Overall Management > Statistical Analyses

Abstract

A meta-analysis of radiation therapy in adult low-grade glioma

C. C. Leighton

University of Western Ontario, London, ON, Canada

Purpose. Post-operative radiotherapy (RT) for fibrillary LGG (low-grade glioma: astrocytoma, A, mixed oligo-astrocytoma, OA, and oligodendroglioma, O) is controversial.
A systematic review of published randomized trials (RCT) after 1980 was completed to evaluate (RT) under the following endpoints:
(1) Dose Escalation,
(2) Efficacy.

Methods. A search strategy of RCTs on LGG and RT in the era of CT/MRI was devised.
Key search terms were: [GLIOMA or ASTROCYTOMA] and [LOW-GRADE and RADIOTHERAPY and RADIATION].
RCTs, published after 1980 were searched for in :
(1) Cochrane Collaborative Research Database,
(2) Cancerlit,
(3) Medline,
(4) Annual Proceedings of ASCO,
(5) Annual Proceedings of ASTRO.
All RCTs were reviewed.

Results. 1. A single published multicentre trial (EORTC22844) compared post-operative RT to observation (N=343).
Though no overall survival improvement was evident, a significant improvement in the progression-free interval (PFS) was reported, favouring post-operative RT (44 v 37%, NNT = 6 persons, log rank P=0.02).
However, significant discrepancies in pathologic diagnoses have been reported.
Central pathology review of 237 subjects revealed 26% were misclassified and not eligible.
A reanalysis of the remaining patients lacked power to confirm a significant improvement in PFS.
2. Two multi-centre dose-response trials (EORTC, RTOG-ECOG-NCCTG) evaluated the hypothesis that dose-escalation improves survival, OS, or PFS.
Both failed to demonstrate a benefit with higher dose schedules of 59.4 Gy (v. 45 Gy, EORTC 22844) or 64.8 Gy (v. 50.4 Gy, NCCTG-RTOG-ECOG).
Pooled OS analysis (PS) and pooled PFS (PPFS) of high v. low dose schedules (N=546), provided summary hazard ratios of 1.10 (CL, 0.96-1.13) for PS and 1.05 (CL 0.82-1.33) for PPFS (heterogeneity stastistic p=0.73, random effects model p=0.77).
Older age, A histology, poor performance status, and large tumour size were poor prognostic features.

Conclusion. Additional level I evidence is necessary to support the routine use of RT in adult LGG patients.
Future trials should formally evaluate quality of life and neuro-cognitive parameters as primary endpoints.
These outcomes may ultimately prove the worth of RT in LGG.

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