Brain-Directed Stereotactic Radiation Demonstrates Benefit vs Whole-Brain Radiation Among Certain Patients With SCLC Brain Metastases

According to results from a phase 2 trial, brain-directed stereotactic radiation demonstrated lower rates of neurologic death compared to whole-brain radiation among patients with small cell lung cancer (SCLC) who have 1 to 10 brain metastases. 

“Stereotactic radiation as opposed to whole-brain radiation represents the standard of care for patients with a limited number of brain metastases given the relatively favorable toxicity profile associated with stereotactic treatment,” stated Ayal Aizer, MD, Dana-Farber Cancer Institute, Boston, Massachusetts, and coauthors. “However, in patients with [SCLC], [whole-brain radiation] remains standard because of a lack of prospective data supporting [stereotactic radiation] and concerns related to intracranial progression and neurologic death when [whole-brain radiation] is omitted.” 

In this single-arm, prospective trial, researchers enrolled 100 patients with either SCLC or an extrathoracic small cell primary with 1 to 10 brain metastases to undergo brain-directed stereotactic radiation. Patients were not permitted to have undergone prior brain-directed radiation including prophylactic cranial irradiation. Brain MRIs were conducted 4 weeks after radiation, 6 weeks later, and then subsequently once every 8 weeks for 1 year. Primary end points included overall survival (OS) and neurologic death. 

At analysis, the median OS was 10.2 months. There were 20 neurologic deaths and 64 non-neurologic deaths. The 1-year neurologic death rate was 11% and the 2-year neurologic death rate was 20.3%. Historical whole-brain radiation neurologic death rates were 17.5% at 1 year and 35.2% at 2 years. Univariable analysis results demonstrated that age, number of brain metastases, size of brain metastases, presence or absence of neurologic symptoms, presence or absence of distant extracranial metastases, and pre-enrollment neurosurgical resection were not covariates for neurologic death. New brain metastases were developed in 61% of patients. Following the initial treatment, 22% of patients went on to receive whole-brain radiation.

“Our prospective, multi-institutional study demonstrated low rates of neurologic death when [stereotactic radiation] as opposed to [whole-brain radiation] is used in patients with SCLC and 1 [to] 10 brain metastases who are surveilled closely post-treatment, supporting the utility of stereotactic approaches in this population,” concluded Dr Aizer et al. 

“The study is relevant to decision making regarding consideration of stereotactic radiosurgery in lieu of [whole-brain radiation] in the management of SCLC with brain metastasis,” added Journal of Clinical Oncology associate editor Bruce Haffty, MD, Rutgers Cancer Institute, New Brunswick, New Jersey. 

Source:

Aizer AA, Tanguturi SK, Shi DD, et al. Stereotactic radiosurgery in patients with small cell lung cancer and 1-10 brain metastases: A multi-institutional, phase II, prospective clinical trial. J Clin Oncol. Published online: July 11, 2025. doi: 10.1200/JCO-25-00056