BACKGROUND: Cerebral 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. METHODS: This 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. RESULTS: The 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. CONCLUSION: Single-session SRS for haemorrhagic CCM is associated with a decrease in haemorrhage rate. Margin doses ≤13 Gy seem advisable.

Department of Clinical Oncology Ain Shams University Cairo Egypt

Department of Neurological Surgery Hospices Civils de Lyon Lyon France

Department of Neurological Surgery University of Virginia Charlottesville Virginia USA

Department of Neurosurgery Koc University School of Medicine Istanbul Turkey

Department of Radiation Oncology National Cancer Institute Cairo University Giza Egypt

Department of Radiosurgery Rúber Internacional Hospital Madrid Spain

Department of Stereotactic and Radiation Neurosurgery Na Homolce Hospital Prague Czech Republic

Departments of Neurosurgery Ain Shams University Cairo Egypt

Division of Radiation Oncology Department of Oncology University of Alberta Edmonton Alberta Canada

Dominican Gamma Knife Center and Radiology Department CEDIMAT Santo Domingo Dominican Republic

Faculty of Medicine Extended Modular Program Ain Shams University Cairo Egypt

Gamma Knife Center Mayfield Clinic The Jewish Hospital Mercy Health Cincinnati Ohio USA

Gamma knife Center Nasser institute Hospital Cairo Egypt

Neurosurgery Centre de recherche du CHUS Université de Sherbrooke Sherbrooke Quebec Canada

Neurosurgery Department Benha University Benha Egypt

Neurosurgery IRCCS Istituto Clinico Humanitas Rozzano Milan Italy

Neurosurgery NYU Langone Health New York New York USA

Neurosurgery PGIMER Chandigarh Chandigarh India

Neurosurgery University of Alberta Edmonton Alberta Canada

Radiation Therapy PGIMER Chandigarh Chandigarh India

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Stereotactic radiosurgery (SRS) for patients with brainstem cerebral cavernous malformations (CCMs): an international, multicentric study