Brain Metastases in Children and Adolescents with Extracranial Germ Cell Tumor – Data of the MAHO/MAKEI-Registry

Abstract

Background: We analyzed 15 children and adolescents with extracranial germ cell tumor (GCT) and brain metastases reported to the MAHO/MAKEI registry.

Patients and Methods: Between 1982 and 2009, 2 077 patients were prospectively enrolled onto the MAHO/MAKEI studies (overall survival: 0.88±0.03). All patients with advanced malignant GCTs received cisplatin-based chemotherapy (overall survival: 0.81±0.04 (734/823).

Results: 15 patients with brain metastases were reported; in 6 of them at diagnosis and 9 respectively during follow-up (6weeks-28months after end of therapy, mean=10 months). Most patients were male (13/15) and adolescent (10/15). 8 patients suffered from mediastinal GCTs. Pure Choriocarcinoma (CC) or CC in combination with other histologies was diagnosed in 12 paüütients. Clinical symptoms were reported in most patients. In all patients with secondary brain metastases the previously normalised tumor markers AFP and/ or HCG increased again prior to the onset of neurological symptoms. Only 1 of the patients with primary brain metastases survived, whereas 4 of 9 with secondary metastases are in remission after additional treatment.

Conclusion: The risk for intracranial metastases increases with age, male gender and mediastinal or testicular primary site and choriocarcinoma histology. Development of neurological sympüütoms at initial diagnosis or during follow-up should lead to rapid clinical re-evaluation including CNS imaging and assessment of tumor markers. Treatment of brain metastases includes intensified chemotherapy and surgical resection, irradiation has to be considered in special clinical situations.

Zusammenfassung

Hintergrund: Wir analysierten 15 Kinder und Jugendliche mit extrakranialen Keimzelltumoren und Hirnmetastasen des MAHO/MAKEI-Registers.

Patienten und Methoen: Zwischen 1982 und 2009 sind 2 077 Patienten prospektiv in die MAHO/MAKEI-Studien gemeldet worden (overall survival 0,88±0,03). Patienten mit fortgeschrittenen malignen Keimzelltumoren erhielten eine Cisplatin-basierte Chemotherapie (overall survival: 734/823; 0,81±0,04).

Ergebnisse: 15 Patienten mit Hirnmetastasen wurden gemeldet, davon 6 bei Diagnosestellung und 9 während der Nachbeobachtung (6 Wochen-28 Monate nach Therapieende, Median=10 Monate). 13 Patienten waren männlich und 10 adoleszent; 8 Patienten hatten einen Mediastinaltumor. Ein reines Choriokarzinom oder kombiniert mit anderer Histologie wurde in 12 Paüütienten diagnostiziert. Neurologische Symptome waren häufig. Bei allen Patienten mit sekundären Hirnmetastasen waren die vorher normalisierten Tumormarker AFP und/oder HCG vor dem Auftreten von üüneurologischen Symptomen wieder angestiegen. Nur einer von 6 Patienten mit primären Metastasen und 4 von 9 mit sekundären Metastasen erreichten eine anhaltende Zweitremission durch Operation und/oder Chemotherapie sowie Bestrahlung in Einzelfällen.

Schlussfolgerungen: Das Risiko für intrakraniale Metastasen scheint mit zunehmendem Alter, männlichem Geschlecht, Mediastinaltumor und Choriokarzinom erhöht zu sein. Neurologische Symptome bei diesen Patienten bedürfen der schnellen klinischen Klärung. Bei Hirnmetastasen sind eine intensivierte Chemotherapie, Operation und in besonderen Situationen eine Bestrahlung zu verabfolgen.

Key words

germ cell tumors - brain metastases - adolescent male - mediastinum

Schlüsselwörter

Keimzelltumoren - Hirnmetastasen - jugendliche - Männer - Mediastinum

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