Radiation-induced neuropathy in cancer survivors

Abstract

Radiation-induced peripheral neuropathy is a chronic handicap, frightening because progressive and usually irreversible, usually appearing several years after radiotherapy. Its occurrence is rare but increasing with improved long-term cancer survival. The pathophysiological mechanisms are not yet fully understood. Nerve compression by indirect extensive radiation-induced fibrosis plays a central role, in addition to direct injury to nerves through axonal damage and demyelination and injury to blood vessels by ischaemia following capillary network failure. There is great clinical heterogeneity in neurological presentation since various anatomic sites are irradiated. The well-known frequent form is radiation-induced brachial plexopathy (RIBP) following breast cancer irradiation, while tumour recurrence is easier to discount today with the help of magnetic resonance imaging and positron emission tomography. RIBP incidence is in accordance with the irradiation technique, and ranges from 66% RIBP with 60Gy in 5Gy fractions in the 1960s to less than 1% with 50Gy in 2Gy fractions today. Whereas a link with previous radiotherapy is forgotten or difficult to establish, this has recently been facilitated by a posteriori conformal radiotherapy with 3D-dosimetric reconstitution: lumbosacral radiculo-plexopathy following testicular seminoma or Hodgkin's disease misdiagnosed as amyotrophic lateral sclerosis. Promising treatments via the antioxidant pathway for radiation-induced fibrosis suggest a way to improve the everyday quality of life of these long-term cancer survivors.

Delayed radiation-induced lumbosacral radiculoplexus neuropathy – a diagnostic dilemma

“…>50 Gy to a nerve plexus), dose per fraction or hot spot, treatment fields encompassing a high concentration of nerve fibers, body positioning, and combined treatment with neurotoxic chemotherapeutic agents or surgery [1,2]. Patient-related risk factors for delayed nerve injury include, as in the case of our patient, advanced age, diabetes (with or without an associated neuropathy), other cardiovascular comorbidities, and tobacco use [1].…”

“…Neurological deficits are typically asymmetric and unilateral, however bilateral involvement may occur. A gradual progression of deficits follows in a step-wise manner, owing to the pathophysiologic cycle of inflammation and sclerosis which underlies this condition [1]. Radiotherapy may cause an (initially) asymptomatic microvascular injury to exposed tissues, related to an endothelial cell-mediated inflammatory response to increased oxidative stress.…”

“…Over time, cytokine-driven fibroblast proliferation and extracellular matrix deposition incite a cycle of fibrosis, further perpetuated by the continued production of reactive oxygen species. Late (often monthsto-years) after radiotherapy, a terminal disease phase, characterized by irreversible ischemia, fibroatrophy, and finally tissue necrosis, develops [1].…”

“…Due to the delayed clinical presentation of radiculoplexus neuropathy, often many years after radiotherapy is complete, the association with this exposure may initially be missed [1], thereby delaying diagnosis, and potentially exposing patients to unnecessary testing and ineffective treatments [1]. Our patient was initially recognized as a poorly controlled diabetic, and in this context, was treated for presumed diabetic amyotrophy -a generally monophasic microvasculitis of acute-to-subacute onset, accompanied by pain (a painless motor form exists) [6].…”

Jaw position uncertainty and adjacent fields in breast cancer radiotherapy

“…However, more detailed knowledge is needed on the risk for recurrence in the junction region and the clinical significance of the local increase of the lung dose before the effects can be properly evaluated. Risk factors like radiation induced brachial plexopathy, for example, should be taken into account, as well, and a maximum dose of 54 Gy (or lower to take into account the risk of increased dose due to uncertainties in jaw positioning) to plexus brachialis should be added to the analysis 13 , 14 . Elaboration on specific clinical recommendations might require different approaches, depending on treatment technique, diagnosis, and other patient specific circumstances, which is outside the scope of this study.…”