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Introduction
Many aspects of treatment for low-grade glioma are
controversial. No evidence-based guidelines exist for the
“wait and see” policy in young patients with low-grade
glioma who present with seizures only; the effectiveness
of extensive resection compared with more limited
surgical procedures and the use of chemotherapy is
unknown. The effectiveness of radiotherapy is also
unclear.
In the mid 1980s, European investigators explored the
role of radiotherapy in two randomised studies. The first
study (EORTC 22844)1 investigated the presence of a
dose–response relation for patients with low-grade glioma
(the “wait-and-see” policy). Thestudy assessed theefficacy
of early radiotherapy versus deferred treatment (including
radiotherapy) at the time of progression. An interim
analysis of this study was done in 1998, which found no
overall survival benefit of early radiotherapy, although it
did show asmall increase in progression-freesurvival. 3 At
the interim analysis which was done after a minimum
follow-up duration of 14 months (median 60 months),
only 30% of patients had died and 49% had progressed.
We now present the long-term results of the study with a
median follow-up of 93months.
Methods
Lancet 2005;366:985–90
PublishedonlineAugust 18,2005
DOI:10.1016/S0140-6736(05)
67070-5
ErasmusMedical Centrum
Daniel denHoedOncology
Center,Rotterdam
(MJvandenBent MD);National
Instituteof Neurosurgery,
Budapest,Hungary
(DAfraMD);Hopital
UniversitaireErasme,
Brussels(OdeWitteMD);
EORTCDataCenter,Brussels,
Belgium (LColletteMSc,
MPiérart MSc);CentreEugène
Marquis,Rennes
(MBenHassel MD);Hopital Jean
Minjoz,Besançon
(SSchraubMD);Centre
UniversitairePitié-Salpétrière,
Paris,France
(KHoang-XuanMD);Lund
UniversityHospital,Lund,
Sweden (POMalmströmMD);
CentreHospitalier Universitaire
Vaudois,Lausanne,Switzerland
(RMirimanoff MD);andVrije
UniversityAmsterdam,
Amsterdam,Netherlands
(ABMFKarimMD)
Correspondenceto:
MJvandenBent,
Neuro-OncologyUnit,
Daniel denHoedOncology
Center,ErasmusUniversity
Hospital Rotterdam,POBox
5201,3008AERotterdam,
Netherlands
Long-termefficacyof early versusdelayed radiotherapy for
low-gradeast rocytomaandoligodendrogliomainadults: the
EORTC22845 randomised t rial
MJvandenBent,DAfra,OdeWitte,MBenHassel,SSchraub,K Hoang-Xuan, P-OMalmström,LCollette,MPiérart,RMirimanoff ,
ABMFKarim,fortheEORTCRadiotherapyandBrainTumorGroupsandtheUKMedical ResearchCouncil
Summary
Background Postoperative policiesof “wait-and-see” and radiotherapy for low-grade gliomaarepoorlydefined. A trial in
the mid 1980s established the radiation dose. In 1986 the EORTC Radiotherapy and Brain Tumor Groups initiated a
prospective trial to compare early radiotherapy with delayed radiotherapy. An interim analysis has been reported. We
nowpresent the long-term results.
Methods After surgery, patients from 24 centresacrossEuropewere randomly assigned to either early radiotherapy of
54 Gy in fractions of 1· 8 Gy or deferred radiotherapy until the time of progression (control group). Patientswith low-
grade astrocytoma, oligodendroglioma, mixed oligoastrocytoma, and incompletely resected pilocytic astrocytoma, with
aWHO performance status 0–2 were eligible. Analysis was by intention to treat, and primary endpoints were overall
andprogression-freesurvival.
Findings 157 patients were assigned early radiotherapy, and 157 control. Median progression-free survival was
5· 3 years in the early radiotherapy group and 3· 4 years in the control group (hazard ratio 0· 59, 95% CI 0· 45–0· 77;
p 0· 0001). However, overall survival was similar between groups: median survival in the radiotherapy group was
7· 4 yearscomparedwith 7· 2 yearsin thecontrol group (hazard ratio0· 97, 95%CI 0· 71–1· 34; p=0· 872). In thecontrol
group, 65% of patients received radiotherapy at progression. At 1 year, seizures were better controlled in the early
radiotherapygroup.
Interpretation Early radiotherapy after surgery lengthens the period without progression but does not affect overall
survival. Because quality of life was not studied, it is not known whether time to progression reflects clinical
deterioration. Radiotherapy couldbedeferred for patientswith low-grade gliomawhoare in agood condition, provided
theyarecarefullymonitored.
Van den Bent MJ et al. Lancet 2005
OS PFS
314 pts ith LGG mOS 5y-OS mPFS 5y-PFS Seizure control @1 y
Early RT (54 Gy) 7.4 y 68.4% 5.3 y 55% 75%
Delayed RT 7.2 y 65.7% 3.4 y 35% 59%
p = 0.03 p = 0.003
RT timing: EORTC 22845