Low-Dose Radiation Spillage During Stereotactic Radiosurgery for Brain Metastases is Associated with a Decreased Incidence of New Supratentorial Brain Metastases.

Abstract

Stereotactic radiosurgery (SRS) for brain metastases is increasingly used in lieu of whole brain radiation (WBRT), with reduced risk of cognitive side effects but at the expense of an increased risk of developing new lesions in non-treated parts of the brain. Here we investigated whether the low dose fall-off during SRS is associated with a lower incidence of brain metastases. We reviewed 130 patients treated with single or fractionated SRS for definitive or post-op brain metastases at our institution during 2016-2017. Patients with MRI findings of local recurrence or new brain metastases within 18 months of the first SRS were selected. WBRT before SRS was an exclusion. MRI or CT simulation for repeat treatment was fused with the initial SRS treatment plan. The new lesions and the corresponding contralateral anatomical site were outlined on the initial planning scan. The mean doses delivered to the site of these new lesions from the initial SRS treatment were tabulated. Comparison of mean doses to the new lesions and contralateral site were performed using t-test, and the difference in number of lesions at varying low dose levels was examined using Z-test for proportion. Thirty-six patients met the inclusion criteria. 24 patients (67%) had lung primary (2 squamous cell carcinoma and 19 adenocarcinoma), 6 breast (17%), 2 renal cell carcinoma (RCC), one each of esophagus, melanoma, cervix and unknown primary. 21 patients (58%) received chemotherapy during the time interval of 18 months, and 20 (56%) received immunotherapy. One hundred sixty-six new brain lesions were evaluated. Three of the 7 cerebellar lesions (43%) showed local recurrence. In patients with initial supratentorial metastasis, only 5 of total 159 lesions (3%) appeared when exposed to >6 Gy from prior SRS. 11 (6.9%), 30 (19%) and 49 (31%) lesions occurred in the >4 Gy, >2 Gy and >1 Gy dose levels, respectively. 14 lesions (9%) had no recurrences in their contralateral comparable site which received >6 Gy (p= 0.033) and 21 lesions had no recurrences in their contralateral comparable site if >4 Gy was received (13%) (p=0.063). Among the lesions that appeared after exposure to >6 Gy and >4 Gy dose, 2/5 (40%) and 5/11 (55%) lesions, respectively, were from RCC primaries. New metastases developed in sites that received less mean dose from prior treatments as compared to mean dose received in the corresponding contralateral hemisphere, where the patients did not experience recurrence. This was true for all dose levels, >1Gy through >6 Gy (all p values ≤0.02). New lesions appeared more often on the side that received lower dose of radiation compared to their contralateral site. Dose levels of >6 Gy or >4 Gy were associated with decreased incidence of new supratentorial brain metastases, less so for RCC primaries. Low dose bath to the non-target brain may be protective. Validation in larger dataset is warranted.