Evidence-based risk stratified monitoring protocol for optic pathway late toxicity following head and neck & CNS radiotherapy

Purpose: CNS tissues such as optic nerves and chiasm are sensitive to late toxicity from radiation therapy (RT). Treatment with systemic bevacizumab may stabilize but rarely improve vision in radiation-induced optic neuropathy (RION), indicating the need for early identification. We aim to develop an evidence-based, risk-stratified monitoring protocol.

Methodology: Pubmed database was searched for manuscripts with primary data on rates of radiation optic neuropathy. Articles lacking patient level data on dose to optic structures were excluded (those with only median, mean, range of dose if non-uniform doses were given). Individual patients were excluded if they had vision acuity of Counting Fingers or worse prior to RT, vision loss within the first 6 months following RT, follow-up < 2 years, received stereotactic radiosurgery or hypofractionated RT (dose of >3 Gy per fraction, or < 20 fractions), or had unclear cause for decline in vision. Patients were included and deemed “at risk” for RION if they received > 50 Gy to an optic structure.

Results: Fifty-three manuscripts met inclusion & exclusion criteria with a total of 3155 patients deemed to be at risk of RION. The overall rare of RION was 4.4%. A dose-dependent relationship was noted with increasing rate per 5 Gy intervals (50 – 54.9 Gy: 2.4%; 55 – 59.9 Gy: 3%; 60 – 64.9 Gy: 4.6%; 65 – 69.9 Gy 5.3%; 70 Gy and above 10.1%) as well as per 10 Gy intervals (50-59.9 Gy: 2.6%; 60-69.9 Gy: 4.9%; 70 Gy and above: 10.1%).

Conclusions: With the advancement of Level 1 evidence from randomized controlled trials for the use of bevacizumab for CNS radiation necrosis and evidence for benefit in RION, early detection is key to vision preservation. For patients with less than 5% risk we propose annual monitoring, 5-10% risk monitoring every 6 months, and those with 10% or higher risk quarterly monitoring.

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