Effect of cumulative dexamethasone dose on the outcome of patients with radiosurgically treated brain metastases in the era of modern oncological therapy

OBJECTIVE Recent treatment guidelines state that in patients with asymptomatic brain metastases (BMs), local treatment can be delayed until there is evidence of intracranial progression. However, while patients with symptomatic BMs typically require dexamethasone treatment, recent data on the impact of this medication on the outcomes of patients with BMs are lacking. Therefore, the authors conducted a prospective study to evaluate concomitant dexamethasone treatment in a population of radiosurgically treated patients with BMs from non–small cell lung cancer (NSCLC). METHODS This prospective observational study included 129 radiosurgically treated patients with NSCLC BMs, a Karnofsky Performance Status ≥ 70, and no previous radiosurgical treatment. Patients were enrolled in the study between December 2019 and May 2023. For patient allocation, data on concomitant immunotherapy (IT) or targeted therapy (TT) and dexamethasone treatment were analyzed 30 days before and after the first Gamma Knife radiosurgery treatment (GKRS1). A cumulative dose threshold of 100 mg of dexamethasone was evaluated. RESULTS The estimated median survival time after GKRS1 was significantly longer in female patients than in male patients and in patients with concomitant IT or TT versus those without. Of note, patients with a cumulative concomitant dexamethasone dose ≥ 100 mg at GKRS1 had a significantly shorter median survival after GKRS1 than the patients with a dose < 100 mg. Moreover, a univariable followed by multivariable Cox regression model revealed that a cumulative dexamethasone dose ≥ 100 mg at GKRS1 and male sex were independent prognostic factors for an increased risk of death. CONCLUSIONS A cumulative dexamethasone dose ≥ 100 mg within 30 days before and after radiosurgery was identified as an independent risk factor for death. Consequently, even in the modern oncological era, the recommendation to delay local BM treatment should be critically reviewed, as the main reason for dexamethasone treatment is the presence of neurological symptoms caused by larger BMs and perifocal edema. Thus, the study data support early local BM treatment to avoid dexamethasone treatment for neurological symptoms caused by progressive BMs.