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

Sam Dayawansa¹, Chloe Dumot^{2

3}, Georgios Mantziaris², Zhiyuan Xu², Stylianos Pikis², Selcuk Peker⁴, Yavuz Samanci⁴, Gokce D Ardor⁴, Ahmed M Nabeel^{5

6}, Wael A Reda^{5

7}, Sameh R Tawadros^{5

7}, Khaled Abdelkarim^{5

8}, Amr M N El-Shehaby^{5

7}, Reem M Emad Eldin^{5

9}, Ahmed H Elazzazi¹⁰, Nuria Martínez Moreno¹¹, Roberto Martínez Álvarez¹¹, Roman Liscak¹², Jaromir May¹², David Mathieu¹³, Jean-Nicolas Tourigny¹³, Manjul Tripathi¹⁴, Akshay Rajput¹⁴, Narendra Kumar¹⁵, Rupinder Kaur¹⁴, Piero Picozzi¹⁶, Andrea Franzini¹⁶, Herwin Speckter¹⁷, Wenceslao Hernandez¹⁷, Anderson Brito¹⁷, Ronald E Warnick¹⁸, Juan Alzate¹⁹, Douglas Kondziolka¹⁹, Greg N Bowden²⁰, Samir Patel²¹, Jason P Sheehan²

Affiliations

¹ Department of Neurological Surgery, University of Virginia, Box 800212, Charlottesville, VA, 22908, USA. samwansa20@gmail.com.
² Department of Neurological Surgery, University of Virginia, Box 800212, Charlottesville, VA, 22908, USA.
³ Department of Neurological Surgery, Hospices Civils de Lyon, Lyon, France.
⁴ Department of Neurosurgery, Koc University School of Medicine, Istanbul, Turkey.
⁵ Gamma Knife Center Cairo, Nasser Institute Hospital, Cairo, Egypt.
⁶ Neurosurgery Department, Faculty of Medicine, Benha University, Qalubya, Egypt.
⁷ Department of Neurosurgery, Ain Shams University, Cairo, Egypt.
⁸ Department of Clinical Oncology, Ain Shams University, Cairo, Egypt.
⁹ Department of Radiation Oncology, National Cancer Institute, Cairo University, Cairo, Egypt.
¹⁰ Extended Modular Program- Faculty of Medicine, Ain Shams University, Cairo, Egypt.
¹¹ Department of Radiosurgery, Rúber Internacional Hospital, Madrid, Spain.
¹² Department of Stereotactic and Radiation Neurosurgery, Na Homolce Hospital, Prague, Czech Republic.
¹³ Division of Neurosurgery, Université de Sherbrooke, Centre de Recherche du CHUS, Sherbrooke, QC, Canada.
¹⁴ Department of Neurosurgery, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
¹⁵ Department of Radiation Therapy, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
¹⁶ Department of Neurosurgery, Scientific Institute for Research, Hospitalization and Healthcare - IRCCS Humanitas Research Hospital, Milan, Italy.
¹⁷ Dominican Gamma Knife Center and Radiology Department, CEDIMAT, Santo Domingo, Dominican Republic.
¹⁸ Gamma Knife Center, Jewish Hospital, Mayfield Clinic, Cincinnati, OH, USA.
¹⁹ Department of Neurosurgery, NYU Langone, New York City, NY, USA.
²⁰ Department of Neurosurgery and Department of Oncology, University of Alberta, Edmonton, AB, Canada.
²¹ Division of Radiation Oncology, Department of Oncology, University of Alberta, Edmonton, AB, Canada.

PMID: 39472707
PMCID: PMC11522693
DOI: 10.1038/s41598-024-77140-z

Multicenter Study

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

Sam Dayawansa et al. Sci Rep. 2024.

. 2024 Oct 29;14(1):25933.

doi: 10.1038/s41598-024-77140-z.

Authors

Affiliations

¹ Department of Neurological Surgery, University of Virginia, Box 800212, Charlottesville, VA, 22908, USA. samwansa20@gmail.com.
² Department of Neurological Surgery, University of Virginia, Box 800212, Charlottesville, VA, 22908, USA.
³ Department of Neurological Surgery, Hospices Civils de Lyon, Lyon, France.
⁴ Department of Neurosurgery, Koc University School of Medicine, Istanbul, Turkey.
⁵ Gamma Knife Center Cairo, Nasser Institute Hospital, Cairo, Egypt.
⁶ Neurosurgery Department, Faculty of Medicine, Benha University, Qalubya, Egypt.
⁷ Department of Neurosurgery, Ain Shams University, Cairo, Egypt.
⁸ Department of Clinical Oncology, Ain Shams University, Cairo, Egypt.
⁹ Department of Radiation Oncology, National Cancer Institute, Cairo University, Cairo, Egypt.
¹⁰ Extended Modular Program- Faculty of Medicine, Ain Shams University, Cairo, Egypt.
¹¹ Department of Radiosurgery, Rúber Internacional Hospital, Madrid, Spain.
¹² Department of Stereotactic and Radiation Neurosurgery, Na Homolce Hospital, Prague, Czech Republic.
¹³ Division of Neurosurgery, Université de Sherbrooke, Centre de Recherche du CHUS, Sherbrooke, QC, Canada.
¹⁴ Department of Neurosurgery, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
¹⁵ Department of Radiation Therapy, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
¹⁶ Department of Neurosurgery, Scientific Institute for Research, Hospitalization and Healthcare - IRCCS Humanitas Research Hospital, Milan, Italy.
¹⁷ Dominican Gamma Knife Center and Radiology Department, CEDIMAT, Santo Domingo, Dominican Republic.
¹⁸ Gamma Knife Center, Jewish Hospital, Mayfield Clinic, Cincinnati, OH, USA.
¹⁹ Department of Neurosurgery, NYU Langone, New York City, NY, USA.
²⁰ Department of Neurosurgery and Department of Oncology, University of Alberta, Edmonton, AB, Canada.
²¹ Division of Radiation Oncology, Department of Oncology, University of Alberta, Edmonton, AB, Canada.

PMID: 39472707
PMCID: PMC11522693
DOI: 10.1038/s41598-024-77140-z

Abstract

Brainstem cerebral cavernous malformations (CCM) are clinically more aggressive compared to superficial CCMs. Due to their location, resection can be challenging, making stereotactic radiosurgery (SRS) an attractive alternative for symptomatic patient. Brainstem CCM patients (n = 170) were treated with Gamma Knife SRS at 11 radiosurgical centers. Hemorrhagic risk reduction, risk factors of post-SRS hemorrhage, and clinical outcomes were retrospectively analyzed. Most patients had a single (165/170 patients) brainstem CCMs treated; the majority of CCMs (165/181) presented with bleeding. Single-session SRS decreased the risk of repeat hemorrhage in patients with hemorrhagic brainstem CCM (HR: 0.17, p < 0.001) using recurrent multivariate analysis. The annual hemorrhage rate decreased from 14.8 per 100 CCM-years before SRS to 2.3 after treatment. Using univariate Cox-analysis, the probability of a new hemorrhages after SRS was reduced for patient older than 35 years (HR = 0.21, p = 0.002) and increased with a margin dose > 13 Gy (HR = 2.57, p = 0.044). Adverse radiation effect (ARE) occurred in 9 patients (5.3%) and was symptomatic in four (2.4%). At a median follow-up of 3.4 years (Inter-quartile range: 5.4), 13 patients (8.0%) had a worsened clinical status, with the treated CCM being the cause in 5.6% (10) of the patients. Single-session SRS decreased the risk of repeat hemorrhage in patients with hemorrhagic brainstem CCM and conveyed this benefit with a low risk of advrse radiation effects (ARE) and worsening clinical status.

Keywords: Cerebral cavernous malformation; Hemorrhagic; Stereotactic radiosurgery; brainstem.

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Conflict of interest statement

The authors declare no competing interests.

Figures

**Fig. 1**
Probability of new hemorrhage after SRS.

See this image and copyright information in PMC

References

1. Gross, B. A., Batjer, H. H., Awad, I. A., Bendok, B. R. & Du, R. Brainstem cavernous malformations: 1390 surgical cases from the literature. World Neurosurg.80(1–2), 89–93. 10.1016/j.wneu.2012.04.002 (2013). - PubMed
1. Porter, R. W. et al. Cavernous malformations of the brainstem: Experience with 100 patients. J. Neurosurg.90(1), 50–58. 10.3171/jns.1999.90.1.0050 (1999). - PubMed
1. Horne, M. A. et al. Clinical course of untreated cerebral cavernous malformations: A meta-analysis of individual patient data. Lancet Neurol.Bold">15(2), 166–173. 10.1016/S1474-4422(15)00303-8 (2016). - PMC - PubMed
1. Garcia R.M., Ivan M.E., & Lawton, M.T. Brainstem cavernous malformations: Surgical results in 104 patients and a proposed grading system to predict neurological outcomes. Neurosurgery. 76(3), 265–277. 10.1227/NEU.0000000000000602 (2015). discussion 277–278. - PubMed
1. Fritschi, J. A., Reulen, H. J., Spetzler, R. F. & Zabramski, J. M. Cavernous malformations of the brain stem. A review of 139 cases. Acta Neurochir. (Wien). 130(1–4), 35–46. 10.1007/BF01405501 (1994). - PubMed

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

Affiliations

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

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

References

Publication types

MeSH terms

LinkOut - more resources

Full Text Sources