Is Whole-Brain Radiotherapy for Brain Metastases an Overestimated Therapy? A Retrospective Study of Real-World Data Using Landmark Analyses

Background: The role of whole-brain radiotherapy for patients with brain metastases is changing as immunotherapy and molecularly targeted therapies advance. However, whole-brain radiotherapy continues to be part of the multimodal concept.

Methods: This retrospective study included 285 patients who received whole-brain radiotherapy for brain metastases, using a median dose of 30 Gy. The study analyzed prognostic factors for survival using Cox regression analyses, while two landmark analyses, reflecting a minimum survival of 60 and 90 days, accounted for early deaths. Neurological symptoms were compared before and after treatment using the McNemar test.

Results: The median patient age was 62 years. Non-small cell lung cancer (n = 95), breast cancer (n = 53), and small cell lung cancer (n = 48) were the most frequent cancer types. Median survival was 4.3 months (interquartile range 1.8-11.1). In the multivariable Cox regression model, patients who received additional immunotherapy/molecularly targeted therapy had a higher chance of survival than others. Overall survival was influenced by control of primary cancer, extracranial metastases, age, Karnofsky performance status, and number of brain metastases. The 90-day landmark analysis included 181 patients who survived at least 90 days, reflecting that 104 patients (36.5%) died within the first 90 days. The 90-day landmark analysis confirmed all predictive variables for survival. Patients who died before the 90-day landmark endpoint had more brain metastases, lower Karnofsky performance status, higher age, and were less frequently treated with immunotherapy/molecularly targeted therapy than those surviving at least 90 days. The treatment significantly improved neurological symptoms.

Conclusion: These results indicate an insufficient patient selection, as one-third of patients treated with whole-brain radiotherapy died within 90 days. However, neurological symptoms improved, and the addition of immunotherapy and/or molecularly targeted therapy to whole-brain radiotherapy was associated with better survival. Patients receiving whole-brain irradiation should be more carefully selected.

Trial registration: ClinicalTrials: 24-3626-104.