Radiosurgery for symptomatic cavernous malformations: A multi-institutional retrospective study in Japan

Abstract

Background: A group study for symptomatic cavernous malformation (CM) treated with gamma knife (GK) surgery was performed.

Methods: A total of 298 cases collected from 23 GK centers across Japan were included. Hemorrhage was the most common manifestation, followed by seizures and neurological deficits. Most of the lesions were located in the brainstem and basal ganglia, followed by the cerebral or cerebellar hemispheres. The CMs, which had a mean diameter of 14.8 mm, were treated using GK surgery with a mean marginal dose of 14.6 Gy.

Results: In terms of hemorrhage-free survival (HFS), a marked dissociation was confirmed between the hemorrhage and seizure groups, while no obvious difference was noted between sexes. Superficial CMs located in cerebellum or lobar regions responded to the treatment better than deeply located CMs in the basal ganglia or brainstem. No significant difference of dose-dependent response was seen for three different ranges of marginal dose: Less than 15 Gy, between 15 and 20 Gy, and more than 20 Gy. Complications were more frequent after a marginal dose of over 15 Gy and in patients with lesions more than 15 mm in diameter. The rates of annual hemorrhage were estimated to be 7.4% during the first 2 years after radiosurgery and 2.8% thereafter. The overall hemorrhage rate after radiosurgery was 4.4%/year/patient.

Conclusion: The risk of hemorrhage is considerably reduced after GK treatment. The HFS as well as annual hemorrhage rate after GK treatment was apparently superior to that after conservative treatment for symptomatic CMs. To optimize the success of GK treatment, it is important to reduce the incidence of complications.

Keywords: Cavernous malformation; gamma knife; radiosurgery; symptomatic lesion; vascular anomaly.

Figure 1

Location of the lesions treated with radiosurgery. Almost a half of lesions are located in brainstem

Figure 2

Radiological responses of CMs to radiosurgery. Approximately a half of them showed a shrinkage, and the others were unchanged

Figure 3

Hemorrhage-free survival (HFS) following radiosurgery according to various factors. (a) Onset, a: Single hemorrhage b: Two or more hemorrhages c: No hemorrhage (a vs b: Not significant, a vs c: Significant, b vs c: Significant) (b)Location the HFS was reasonably long in cases with superficial locations of the lesions, such as lobar and cerebellar lesions. In contrast, it was apparently worse in cases with deep locations of the lesions, such as the basal ganglia, thalamus, and brainstem. Superficial: Lobar, Cerebellar Deep: Brainstem, Basal ganglia, Thalamus (P =0.0077) (d) Marginal dose (a) <15 Gy 15 Gy< (b)<20 (c)<20 Gy (P =0.2309) (d) Sex: Male and female (P =0.2704)

Figure 4

(a)Undesirable events and rebleeding occurring after gamma knife treatment and relation to the marginal dose variations during radiosurgery. (b) Complications occurred more frequently among cases more than 15 mm in diameter and cases treated with more than 15 Gy. (c) Changes of annual hemorrhage rate (AHR). Although AHR since birth to first episode was low, it jumped up to 28.7% during first episode and radiosurgery. The rate gradually dropped down to 8.4% in the first 2 years after radiosurgery and 3.0% thereafter. Overall AHR after radiosurgery was 4.8%/year/case

Figure 5

Hemorrhage-free survival after surgery (S) (29 cases), radiosurgery with gamma knife (R) (298 cases) and conservative treatment^© (49 cases). The difference of HFS is statistically significant between S and C groups (P=0.0176), as well as R and C groups (P=0.0026), however, not significant between S and R groups (P=0.2489)

Figure 6

Comparison of annual hemorrhage rate between radiosurgery and conservative groups. Since the mean interval between the onset and radiosurgery was 33 months (mean: 7 months), this time differences were carefully adjusted to zero. The annual hemorrhage rate apparently decreased after radiosurgery when compared with that of conservative treatment for symptomatic cavernous malformations. In the latter (conservative group: 49 cases), hemorrhagic episodes were frequent especially within 5 years after the onset, forming peaks of high hemorrhage rate