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

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Date
2017-11
ICR Author
Marsden,
Author
Calaminus, G
Frappaz, D
Kortmann, RD
Krefeld, B
Saran, F
Pietsch, T
Vasiljevic, A
Garre, ML
Ricardi, U
Mann, JR
Göbel, U
Alapetite, C
Murray, MJ
Nicholson, JC
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Type
Journal Article
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Abstract
Background Following promising results to increase survival and reduce treatment burden in intracranial non-germinomatous germ cell tumors (NGGCTs), we conducted a European study using dose-intense chemotherapy followed by risk-adapted radiotherapy.Methods All patients received 4 courses of cisplatin/etoposide/ifosfamide. Non-metastatic patients then received focal radiotherapy only (54 Gy); metastatic patients received 30 Gy craniospinal radiotherapy with 24 Gy boost to primary tumor and macroscopic metastatic sites.Results Patients with localized malignant NGGCT (n = 116) demonstrated 5-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, 5 bifocal, 9 others. One patient died postsurgery in clinical remission; 3 patients progressed during treatment and 27 (23%) relapsed afterward. Fourteen were local, 6 combined, and 7 distant relapses (outside radiation field). Seventeen of the 27 relapsed patients died of disease. Patients with metastatic disease (n = 33) demonstrated 5-year PFS and OS of 0.68 ± 0.09 and 0.75 ± 0.08, respectively; 1 patient died following progression on treatment and 9 (27%) relapsed afterward (5 local, 1 combined, 3 distant). Only one metastatic patient with recurrence was salvaged. Multivariate analysis identified diagnostic alpha-fetoprotein level (serum and/or cerebrospinal fluid level >1000 ng/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 remain the gold standard for metastatic disease.
URI
https://repository.icr.ac.uk/handle/internal/1482
DOI
https://doi.org/10.1093/neuonc/nox122
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Subject
Humans
Neoplasms, Germ Cell and Embryonal
Testicular Neoplasms
Brain Neoplasms
Lymphatic Metastasis
Neoplasm Recurrence, Local
Cisplatin
Ifosfamide
Etoposide
Antineoplastic Combined Chemotherapy Protocols
Prognosis
Cranial Irradiation
Survival Rate
Follow-Up Studies
Prospective Studies
Adolescent
Adult
Child
Child, Preschool
International Agencies
Female
Male
Young Adult
Chemoradiotherapy
Biomarkers, Tumor
Language
eng
License start date
2017-11
Citation
Neuro-oncology, 2017, 19 (12), pp. 1661 - 1672

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