Multimodal treatment of malignant sacrococcygeal germ cell tumors: a prospective analysis of 66 patients of the German cooperative protocols MAKEI 83/86 and 89.

PURPOSE: To evaluate a multimodal approach including surgery and cisplatinum chemotherapy for treatment of children with malignant sacrococcygeal germ cell tumors (GCT) and to compare adjuvant and neoadjuvant strategies in advanced tumors. PATIENTS AND METHODS: Between 1983 and 1995, 71 patients with malignant sacrococcygeal GCT were prospectively enrolled onto the German protocols for nontesticular GCT Maligne Keimzelltumoren 83/86 and 89. Five patients who received no chemotherapy (n = 2) or nonplatinum chemotherapy (n = 2) or who did not undergo tumor resection (n = 1) were excluded from this analysis. Among the 66 patients analyzed were 14 boys and 52 girls. The median age was 17.4 months (range, 7 months to 119 months). Median follow-up was 79 months (range, 4 months to 145 months). RESULTS: Fifty-two patients presented with locally advanced stage T2 tumors, and 30 patients had distant metastases at diagnosis. Patients received a median of eight cycles (range, four to nine cycles) of cisplatinum-based chemotherapy. Thirty-five patients underwent tumor resection at diagnosis and received adjuvant cisplatinum-based chemotherapy (group A). Thirty-one patients received up-front chemotherapy followed by delayed tumor resection (group B). Group B included more metastatic tumors than group A (group B, 19 of 31 patients; group A, 11 of 35 patients, P =.01). Preoperative chemotherapy facilitated complete tumor resections (group B, 20 of 31 patients; group A, five of 35 patients, P <.001) and avoided second-look surgery. Metastases at diagnosis and completeness of the first attempt of tumor resection were significant prognostic predictors; however, metastases were not predictive for patients treated with up-front chemotherapy. At 5 years follow-up, event-free survival was 0.76 +/- 0.05 (50 of 66 patients), and overall survival was 0.81 +/- 0.05 (54 of 66 patients). Four patients died as a result of therapy-related complications, and eight patients died of their tumors. Patients with locally advanced and metastatic tumors (T2b M1) fared better with neoadjuvant treatment [overall survival: 0.83 +/- 0.09 (16 of 19 patients) versus 0.45 +/- 0.15 (five of 11 patients), P =.01]. CONCLUSION: Even locally advanced and metastatic sacrococcygeal GCT can be successfully treated with up-front cisplatinum-based chemotherapy followed by delayed but complete tumor resection.

Patient stratification based on prednisolone-vincristine-asparaginase resistance profiles in children with acute lymphoblastic leukemia.

PURPOSE: To confirm the prognostic value of a drug resistance profile combining prednisolone, vincristine, and l-asparaginase (PVA) cytotoxicity in an independent group of children with acute lymphoblastic leukemia (ALL) treated with a different protocol and analyzed at longer follow-up compared with our previous study of patients treated according to the Dutch Childhood Leukemia Study Group (DCLSG) ALL VII/VIII protocol. PATIENTS AND METHODS: Drug resistance profiles were determined in 202 children (aged 1 to 18 years) with newly diagnosed ALL who were treated according to the German Cooperative Study Group for Childhood Acute Lymphoblastic Leukemia (COALL)-92 protocol. RESULTS: At a median follow-up of 6.2 years (range, 4.1 to 9.3 years), the 5-year disease-free survival probability (pDFS) rate +/- SE was 69% +/- 7.0%, 83% +/- 4.4%, and 84% +/- 6.8% for patients with resistant (PVA score 7 to 9), intermediate-sensitive (PVA score 5 to 6), and sensitive (SPVA score 3 to 4) profiles, respectively (sensitive and intermediate-sensitive v resistant, P

Combination chemotherapy in malignant non-seminomatous germ-cell tumors: results of a cooperative study of the German Society of Pediatric Oncology (MAKEI 83).

In January 1983, the German Society of Pediatric Oncology started a cooperative trial (MAKEI 83) for non-testicular germ-cell tumors. The pilot phase closed in December 1985. The treatment regimen was stratified according to histology, tumor site and tumor stage. In malignant non-seminomatous germ-cell tumors (mNSGCTs), chemotherapy consisted of four courses of 3 mg/m2 vinblastine, on days 1 and 2 and 15 mg/m2 bleomycin on days 1-3, given by continuous infusion, and 20 mg/m2 cisplatin on days 4-8 with mannitol diuresis. Courses were repeated every 3 weeks. In mNSGCT patients with ovarian FIGO stages III-IV or extragonadal primaries, second-look surgery was carried out, followed by four additional courses of chemotherapy with 100 mg/m2 VP-16 on days 1-3, 1.5 g/m2 ifosfamide on days 1-5 with mesna uroprotection and 20 mg/m2 cisplatin on days 1-5 with mannitol diuresis. In patients with sacrococcygeal germ-cell tumors, en bloc resection of the tumor, including the coccygeal bone, was mandatory. During the registration period, 57 patients with mNSGCTs were entered: 37 protocol patients and 20 follow-up patients. The event-free survival for protocol patients at 57 months was 78% +/- 6% and that for follow-up patients was 40% +/- 10% (Kaplan-Meier): the crude survival for both groups was 83% +/- 6% and 54% +/- 12%, respectively. After a review by a panel of pathologists, the histological diagnoses in 7% of all registered cases of germ-cell tumors were changed. The results of the present studies show that the histological subclassification of mNSGCTs, tumor site and tumor stage no longer had prognostic value.

Embryonal rhabdomyosarcoma of the common bile duct.

A 2 4/12-year-old boy with obstructive jaundice caused by a tumor of the portal area that proved to be an embryonal rhabdomyosarcoma of the common bile duct is reported. The diagnosis was made clinically, radiographically, ultrasonographically, and histologically. Surgery was elected as the primary therapy; there were no intra- or postoperative complications. The prognosis and its improvement by means of aggressive chemotherapy and local irradiation are discussed.

Daunorubicin-induced cell kill with 1-hour versus 24-hour infusions: a randomized comparison in children with newly diagnosed acute lymphoblastic leukemia.

BACKGROUND: Daunorubicin (DNR) is one of the most important drugs in treatment of acute lymphoblastic leukemia (ALL). Prolonged infusions of anthracyclines are less cardiotoxic but it has not been investigated whether the in vivo leukemic cell kill is equivalent to short-term infusions. PROCEDURE: In the cooperative treatment study COALL-92 for childhood ALL 178 patients were randomized to receive in a therapeutic window a single dose of 36 mg/m (2) DNR either as a 1-h (85 patients) or 24-h infusion (93 patients). Daily measurements of white blood cell count (WBC) and peripheral blood smears for seven days could be evaluated centrally in 101 patients (1-h: 43 patients, 24-h: 58 patients). RESULTS: The proportional decline of blasts at day 7 after DNR infusion showed no statistically significant difference between the two treatment arms. At day 3 the median percentage of blasts was less than 10%, at day 7 less than 2% for either the 1-h or 24-h infusion. Twelve patients (1-h: 5 patients, 24-h: 7 patients) had an absolute number of more than 1000 blasts per mul peripheral blood (PB) at day 7 after DNR infusion (DNR poor responders). Kaplan-Meier analysis showed an equal probability of EFS for the short- and long-term infusion group (24-h: 83%+/-5; 1-h: 81+/-6) after a median observation time of 12.3 years. CONCLUSIONS: We conclude that in children with ALL a 24-h infusion of DNR has the same in vivo cytotoxicity for leukemic cells as a 1-h infusion. This offers the possibility to use prolonged infusions with hopefully less cardiotoxicity without loss of efficacy.

[Acute lymphoblastic leukemia in childhood: the COALL studies]. / Akute lymphoblastische Leukämie im Kindesalter: Die COALL-Studien.

In the cooperative study COALL-80 151 children with acute lymphoblastic leukemia were treated according to the modified protocol BFM 79/81. The probability of continuous complete remission (CCR) for the total group is 74% after 6 years. In the subsequent study COALL-82 high-risk patients (initial white blood count greater than or equal to 25/nl or T-cell leukemia and acute undifferentiated leukemia) received additional high-dose methotrexate as fifth drug in the intensive phase and the combination VM-26/arabinosyl-cytosine in the reinduction phase. In all others patients (low-risk group) intermediate-dose methotrexate was substituted for the myelosuppressive agent cyclophosphamide in the intensive phase. Reinduction was no longer given in the low-risk group. In both risk groups cranial irradiation was postponed until after the intensive phase therapy. Radiotherapy was withheld for a group with minimal risk (white blood count less than 3/nl, liver/spleen less than 3 cm). The probability of CCR for the total group of 129 patients is 64% after 3.5 years. The comparative analysis between the studies COALL-82 and COALL-80 shows that low-risk patients have an equally high probability of continuous hematologic remission (91% vs. 85%) despite reduction of therapy in COALL-82. High-risk patients, however, had a significantly higher rate of bone marrow relapses; in this group the probability of continuous hematologic remission is 52% in COALL-82 vs. 73% in COALL-80. Also relapses in the central nervous system in irradiated patients were significantly more frequent in COALL-82 than in COALL-80 (12% vs. 4%) whereas the group of patients without radiotherapy has remained free of relapse. The possible influence of the modifications in therapy in study COALL-82 on the higher relapse rate is discussed.

Medullomyoblastoma: a histological, immunohistochemical, ultrastructural and molecular genetic study.

Medullomyoblastoma is a rare variant of medulloblastoma containing myoblastic elements. A 9-year-old boy developed a cerebellar syndrome and signs of increased intracranial pressure, the cause of which was a tumor of the cerebellar vermis measuring 7 x 4.5 x 4.5 cm. Morphologically the tumor largely consisted of a medulloblastoma component but displayed glial, myoblastic and ganglionic differentiation on light microscopic, immunohistochemical and ultrastructural examination. The non-enhancing rim of the tumor on magnetic resonance imaging showed extensive ganglionic differentiation. The tumor did not express bcl-2, c-myc, or c-erb-B2 oncoproteins and was negative for the p53 gene product. On molecular genetic studies, the tumor did not show allelic loss on chromosome loci, frequently altered in medulloblastomas, such as 17p, 1q and 9q.

Successful liver treatment of a juvenile granulosa cell tumor in a 4-year-old child by regional deep hyperthermia, systemic chemotherapy, and irradiation.

Juvenile granulosa cell tumors (JGCT) of the ovary are rare in children and adolescents. About 90% are diagnosed in early-stage FIGO I with favorable prognosis. More advanced stages (FIGO II-IV) have a poor clinical outcome and chemotherapy alone cannot avoid tumor progression. Regional deep hyperthermia (RHT) induced by microwave technique has been established as an additional modality for treatment of different tumors. However, in cases with liver involvement there are technical problems which have not yet been solved. We report on a 4-year-old child who suffered from diffuse liver metastases 10 months after JGCT of the left ovary. After chemotherapy including ifosfamide, etoposide, and carboplatin in combination with RHT and consolidation radiotherapy, the patient has been in complete remission for 1 year of follow-up. This Case Report indicates the feasibility of combining surgery, chemotherapy, hyperthermia, and radiation therapy (which can also be an effective treatment modality for advanced granulosa cell tumor) for the treatment of liver metastases of JGCT, but does not allow comparisons of these treatments.

Preliminary results of the GPO-trial for treatment of non-testicular germ-cell tumors in children and adolescents.

Germ cell tumors account for a 3% mortality rate of childhood malignancies. The combined chemotherapy, vinblastine, bleomycin and cis-platinum, is probably associated with more toxicity and treatment-induced mortality in children. Based on pharmacokinetic findings concerning the renal elimination of bleomycin and the well known cis-platinum nephrotoxicity, these two drugs were given sequentially. In addition, the cumulative dose of bleomycin was limited to 180 mg/m2. 61 patients entered the trial whereby 42 of these are evaluable. The chemotherapeutic regimen was well tolerated and was completed in 19 patients without treatment induced mortality and without evidence of pulmonary fibrosis. The treatment regimen seems to be successful despite the relatively low cumulative doses of vinblastine and bleomycin, as only 4 of 19 patients relapsed after a median observation period of 12 months.

[Cooperative therapy study of nontesticular germ cell tumors MAKEI 83 of the Society of Pediatric Oncology: analysis after 3 years]. / Die kooperative Therapiestudie für nichttestikuläre Keimzelltumoren MAKEI 83 der GPO: Analyse nach 3 Jahren.

The German Society of Pediatric Oncology has initiated in 1983 a cooperative trial for the treatment of extratesticular germ cell tumors. The treatment plan is stratified according to histology, tumor site and tumor extension. Patients with unfavourable histology received depending on prognostic factors 4 courses of either vinblastine, actinomycin D and cyclophosphamide, or the combination of vinblastine, bleomycin and cisplatinum (4 courses) completed by 4 additional courses of VP 16, ifosfamide and cisplatinum. Within 3 years, 115 patients from 37 different institutions were entered into the trial. 55 of 72 protocol patients are under observation for at least 10 months since diagnosis. The disease-free survival rate according to Kaplan-Meier is 80% (+/- 6%) at 36 months. From the interim results of this ongoing study, the following conclusions are drawn: The chemotherapeutic regimens as delivered are tolerable. Radiotherapy does not seem necessary with the exception of ovarian dysgerminomas stage I a. In coccygeal teratomas the resection of the coccygeal bone decreases the hazard of local recurrences. Using the risk adapted regimen, the prognosis for teratomas with Yolk sac origin appears as favourable as for patients with mature teratomas.

[Langerhans cell histiocytosis in childhood--results of the DAL-HX 83 study]. / Langerhanszell-Histiozytose im Kindesalter--Ergebnisse der DAL-HX 83 Studie.

Owing to the unclear and mostly unknown etiology of Langerhans' cell Histiocytosis (LCH) and the unsatisfactory results in treating disseminated LCH a prospective multicentric study DAL-HX 83 was commenced, including 45 different clinics of West-Germany, Austria and Netherlands. From June 1st, 1983 to October 31st, 1986, 97 patients (pts) were involved in this study. 35 pts (9 females, 26 males, medium age 6 2/12 years, age range 0/12-14 2/12 years) suffering from localized disease (28x unifocal bone, 6x isolated skin, 1x isolated lymphnode involvement) were treated by surgery and/or radiation or were just kept in observation. 2 children (1 pt with primary localized bone lesion, 1 child with isolated skin rash) developed a new bone lesion after 1/2 year and 1 1/2 years respectively. 62 pts (33 females, 29 males, medium age 2 years, range 0/12-17 1/2 years) with previously untreated disseminated disease were assigned to 3 different risk groups (A, B and C) and were treated according to a standardized induction and risk adapted maintenance protocol. The whole treatment period was limited to 1 year. 19 pts with multifocal bone involvement (group A, medium age 6 1/2 years) were allocated to regimen A, 30 pts with bone and soft tissue involvement or soft tissue involvement alone (group B, medium age 1 8/12 years) to regimen B and 13 pts with dysfunction of the liver, lungs and/or haematopoietic system (group C, medium age 1 year) to regimen C. So far, 1 pt of group A (19 available pts) developed a new bone lesion after 10 months, another pt a suspicious bone involvement 16 months after diagnosis. A 4 months old girl of group B (27 available pts) died 11 months after diagnosis with progressive organ dysfunction, 2 pts are still alive with recurrent multifocal bone lesions and 1 pt achieved stable 2nd clinical remission after a local relapse (mediastinum). 4 pts of group C (11 available pts) died because of progressive disease between 5 days and 3 years after diagnosis, 3 pts are in partial remission after persistent and recurrent disease episodes. All the others are in clinical remission. The medium observation time of the whole group of pts with disseminated LCH is 1 9/12 years (range 0/12-3 5/12 years). The worst prognostic criteria were found to be the presence of organ dysfunction at diagnosis or its development during the course of disease and the age under two years.(ABSTRACT TRUNCATED AT 400 WORDS)

Intermediate-dose methotrexate in the treatment of childhood acute lymphocytic leukaemia: lack of benefit during maintenance therapy following intensive induction therapy.

One hundred and fifty-one children with acute lymphocytic leukaemia (ALL) received multiple agent induction chemotherapy followed by intensive phase treatment. One hundred and thirty-seven patients were randomised for the first year of maintenance treatment to receive reinforcement therapy (pulses) with either intermediate-dose methotrexate (ID-MTX) and prednisone (PRED) or vincristine (VCR) and PRED. The probability of continuous complete remission (CCR) at 5.5 years is 0.80 for the ID-MTX group and 0.84 for the VCR group. Extramedullary relapses were not prevented either in the ID-MTX group nor in the VCR group. Since in previous studies VCR/PRED pulses did not increase CCR rates when given after intensive combination chemotherapy, it can be concluded from this study that neither did ID-MTX reinforcement therapy further improve treatment results in our patients with ALL when given after aggressive chemotherapy.

[Results of treatment of rhabdomyosarcomas (RMS) in children. A report of the Cooperative Soft Tissue Sarcoma Study (CWS-81) of the Society of Pediatric Oncology]. / Ergebnisse der Behandlung von Rhabdomyosarkomen (RMS) bei Kindern. Ein Bericht der Cooperativen Weichteilsarkomstudie (CWS-81) der Gesellschaft für Pädiatrische Onkologie.

This analysis refers to 129 children with RMS who were treated between 1981 and 1985 according to the protocol guidelines of the CWS-81 study. The duration of chemotherapy depended on the initial post-operative stage. Patients with stage I and IIA were not to receive any radiotherapy, and patients with primary stage III were treated according to the results of a 16-week chemotherapy treatment: either without radiation (stage Ipc), or with radiotherapy using 40 Gy (stage (IIpc) or 50 Gy (stage IIIpc). The median time of observation was 27 months (Juni 1985). The essential results of the study are as follow: RMS of the extremities in stages I and IIA need radiotherapy, contrary to all other localisations with the same stages. Patients with RMS stage III who are tumor-free after initial chemotherapy (histologically checked) do not need radiotherapy. Patients with microscopic residue (IIpc) or macroscopic residue (IIIpc) after pretreatment showed no difference in their local relapse rate, whereas metastases were found only in the group having macroscopic tumor residue up to week 16. An additional examination of this study observed tumor response during initial chemotherapy and its relationship to prognosis. This analysis showed that the degree of tumor regression per unit of time permits the most favorable prognostic statement. Patients with clinical complete remission after 7/9 weeks showed a 100% relapse-free chance of survival, independent of localisation, tumor size or histological subtype. Those with a tumor reduction of greater than 2/3 but no complete remission showed 67% chance of survival, and those with greater than 1/3-2/3 tumor reduction had 25%. Tumor response kinetics under initial chemotherapy allows better individual therapy in the future. The overall result of the study concerning localisation and stage corresponds to that of the IRS I and II studies. Patients with undifferentiated sarcomas, extraossary Ewing's sarcoma and synovial sarcomas can be treated according to the same principles as RMS, since no significant differences in prognosis could be found.

[Analysis of prognostic factors in rhabdomyosarcoma. Preliminary univariate and multivariate results of the Cooperative Soft Tissue Sarcoma Study (CWS-81)]. / Analyse prognostischer Faktoren beim Rhabdomyosarkom. Vorläufige univariate und multivariate Ergebnisse der cooperativen Weichteilsarkomstudie (CWS-81).

The characteristics of 129 children with rhabdomyosarcoma entered into the CWS-81 study between 1981 and 1984 were examined for their relationship to prognosis. Prognosis was defined as relapse-free survival time. The trial was stratified to clinical groups depending on the surgical procedure at onset. So, each group had to be analysed separately. The patient characteristics of group I/IIA mostly related to prognosis were primary site (disease in extremities, unfavorable; paratesticular primary, favorable) and tumor infiltration into adjacent bone (bone infiltration, unfavorable). In group IIB/III the degree of tumor response within 7-9 weeks, chemotherapy exclusively given, was the only characteristic significantly related to prognosis (greater than 2/3 tumor reduction, favorable; less than 2/3 tumor reduction, unfavorable). Other prognostic factors as histological subtype, primary site, tumor diameter, lymph node involvement, bone infiltration, sex and age had no significant influence. The tumor diameter was the only characteristic with significant influence in group IV. The larger the tumor diameter, the poorer was prognosis. Furthermore, the alveolar subtype was seen predominantly in non-responding tumors of group IV. In group III, we fitted the patient characteristics in a multivariate regression model (Cox's model). The degree of tumor response within 7-9 weeks was analysed to be the main hazard function related to prognosis. In future, the degree of tumor response within a certain time can be used as the measurement of effectiveness of chemotherapy. So, in patients of group III and IV a risk adapted therapeutic procedure can be undertaken.

[Effect of dose intensity and therapy-induced leukocytopenia in intensive therapy on the prognosis of acute lymphatic leukemia in childhood. Results in 213 patients of the COALL-85 study]. / Einfluss von Dosisintensität und therapiebedingter Leukozytopenie in der Intensivtherapie auf die Prognose bei akuter lymphatischer Leukämie im Kindesalter. Untersuchungen bei 213 Patienten der Studie COALL-85. COALL-Studiengruppe.

Dose intensity (DI) plays an important role in the treatment of neoplastic diseases. The individual DI within a protocol may vary considerably and thus may be an important prognostic factor. In 213/305 patients treated in the cooperative study COALL-85 for childhood acute lymphoblastic leukemia the following parameters of individual therapy intensity were analyzed: Total time for intensive treatment, cumulative doses of single drugs, mean relative dose (= relation between received and prescribed doses of all drugs), mean relative dose intensity ( = mean relative dose/time) as well as frequency and duration of leukocytopenia. Therapy for LR (low-risk) and HR (high-risk) patients were separately analyzed by both life-table method and multivariate regression analysis. Neither length of time, mean relative dose intensity nor the other parameters had any significant influence on prognosis within the HR protocol. The only significant prognostic factor was the remission status on day 28 (p less than 0.001 in multivariate analysis). In contrast patients treated with the LR protocol had significantly fewer relapses if treatment resulted in leukocytopenic episodes (probability for event free survival (EFS) = 0.76 in patients with one or two leukocytopenic episodes compared to 0.52 in patients with none). Patients with a mean relative dose greater than 0.9 showed a higher EFS of borderline significance than patients with mean relative dose less than = 0.9 (0.72 vs 0.49, p = 0.09). We would like to conclude, that treatment protocols with very intensive and prolonged combination chemotherapy have a certain margin of safety in DI without disadvantage for the patient.(ABSTRACT TRUNCATED AT 250 WORDS)

Primary malignant rhabdoid tumours of the central nervous system: an immunohistochemical and ultrastructural study.

Three cases of primary rhabdoid tumour of the CNS (RT-CNS) are presented. In case 1 a hemispheric tumour developed in a 10.5 months old girl, who survived for 6 months after incomplete resection, radio- and polychemotherapy. Case 2 was a 4 years and 8 months old boy with a large IIIrd ventricle tumour, who died of leptomeningeal tumour dissemination 7 months after diagnosis despite radiotherapy. In case 3 a pineal mass occurring in a 14 month old female was radioresistant and totally exstirpated. The child died due to tumour recurrence two months later. Autopsy examination revealed widespread leptomeningeal dissemination. All three cases fulfilled light and electron microscopic criteria of RT-CNS including abundant eosinophilic cytoplasm, vesicular nuclei with large nucleoli and conspicuous anti-vimentin positive filaments. Extensive immunohistochemical studies showed expression of epithelial (EMA, KL1), macrophage (alpha-1 antichymotrypsin), neuro-ectodermal (GFAP, NSE, beta-tubulin III) and myogenic markers (desmin, actin). Different stress proteins (alpha-B crystallin, HSP70) were also expressed. Tumour cells showed a proliferation (MIB1) index of 28.4% (case 1) and 33.4% (case 2). From our study it can be concluded that RT-CNS reveals significant immuno-morphological heterogeneity thus supporting the view that it is not a specific pathological entity but merely a phenotypic appearance of different neoplasms, some of which are linked to primitive neuro-ectodermal tumours.

[The importance of preoperative chemotherapy and radiotherapy in 373 children with Wilms' tumor]. / Bedeutung der präoperativen Chemotherapie und der Radiotherapie bei 373 Kindern mit Wilms-Tumor.

Between 1980 and 1988, in a prospective study of 373 children with Wilms' tumour throughout the Federal Republic of Germany, the results of various pre- and postoperative treatment schedules were analysed. There were 184 boys and 189 girls, mean age 3 11/12 (0-27) years. One third each was in group I, II or III-V, respectively. In 52% of cases the tumour volume, measured by ultrasound, was more than 400 ml. 218 of the children were called protocol patients, the remaining 155 served as observation patients, because the latter had histological variants or there had been marked treatment deviations. The stage-adapted treatment always included operation, in 30% of children after pre-operative chemo- or radiotherapy. Radiotherapy was given in selected patients in stage II and always to those in stages III, IV or V. Chemotherapy consisted of Actinomycin D and vincristine, adriamycin was added for stages III-V and cyclophosphamide or ifosfamide for histologically highly malignant variants. Of the 218 protocol patients 196 (90%) were alive without recurrence, after a mean observation time of more than 7 years. Radiotherapy was given to only 105 of the 218 protocol patients. The prognosis of the 155 observation patients differed according to the histology: those with clear-cell type had a better prognosis than previously reported. Among the total group of 373 patients 305 (81.8%) have remained without recurrence after more than 6 years.

[Improved prognosis of intracranial germ cell tumors by intensified therapy: results of the MAKEI 89 therapy protocol]. / Verbesserte Prognose intracranialer Keimzelltumoren durch intensivierte Therapie: Ergebnisse des Therapieprotokolls MAKEI 89.

Germ cell tumors of the central nervous system are histological identical to the extracranial tumor sites. According to the localisation germ cell tumors of the CNS are different in symptoms, diagnostic approaches, kind and location of metastases and stratification of therapy. Since 1986 patients with intracranial germ cell tumors are registered in the ongoing study for non-testicular germ cell tumors (MAKEI) of the German Society of Pediatric Oncology and Hematology, and are treated in accordance to therapy guidelines for extracranial sites. In MAKEI 89 therapy strategy was revised with a reduction of radiotherapy and an increased cumulative cisplatinum dose from 200 mg/m2 to 400 mg/m2. Patients with germinoma receive after histologic diagnosis radiotherapy consisting of 30 Gy craniospinal irradiation and 15 Gy tumorboost. Malignant non-germinoma receive after diagnosis by tumor marker in CSF and/or serum 2 courses bleomycin 15 mg/m2 day 1-3, Etoposide 150 mg/m2 day 1 + 2 and cisplatinum 20 mg/m2 days 4-8 (BEP), continued by 2 courses Vinblastine 3 mg/m2 day 1 + 2, Ifosfamide 1500 mg/m2 days 1-5 and cisplatinum 20 mg/m2 days 1-5 (VIP), followed by 30 Gy craniospinal irradiation and 20 Gy tumor boost. In teratoma first line therapy is complete resection. In incomplete resected cases adjuvant chemotherapy according to histological grading is administered. Until 31st January, 1993 101 patients (pts) were registered, containing 69 protocol pts. Diagnosis in protocol pts was teratoma in 8 cases, 2 pts died postnatal because of extended disease, 2/8 pts relapsed, but were salvaged by chemotherapy. 40 pts offered germinomas.(ABSTRACT TRUNCATED AT 250 WORDS)