Are all grade 1 meningioma equal?

The management of meningioma continues to evolve and with a majority classified as Grade 1, optimal patient selection for adjuvant radiation therapy remains to be defined.¹

Although generally considered to be indolent and benign, there is a subset of grade 1 meningioma with more aggressive biological behavior and at a greater risk for recurrence. Molecular classifications are increasingly implemented to better characterize meningioma beyond WHO grade alone.

At this year’s ASTRO, Hale Basak Caglar, MD, presented the study on Rb1-S780 phosphorylation as a potential biomarker for aggressive low-grade meningioma to guide adjuvant radiation therapy decision making. Building upon previously proposed terminology describing a subset of early progressing meningioma, "Grade 1.5" was used to demonstrate the biological heterogeneity among low grade meningioma^1-3. RB1 hyperphosphorylation at the S780 site has been previously described as a potential biomarker associated with poorer progression free survival.² Lead author Caglar Guzel, MD, radiation oncologist at Erzurum City Hospital in Erzurum, Türkiye, and team sought to investigate Rb1-S780 as a potential biomarker. The team hypothesized that an integrated immunohistochemistry (IHC) and radiomic profiling approach could identify a more aggressive phenotype that may benefit from adjuvant RT.

This was a single-institution retrospective study of adults with surgically resected cranial meningioma. Patients with neurofibromatosis type 2, prior cranial RT, or preoperative embolization were excluded. 338 cases met eligibility and the final cohort for analysis included 167 cases (Grade 1 n=116 and Grade 2 n=51). Biomarkers included IHC markers, such as Ki-67, Rb1-S780, among others, and radiomic features extracted from contrast-enhanced T1-weighted images and ADC maps. The primary endpoint was progression-free survival (PFS). Median follow up was impressive at 5.7 years.

In this study, high Rb1-S780 (H-score ≥126) defined a "Grade 1.5" cohort with inferior PFS (63.6 vs. 128.1 months; p<0.001), comparable to the PFS observed in Grade 2 tumors (p=0.125). A significant interaction was noted between adjuvant radiation and Rb1-S780 (HR= 0.054; 95% CI 0.009–0.330; p=0.002), further exemplifying Rb1-S780 status as potentially predictive for adjuvant radiation.

Adjuvant RT improved PFS in Rb1-S780-high patients (98.4 vs. 50.1 months; p=0.046) but showed no benefit in Rb1-S780-low patients. Receipt of adjuvant RT remained independently associated with improved PFS (HR=0.28; p=0.046).

Not unexpectedly, higher Ki-67 was associated with shorter PFS. Using a cutoff of 2.4%, grade 1 tumors with high compared to low Ki-67 scores had statistically significant worse PFS, 70.5 vs 108.7 months, p = 0.005. However, Ki-67 did not carry predictive value for adjuvant RT benefit.

ADC-derived radiomic features have been explored as potential biomarkers for proliferation and tumor cellularity; however no validated ADC threshold exists to distinguish meningioma grading.^{4, 5} In the study, 60 patients had available diffusion imaging, and ADC entropy ≥ 1.51 was associated with higher risk of progression (AUC 0.912), supporting its potential role in risk stratification however, given the small number evaluated, further validation is needed.

Dr. Guzel’s impressive work suggests that the biological heterogeneity of Grade 1 meningioma may not be fully captured with conventional histologic grade alone and integrating molecular, IHC and imaging biomarkers may help identify patients in need of closer surveillance or treatment intensification. The results of this thoughtfully designed study demonstrate that Rb1-S780 may be a promising candidate biomarker in need of further independent validation. Given the expected limitations of a retrospective, single-institution study, the results are hypothesis-generating until confirmed in a prospectively designed study.

Abstract 1066, Rb1-S780 Phosphorylation as a Potential Biomarker for Grade 1.5 Meningiomas and Adjuvant Radiotherapy Decision Making, was presented during QP 12 Molecular Biomarkers and Precision Oncology in CNS Tumors, at ASTRO's 68th Annual Meeting.

References

1. Abikenari, M.A., et al., Spatially Encoded Oncogenesis and Transcriptional Plasticity in Meningioma: Drivers of Therapeutic Resistance and Opportunities for Targeted Intervention. Cancers (Basel), 2025. 17(16).
2. Nazem, A.A., J. Ruzevick, and M.J. Ferreira, Jr., Advances in meningioma genomics, proteomics, and epigenetics: insights into biomarker identification and targeted therapies. Oncotarget, 2020. 11(49): p. 4544–4553.
3. Parada, C.A., et al., Phosphoproteomic and Kinomic Signature of Clinically Aggressive Grade I (1.5) Meningiomas Reveals RB1 Signaling as a Novel Mediator and Biomarker. Clin Cancer Res, 2020. 26(1): p. 193–205.
4. Surov, A., et al., Use of Diffusion Weighted Imaging in Differentiating Between Maligant and Benign Meningiomas. A Multicenter Analysis. World Neurosurgery, 2016. 88: p. 598–602.
5. Tsai, Y.T., et al., Preoperative Apparent Diffusion Coefficient Values for Differentiation between Low and High Grade Meningiomas: An Updated Systematic Review and Meta-Analysis. Diagnostics (Basel), 2022. 12(3).

Published on: September 29, 2026