Title : Clinical outcomes of whole brain radiotherapy in patients with brain metastases from lung adenocarcinoma in the modern radiotherapy era: A five year experience
Abstract:
Objective: To evaluate the clinical outcomes of Whole-Brain Radiotherapy (WBRT) in patients with Brain Metastases (BM) from lung adenocarcinoma who were not suitable candidates for stereotactic radiotherapy.
Methods: The data of 53 patients who underwent WBRT between December 2021 and February 2026 were retrospectively analyzed. Clinical characteristics, systemic treatment modalities, and radiotherapy-related factors associated with overall survival were evaluated.
Results: The median age was 65 years (range, 44–90), and 71.7% of the patients were male. Prior to WBRT, the primary tumor was uncontrolled in 79.2% of patients, and uncontrolled extracranial disease was present in 62.3%. According to the Recursive Partitioning Analysis (RPA) classification, 69.8% of patients were classified as class II, and 71.7% had a Karnofsky Performance Status (KPS) of 80–100. The number of brain metastases was ≤5 in 35.8% of patients, while 43.4% had more than 10 metastases, and 60.4% of metastases were detected synchronously. Molecular analyses revealed EGFR mutations in 15.1%, KRAS mutations in 13.2%, and no driver mutation in 45.3% of patients. PD-L1 expression was negative in 32.1%, 1–50% in 17.0%, and >50% in 11.3% of patients. The median WBRT dose was 30 Gy (range, 8–30 Gy), and the median number of fractions was 10 (range, 1–10). As first-line systemic therapy, 58.5% of patients received platinum-based chemotherapy, while 13.2% received immunotherapy or targeted therapy. Acute toxicity was observed in 35.8% of patients, with the most common events being grade 2 headache (15.1%) and nausea (7.5%). The median follow-up after WBRT was 3 months (range, 1–31 months). Intracranial recurrence occurred in 28.3% of patients, and the most commonly used salvage treatment was stereotactic radiosurgery (46.7%). The median overall survival after WBRT was 3 months (95% CI: 0.63–5.37), and the median intracranial progression-free survival was 3 months (95% CI: 1.76–4.24). At the last follow-up, 69.8% of patients had died. In univariate analyses, mutation status (p=0.010), type of first-line metastatic systemic therapy (p<0.001), radiotherapy dose (p=0.001), performance status (p<0.001), extracranial disease status (p<0.001), number of brain metastases (p=0.002), and advanced age (p=0.050) were significantly associated with overall survival. In multivariate analysis, poor performance status (KPS 60–70) (HR: 55.7; 95% CI: 3.46–896.2; p=0.005) and uncontrolled extracranial disease (HR: 7.93; 95% CI: 1.58–39.93; p=0.012) were independently associated with shorter survival.
Conclusion: Our findings indicate that WBRT is associated with limited survival in patients with brain metastases from lung adenocarcinoma who are not candidates for stereotactic radiotherapy; however, performance status and control of extracranial disease remain the key prognostic determinants.
