BACKGROUND: A higher risk of secondary brain tumor, carotid stenosis, and stroke has been reported after conventional sella irradiation for pituitary neuroendocrine tumors (PitNET). Stereotactic radiosurgery (SRS), which is a more focused approach, is now increasingly used instead. The aim was to assess the risk of secondary brain tumor, carotid stenosis/occlusion, and stroke after SRS. METHODS: In this multicentric retrospective study, 2254 patients with PitNET were studied, 1377 in the exposed group, and 877 in the control group. RESULTS: There were 9840.1 patient-years at risk for the SRS and 5266.5 for the control group. The 15-year cumulative probability of secondary intracranial tumor was 2.3% (95% CI: 0.5%, 4.1%) for SRS and 3.7% (95% CI: 0%, 8.7%) for the control group (P = .6), with an incidence rate of 1.32 per 1000 and 0.95 per 1000, respectively. SRS was not associated with an increased risk of tumorigenesis when stratified by age (HR: 1.59 [95% CI: 0.57, 4.47], Pp = .38). The 15-year probability of new carotid stenosis/occlusion was 0.9% (95% CI: 0.2, 1.6) in the SRS and 2% (95% CI: 0, 4.4) in the control group (P = .8). The 15-year probability of stroke was 2.6% (95% CI: 0.6%, 4.6%) in the SRS and 11.1% (95% CI: 6%, 15.9%) in the control group (P < .001). In Cox multivariate analysis stratified by age, SRS (HR 1.85 [95% CI:0.64, 5.35], P = .26) was not associated with risk of new stroke. CONCLUSIONS: No increased risk of long-term secondary brain tumor, new stenosis or occlusion, and stroke was demonstrated in the SRS group compared to the control in this study with imaging surveillance.

Department of Medicine University of Virginia Charlottesville Virginia USA

Department of Neurological Surgery Hospices Civils de Lyon Lyon France

Department of Neurological Surgery University of Virginia Charlottesville Virginia USA

Department of Neurosurgery Carilion Clinic Virginia Tech Carilion School of Medicine Roanoke Virginia USA

Department of Neurosurgery IRCCS Humanitas Research Hospital Milan Italy

Department of Neurosurgery KOC University Hospital School of Medicine Istanbul Turkey

Department of Neurosurgery Neurological Institute Taipei Veteran General Hospital Taipei Taiwan

Department of Neurosurgery NYU Langone New York City New York USA

Department of Neurosurgery Postgraduate Institute of Medical Education and Research Chandigarh India

Department of Neurosurgery University of Alberta Edmonton Canada

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

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

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

Gamma Knife Center Jewish Hospital Mayfield Clinic Cincinnati Ohio USA

Radiation Oncology NYU Langone New York City New York USA

Radiosurgery Unit Hospital Ruber International Madrid Spain

School of Medicine National Yang Ming Chiao Tung University Taipei Taiwan

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Ostrom QT, Price M, Neff C, et al.CBTRUS statistical report: primary brain and other central nervous system tumors diagnosed in the United States in 2016—2020. Neuro-Oncology. 2023;25(12 Suppl 2):iv1–iv99. PubMed PMC

Tritos NA, Miller KK.. Diagnosis and management of pituitary adenomas: a review. JAMA. 2023;329(16):1386–1398. PubMed

Hamblin R, Vardon A, Akpalu J, et al.Risk of second brain tumour after radiotherapy for pituitary adenoma or craniopharyngioma: a retrospective, multicentre, cohort study of 3679 patients with long-term imaging surveillance. Lancet Diabetes Endocrinol. 2022;10(8):581–588. PubMed

van Westrhenen A, Muskens IS, Verhoeff JJC, Smith TRS, Broekman MLD.. Ischemic stroke after radiation therapy for pituitary adenomas: a systematic review. J Neurooncol. 2017;135(1):1–11. PubMed PMC

Wolf A, Naylor K, Tam M, et al.Risk of radiation-associated intracranial malignancy after stereotactic radiosurgery: a retrospective, multicentre, cohort study. Lancet Oncol. 2019;20(1):159–164. PubMed

Rowe J, Grainger A, Walton L, et al.Risk of malignancy after gamma knife stereotactic radiosurgery. Neurosurgery. 2007;60(1):60–5; discussion 65–66. PubMed

Sheehan JP, Starke RM, Mathieu D, et al.Gamma Knife radiosurgery for the management of nonfunctioning pituitary adenomas: a multicenter study. J Neurosurg. 2013;119(2):446–456. PubMed

Snell JW, Sheehan J, Stroila M, Steiner L.. Assessment of imaging studies used with radiosurgery: a volumetric algorithm and an estimation of its error. Technical note. J Neurosurg. 2006;104(1):157–162. PubMed

Barnett HJM, Taylor DW, Haynes RB, et al.; North American Symptomatic Carotid Endarterectomy Trial Collaborators. Beneficial effect of carotid endarterectomy in symptomatic patients with high-grade carotid stenosis. N Engl J Med. 1991;325(7):445–453. PubMed

Sacco RL, Kasner SE, Broderick JP, et al.; American Heart Association Stroke Council, Council on Cardiovascular Surgery and Anesthesia. An updated definition of stroke for the 21st century: a statement for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2013;44(7):2064–2089. PubMed PMC

R Core Team. R: A Language and Environment for Statistical Computing. webbased: R Foundation for Statistical Computing. https://www.R-project.org/

RStudio Team. RStudio: Integrated Development Environment for R. Boston, MA: RStudio, PBC; 2020. http://www.rstudio.com/

Minniti G, Traish D, Ashley S, Gonsalves A, Brada M.. Risk of second brain tumor after conservative surgery and radiotherapy for pituitary adenoma: update after an additional 10 years. J Clin Endocrinol Metab. 2005;90(2):800–804. PubMed

Tsang RW, Laperriere NJ, Simpson WJ, et al.Glioma arising after radiation therapy for pituitary adenoma. A report of four patients and estimation of risk. Cancer. 1993;72(7):2227–2233. PubMed

Erridge SC, Conkey DS, Stockton D, et al.Radiotherapy for pituitary adenomas: long-term efficacy and toxicity. Radiother Oncol. 2009;93(3):597–601. PubMed

Elsamadicy AA, Babu R, Kirkpatrick JP, Adamson DC.. Radiation-induced malignant gliomas: a current review. World Neurosurg. 2015;83(4):530–542. PubMed

Yamanaka R, Hayano A, Kanayama T.. Radiation-induced meningiomas: an exhaustive review of the literature. World Neurosurg. 2017;97(97):635–644.e8. PubMed

Heymer EJ, Hawkins MM, Winter DL, et al.Risk of subsequent gliomas and meningiomas among 69,460 5-year survivors of childhood and adolescent cancer in Europe: the PanCareSurFup study. Br J Cancer. 2024;130(6):976–986. PubMed PMC

Lim YJ, Leem W, Park JT, et al.Cerebral infarction with ICA occlusion after gamma knife radiosurgery for pituitary adenoma: a case report. Stereotact Funct Neurosurg. 1999;72(Suppl 1):132–139. PubMed

Ito H, Onodera H, Sase T, et al.Percutaneous transluminal angioplasty in a patient with internal carotid artery stenosis following gamma knife radiosurgery for recurrent pituitary adenoma. Surg Neurol Int. 2015;6(Suppl 7):S279–S283. PubMed PMC

Spatola G, Frosio L, Losa M, et al.Asymptomatic internal carotid artery occlusion after gamma knife radiosurgery for pituitary adenoma: report of two cases and review of the literature. Rep Pract Oncol Radiother. 2016;21(6):555–559. PubMed PMC

Patibandla MR, Xu Z, Schlesinger D, Sheehan JP.. Cavernous carotid stenosis following stereotactic radiosurgery for Cushing’s disease: a rare complication and review of the literature. J Clin Neurosci. 2018;47(1):151–154. PubMed

Graffeo CS, Link MJ, Stafford SL, et al.Risk of internal carotid artery stenosis or occlusion after single-fraction radiosurgery for benign parasellar tumors. J Neurosurg. 2019;133(5):1388–1395. PubMed

Pikis S, Bunevicius A, Sheehan J.. Internal carotid artery stenosis and risk of cerebrovascular ischemia following stereotactic radiosurgery for recurrent or residual pituitary adenomas. Pituitary. 2021;24(4):574–581. PubMed

Pollock BE, Nippoldt TB, Stafford SL, Foote RL, Abboud CF.. Results of stereotactic radiosurgery in patients with hormone-producing pituitary adenomas: factors associated with endocrine normalization. J Neurosurg. 2002;97(3):525–530. PubMed

Faggiano A, Pivonello R, Spiezia S, et al.Cardiovascular risk factors and common carotid artery caliber and stiffness in patients with Cushing’s disease during active disease and 1 year after disease remission. J Clin Endocrinol Metab. 2003;88(6):2527–2533. PubMed

Colao A, Spiezia S, Cerbone G, et al.Increased arterial intima-media thickness by B-M mode echodoppler ultrasonography in acromegaly. Clin Endocrinol (Oxf). 2001;54(4):515–524. PubMed

Osorio RC, Oh JY, Choudhary N, et al.Pituitary adenomas and cerebrovascular disease: A review on pathophysiology, prevalence, and treatment. Front Endocrinol. 2022;13(1):1064216. PubMed PMC

van Varsseveld NC, van Bunderen CC, Ubachs DHH, et al.Cerebrovascular events, secondary intracranial tumors, and mortality after radiotherapy for nonfunctioning pituitary adenomas: a subanalysis from the Dutch National Registry of Growth Hormone Treatment in Adults. J Clin Endocrinol Metab. 2015;100(3):1104–1112. PubMed

Brada M, Burchell L, Ashley S, Traish D.. The incidence of cerebrovascular accidents in patients with pituitary adenoma. Int J Radiat Oncol Biol Phys. 1999;45(3):693–698. PubMed

Flickinger JC, Nelson PB, Taylor FH, Robinson A.. Incidence of cerebral infarction after radiotherapy for pituitary adenoma. Cancer. 1989;63(12):2404–2408. PubMed

Sattler MGA, Vroomen PC, Sluiter WJ, et al.Incidence, causative mechanisms, and anatomic localization of stroke in pituitary adenoma patients treated with postoperative radiation therapy versus surgery alone. Int J Radiat Oncol Biol Phys. 2013;87(1):53–59. PubMed

Sheehan J, Lee CC, Bodach ME, et al.Congress of neurological surgeons systematic review and evidence-based guideline for the management of patients with residual or recurrent nonfunctioning pituitary adenomas. Neurosurgery. 2016;79(4):E539–E540. PubMed

Kotecha R, Sahgal A, Rubens M, et al.Stereotactic radiosurgery for non-functioning pituitary adenomas: meta-analysis and International Stereotactic Radiosurgery Society practice opinion. Neuro-Oncology. 2020;22(3):318–332. PubMed PMC