1066 - Rb1-S780 Phosphorylation as a Potential Biomarker for Grade 1.5 Meningiomas and Adjuvant Radiotherapy Decision Making

05:05pm - 05:10pm ET

Room 153

Presenter(s)

Hale Basak Caglar, MD - Memorial Goztepe Hospital, Istanbul, Istanbul

C. Guzel^1,2, M. A. Inan³, A. Karanfil⁴, I. H. Saribiyik⁵, E. Cindil⁴, O. H. Emmez⁶, A. M. Kaymaz⁶, P. Erpolat¹, and H. B. Caglar⁷; ¹Department of Radiation Oncology, Gazi University Faculty of Medicine, Ankara, Turkey, ²Department of Radiation Oncology, Erzurum City Hospital, Erzurum, Turkey, ³Department of Pathology, Acibadem Mehmet Ali Aydinlar University, Istanbul, Turkey, ⁴Department of Radiology, Gazi University Faculty of Medicine, Ankara, Turkey, ⁵Department of Pathology, Gazi University Faculty of Medicine, Ankara, Turkey, ⁶Department of Neurosurgery, Gazi University Faculty of Medicine, Ankara, Turkey, ⁷Anadolu Medical Center Hospital, Department of Radiation Oncology, Kocaeli, Turkey

Purpose/Objective(s):

Identifying patients who benefit from adjuvant radiotherapy (RT) remains an unmet need in meningioma management. A subset of WHO Grade 1 meningiomas, termed "Grade 1.5", demonstrates early progression despite favorable histology, complicating treatment decisions. We hypothesized that an integrated immunohistochemistry (IHC) and radiomic profiling approach could identify this aggressive phenotype and predict benefit from adjuvant RT.

Materials/Methods: This single-institution retrospective study included adults with surgically resected cranial meningioma (2010–2022) who underwent preoperative MRI within 30 days of surgery and had =2 years of follow-up. Patients with neurofibromatosis type 2, prior cranial RT, or preoperative embolization were excluded. Of 1,117 screened cases, 338 met eligibility criteria; a balanced recurrence–control sampling strategy was applied. After quality control, the final cohort consisted of 167 patients. Seven IHC markers were evaluated using tissue microarrays, including proliferation markers (Ki-67, Rb1-S780, MCM6) and candidate biomarkers (TRAF7, HIF-1a, H3K27me3, TERT). Radiomic features (entropy, skewness, and kurtosis) were extracted from contrast-enhanced T1-weighted images and ADC maps. The primary endpoint was progression-free survival (PFS). Optimal thresholds of markers were identified using receiver operating characteristic (ROC) analysis, and prognostic and predictive values were evaluated using Kaplan-Meier and multivariable Cox regression.

Results: Primary analyses included Grade 1 (n=116) and Grade 2 (n=51) tumors; median follow-up was 68.4 months (IQR 43.7–108.9). Among Grade 1 tumors, elevated Ki-67 (=2.4%) was associated with shorter PFS (70.5 vs. 108.7 months; p=0.005) but lacked predictive value for RT benefit. In contrast, 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 Grade 2 (p=0.125). A significant RT×Rb1-S780 interaction supported the predictive value of Rb1-S780 (HR for interaction =0.054; 95% CI 0.009–0.330; p=0.002). Accordingly, 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. On multivariable Cox regression, adjuvant RT remained independently associated with improved PFS (HR=0.28; p=0.046). Among patients with available diffusion imaging (n=60), ADC entropy =1.51 discriminated patients at higher risk of progression (AUC=0.91), supporting its potential role in risk stratification and warranting further validation.

Conclusion: Rb1-S780 phosphorylation identifies a Grade 1.5 phenotype not detected by standard histology. To our knowledge, this study provides the first evidence that an IHC marker can serve as a predictive biomarker for adjuvant RT in meningiomas. These findings support precision-guided RT for high-risk Grade 1 tumors while avoiding overtreatment in indolent cases.