Radiation-Induced Malignancy following Stereotactic Radiosurgery for Benign Intracranial Pathology

Abstract

Radiation-induced malignant transformation is a risk associated with stereotactic radiosurgery (SRS); however, prevalence is uncertain. We sought to characterize the cumulative incidence of radiation-induced malignancy at our institution. Based on other retrospective studies, we hypothesized that the five-year incidence of malignant transformation and radiation-associated secondary central nervous system (CNS) cancer after SRS is less than 1%. After IRB approval, we undertook a retrospective consecutive case series evaluating patients with at least 5 years of event-free clinical follow-up treated with non-invasive SRS or Linac-based SRS between 1990 and 2014 for benign CNS pathology including: arteriovenous malformation (AVM), pituitary adenoma, WHO grade I-II meningiomas, vestibular schwannoma, paraganglioma, angiofibroma, chordoma, craniopharyngioma, epilepsy, ganglioglioma, hemangioblastoma, hemangiopericytoma, oligodendroglioma, papilloma, parotid adenoma, tremor, and trigeminal neuralgia. Radiation-associated secondary intracranial cancer was defined as a new primary CNS malignancy within the plan’s 2 Gy isodose line. Biologically effective dose (BED) was calculated using an alpha/beta ratio of 2. Baseline characteristics and treatment details were recorded and summarized with descriptive statistics. After exclusion of 362 patients lacking follow-up, a total of 273 patients were enrolled. Median age at treatment was 44 years (range 2-82) including pediatric (n=33) and adult (n=240) patients. SRS indications included AVM (n=100, 37%), pituitary adenoma (n=67, 25%), WHO grade I-II meningioma (n=39, 14%), vestibular schwannoma (n=32, 12%), paraganglioma (n=13, 4.8%), and other (n=22, 8%). Median prescription dose was 18 Gy (range 6-140 Gy), median number of fractions was 1 (range 1-5), and median BED was 131 Gy2(range 24-9940 Gy2). Median follow-up after SRS was 10.5 years (range 4.7-27). Over 3,216 patient-years following SRS, two cases of radiation-induced malignant transformation occurred for a per-patient rate of 0.73% or case rate of 0.62 per 1,000 patient-years. The first patient was treated with Linac SRS for vestibular schwannoma with 21 Gy in 3 fractions, and 16 years later developed an ipsilateral malignant peripheral nerve sheath tumor in the cerebellopontine angle. The second patient was treated with non-invasive stereotactic radiosurgery for vestibular schwannoma and 3 years later developed a malignant peripheral nerve sheath tumor. The five-year incidence of radiation-associated malignant transformation and radiation-induced secondary malignancy following SRS for benign CNS pathology at our institution is reassuringly low at 0.62 cases per 1,000 patient-years. These data support the safety of SRS for benign intracranial pathology.