Significant Hemorrhage Rate Reduction after Gamma Knife Radiosurgery in Symptomatic Cavernous Malformations: Long-Term Outcome in 95 Case Series and Literature Review

Abstract

Background: The natural history of cavernous malformations (CMs) has remained unclear. This lack of knowledge has made treatment decisions difficult. Indeed, the use of stereotactic radiosurgery is nowadays controversial. The purpose of this paper is to throw light on the effectiveness of Gamma Knife radiosurgery (GKRS) therapy. Methods: The authors reviewed data collected from a prospectively maintained database. A total of 95 patients (57 female and 38 male) underwent GKRS for high-surgical-risk CMs. A total of 76 cavernomas were deeply located (64 lesions in the brainstem and 12 lesions in the thalamus). All of them were located in eloquent regions. The median malformation volume was 1,570 mm³. The median tumor margin dose was 11.87 Gy, and the mean tumor maximum dose was 19.56 Gy. Results: Ninety-five cavernous CMs were managed from 1994 to 2014. All patients had experienced at least 1 symptomatic bleeding incident before treatment (only 1 hemorrhage event in 81%). The median length of follow-up review was 78 months. The pretreatment annual hemorrhage rate was 3.06% compared with 1.4% during the first 3-year latency interval, and 0.16% thereafter (p = 0.004). Four patients developed new location-dependent neurological deficits, and 3 patients had edema-related headache after radiosurgery. All of them presented full recovery. Conclusions: The best dosage range for preventing bleeding was identified as between 11 and 12 Gy in our series. Although the efficacy of radiosurgery in CMs remains impossible to quantify, a very significant reduction in the bleeding rate occurs after a 3-year latency interval. No permanent neurological morbidity is reported in our series. These results defend the safety of GKRS in surgical high-risk CM from the first bleeding event.

Target Volume Definition for Stereotactic Radiosurgery (SRS) Of Cerebral Cavernous Malformations (CCMS)

“…Alternative therapeutic strategies are considered when there is excessive risk of surgical complications. In this context, SRS has emerged as a viable treatment alternative for selected patients with CCMs [17,[31][32][33][34]. Given the hazards of rebleeding from a CCM with previous hemorrhage history, a more active approach with radiosurgical management of surgically inaccessible deep-seated CCMs has been suggested in the literature [35][36][37].…”

Radiosurgery for cerebral cavernous malformations

“…Pollock et al [40] 18 Gy, Kondziolka et al [65], and Liscak et al [66] applied a marginal dose of 16 Gy and tried to reduce ARE. Azimi et al [67], and Park and Hwang [68] prescribed a low marginal dose of 13 Gy on average (Table 2) [19,22,29,40,[66][67][68][69][70][71][72]. In 2019, Lunsford et al [32] wrote that the median radiation dose to the CM margin was 13 Gy to reduce hemorrhagic risk and radiation-induced complications.…”

Presentation and management of nervous system cavernous malformations in children: A systematic review and case report

“…[ 41 ] A recent meta-analysis on gamma knife radiosurgery for CMs demonstrated effectiveness at preventing hemorrhage in the first 2 years following radiosurgery as well as afterward. [ 42 ] Although multiple recent studies have shown promising radiosurgery outcomes for CM,[ 43 44 ] limited data exist on the use of radiosurgery in pediatric patients as well as long-term outcomes. Given that transient postradiation associated changes such as perilesional edema are present in 25% of patients, and up to 10% of patients have permanent complications, radiation is not a widely recommended treatment for CMs.…”

“…[ 1 ] Indeed, in patients treated with stereotactic radiosurgery, hemorrhage-free survival is markedly better in children compared to adults. [ 44 ] In patients treated with surgery, earlier age at presentation was highly associated with favorable 1-year outcome. [ 18 ] Our pooled analysis revealed that 85.2% of patients who had epilepsy were Engel Class 1 after surgery.…”