyzed for cause of death, distribution of tumor and histologic patterns in relation to the amount of chemotherapy. Tumor hemorrhage and/or pulmonary insufficiency were the most common causes of death, irrespective of the amount of therapy although other factors including drug toxicity, sepsis, and uremia led to death in six cases. The amount of chemotherapy generally did not affect the number or distribution of metastases. Histologically, nine cases showed extensive or complete necrosis. Eighteen of the remaining tumors had typical biphasic patterns, but four patients who received multiple courses of chemotherapy had atypical patterns with a marked predominance of cytotrophoblast and infiltrative growth. These atypical patterns do not appear to be a direct result of chemotherapy but may represent a more aggressive form of this tumor. This study shows that fatal gestational choriocarcinoma can have a variety of clinicopathologic features which reflect not only the biologic capabilities of the neoplasm but also the effects of chemotherapy and prolonged disease.

Twenty-three patients with advanced (Stage III) mixed germ cell tumors underwent laparotomy and thoracotomy or neck dissection for excision of persistent radiographic masses after systemic chemotherapy. In those who received multidrug regimens incorporating high-dose cisplatin, 4 of 15 (27%) harbored persistent tumor in at least one site, 6 of 15 (40%) demonstrated necrotic tumor or fibrosis only in all sites examined, and the remaining 5 of 15 (33%) harbored mature teratoma in at least one area. In patients treated with high-dose platinum chemotherapy regimens 11 of 15 (73%) remain disease-free with a median follow-up period of 29 months (range, 1-58 months). Histologic comparison of tissues resected during thoracotomy and retroperitoneal node dissection indicated that patterns were dissimilar in 8 of 23 patients (35%). These data indicate the favorable impact of combined sequential chemotherapy and surgery in patients with advanced mixed germ cell tumors. In patients with Stage III tumors, persistent radiographic disease after cyclic cisplatin-based chemotherapy is appropriately managed by excision of both thoracic and retroperitoneal deposits.

Twenty-one patients with refractory germ cell tumors were treated with a chemotherapy regimen containing etoposide (VP-16) (V) 75 mg/m2/day (days 1 to 5), ifosfamide (I) 3 g/m2/day (days 1 and 2) with a 3.6 g/m2 continuous infusion of mesna (days 1 and 2), and high-dose cisplatin (hP) 40 mg/m2/day (days 1 to 5). The regimen is referred to as VIhP. Nineteen patients were evaluable for response. Five patients (26%) achieved a complete remission (CR) with chemotherapy alone, and three patients (16%) were in CR after resection of a residual nonactive tumoral mass (e.g., necrosis and/or fibrosis and/or mature teratoma). Thus, a CR rate of 42% was achieved with the entire treatment. One additional patient achieved a CR after resection of active, bulky disease. Among the responders, five patients (26%) are still alive and disease-free at 6, 7, 9, 10, and 18 months after the initiation of the chemotherapy. However, toxicity was heavy in this protocol. Severe myelosuppression was observed with 10 patients developing aplasia and six patients documented sepsis. Reversible Grade 1-2 renal toxicity occurred in 14 patients, and Grade 2-3 peripheral neurotoxicity occurred in six patients. No hemorrhagic cystitis was encountered. We conclude that a VIhP regimen seems to play an active role in refractory germ cell tumors although the presence of high-dose cisplatin in this regimen does not appear to improve the response rate compared to that of a conventional dose. Toxicity, which seems to be enhanced, is currently under detailed study. However, the contribution of VIhP as a first-line treatment in poor prognosis, advanced germ cell tumors warrants further study.

Thirty-eight patients with nonseminomatous testicular cancer were treated with cis-platinum, bleomycin, and vinblastine in combination without a prolonged maintenance phase. Twenty-Six patients with Stage III disease were treated. Seventy-six percent of those patients treated achieved complete remission. At a median survival time of 30 months, no patient who achieved a complete remission has relapsed. Twelve Stage II patients given adjuvant therapy remain free of disease at a median time of 23 months. Markedly elevated serum lactate dehydrogenase levels and massive disease were common findings in the patients who did not achieve complete remission. One drug death occurred secondary to sepsis. Symptoms of depression and anxiety were significant dose-limiting factors in this group of patients.

NaUCC-2, a choriocarcinoma cell line, was derived from a patient who had a very poor clinical response to combination chemotherapy. Methotrexate (MTX) might have inhibited the antitumor effect of dactinomycin. To investigate this point, in vitro studies were performed to determine the sensitivity and uptake of MTX and dactinomycin (administered individually and in combination) to NaUCC-2 and three other choriocarcinoma cell lines. Dihydrofolate reductase (DHFR) concentrations were studied as well. Although NaUCC-2 showed sensitivity to MTX and dactinomycin, which were comparable to the other cell lines when they were given separately, NaUCC-2 was unique in that the combination of MTX and dactinomycin was less lethal than dactinomycin given by itself. The uptake of MTX in NaUCC-2 was significantly higher than that in the other cell lines, and MTX also induced an increase in dactinomycin uptake in NaUCC-2. There was no significant difference in DHFR activity. Although additional studies are necessary to determine the mechanism responsible for this effect, these findings suggest that a mechanism other than drug uptake or DHFR activity must play a role in the drug resistance for choriocarcinoma. These findings also suggest that the most commonly used combination chemotherapy for choriocarcinoma, dactinomycin and MTX, may not always be the best method.

Thirty-six men with Stage III or bulky Stage II malignant germ cell tumors of the testis who received no prior chemotherapy were treated with the VAB-6 protocol without maintenance and 34 were evaluable. The VAB-6 regimen is a 3-4 month program beginning with successive inductions at 3-4 week intervals: day 1, cyclophosphamide 600 mg/m2 of body surface, bleomycin 30 mg, vinblastine 4 mg/m2 and dactinomycin 1 mg/m2 intravenously; days 1-3, bleomycin 20 mg/m2/day X 3 by continuous 24-hour intravenous infusion; and day 4, cis-platinum 120 mg/m2 intravenously. Complete responders receive a fourth induction and are followed thereafter without further chemotherapy. Incomplete responders have resection of residual disease one month after the third induction. If the resected specimen contains malignant tissue, an additional two inductions are given. Thirty-one of 34 (91%) evaluable patients achieved complete remission and 28 remain in complete remission with median follow up of 24+ months. Chemotherapy alone was most effective in patients with minimal metastatic disease, with no teratoma in primary tumor, and with pure seminoma. Patients with advanced metastatic deposits or with teratoma in the primary tumor frequently required combined chemotherapy and surgery to achieve disease free status. Myelosuppression was the principal potentially serious toxicity. With effective induction, maintenance chemotherapy is not necessary.

Two cases of metastatic gestational choriocarcinoma to the lungs have been encountered that presented unusual histologic patterns. Both lesions were solitary metastases that followed multiple courses of chemotherapy, and the patients had low serum beta-human chorionic gonadotropin (hCG) levels. Surgical excision appeared to be curative in both cases. Both neoplasms were characterized by a predominance of uniform but highly atypical mononucleate trophoblastic cells. These cells infiltrated pulmonary parenchyma, forming nests of tumor with central dense necrotic debris. Syncytiotrophoblastic cells (STB) were present but showed scant cytoplasm and little vacuolization. Hemorrhage was only focal. Immunohistochemistry revealed that some of the multinucleate STB and occasional mononucleate cells produced hCG, while human placental lactogen was focally produced in the tumors. By electron microscopy the STB were identified but lacked open lacunae lined by microvilli. Most mononucleate cells showed greater maturation evidenced by a more complex cytoplasm than is seen in typical cytotrophoblastic cells (CTB). The results suggest that these tumors are a distinctive subtype of choriocarcinoma composed largely of a form of trophoblastic cell with features intermediate between CTB and STB, yet different from the intermediate trophoblast of the placental site tumor. Identification of this morphologic variant of choriocarcinoma may have clinical utility as additional cases are studied.

Extragonadal germ cell tumors may have a worse prognosis than germ cell tumors of gonadal origin, even when tumor bulk and extent of dissemination are equal. Primary retroperitoneal pure choriocarcinoma is one of the least common subgroups of the extragonadal germ cell tumors and has previously appeared to have the worst prognosis. Two new case reports on the treatment and follow-up of two patients with primary retroperitoneal pure choriocarcinoma are discussed. Both patients are disease-free at 24 and 81 months, respectively. After aggressive primary multiagent drug therapy for primary retroperitoneal pure choriocarcinoma, a favorable prognosis may be anticipated.

Between 1957 and February 1981, 782 patients received cytotoxic chemotherapy for gestational trophoblastic tumors (GTT) in the Department of Medical Oncology, Charing Cross Hospital (London, England). Sixty-nine (8.8%) patients had central nervous system (CNS) metastases. Thirty-three of them (48%) presented with CNS disease prior to treatment (CNS presentation group), and 36 (52%) developed CNS disease while on treatment, or relapsed in the CNS after an initial complete or partial remission (late CNS group). Treatment included systemic and intrathecal chemotherapy, and, in several cases neurosurgery, whole brain irradiation, and immunotherapy. Life-table analysis projects an overall survival of 49% for the CNS presentation group and 6% for the late CNS group. Prognosis has improved with time; prior to 1974, 38% of the CNS presentation group and none of the late CNS group survived. After 1974 overall survival has been 80% in the CNS presentation group and 25% in the late CNS group. The principal elements in the successful management of such cases are: (1) CNS prophylaxis with intrathecal methotrexate for patients at risk of developing brain metastases; (2) early detection of CNS lesions by prompt recognition of their clinical features, measurement of the ratio of CSF to serum human chorionic gonadotropin concentration, and appropriate use of computerized tomography of the brain; and (3) a combination of systemic and intrathecal therapy for patients developing brain secondaries.

Ninety-one patients with disseminated testicular non-seminomas were treated with 3 to 4 cycles of cisplatin, vinblastine, and bleomycin (PVB) induction chemotherapy followed by cisplatin and vinblastine maintenance therapy for 1 year. The follow-up of these patients ranges from 24 to 66 months. Forty-nine (54%) patients achieved complete remission by chemotherapy alone and 14 (15%) were rendered free of tumor by surgery after chemotherapy, for a total complete remission rate of 69%. Three complete responders relapsed within 13 months, and two died. One additional complete responder died of a noncancer-related cause. One of the surgical complete responders relapsed and died. Overall, 58 (64%) patients remain free of disease. The 5-year survival is 95% for complete responders, 32% for partial responders, and 72% overall. This combination regimen has significantly improved the survival of disseminated testicular cancer patients, equaling that of Stage II patients in older literature.

Thirty-one patients with nonmetastatic trophoblastic disease (NMTD) and 39 patients with metastatic trophoblastic disease (MTD) of gestational origin were treated primarily with actinomycin D. Complete and sustained remission was achieved with actinomycin D alone in 94% of patients with NMTD and 67% with MTD. In the nonmetastatic group, 93% of patients without choriocarcinoma (non-CCA) achieved remission with actinomycin D, as compared to 100% (only 3 patients) with CCA. in the metastatic group, 76% of patients without CCA achieved remission with actinomycin D, as compared to 56% where CCA was present. Fourteen of the 15 patients who failed to respond completely to actinomycin D alone subsequently responded to methotrexate (10 patients), triple therapy (3 patients), methotrexate plus triple therapy (1 patient), and methotrexate plus vinblastine (1 patient). One patient died with widespread metastases despite intensive chemotherapy with actinomycin D and triple therapy. No serious toxic side effects were encountered even in treated patients with pre-existing laboratory evidence of impaired hepatic function.

Of 36 cases of choriocarcinoma treated at the University Hospital Kuala Lumpur during 1980-84 inclusive, 6 patients were found to have cerebral metastases. Intrathecal methotrexate and combination chemotherapy were started in all cases, with monitoring of tumor growth by serial beta-HCG assays and CT scanning of brain and lung. Chemotherapy was reduced because of severe toxicity in 2 patients, one of whom received radiotherapy to the brain. Four patients (66%) have now been in remission for 2.5-6 years. Two did not respond to therapy and died. The factors involved in therapy and response are discussed.