By Hasan Murshed, MD, Hope Regional Cancer Center
NRG-CC009 addresses a long-standing evidence gap in brain metastasis management. Patients with small cell lung cancer (SCLC) were excluded from landmark trials establishing stereotactic radiosurgery (SRS) for limited brain metastases because of concerns about diffuse intracranial disease.1 WBRT has therefore remained a standard approach, although hippocampal avoidance (HA-WBRT) plus memantine has improved neurocognitive preservation. NRG-CC009 directly compared SRS with this modern WBRT approach.
The phase III trial randomized 151 patients with SCLC brain metastases ≤4 cm and total volume ≤30 cm³ to SRS or HA-WBRT plus memantine. Although the median number of metastases was 2 (IQR 1–5), the range extended to 26 after removal of the original 10-lesion limit. This broad range makes subsequent analyses by lesion number and total intracranial tumor volume particularly important.
The primary endpoint was negative: there was no significant difference in neurocognitive failure (adjusted HR=0.83, 95% CI 0.53–1.28, p=0.39). Importantly, the comparator was HA-WBRT plus memantine rather than conventional WBRT, providing a contemporary comparison specifically designed to mitigate neurocognitive toxicity.
The most striking secondary finding was overall survival, which favored SRS substantially: median OS was 17.4 versus 8.6 months (adjusted HR=0.60, 95% CI 0.39–0.91, p=0.016). This unexpected survival difference is intriguing but warrants cautious interpretation. OS was a secondary endpoint, and median follow-up among surviving patients was only 9.5 months. Additional information regarding systemic therapy, extracranial disease status, subsequent treatment, and causes of death will be important in understanding the survival difference.
No significant differences were observed in intracranial failure on multivariable analysis, nor in neurological mortality or grade 3–5 treatment-related toxicity. However, detailed event rates were not provided in the abstract. Given the inclusion of patients with as many as 26 metastases, intracranial outcomes stratified by lesion number and total tumor volume will be particularly informative.
The NRG investigators should be congratulated for completing a landmark randomized trial in a population historically excluded from SRS trials. NRG-CC009 provides important evidence supporting SRS as a treatment option for appropriately selected patients with SCLC brain metastases. However, the primary neurocognitive endpoint did not demonstrate superiority of SRS over modern HA-WBRT plus memantine, while the unexpected survival advantage arose from a secondary endpoint. Longer follow-up and detailed analyses of intracranial disease burden, systemic therapy, extracranial disease control, and salvage treatment will help determine how broadly these findings should change practice and which patients are most likely to benefit from an SRS-based approach.
Reference
LBA 02, NRG-CC009: A Phase III Trial of Stereotactic Radiosurgery (SRS) vs. Hippocampal-Avoidant Whole Brain Radiotherapy (HA-WBRT) for Brain Metastases from Small Cell Lung Cancer (SCLC), was presented during PL 01- Plenary 01, at ASTRO's 68th Annual Meeting.
Published on: September 29, 2026
