Peripheral nerve damage from radiotherapy is uncommonly seen with conventionally fractionated doses under 50 Gy. It is more frequent when doses climb above 60 Gy, which is sometimes seen in radiotherapy for advanced head and neck cancers, oesophageal cancer, thyroid cancer and prostate cancer.
Most cases of peripheral neuropathy are not thought to be due to axonal damage, although this is a possibility. Rather, the damage appears to stem from:
- Soft tissue fibrosis
- Vascular impairment
The exact mechanism of pathogenesis is unclear but it appears that the radiation insult stimulates fibrosis, either by hypoxia from damage to endothelial cells or by induction of an inflammatory response by other stromal cells (fibroblasts, macrophages). The cytokine TGF-beta appears to be an important mediator of this ongoing effect. This can lead to progressive fibrosis around the nerve, eventually damaging the myelin sheath or axon itself.
Patients commonly present with sensory abnormalities first followed by motor weakness related to the involved nerves. The most common cause of these symptoms is recurrent cancer and MRI is helpful in determining fibrosis versus malignancy.