The Effect of Timing and Dose Fractionation on Stereotactic Radiation Therapy for Lung Cancer Metastatic to the Brain

Stereotactic radiation therapy has been shown to increase local tumor control and improve survival in select lung cancer patients with brain metastases. The optimal timing and most effective dose scheme for stereotactic therapy have not been determined. In this study we evaluate the effect of stereotactic dose fractionation and the timing of stereotactic radiation therapy on clinical outcomes in patients with lung cancer metastatic to the brain. Between 1995 and 2005 a series of 114 patients were identified with primary lung carcinoma metastatic to the brain. These patients were treated with whole brain radiation alone (n = 25) or in combination with stereotactic therapy (n = 89). Patients were treated for single or multiple brain metastases with the number of treated isocenters ranging from 1 to 10. We evaluated the effect of dose fractionation between single fraction stereotactic radiosurgery (SRS) and hypofractionated stereotactic radiotherapy (SRT) on patient outcome. We also examined the timing of stereotactic therapy by treating one patient cohort with immediate adjuvant stereotactic radiation (n = 28) and reserving stereotactic treatment for salvage therapy at time of intracranial disease progression in other patients (n = 51). Patients were retrospectively analyzed with the primary outcome of survival. Secondary outcomes were treatment related toxicity, tumor response, intracranial recurrence, sites of distant failure, and cause of death. Stereotactic radiation therapy was well tolerated in this study. Mild headache and ataxia were the most frequently reported complications from therapy. There was no increase in late effect toxicity noted in stereotactic treated patients. The addition of stereotactic therapy to whole brain radiation dramatically increased the median survival time from 8.9 months to 41.2 months. The dose fractionation scheme did not significantly alter outcomes with SRS and SRT treatment groups demonstrating median survival times of 41.1 and 42.4 months respectively. However, the timing of stereotactic therapy demonstrated a significant impact on patient outcome. Salvage stereotactic treatment was superior to immediate adjuvant therapy with median survival times of 49 and 26 months. Stereotactic radiation therapy dramatically improves survival in metastatic lung cancer. Dose fractionation studies suggest that SRS is equivalent to hypofractionated SRT. These results suggest that survival is most improved by delaying SRS treatment until salvage at the time of tumor progression.