Background
Phase III, multicenter RCT (NCCTG 86-72-51 / RTOG 83-02 / ECOG). 203 patients with supratentorial low-grade glioma (WHO grade II astrocytoma, oligodendroglioma, or oligoastrocytoma), enrolled 1986–1994. First large randomized trial addressing optimal radiation dose for LGG. The central question: does higher-dose RT improve survival or merely increase toxicity?
Interventions and follow up
Arm A: Low-dose radiotherapy — 50.4 Gy in 28 fractio
Arm B: High-dose radiotherapy — 64.8 Gy in 36 fractio
Primary endpoint: Overall survival
mFollow up: Median 6.43 years (initial report); updated median 17.2 years (final report PMID 32002556)
Arm B: High-dose radiotherapy — 64.8 Gy in 36 fractio
Primary endpoint: Overall survival
mFollow up: Median 6.43 years (initial report); updated median 17.2 years (final report PMID 32002556)
Results
OS (initial report): Median OS similar — 7.4 years (50.4 Gy) vs 6.0 years (64.8 Gy); not statistically different
2-year OS: 94% vs 95%; 5-year OS: 68% vs 66%
PFS: No significant difference
Radiation necrosis: 2.5% (low-dose) vs 5% (high-dose) — numerically more with high dose
2-year OS: 94% vs 95%; 5-year OS: 68% vs 66%
PFS: No significant difference
Radiation necrosis: 2.5% (low-dose) vs 5% (high-dose) — numerically more with high dose
Adverse events
Main adverse events: Radiation necrosis more common with high-dose arm (5% vs 2.5%). No difference in late cognitive effects reported at initial analysis. High-dose arm had non-significantly worse outcomes in some analyses, consistent with toxicity without benefit.
Conclusions
High-dose RT (64.8 Gy) provided no survival benefit over standard-dose RT (50.4 Gy) for LGG, while causing more radiation necrosis. Established 50.4–54 Gy as the standard RT dose for low-grade glioma.
Key Limitations
Key Limitations: No molecular stratification (pre-IDH era) — the "low-grade glioma" category included IDH-mutant and IDH-wildtype tumors with very different prognoses. No chemotherapy arm; the role of PCV or TMZ was not tested. The final report (PMID 32002556, median 17yr follow-up) showed that the overall OS was similar between arms even with matured data. Observer variability in histologic diagnosis was substantial for LGG in this era.
Clinical Context
Established 50.4 Gy as standard RT dose for LGG — higher doses increase toxicity without benefit. RTOG 9802 later showed that adding PCV to RT significantly improves OS in high-risk LGG. Modern LGG management is guided by IDH/1p19q/ATRX status (WHO 2021): IDH-mutant 1p/19q codeleted oligodendroglioma → RT+PCV; IDH-mutant non-codeleted astrocytoma → RT+TMZ or RT+adjuvant TMZ (CATNON-type). "High-dose" RT is not used for LGG.
References