Background
Long-term follow-up (10+ years) of the RTOG 9402 phase III trial in anaplastic oligodendroglial tumors (anaplastic oligodendroglioma + anaplastic oligoastrocytoma). 289 eligible patients, originally reported in 2006 with no OS benefit. This 2013 paper reports the 10-year follow-up with full 1p/19q codeletion analysis and confirmed OS data — including the landmark finding that 1p/19q codeleted patients have dramatically improved survival with PCV+RT.
Interventions and follow up
Arm A: PCV + radiotherapy (59.4 Gy)
Arm B: Radiotherapy alone (59.4 Gy)
Primary endpoint: Overall survival (long-term follow-up analysis)
mFollow up: 11.3 years median (PCV+RT arm)
Arm B: Radiotherapy alone (59.4 Gy)
Primary endpoint: Overall survival (long-term follow-up analysis)
mFollow up: 11.3 years median (PCV+RT arm)
Results
OS (1p/19q codeleted, PCV+RT vs RT): Median 14.7 vs 7.3 years, P<.001
OS (non-codeleted, PCV+RT vs RT): 2.6 vs 2.7 years — no benefit
OS (all patients): 4.6 vs 4.7 years — still not significantly different overall
PFS (1p/19q codeleted): Marked improvement with PCV+RT
OS (non-codeleted, PCV+RT vs RT): 2.6 vs 2.7 years — no benefit
OS (all patients): 4.6 vs 4.7 years — still not significantly different overall
PFS (1p/19q codeleted): Marked improvement with PCV+RT
Adverse events
Main adverse events: Long-term toxicity analysis shows PCV toxicity burden was high (grade 3–4 in majority during treatment); no new late-effect signals emerged beyond acute chemotherapy toxicity. Neurological late effects from RT similar between arms.
Conclusions
With 10-year follow-up, PCV+RT dramatically improved OS in 1p/19q codeleted anaplastic oligodendroglioma (14.7 vs 7.3yr) — a benefit invisible at 3-year follow-up. For non-codeleted patients, PCV+RT provided no OS benefit. Together with EORTC 26951, established PCV+RT as the standard of care for 1p/19q codeleted anaplastic oligodendroglioma.
Key Limitations
Key Limitations: 1p/19q was not available for all patients (retrospective testing). The dramatic benefit in 1p/19q codeleted patients was not detectable at initial follow-up — highlights the need for very long follow-up in LGG/AO trials. Non-codeleted "anaplastic oligoastrocytoma" is now largely reclassified as IDH-mutant astrocytoma or GBM under WHO 2021. Open-label design. PCV toxicity (65% grade 3–4) is high — fewer patients in clinical practice complete full PCV.
Clinical Context
The 2013 long-term RTOG 9402 report, together with EORTC 26951 (van den Bent 2013), definitively established RT+PCV as the standard of care for 1p/19q codeleted anaplastic oligodendroglioma. These findings directly shaped the WHO 2021 classification emphasizing 1p/19q codeletion as a defining feature of oligodendroglioma. Current NCCN/ESMO recommendations: RT+PCV for 1p/19q codeleted oligodendroglioma (grade 2 and 3).
References