Stereotactic radiosurgery for haemorrhagic cerebral cavernous malformation: a multi-institutional, retrospective study

Abstract

BackgroundCerebral cavernous malformations (CCMs) frequently manifest with haemorrhages. Stereotactic radiosurgery (SRS) has been employed for CCM not suitable for resection. Its effect on reducing haemorrhage risk is still controversial. The aim of this study was to expand on the safety and efficacy of SRS for haemorrhagic CCM.MethodsThis retrospective multicentric study included CCM with at least one haemorrhage treated with single-session SRS. The annual haemorrhagic rate (AHR) was calculated before and after SRS. Recurrent event analysis and Cox regression were used to evaluate factors associated with haemorrhage. Adverse radiation effects (AREs) and occurrence of new neurological deficits were recorded.ResultsThe study included 381 patients (median age: 37.5 years (Q1–Q3: 25.8–51.9) with 414 CCMs. The AHR from diagnosis to SRS excluding the first haemorrhage was 11.08 per 100 CCM-years and was reduced to 2.7 per 100 CCM-years after treatment. In recurrent event analysis, SRS, HR 0.27 (95% CI 0.17 to 0.44), p<0.0001 was associated with a decreased risk of haemorrhage, and the presence of developmental venous anomaly (DVA) with an increased risk, HR 1.60 (95% CI 1.07 to 2.40), p=0.022. The cumulative risk of first haemorrhage after SRS was 9.4% (95% CI 6% to 12.6%) at 5 years and 15.6% (95% CI% 9 to 21.8%) at 10 years. Margin doses> 13 Gy, HR 2.27 (95% CI 1.20 to 4.32), p=0.012 and the presence of DVA, HR 2.08 (95% CI 1.00 to 4.31), p=0.049 were factors associated with higher probability of post-SRS haemorrhage. Post-SRS haemorrhage was symptomatic in 22 out of 381 (5.8%) patients, presenting with transient (15/381) or permanent (7/381) neurological deficit. ARE occurred in 11.1% (46/414) CCM and was responsible for transient neurological deficit in 3.9% (15/381) of the patients and permanent deficit in 1.1% (4/381) of the patients. Margin doses >13 Gy and CCM volume >0.7 cc were associated with increased risk of ARE.ConclusionSingle-session SRS for haemorrhagic CCM is associated with a decrease in haemorrhage rate. Margin doses ≤13 Gy seem advisable.

Stereotactic radiosurgery (SRS) for patients with brainstem cerebral cavernous malformations (CCMs): An International, Multicentric Study

“…In univariate Cox analysis, patients treated with a margin dose >13Gy were more likely to bleed after SRS (HR: 2.57 (95% CI= (1.03-6.45), p=0.044), a recent observation. This result replicated one previous study which included part of this population with hemorrhagic CCMs irrespective of their location 12 . One potential explanation is that high radiation doses induce overexpression of VEGF, leading to neovascularization and subsequent bleeding.…”

“…Volumetric changes were categorized based on pre-speci ed cutoff points: increase with enlargement by more than 20%, decrease with volumetric reduction exceeding 20% of baseline volume, and stable otherwise. 12…”

Hemorrhagic Outcome of Brainstem Cavernous Malformations following Radiosurgery: Dose-Response Relationship

“…Post-radiosurgery AHR tends to decrease in most radiosurgery reports, especially after the initial 2 years [15,[18][19][20][21][22][23]. Factors associated with a higher risk of postradiosurgery hemorrhage include deep CCMs [24,25], pre-treatment hemorrhage [22,24,25], female gender [25], DVA presence [26], younger age [24], larger volume [18,22], and margin doses below 20 Gy [13] or 13 Gy [27]. However, conflicting findings have been reported.…”

“…However, conflicting findings have been reported. For instance, Liscák et al [27] highlighted the relationship between maximum dose and rebleeding [28,29], while Dumot et al [26] suggested that margin doses exceeding 13 Gy could elevate the risk of post-radiosurgery hemorrhage. Dose variations have been observed across different lesions and studies.…”

“…In a recent systematic review, symptomatic AREs were observed in 7.3% (42/576) of patients, with permanent AREs developing in 2.2% (11/576) [8]. Marginal doses exceeding 13 Gy were significantly associated with symptomatic AREs [8,26], and edema was more likely to develop when doses exceeded 15 Gy [30]. Various studies have proposed safe marginal doses, such as 11 Gy [32], 11.9 Gy [21], or ≤13 Gy [8].…”