Delayed complications in patients surviving at least 3 years after stereotactic radiosurgery for brain metastases

Purpose: Little is known about delayed complications after stereotactic radiosurgery in long-surviving patients with brain metastases. We studied the actual incidence and predictors of delayed complications. Patients and Methods: This was an institutional review board-approved, retrospective cohort study that used our database. Among our consecutive series of 2000 patients with brain metastases who underwent Gamma Knife radiosurgery (GKRS) from 1991-2008, 167 patients (8.4%, 89 women, 78 men, mean age 62 years [range, 19-88 years]) who survived at least 3 years after GKRS were studied. Results: Among the 167 patients, 17 (10.2%, 18 lesions) experienced delayed complications (mass lesions with or without cyst in 8, cyst alone in 8, edema in 2) occurring 24.0-121.0 months (median, 57.5 months) after GKRS. The actuarial incidences of delayed complications estimated by competing risk analysis were 4.2% and 21.2% at the 60th month and 120th month, respectively, after GKRS. Among various pre-GKRS clinical factors, univariate analysis demonstrated tumor volume-related factors: largest tumor volume (hazard ratio [HR], 1.091; 95% confidence interval [CI], 1.018-1.154; P=.0174) and tumor volume ≤10 cc vs >10 cc (HR, 4.343; 95% CI, 1.444-12.14; P=.0108) to be the only significant predictors of delayed complications. Univariate analysis revealed no correlations between delayed complications and radiosurgical parameters (ie, radiosurgical doses, conformity and gradient indexes, and brain volumes receiving >5 Gy and >12 Gy). After GKRS, an area of prolonged enhancement at the irradiated lesion was shown to be a possible risk factor for the development of delayed complications (HR, 8.751; 95% CI, 1.785-157.9; P=.0037). Neurosurgical interventions were performed in 13 patients (14 lesions) and mass removal for 6 lesions and Ommaya reservoir placement for the other 8. The results were favorable. Conclusions: Long-term follow-up is crucial for patients with brain metastases treated with GKRS because the risk of complications long after treatment is not insignificant. However, even when delayed complications occur, favorable outcomes can be expected with timely neurosurgical intervention.