207_Combined course Presentations

Long-termefficacyof early versusdelayed radiotherapy for low-gradeast rocytomaandoligodendrogliomainadults: the EORTC22845 randomised t rial

RT timing: EORTC 22845

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. PFS

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

OS

(KHoang-XuanMD);Lund UniversityHospital,Lund,

Sweden (POMalmströmMD); CentreHospitalier Universitaire Vaudois,Lausanne,Switzerland (RMirimanoff MD);andVrije

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 314 pts ith LGG Early RT (54 Gy) Delayed RT

UniversityAmsterdam, Amsterdam,Netherlands (ABMFKarimMD)

(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. mOS 5y-OS mPFS 5y-PFS 7.4 y 68.4% 5.3 y 55% 7.2 y 65.7% 3.4 y 35%

Seizure control @1 y

Correspondenceto: MJvandenBent, Neuro-OncologyUnit,

75%

Daniel denHoedOncology Center,ErasmusUniversity Hospital Rotterdam,POBox 5201,3008AERotterdam, Netherlands m.vandenbent@erasmusmc.nl 59%

p = 0.003

p = 0.03

Van den Bent MJ et al. Lancet 2005

Methods