In-depth study of radiation necrosis after Gamma Knife radiosurgery for brain metastases

Keywords: brain metastasis, gamma knife, radiation injury, complications, radiosurgery

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     Radiation injury can occur following brain metastasis radiosurgery.
Our purpose was to determine the incidence, time-course, and risk factors for radiation necrosis after stereotactic radiosurgery (SRS) for brain metastases.
     We evaluated images from a series of 900 patients.
     Brain-metastasis patients/lesions treated with Gamma Knife SRS September 1998 through 2009 were reviewed and excluded for death <2 months after SRS or insufficient follow-up (<3 months of imaging follow-up, >8-month gap in the first year, or inadequate imaging availability). Follow-up imaging was re-reviewed to ensure consistency. Dates of necrosis were recorded, validated by surgical pathology showing necrosis ± tumor, serial MRI ± perfusion studies, or both. Freedom from necrosis after SRS was calculated using the Kaplan-Meier method with censoring at last imaging.
     This study is in progress; full results will be presented. Of 900 patients, >363 are eligible; 93 died <2 months after SRS; 311 had insufficient follow-up; 133 remain to be screened. To date, 170 patients with 637 eligible metastases have been fully reviewed, with median survival 17.3 months, median follow-up >2 years in living patients, and median imaging follow-up 8.7 months in censored lesions. The appearance of necrosis was variable and frequently indistinguishable from tumor progression at single points in time; serial imaging review was key, along with pathology when available. Overall, 9% of lesions developed necrosis at a median of 8.0 months after SRS (range, 0.9-52.0 months; 85% between 3-18 months); another 5% were indeterminate for failure vs. necrosis. Higher necrosis risk was associated with larger target volume, larger maximum diameter, primaries other than breast and kidney, and other radiation; 1-year necrosis probabilities were 9%, 12%, 21%, and 37% for SRS performed alone, after prior radiotherapy, concurrent with radiotherapy, or after prior SRS to the same lesion (p = 0.019). The 1-year necrosis risk was 5% for breast and kidney brain metastases vs. 18% for other primaries (p = 0.0003), and 4%, 7%, 18%, 36%, and 37% for targets ?1, 1.1-1.5, 1.6-2.0, 2.1-3.0, and >3.0 cm (p < 0.0001). Primary site, other radiation, and diameter all retained significance on multivariate analysis.
     This was a retrospective analysis.
     Necrosis probabilities were higher than expected, particularly for metastases >1.5-2 cm.  
     Other risk factors for radiation injury included non-breast/non-kidney primary, prior or concurrent radiotherapy, and prior SRS.


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