Three-staged stereotactic radiosurgery for brain metastases: a single institution experience
Authors: Rozati Hamoun , Paddick Ian , Sabin Ian 
Published: October 2021

Abstract

Aims
Stereotactic radiosurgery (SRS) using the Leksell Gamma Knife system is a commonly used modality for the treatment of brain metastases (BMs). As the size of the target volume (TV) increases, so too does the dose of radiation delivered to surrounding healthy tissue. Large BMs are therefore a contraindication to the use of SRS. Critical organs adjacent to the TV may also be a contraindication to SRS. Staged SRS was proposed as a novel method of delivering three SRS treatments at a reduced radiation dose with a gap of two weeks between each session as a way of shrinking the TV. This allows treatment of TVs otherwise considered untreatable with standard, single-fraction SRS. Little data exists in the literature as to its efficacy. The objective of this study was to evaluate the efficacy of this novel approach and to identify factors which may predict treatment failure.

Method
A retrospective analysis was undertaken at a single, tertiary Gamma Knife centre. All patients who underwent treatment of their BMs with three-staged Gamma Knife SRS from January 2014 to December 2020 were identified and included. Patient demographics and primary cancer status was ascertained. SRS treatment details for each lesion were collected, including TV, dose and dosimetric data. The percentage reduction in volume of the TVs between the first and second stage, the second and third stage and the first and third stage were calculated. Follow-up data was collected to include follow-up imaging, further intracranial treatments received and survival status. The percentage reduction in volume between each stage was demonstrated on box-and-whisker plots. Statistical significance in reduction in TV between each stage was ascertained by paired samples T-tests. Correlation between initial TV size and percentage reduction post-SRS was determined by a correlation coefficient. Differences were deemed significant with p-values &lt;0.05.

Results
12 patients with 14 staged BMs were identified and included. The median age was 61.5 (range 45-79). Seven had a primary malignancy of breast cancer, five non-small cell lung cancer, one melanoma and one colorectal. Median follow-up was 140.5 days (range 10-821). Median TV was 7.44cc (range 1.14-21.53). All TVs received 10Gy at each stage. The median percentage reduction in size of the TV was 7.41% between 1st-2nd stage (range -16.0-42.49%, p-value 0.06), 19.47% between 2nd-3rd stage (range -5.38-53.53%, p-value &lt;0.01) and 24.25% between 1st-3rd stage (range 10.69-68.67%, p-value &lt;0.01). The correlation coefficient between initial TV size and percentage reduction post-SRS was -0.41 (p-value 0.07). 13/14 lesions showed a partial response on first follow-up scan post-SRS, 1/14 lesions showed a mixed response. One patient died 184 days from completion of treatment but without intracranial progression. Two patients had salvage intracranial surgery, 154 and 536 days from completion of treatment respectively.

Conclusion
Three-staged Gamma Knife is shown to be effective at shrinking the TV and can therefore be used to treat lesions otherwise considered unsuitable for SRS. The presence of extra-cranial metastases did not predict for poor outcomes. Though local control with SRS is thought to diminish with increasing TV size, all staged lesions showed a reduction in size between first and last treatment, and no significant effect was seen between initial TV size and percentage reduction in TV. No patients experienced disease progression on first follow up scan, with 13 of 14 lesions showing disease response. There were only two cases of intracranial progression, with one occurring 536 days post-SRS. Though limited by small numbers and short median follow up period, our data demonstrate encouraging results for three-stage SRS for lesions otherwise unsuitable for single fraction treatment, and should lead to further study.