Small cell lung cancer: © Констянтин Батыльчук- stock.adobe.com
A phase 2 clinical trial by Mass General Brigham has shown that patients with small cell lung cancer (SCLC) and 1 to 10 brain metastases treated with stereotactic radiation (SRS/SRT) had low rates of neurologic death compared with the traditional whole brain radiation therapy (WBRT).1
The study demonstrated a 1‑year neurologic death rate of 11% (95% CI, 5.8%-18.1%), significantly lower than the 17.5% historical benchmark associated with WBRT.2 Just 22% of patients went on to require salvage WBRT, supporting the potential of targeted radiation to preserve neurologic function without compromising survival.
“Despite being the historical standard, whole brain radiation might not be necessary for all patients,” first author Ayal Aizer, MD, MHS, director of Central Nervous System Radiation Oncology at Brigham and Women’s Hospital, a founding member of the Mass General Brigham health care system, said in a press release.1 “Our findings demonstrate that targeted, brain-directed radiation may be a viable treatment for patients with limited brain metastases from small cell lung cancer and potentially spare them from the side effects of whole brain radiation.”
Between 2018 and 2023, investigators enrolled 100 patients across multiple centers. Eligibility required a confirmed SCLC diagnosis with 1 to 10 brain metastases and no prior brain-directed radiation therapy, including prophylactic cranial irradiation.
The median number of metastases was 2, and the median overall survival was 10.2 months. Neurologic death was rigorously defined as radiographic progression in the brain, neurologic symptoms, and absence of systemic progression.
With 20 neurologic deaths observed and 64 nonneurologic deaths, the 1‑year neurologic death rate was calculated at 11.0%. This finding is particularly notable given that SCLC has historically warranted WBRT due to concerns about rapid intracranial progression. The close imaging-based surveillance protocol likely contributed to early detection and management of new lesions, sparing many patients from the cognitive risks of WBRT.
WBRT has long been the standard for patients with SCLC brain metastases due to its broad coverage. However, it is associated with significant long-term neurocognitive toxicity, affecting memory, executive function, and overall quality of life. SRS/SRT offers a more precise alternative, irradiating only the metastatic sites and minimizing collateral damage to healthy brain tissue.
The prospective nature of this multicenter study provides much-needed data in a patient population previously excluded from stereotactic radiation trials. Its findings support a shift toward individualized, targeted therapeutic approaches in SCLC.
These results suggest that select patients with limited SCLC brain metastases could benefit from first-line stereotactic radiation combined with vigilant follow-up imaging. Even if intracranial progression occurs, only a minority may subsequently require WBRT, limiting exposure to its enduring adverse events. Stereotactic radiation may now be considered a viable standard option for patients with SCLC with limited brain involvement rather than being reserved for non–small cell lung cancer. However, to safely implement this approach, practices must include frequent and reliable brain imaging, clear salvage protocols, and coordinated follow-up.
Overall, results from this phase 2 trial underscore that targeted brain-directed radiation can lead to durable control of metastases in SCLC with low neurologic mortality and reduced need for WBRT. As more data emerge, SRS/SRT may become a new standard for treating limited brain metastases in SCLC, improving both survival and quality of life.
“These results support a shift toward more personalized, targeted treatment approaches that can help maintain quality of life while effectively managing brain metastases,” Aizer said. “By avoiding whole brain radiation in select patients, we may be able to improve quality of life and reduce cognitive [adverse events] without compromising outcomes.”