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Outcome of patients with intracranial non-germinomatous germ cell tumors – lessons from the SIOP-CNS-GCT-96 trial.

Accepted version
Peer-reviewed

Type

Article

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Authors

Murray, MJ 

Abstract

Background. Following promising results to increase survival and reduce treatment burden in intracranial non-germinomatous germ-cell-tumors (NGGCT), we conducted a European study using dose-intense chemotherapy followed by risk-adapted radiotherapy. Methods. All patients received four courses of Cisplatin/Etoposide/Ifosfamide. Non-metastatic patients then received focal radiotherapy only (54Gy); metastatic patients received 30Gy craniospinal radiotherapy with 24Gy boost to primary tumor and macroscopic metastatic sites. Results. Patients with localized malignant NGGCT (n=116) demonstrated five-year progression-free-survival (PFS) and overall-survival (OS) of 0.72±0.04 and 0.82±0.04, respectively. Primary tumor sites were: 67 pineal, 35 suprasellar, five bifocal, nine others. One patient died post-surgery in clinical remission; three patients progressed during treatment and 27 (23%) relapsed afterwards. Fourteen were local, six combined and seven distant relapses (outside radiation field). Seventeen of the 27 relapsed patients died of disease. Patients with metastatic disease (n=33) demonstrated five-year PFS and OS of 0.68±0.09 and 0.75±0.08, respectively; one patient died following progression on treatment and nine (27%) relapsed afterwards (five local, one combined, three distant). Only one metastatic patient with recurrence was salvaged. Multivariate analysis identified diagnostic alpha-fetoprotein level (serum and/or cerebrospinal fluid) (>1000ng/ml, 19/149 patients, of whom 11 relapsed; p<0.0003) and residual disease following treatment, including after second–look surgery (n=52/145 evaluable patients, 26 relapsed; p=0.0002), as significant prognostic indicators in this cohort. Conclusion. In localized malignant NGGCT craniospinal radiotherapy could be avoided without increased relapses outside the radiotherapy field. Chemotherapy and craniospinal radiotherapy remains the gold standard for metastatic disease.

Description

Keywords

chemotherapy, intracranial non-germinoma, radiotherapy, relapse, toxicity

Journal Title

Neuro-Oncology

Conference Name

Journal ISSN

1522-8517
1523-5866

Volume Title

19

Publisher

Oxford University Press
Sponsorship
The work was supported in part by Deutsche Krebshilfe e. V., Bonn, Germany and Elisabeth Dreves Stiftung, Germany.
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