Risk of Intracranial Malignancy After Stereotactic Radiosurgery for Nonmalignant Conditions


Key Points

  • The overall incidence of radiosurgery-associated malignancy was 6.80 per 100,000 patient-years.
  • Risk was similar to risk of a primary CNS tumor in the general population.

In a retrospective cohort study reported in The Lancet Oncology, Wolf et al found that patients undergoing Gamma Knife stereotactic radiosurgery for nonmalignant neurosurgical conditions did not appear to be at long-term increased risk of radiation-associated secondary intracranial malignancy or malignant transformation.

Study Details

The study involved data from 4,905 eligible patients who had Gamma Knife stereotactic radiosurgery between August 1987 and December 2011 at five radiosurgery centers (one in Czech Republic, one in Spain, there in the United States). Patients had to have received no prior radiotherapy and had to have minimum follow-up time of 5 years. Gamma Knife radiosurgery was performed for arteriovenous malformation; trigeminal neuralgia; or benign intracranial tumors, which included including vestibular or other benign schwannomas, WHO grade 1 meningiomas, pituitary adenomas, and hemangioblastoma. Stereotactic radiosurgery-associated intracranial malignancy, including malignant transformation of a benign lesion or development of radiation-associated secondary intracranial cancer, was defined as occurring within the 2 Gy isodose line.

Risk of Malignancy

Median follow-up was 8.1 years. A total of 2 (0.0006%) of 3,251 patients with benign tumors were diagnosed with suspected malignant transformation and 1 (0.0002%) of 4,905 patients was considered to have radiosurgery-associated intracranial malignancy; these figures yielded an incidence of 6.87 per 100,000 patient-years for malignant transformation and 2.26 per 100,000 patient-years for radiosurgery-associated intracranial malignancy. Two (0.0004%) of the 4,905 patients developed intracranial malignancies that were considered unrelated to the radiation field.

The overall incidence of radiosurgery-associated malignancy of 6.80 per 100,000 patient-years (cumulative incidence of 0.00045% over 10 years) was similar to risk of developing a malignant central nervous system (CNS) tumor in the general population of the U.S. and some European countries, according to estimates from the Central Brain Tumor Registry of the United States and the International Agency for Research on Cancer Global Cancer statistics.

The investigators concluded, “These data show that the estimated risk of an intracranial secondary malignancy or malignant transformation of a benign tumour in patients treated with stereotactic radiosurgery remains low at long-term follow-up, and is similar to the risk of the general population to have a primary CNS tumour. Although prospective cohort studies with longer follow-up are warranted to support the results of this study, the available evidence suggests the long-term safety of stereotactic radiosurgery and could support physicians counselling patients on Gamma Knife stereotactic radiosurgery.”

Douglas Kondziolka, MD, of NYU Langone Health System, is the corresponding author for The Lancet Oncology article.

Disclosure: The investigators reported that there was no funding for the study. The study authors’ full disclosures can be found at

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