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Neuropediatrics 2005; 36(2): 71-77
DOI: 10.1055/s-2005-837582
Original Article

Georg Thieme Verlag KG Stuttgart · New York

AFP/β-HCG Secreting CNS Germ Cell Tumors: Long-Term Outcome with Respect to Initial Symptoms and Primary Tumor Resection. Results of the Cooperative Trial MAKEI 89

G. Calaminus1 , M. Bamberg2 , D. Harms3 , H. Jürgens4 , R. D. Kortmann5 , N. Sörensen6 , O. D. Wiestler7 , U. Göbel1
  • 1Department of Pediatric Hematology and Oncology Children's Hospital, University of Düsseldorf, Düsseldorf, Germany
  • 2Department of Radiooncology, University of Tübingen, Tübingen, Germany
  • 3Department of Pediatric Pathology, University of Kiel, Kiel, Germany
  • 4Department of Pediatric Hematology and Oncology, Children's Hospital, Münster, Germany
  • 5Department of Radiooncology, University of Leipzig, Leipzig, Germany
  • 6Department of Pediatric Neurosurgery, University of Würzburg, Würzburg, Germany
  • 7Neuropathology, DKFZ, Heidelberg, Germany
Further Information

Publication History

Received: November 15, 2004

Accepted after Revision: January 29, 2005

Publication Date:
18 March 2005 (online)

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Abstract

Purpose: The aim of the present study was to evaluate survival and factors influencing long-term outcome of patients with AFP/β-HCG secreting (non-seminomatous) central nervous system germ cell tumors (secCNSGCT), who were prospectively collected in the cooperative MAKEI (German: maligne Keimzelltumoren) 89 protocol. Patients and Methods: Between January 1989 and January 1994, 28 patients with secCNS GCT were registered and treated according to the MAKEI 89 protocol. The protocol recommended, after a clinically or histologically proven diagnosis and cisplatin-based chemotherapy, a resection of residual tumor and craniospinal irradiation (30 Gy) with a tumor boost (20 Gy). Results: The estimated (Kaplan-Meier) event-free survival (EFS) of protocol patients is 0.57 ± 0.09 (n = 28) and the relapse-free survival (RFS) is 0.67 ± 0.10 (at five and ten years). With respect to long-term survival, the combination of marked neurological symptoms at diagnosis along with primary tumor resection seem to be the main negative prognostic risk factors (Fisher exact test p < 0.05). CNS dissemination at diagnosis can also be considered as a negative risk factor as 3 of 5 patients with primary dissemination died of the disease. Conclusion: Cisplatin-based three agent chemotherapy followed by resection of the residual tumor and craniospinal irradiation (CSI) with tumor boost is a successful and well-tolerated treatment for secCNSGCTs. The possibility of a clinical diagnosis based on MRI and tumor markers together with the use of modern neurosurgical techniques gives us the chance to postpone or even avoid major surgery. This gives an additional chance to reduce acute morbidity and further decrease late effects.

Key words

Non-seminomatous germ cell tumors - initial presentation - multimodal treatment

References

  • 1 Allen J C, Kim J H, Packer R J. Neoadjuvant chemotherapy for newly diagnosed germ cell tumors of the central nervous system.  J Neurosurg. 1987;  67 65-70
    PubMedGoogle Scholar
  • 2 Balmaceda C, Heller G, Rosenblum M, Diez B, Villablanca J C, Kellie S. et al . Chemotherapy without irradiation - A novel approach for newly diagnosed CNS germ cell tumors: Results of an international cooperative trial.  J Clin Oncol. 1996;  14 2908-2915
    PubMedGoogle Scholar
  • 3 Bamberg M, Kortmann R D, Calaminus G, Becker G, Meisner C, Harms D. et al . Radiation therapy for intracranial germinoma: Results of the German cooperative prospective trials MAKEI 83/86/89.  J Clin Oncol. 1999;  17 2585-2592
    PubMedGoogle Scholar
  • 4 Baranzelli M C, Patte C, Bouffet E. An attempt to treat pediatric intracranial AFP and β-HCG secreting germ cell tumors with chemotherapy alone. SFOP experience with 18 cases.  J Neuro Oncol. 1998;  37 229-239
    CrossrefPubMedGoogle Scholar
  • 5 Calaminus G, Bamberg M, Baranzelli M C, Benoit Y, di Montezemolo L C, Fossati-Bellani F. et al . Intracranial germ cell tumors: A comprehensive update of the European data.  Neuropediatrics. 1994;  25 26-32
    PubMedGoogle Scholar
  • 6 Calaminus G, Andreussi L, Garre M L, Kortmann R D, Schober R, Göbel U. Secreting germ cell tumors of the central nervous system (CNS). First results of the cooperative German/Italian pilot study (CNS sGCT).  Klin Pädiatr. 1997;  209 222-227
    PubMedGoogle Scholar
  • 7 Calaminus G, Bamberg M, Jürgens H, Kortmann R D, Sörensen N, Wiestler O D. et al . 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.  Klin Pädiatr. 2004;  216 141-149
    Article in Thieme ConnectPubMedGoogle Scholar
  • 8 Diez B, Balmaceda C, Matsutani M. et al . Germ cell tumors of the CNS in children: Recent advances in therapy.  Child's Nervous Syst. 1999;  15 578-585
    PubMedGoogle Scholar
  • 9 Drummond K J, Rosenfeld J V. Pineal region tumours in childhood. A 30-year experience.  Child's Nerv Syst. 1999;  15 119-127
    PubMedGoogle Scholar
  • 10 Edwards M SB, Hudgins R J, Wilson C B. et al . Pineal region tumors in children.  J Neurosurg. 1988;  68 689-697
    Google Scholar
  • 11 Einhorn L H, Donohue J. Cis-diamminedichloro-platinum, vinblastine and bleomycin combination chemotherapy in disseminated testicular cancer.  Ann Intern Med. 1977;  87 293-298
    CrossrefPubMedGoogle Scholar
  • 12 Göbel U, Bamberg M, Calaminus G, Gnekow A K, Herrmann H D, Lenard H G. Improved prognosis of intracranial germ cell tumors with intensified treatment. Results of the MAKEI 89 protocol.  Klin Pädiatr. 1993;  205 217-224
    PubMedGoogle Scholar
  • 13 Göbel U, Calaminus G, Engert J, Kaatsch P, Gadner H, Bökkerink J P. et al . Teratomas in infancy and childhood.  Med Pediatric Oncol. 1998;  31 8-15
    PubMedGoogle Scholar
  • 14 Göbel U, Schneider D T, Calaminus G, Jürgens H, Spaar H J, Sternschulte W. et al . Multimodal treatment of malignant sacrococcygeal germ cell tumors: a prospective analysis of 66 patients of the German cooperative protocols MAKEI 83/86 and 89.  J Clin Oncol. 2001;  19 1943-1950
    PubMedGoogle Scholar
  • 15 Herrmann H D, Westphal M, Winkler K, Laas R W, Schulte F J. Treatment of nongerminomatous germ cell tumors of the pineal region.  Neurosurgery. 1993;  34 524-529
    PubMedGoogle Scholar
  • 16 Itoyama Y, Kochi M, Kuratsu J. Treatment of intracranial non-germinomatous malignant germ cell tumors producing alpha-fetoprotein.  Neurosurgery. 1999;  36 459-464
    PubMedGoogle Scholar
  • 17 Jennings M T, Gelma R, Hochberg F. Intracranial germ cell tumors: natural history and pathogenesis.  J Neurosurg. 1985;  63 155-167
    CrossrefPubMedGoogle Scholar
  • 18 Kida Y, Kobayashi T, Yoshida J, Kato K, Kageyama N. Chemotherapy with cisplatin for AFP-secreting germ-cell tumors of the central nervous system.  J Neurosurg. 1986;  65 470-475
    PubMedGoogle Scholar
  • 19 Kiltie A E, Gattamaneni H R. Survival and quality of life of pediatric intracranial germ cell tumor patients treated at the Christie Hospital, 1972 - 1993.  MPO. 1995;  25 450-456
    PubMedGoogle Scholar
  • 20 Kobayashi T, Yoshida J, Ishiyama J, Noda S, Kito A, Kida Y. Combination chemotherapy with cisplatin and etoposide for malignant intracranial germ cell tumors. An experimental and clinical study.  J Neurosurg. 1989;  70 676-681
    PubMedGoogle Scholar
  • 21 Mann J R, Raafat F, Robinson K, Imeson I, Gornall P, Sokal M. The United Kingdom Children's Cancer Study Group's Second Germ Cell Tumor Study: Carboplatin, etoposide, and bleomycin are effective treatment for children with malignant extracranial germ cell tumors with acceptable toxicity.  J Clin Oncol. 2000;  18 3809-3818
    PubMedGoogle Scholar
  • 22 Matsutani M, Sano K, Takakura K, Fujimaki T, Nakamura O. Combined treatment with chemotherapy and radiation therapy for intracranial germ cell tumors.  Child's Nerv Syst. 1998;  14 59-62
    PubMedGoogle Scholar
  • 23 Nam Dh, Cho B K, Shin C H, Ahn H S, Kim I H, Wang K C. Treatment of intracranial non-germinomatous malignant germ cell tumor in children: the role of each treatment modality.  Child's Nerv Syst. 1999;  15 185-191
    PubMedGoogle Scholar
  • 24 Nicholson J C, Punt J, Hale J, Saran F, Calaminus G. Neurosurgical management of paediatric germ cell tumours of the central nervous system - a multi-disciplinary team approach for the new millenium.  Br J Neurosurg. 2002;  16 93-95
    CrossrefPubMedGoogle Scholar
  • 25 Packer R J, Bruce H C, Cooney K. Intracranial germ cell tumors.  The Oncologist. 2000;  5 312-320
    PubMedGoogle Scholar
  • 26 Warmuth-Metz M, Gnekow A K, Müller H, Solymosi L. Differential diagnosis of suprasellar tumors in children.  Klin Pädiatr. 2004;  216 323-330
    PubMedGoogle Scholar
  • 27 Weiner H L, Finlay J L. Surgery in the management of primary intracranial germ cell tumors.  Child's Nerv Syst. 1999;  15 770-773
    PubMedGoogle Scholar
  • 28 Weiner H L, Lichtenbaum R A, Wisoff J H. et al . Delayed surgical resection of central nervous system germ cell tumors.  Neurosurgery. 2002;  51 727-734
    PubMedGoogle Scholar
  • 29 Sands S A, Kellie S J, Davidow A L, Diez B, Villablanca J, Weiner H L. Long-term quality of life and neuropsychologic functioning for patients with CNS germ-cell tumors: from the First International CNS Germ-Cell Tumor Study.  J Neuro-oncol. 2001;  3 174-183
    PubMedGoogle Scholar
  • 30 Sutton L N, Radcliffe J, Goldwein J W, Phillips P, Janns A J, Packer R J. Quality of life of germinomas treated with craniospinal irradiation.  Neurosurgery. 1999;  45 1292-1298
    PubMedGoogle Scholar

MD Gabriele Calaminus

Heinrich Heine University Medical Center
Department of Pediatric Hematology and Oncology

Moorenstraße 5

40225 Düsseldorf

Germany

Email: calaminus@med.uni-duesseldorf.de

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