Role of radiotherapy in the treatment of supratentorial primitive neuroectodermal tumors in childhood: results of the prospective German brain tumor trials HIT 88/89 and 91.
OBJECTIVE
To evaluate the outcome of children with supratentorial primitive neuroectodermal tumors after surgery, irradiation, and chemotherapy and to identify factors predictive for survival.


METHODS
Sixty-three children in the prospective trials HIT 88/89 and HIT 91 were eligible. Complete resection was performed in 21 patients. Patients were randomized for preirradiation chemotherapy, consisting of two cycles of ifosfamide, etoposide, methotrexate, cisplatin, and cytarabine (n = 40), or chemotherapy after irradiation, consisting of eight cycles with cisplatin, vincristine, and lomustine (n = 23). Irradiation volume was recommended to encompass the neuraxis with 35.2-Gy total dose followed by a boost (20.0 Gy) to the primary tumor site (n = 54). Seven patients were irradiated to the tumor region only with a total dose of 54.0 Gy.


RESULTS
Overall survival at 3 years was 48.4%. Progression occurred in 38 children, with local recurrences in 27 patients. The only significant prognostic factor was dose and volume of radiotherapy (progression-free survival after 3 years was 49.3% with correct treatment compared with 6.7% for 15 children with major violations of radiotherapy). Ten early progressions occurred during adjuvant therapy (eight before and two during radiotherapy), nine of them treated with preirradiation chemotherapy. There was a positive trend in outcome for nonmetastatic and pineal tumors.


CONCLUSIONS
Significant predictive factors were dose and volume of radiotherapy. Volume of irradiation should encompass the whole CNS with additional boost to the tumor region. Local doses of at least 54 Gy and a craniospinal dose of 35 Gy are necessary. Preirradiation chemotherapy seems to increase risk of early progression.
Timmermann
Beate
B
Department of Radiooncology, and Institute of Medical Information Processing, University of Tübingen, Tübingen, Germany. betimmer@med.uni-tuebingen.de
Kortmann
Rolf-Dieter
RD
Kühl
Joachim
J
Meisner
Christoph
C
Dieckmann
Karin
K
Pietsch
Torsten
T
Bamberg
Michael
M
D000293:Adolescent; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage; D002648:Child; D002675:Child, Preschool; D002945:Cisplatin / Q000008:administration & dosage; D003131:Combined Modality Therapy; D003561:Cytarabine / Q000008:administration & dosage; D004334:Drug Administration Schedule; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D006801:Humans; D007069:Ifosfamide / Q000008:administration & dosage; D008130:Lomustine / Q000008:administration & dosage; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage; D009364:Neoplasm Recurrence, Local; D017599:Neuroectodermal Tumors / Q000401:mortality / Q000532:radiotherapy* / Q000628:therapy; D011879:Radiotherapy Dosage; D015173:Supratentorial Neoplasms / Q000401:mortality / Q000532:radiotherapy* / Q000628:therapy; D015996:Survival Rate; D016896:Treatment Outcome; D014750:Vincristine / Q000008:administration & dosage
D003561:Cytarabine; D014750:Vincristine; D005047:Etoposide; D008130:Lomustine; D002945:Cisplatin; D007069:Ifosfamide; D008727:Methotrexate