A randomized trial on dose-response in radiation therapy of low-grade cerebral glioma: European Organization for Research and Treatment of Cancer (EORTC) Study 22844.
OBJECTIVE
Cerebral low-grade gliomas (LGG) in adults are mostly composed of astrocytomas, oligodendrogliomas, and mixed oligoastrocytomas. There is at present no consensus in the policy of treatment of these tumors. We sought to determine the efficacy of radiotherapy and the presence of a dose-response relationship for these tumors in two multicentric randomized trials conducted by the European Organization for Research and Treatment of Cancer (EORTC). The dose-response study is the subject of this article.


METHODS
For the dose-response trial, 379 adult patients with cerebral LGGs were randomized centrally at the EORTC Data Center to receive irradiation postoperatively (or postbiopsy) with either 45 Gy in 5 weeks or 59.4 Gy in 6.6 weeks with quality-controlled radiation therapy. All known parameters with possible influences on prognosis were prospectively recorded. Conventional treatment techniques were recommended.


RESULTS
With 343 (91%) eligible and evaluable patients followed up for at least 50 months with a median of 74 months, there is no significant difference in terms of survival (58% for the low-dose arm and 59% for the high-dose arm) or the progression free survival (47% and 50%) between the two arms of the trial. However, this prospective trial has revealed some important facets about the prognostic parameters: The T of the TNM classifications as proposed in the protocol appears to be one of the most important prognostic factors (p < 0.0001) on multivariate analysis. Other prognostic factors, most of which are known, have now been quantified and confirmed in this prospective study.


CONCLUSIONS
The EORTC trial 22844 has not revealed the presence of radiotherapeutic dose-response for patients with LGG for the two dose levels investigated with this conventional setup, but objective prognostic parameters are recognized. The tumor size or T parameter as used in this study appears to be a very important factor.
Karim
A B
AB
Department of Radiation Oncology, Free University Hospital, Amsterdam, The Netherlands. radiother@azvu.nl
Maat
B
B
Hatlevoll
R
R
Menten
J
J
Rutten
E H
EH
Thomas
D G
DG
Mascarenhas
F
F
Horiot
J C
JC
Parvinen
L M
LM
van Reijn
M
M
Jager
J J
JJ
Fabrini
M G
MG
van Alphen
A M
AM
Hamers
H P
HP
Gaspar
L
L
Noordman
E
E
Pierart
M
M
van Glabbeke
M
M
D000293:Adolescent; D000328:Adult; D001254:Astrocytoma / Q000473:pathology / Q000532:radiotherapy; D001932:Brain Neoplasms / Q000473:pathology / Q000532:radiotherapy*; D004307:Dose-Response Relationship, Radiation; D005260:Female; D005500:Follow-Up Studies; D005910:Glioma / Q000473:pathology / Q000532:radiotherapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D009837:Oligodendroglioma / Q000473:pathology / Q000532:radiotherapy*; D011379:Prognosis; D011446:Prospective Studies