Although stereotactic radiosurgery (SRS) is preferred for brain metastases from most tumour histologies because it better preserves neurocognitive function and quality of life compared with whole-brain radiotherapy (WBRT), WBRT has remained the standard of care for patients with small cell lung cancer (SCLC) and brain metastases.

This is largely because patients with SCLC have been excluded from the clinical trials that established the role of SRS.

Recently reported results from the NRG-CC009 clinical trial, which evaluated SRS versus hippocampal avoidant WBRT (HA-WBRT) with memantine in patients with SCLC and brain metastases, found that SRS did not significantly improve neurocognitive outcomes compared with HA-WBRT and therefore the trial failed to meet its primary endpoint.

However, the results demonstrated a potential survival benefit with SRS, along with comparable central nervous system control, suggesting that SRS may offer an effective alternative to HA-WBRT for appropriately selected patients with SCLC brain metastases.

These results were presented during the Plenary Session of the 2026 American Society for Radiation Oncology Annual Meeting in Boston, Massachusetts.

“One of the fundamental concerns with upfront SRS alone for SCLC is that patients might develop diffuse CNS progression leading to worse neurologic and survival outcomes. However, that is not what we observed in NRG CC009. Although there were no differences in neurocognitive failure, treatment with SRS was associated with superior overall survival compared to HA-WBRT. These findings support SRS as a reasonable standard of care option for patients with SCLC brain metastases,” stated Chad Rusthoven, MD at the University of Colorado Anschutz and the lead author of the NRG-CC009 abstract.

“NRG-CC009 provides results that will help physicians better counsel their patients on treatment approaches for SCLC brain metastases.  The overall survival difference is an important factor to be discussed with patients,” said Vinai Gondi, MD at the Northwestern University Feinberg School of Medicine and the lead Principal Investigator of the NRG-CC009 trial.

This Phase III trial accrued 151 eligible patients with SCLC brain metastases and stratified them by disease-specific graded prognostic assessment score and number of brain metastases.

Patients were then randomised 1:1 to receive SRS or HA-WBRT with memantine.

The baseline characteristics of patients were well balanced between the two treatment arms, and the median number of brain metastases was 2 (range, 1-26; interquartile range, 1-5).

The primary endpoint was time to neurocognitive failure and the secondary endpoints included overall survival, intracranial disease progression, neurological death, salvage therapies, and adverse events.

With 91 events, the study had 85% power to detect a 17% absolute reduction in neurocognitive failure between arms using a two-sided type I error of 0.05, assuming a rate of death without failure of 29.8% in both arms.

At the median follow up of 9.5 months for surviving patients, there was no significant difference in neurocognitive failure between arms (Grey’s test, p=0.66; adjusted HR for SRS arm = 0.83; 95% CI, 0.53–1.28; p=0.39).

Overall survival was superior in the SRS arm (median 17.4 vs.

8.6 months; adjusted HR for SRS arm = 0.60; 95% CI, 0.39–0.91; p=0.016).

There were also no differences observed in adjusted analyses of intracranial failure, neurological mortality, salvage therapy, or treatment-related grade 3-5 adverse events.

This project was supported by grants U10CA180822 (NRG Oncology SDMC), UG1CA189867 (NCORP), U24CA180803 (IROC), 3UG1CA239769, 3UG1CA190140, 3UG1CA189859, 3UG1CA189869, 3UG1CA189960, and 3UG1CA189956 from the National Cancer Institute (NCI), part of National Institutes of Health.

The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Source: NRG Oncology