Radiation Oncology
Chair: Serah Choi, MD, and Daniel Trifiletti, MD
Recent advancements in central nervous system (CNS) radiation oncology have introduced promising therapies and biomarkers alongside challenges in clinical trial enrollment. A significant milestone was the FDA approval of vorasidenib, an IDH inhibitor for treating Grade 2 astrocytoma or oligodendroglioma with IDH1 or IDH2 mutations. Click here for more information. This targeted therapy provides a new approach to managing these tumors, addressing the genetic mutations that drive their growth and potentially improving patient outcomes. While exciting to see a new therapy offered in glioma, it remains unclear how and when to delay radiotherapy in favor of vorasidenib, or if they can be safely given concurrently. This will be an important area for future research.
Conversely, the early closure of the NRG-BN009 trial (salvage HA-WBRT vs. SRS for high brain metastases velocity) due to poor accrual reflects ongoing difficulties in clinical trial recruitment within this patient population. This situation highlights the need for innovative trial designs and enhanced patient engagement strategies to ensure the successful completion of studies that could further advance the field. Click here for more information.
The recently published V-REX study is a randomized clinical trial that investigated whether upfront radiosurgery is more effective at reducing tumor volume in patients with small- to medium-sized vestibular schwannoma compared to a wait-and-scan approach, where treatment is only administered after documented tumor growth. The trial included 100 patients, with 50 receiving upfront radiosurgery and 50 following the wait-and-scan protocol. After four years, tumor volume was significantly lower in the upfront radiosurgery group compared to the wait-and-scan group. No radiation-associated complications were observed, highlighting the safety of upfront radiosurgery. While the primary outcome showed a significant difference, 25 out of 26 secondary outcomes, including patient-reported symptoms and quality-of-life measures, did not differ significantly between the two groups, bringing the question to its practical significance. Further follow-up will be enlightening.
The clinical benefit of adjuvant radiation following surgery for gross totally resected grade 2 meningiomas is controversial and under active investigation with NRG Oncology BN003: phase III clinical trial of observation versus irradiation for a gross totally resected grade 2 meningioma. However, there is a lack of effective biomarkers that predict for benefit from post-operative radiotherapy. A recent study published in Nature Medicine (Targeted gene expression profiling predicts meningioma outcomes and radiotherapy responses – PubMed (nih.gov) showed that a targeted gene expression biomarker improves discrimination of meningioma outcomes, including prediction of postoperative radiotherapy responses. Using a discovery cohort of 173 meningiomas, a 34-gene expression risk score was generated and clinical and analytical validation of this biomarker was performed on meningiomas from 12 institutions across three continents (N=1,856), including 103 meningiomas from a prospective clinical trial. The gene expression biomarker identified meningiomas benefiting from postoperative radiotherapy. We look forward to the incorporation of genomic biomarkers into future clinical trials to help refine indications for radiotherapy in meningiomas.