title: Leukoencephalopathy in long term brain metastases survivors  treated with radiosurgery.
abstract: Brain metastases (BM) develop in 10-30 % of patients. Stereotactic radiosurgery (SRS) was shown to improve local control, and performance status, in certain cohorts of brain metastasis patients. The cumulative neurocognitive effect of numerous SRS sessions remains unknown. Leukoencephalopathy is significant diffuse white matter changes and it usually implies a neurocognitive decline. We report patients with BM who survived >2 years after SRS. Clinical and treatment parameters were analyzed for development of leukoencephalopathy. Multiple parameters as well as leukoencephalopathy grade changes were recorded. The median clinical and radiological follow-up was 42 and 41 months (range 24–115 and 24–115) respectively. The cohort included 92 patients and 704 lesions. The most common malignancies were non-small cell lung carcinoma (44.5 % n = 41), breast adenocarcinoma (23.9 %, n = 22) and melanoma (16.3 %,n = 15). 27.6 % (n = 26) of patients underwent adjuvant WBRT. At last follow up, local tumor control was achieved in 76.3 % (n = 61) of patients and 71.8 % (n = 461) of lesions. Overall prevalence of leukoencephalopathy was 42, 60, 73 and 84 % at 1, 2, 3, and 4 years after SRS. Moderate-severe leukoencephalopathy development was related to an integral dose to skull >3 Joules (p = 0.012) at any radiosurgical treatment and prior WBRT (p<0.042). Leukoencephalopathy incidence was consistently higher in the WBRT + SRS group at each following year of survival from initial SRS. Long-term BM survivors treated with SRS are at progressive risk for developing leukoencephalopathy.Those with a higher BM burden, higher integral SRS dose to the skull, and treatment with WBRT are at increased risk of leukoencephalopathy.
authors.forename: Or
authors.initials: O
authors.lastname: Cohen-Inbar
authors.forename: Patrick
authors.initials: P
authors.lastname: Melmer
authors.forename: Cheng-chia
authors.initials: CC
authors.lastname: Lee
authors.forename: Zhiyuan
authors.initials: Z
authors.lastname: Xu
authors.forename: David
authors.initials: D
authors.lastname: Schlesinger
authors.forename: Jason P
authors.initials: JP
authors.lastname: Sheehan
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001932:Brain Neoplasms / Q000150:complications / Q000401:mortality / Q000556:secondary* / Q000601:surgery*; D005260:Female; D006801:Humans; D056784:Leukoencephalopathies / Q000209:etiology* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D016634:Radiosurgery / Q000009:adverse effects*; D012189:Retrospective Studies; D012720:Severity of Illness Index; D016019:Survival Analysis; D016896:Treatment Outcome