Background
cancer, tumor, death, SRS
TUMOR, BRAIN METASTASES, CANCER, DNA DAMAGE, EVENTS
In addition to surgery, targeted agents and/or immunotherapy can effectively treat brain metastases from several subtypes of cancer [The number of long-term survivors with brain metastases has increased due to the introduction of more effective systemic therapies including immunotherapy and targeted agents [Fractionated radiosurgery (fSRS) has been used to reduce the risk of side effects compared to single fraction SRS. With fSRS, the ablative dose is delivered in multiple fractions over several days, instead of delivering the ablative dose within half an hour [Randomized trials comparing fSRS with single fraction SRS are lacking. To achieve local tumor control rates of ≥ 90% at one year, a cumulative BED of at least 50 Gy should be delivered. This is achieved with 35 Gy in five fractions (BED is greater than 50 Gy). Another potential benefit of fSRS over single fraction SRS is better induction of the abscopal effect. This is a systemic anticancer response due to radiation-induced DNA damage. It is hypothesized that this effect is caused by the activation of a cytosolic DNA sensing pathway mediated by cyclic GMP-AMP synthase (cGAS) and stimulator of interferon genes (STING). This pathway leads to adaptive immune responses which induce cell death even outside of the targeted sites [To our knowledge, no prospective studies have been performed to compare fSRS with single fraction SRS in the treatment of brain metastases. In this randomized study, we aim to compare the incidence of adverse local events in patients with brain metastases treated with 1 or 3 fractions versus fSRS (5 fractions).