Brain Radiotherapy Plus ICIs Boost Survival in SCLC With Brain Metastases

Brain radiotherapy combined with immune checkpoint inhibitors (ICIs) should be considered as a possible treatment pathway for people with small cell lung cancer (SCLC) with brain metastases, according to a new report. The study, which was based on a retrospective analysis of 42 patients, was published in the journal Thoracic Cancer.1

Approximately 4 out of every 5 patients with SCLC have distant metastases at the time of diagnosis, and the most common type of distant metastases in these patients is brain metastases, explained corresponding author Yajing Yuan, PhD, of Tianjin Medical University, in China, and colleagues. As a result, these patients have grim survival outcomes, they said.

Radiotherapy can work synergistically with immunotherapy by reprogramming the tumor microenvironment. | Image credit: Crystallight-stock.adobe.com

Patients with brain metastases often are treated with surgery, chemotherapy, radiotherapy, and immunotherapy. Whole brain radiation therapy (WBRT) has also been widely used, Yuan and colleagues said, but recent studies have called into question the efficacy of WBRT in extending patient survival.2

Immunotherapies targeting PD-L1 have been shown to boost patient survival when combined with platinum-based chemotherapy in patients with extensive-stage SCLC. Yet, Yuan and colleagues said the blood-brain barrier limits the efficacy of certain systemic drugs.1

“Some systemic drugs cannot reach intracranial blood levels, which makes the central nervous system a refuge for metastasis,” they said.

The authors said radiotherapy can work synergistically with immunotherapy by reprogramming the tumor microenvironment. Yet, they said the optimal role of radiation therapy with ICIs in this patient group remains unclear. Therefore, the authors decided to retrospectively analyze cases of SCLC with brain metastases who received brain radiotherapy combined with ICIs.

The 42 patients in the study received care at the authors’ hospital between 2020 and 2024. The patients each received a regimen of chemotherapy plus ICIs and brain radiotherapy. They also received either concurrent or sequential thoracic radiotherapy.

Nineteen of the patients received standard WBRT, and 23 patients received WBRT plus simultaneous integrated boost (SIB), in which different doses of radiation were delivered simultaneously to different parts of the tumor.

At a median follow-up of 19.2 months, the 2-year overall survival (OS) rate was 42.3%, while the intracranial local control (iLC) rate was 68.8%. Yuan and colleagues described those rates as “brilliant.”

Twenty-six patients died of disease progression, and 2 patients developed radiation-induced brain necrosis, one in the WBRT group and one in the WBRT+SIB group. However, the authors said patients in the WBRT group experienced higher rates of headache, nausea, dizziness, and radiodermatitis

The authors said the use of SIB can shorten the treatment time for patients while allowing higher doses of radiotherapy to the brain metastasis lesions themselves. They added that other new research has shown that the ability to deliver synchronous dose-escalated radiotherapy to brain metastasis lesions can control intracranial lesions and boost survival.3

Based on those and other data, the authors said they conclude that WBRT+SIB has a better curative effect on SCLC brain metastases than WBRT alone.

Still, the authors said their findings demonstrate that the combination of radiotherapy with ICIs, whether WBRT or WBRT+SIB, has a significant positive benefit on OS and iLC with tolerable side effects. Thus, they said it deserves to be considered as a promising treatment option.

They added that advanced techniques like image-guided radiotherapy and stereotactic radiosurgery should allow for more precision in the delivery of radiotherapy, thus lowering the risk of severe adverse events.

Yuan and colleagues said their study was limited by its retrospective nature and small sample sizes. They said prospective studies should be conducted to verify their findings.

References

1. Xu J, Yang Y, Chen T, Liu D, Yuan Y, Xu L. The efficacy and safety of brain radiotherapy combined with immune checkpoint inhibitors (ICIs) for small-cell lung cancer (SCLC) patients with brain metastases (BMs). Thorac Cancer. 2025;16(12):e70112. doi:10.1111/1759-7714.70112

2. Chiang CL, Yang HC, Liao YT, et al. Treatment and survival of patients with small cell lung cancer and brain metastasis. J Neurooncol. 2023;165(2):343-351. doi:10.1007/s11060-023-04512-2

3. Zhong J, Waldman AD, Kandula S, et al. Outcomes of whole-brain radiation with simultaneous in-field boost (SIB) for the treatment of brain metastases. J Neurooncol. 2020;147(1):117-123. doi:10.1007/s11060-020-03405-y