title: Impact of surgery, chemotherapy and irradiation on long term outcome of intracranial malignant non-germinomatous germ cell tumors: results of the German Cooperative Trial MAKEI 89.
abstract: Malignant non-germinomatous intracranial germ cell tumors (MNGGCTs) are a heterogenous group of neoplastic lesions. Their treatment concept follows a multimodal concept that may include tumor resection for local tumor control, craniospinal irradiation to cover leptomenigeal tumor spread and chemotherapy to eliminate systemic tumor dissemination. A Platinum-based chemotherapy proven to be highly effective in testicular and non-testicular malignant germ cell tumors in adults as well as in children has also been chosen for intracranial sites. While therapeutic concepts have been thoroughly evaluated for children and adolescents with extracranial nongonadal GCTs, no such detailed long term follow-up data are available for intracranial MNGGCTs. This paper reports on the long-term outcome of 41 patients with intracranial malignant non-germinomatous GCTs enrolled into the German prospective protocol MAKEI 89. The analysis focuses on the impact of surgery, radio- and chemotherapy.
  
  
  METHODS
  Between January 1989 and January 1994, 41 patients with malignant intracranial non-germinomatous GCTs were registered. Patients were compared in respect to protocol (n = 27) and non-protocol treatment (n = 14). Estimated were with chi (2) and Fisher exact test the impact of surgery, chemotherapy and irradiation on outcome.
  
  
  RESULTS
  The estimated (Kaplan-Meier) 5-year event free survival (EFS) of patients treated according to protocol recommendations was 0.59 +/- 0.06 (n = 27), compared to an EFS of 0.37 +/- 0.33 for patients with different treatments (n = 14) (p = 0.70, log-rank). The 5-year relapse-free survival rate (RFS) was 0.74 +/- 0.06 in protocol patients and 0.38 +/- 0.33 in non-protocol patients (median observation time of 112 months after diagnosis for surviving patients) (p = 0.14, log-rank). Surgery, complete or incomplete had no significant impact on survival (p = 0.12). Radiotherapy, in terms of craniospinal irradiation had a significant influence on survival (p = 0.035) as well as a cumulative cisplatin dose >/= 400 mg/m (2) (p = 0.002).
  
  
  CONCLUSIONS
  Cisplatin chemotherapy and craniospinal irradiation with tumor boost are of significant influence on long term survival in patients with MNGGCTs. The exclusion of major surgery at diagnosis using modern advances in neurosurgery or related tumor resection after neoadjuvant chemotherapy will allow a further reduction of treatment related mortality and long lasting morbidity. The analysis reveals that, given effective treatment, intracranial malignant non-germinomatous GCTs should not longer carry a poor prognosis.
authors.affiliation: Department of Pediatric Hematology and Oncology Children's Hospital, University of Düsseldorf, Germany. calaminus@med.uni-duesseldorf.de
authors.forename: G
authors.initials: G
authors.lastname: Calaminus
authors.forename: M
authors.initials: M
authors.lastname: Bamberg
authors.forename: H
authors.initials: H
authors.lastname: Jürgens
authors.forename: R D
authors.initials: RD
authors.lastname: Kortmann
authors.forename: N
authors.initials: N
authors.lastname: Sörensen
authors.forename: O D
authors.initials: OD
authors.lastname: Wiestler
authors.forename: U
authors.initials: U
authors.lastname: Göbel
mesh_terms: D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000532:radiotherapy / Q000601:surgery*; D017024:Chemotherapy, Adjuvant; D002648:Child; D002675:Child, Preschool; D002945:Cisplatin / Q000008:administration & dosage* / Q000009:adverse effects; D003131:Combined Modality Therapy; D016371:Cranial Irradiation; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D005858:Germany; D006801:Humans; D008297:Male; D020360:Neoadjuvant Therapy; D009373:Neoplasms, Germ Cell and Embryonal / Q000188:drug therapy* / Q000401:mortality / Q000532:radiotherapy / Q000601:surgery*; D010871:Pinealoma / Q000188:drug therapy / Q000401:mortality / Q000532:radiotherapy / Q000601:surgery*; D011379:Prognosis; D011446:Prospective Studies; D018714:Radiotherapy, Adjuvant; D016019:Survival Analysis
chemical_list: D002945:Cisplatin