What is radionecrosis?

What is Radionecrosis?

Radionecrosis (radiation necrosis) is inflammation or injury to brain tissue that develops as a late complication of radiation therapy, typically occurring 3 months to 3 years after treatment, characterized histopathologically by tissue death at or near the radiation site. 1

Pathophysiology and Definition

Radionecrosis represents a long-term adverse radiation effect resulting from the high biologic doses of radiation delivered during treatment. 1 The condition involves:

• Tissue death (necrosis) caused by radiation exposure to brain tissue 2
• Inflammation or injury approximating the radiation treatment site when confirmed histopathologically 1
• Associated radiation-induced edema that can be identified on imaging 1

The underlying pathophysiological mechanism remains incompletely understood, making effective treatment challenging. 2, 3

Incidence and Risk Factors

The reported incidence varies considerably based on multiple factors:

• Overall incidence ranges from 5% to 35% in various retrospective series, with some studies reporting 0-30% 1, 4
• The wide variation reflects inconsistencies in diagnostic definitions and whether symptomatic versus asymptomatic cases are included 1, 4
• Incidence is 5-25% following radiation therapy, with rates varying by modality and dose delivered 4

Key Risk Factors Include:

• Irradiation protocol parameters: total dose, volume treated, and particularly the dose per fraction 1
• Patient age over 50 years old 1
• Pre-existing vascular disease: hypertension, diabetes, hyperlipidemia 1
• Large treatment volumes with generous expansions and interdigitation of target with normal brain 1
• Postoperative stereotactic radiosurgery/radiotherapy (SRS/SRT) is associated with relatively high necrosis rates 1

Clinical Presentation and Timing

Radionecrosis generally develops 3 months to 3 years after radiation treatment. 1 Important temporal considerations include:

• Clinical or radiological deterioration within 2 months after radiotherapy should be interpreted with caution and not automatically considered treatment failure 1
• Asymptomatic radiation necrosis may progress spontaneously before symptoms develop, though progression often ceases without intervention 4

Diagnostic Challenges

Distinguishing radionecrosis from tumor recurrence remains a significant clinical challenge:

• Radiation necrosis is identified radiographically, with or without histopathologic confirmation 4
• Advanced imaging (MRI, CT) is preferred for characterization and surveillance 4
• Technetium-99m MIBI brain scintigraphy can help differentiate between recurrence and radionecrosis 1
• Direct biopsy is not routinely recommended, as the biopsy procedure itself may cause disease progression 4
• Given variation in SRS/SRT delivery patterns and inconsistent diagnostic criteria, the reported incidence varies considerably 1

Clinical Significance

Radionecrosis represents a serious complication with substantial impact:

• Can have tremendous impact on patient quality of life and neurological function 2, 3
• Represents a major dose-limiting adverse event of radiotherapy 5
• May affect morbidity and mortality, particularly with pachymeningeal involvement 1