Adjuvant fractionated radiotherapy following complete surgical resection of WHO grade 2 atypical meningioma significantly improves 5-year disease-free survival to 79.9% compared to 64.3% with observation alone, according to a phase 3 clinical trial published in The Lancet.
Radiation Therapy Halves Risk of Tumor Recurrence
- What was studied: Researchers tested whether radiation therapy given immediately after complete tumor removal prevents atypical meningiomas from returning.
- The core finding: Post-surgical radiation cut the risk of tumor recurrence or death in half, dropping recurrence rates from 30% down to 14% at a median follow-up of 64 months.
- Safety profile: Serious side effects linked to the radiation occurred in only 5 of 66 participants, with no treatment-related deaths and no overall difference in long-term quality of life between groups.
Led by Michael D. Jenkinson, PhD, at the University of Liverpool, the international study spanned 58 hospitals across 11 countries. Out of 990 patients initially assessed for eligibility, 157 individuals aged 16 and older with surgeon-assessed complete resections of newly diagnosed atypical meningiomas were randomized. 78 patients received adjuvant radiotherapy while 79 were placed under observation.
The radiotherapy protocol consisted of external-beam intensity-modulated treatment delivering a cumulative dose of 60 Gy split into 30 fractions administered over a 6-week period. All treatment plans underwent prospective central quality-assurance review before execution. The primary endpoint was disease-free survival, defined as the time elapsed from surgery to either an MRI-confirmed tumor recurrence or death from any cause.
Radiotherapy Improves Recurrence Rates Regardless of Tumor Biology
At the median follow-up mark of 64 months, recurrence was documented in 11 of the 78 radiotherapy patients (14%), contrasted with 24 of the 79 patients in the observation arm (30%). This translated to a statistically significant improvement, with radiotherapy yielding a hazard ratio for recurrence or death of 0.51 at P = .0396.
Post hoc molecular profiling demonstrated that the protective effect of radiotherapy held firm regardless of underlying tumor biology. After adjusting for DNA methylation classes and integrated molecular risk scores, the hazard ratios remained stable at 0.49 and 0.46, respectively. “Adjuvant fractionated radiotherapy halves the risk of recurrence, regardless of methylation class, and with minimal late toxicity,” the authors stated in their published findings.
| Treatment Arm | Patient Count (N) | Recurrence Events | 5-Year Disease-Free Survival (%) |
|---|---|---|---|
| Adjuvant Radiotherapy (60 Gy) | 78 | 11 (14%) | 79.9% |
| Observation Only | 79 | 24 (30%) | 64.3% |
Historical Institutional Data and Prior Prognostic Factors
Earlier retrospective investigations similarly identified surgical completeness and radiation as vital determinants of progression-free survival in atypical meningiomas. Evaluating 88 patients treated between May 1997 and December 2011 where 30 individuals received postoperative adjuvant radiotherapy and 58 underwent surgical intervention alone, researchers reported 5- and 10-year progression-free survival rates of 46.2%.
Those findings highlighted that incomplete resections performed without subsequent radiation yielded significantly worse progression-free outcomes compared to other groups. While the earlier data utilized median doses around 61.2 Gy and observed median times to progression of 24.7 months, the contemporary phase 3 trial published in The Lancet provides rigorous prospective validation across multiple international centers.
Radiation Causes Severe Adverse Events in Some Participants
In the trial, severe adverse events related to the radiation were documented in 5 of 66 participants, comprising both early and late toxicities.
Funding and Trial Limitations
The trial received financial backing from the National Institute for Health and Care Research Health Technology Assessment programme, the European Organisation for Research and Treatment of Cancer Brain Tumour Group and Radiation Oncology Group, and the National Health and Medical Research Council of Australia. Molecular analyses received supplementary support from the Else Kröner-Fresenius-Stiftung Foundation, while multiple authors disclosed individual honoraria, consultancy fees, and research grants.
Study limitations included local assessments of pathology and MRI recurrence without a centralized review board, as well as an open-label design preventing the masking of treatment assignments. The recorded tally of 41 total recurrence or death events fell short of the prespecified target of 46, 12 participants assigned to the radiotherapy group ultimately did not undergo treatment, and substantial missing data constrained long-term quality-of-life and neurocognitive evaluations.
References
- Jenkins, M. D., et al. “Adjuvant Radiotherapy after Complete Resection of Atypical Meningioma.” The Lancet, published online September 25.
