Molecular classification to refine surgical and radiotherapeutic decision-making in meningioma
Justin Z Wang1,2,3, Vikas Patil1,3, Alexander P Landry1,2,3
1MacFeeters Hamilton Neuro-Oncology Program, Princess Margaret Cancer Centre, University Health Network and University of Toronto, Toronto, Ontario, Canada.
Abstract:
Treatment of the tumor and dural margin with surgery and sometimes radiation are cornerstones of therapy for meningioma. Molecular classifications have provided insights into the biology of disease; however, response to treatment remains heterogeneous. In this study, we used retrospective data on 2,824 meningiomas, including molecular data on 1,686 tumors and 100 prospective meningiomas, from the RTOG-0539 phase 2 trial to define molecular biomarkers of treatment response. Using propensity score matching, we found that gross tumor resection was associated with longer progression-free survival (PFS) across all molecular groups and longer overall survival in proliferative meningiomas. Dural margin treatment (Simpson grade 1/2) prolonged PFS compared to no treatment (Simpson grade 3). Molecular group classification predicted response to radiotherapy, including in the RTOG-0539 cohort. We subsequently developed a molecular model to predict response to radiotherapy that discriminates outcome better than standard-of-care classification. This study highlights the potential for molecular profiling to refine surgical and radiotherapy decision-making.
Insights
Molecular profiling can predict meningioma treatment response. This study found gross tumor resection improves survival and radiotherapy response varies by molecular group, guiding personalized therapy decisions.
Area of Science:
- Neuro-oncology
- Genomics
- Clinical Trials
Background:
- Meningioma treatment relies on surgery and radiation, but patient outcomes are inconsistent.
- Molecular classifications offer insights into meningioma biology, yet treatment response remains heterogeneous.
- Identifying biomarkers for treatment response is crucial for personalized meningioma management.
Purpose of the Study:
- To define molecular biomarkers predicting treatment response in meningioma.
- To evaluate the impact of surgical resection and dural margin treatment on progression-free survival (PFS) and overall survival (OS).
- To develop a molecular model for predicting radiotherapy response.
Main Methods:
- Retrospective analysis of 2,824 meningiomas, including molecular data from 1,686 tumors and 100 prospective cases from the RTOG-0539 trial.
- Propensity score matching to assess the impact of surgical interventions.
- Development and validation of a molecular predictive model for radiotherapy response.
Main Results:
- Gross tumor resection was linked to longer PFS across all molecular groups and improved OS in proliferative meningiomas.
- Dural margin treatment (Simpson grade 1/2) significantly prolonged PFS compared to no treatment (Simpson grade 3).
- Molecular group classification accurately predicted radiotherapy response, outperforming standard classification in a developed predictive model.
Conclusions:
- Molecular profiling holds significant potential for refining surgical and radiotherapy decision-making in meningioma treatment.
- Personalized treatment strategies based on molecular biomarkers can improve patient outcomes.
- This research provides a foundation for integrating molecular data into clinical practice for meningioma management.
