Peripheral Nerve Surgery and Chemotherapy: A Review, Index, and Decision Tree for Nerve Surgeons Considering Neurotization After Oncological Nerve Injuries

BACKGROUND AND OBJECTIVES: Chemotherapy-induced peripheral neuropathy (CIPN) is a complication caused by some drugs used to treat cancers including metastatic spine and malignant nerve tumors. Debilitating denervation may result from such tumors directly or from their surgical resection. The inhibitory effects of adjuvant chemotherapy on nerve regeneration in peripheral neurotization surgeries are poorly understood and must be inferred from known mechanisms of CIPN. This narrative review aims to create an index of chemotherapeutics that may cause chemotherapy-associated neurotization failure (CANF) to better inform preoperative counseling, operative timing, and postoperative prognostication by peripheral nerve surgeons. METHODS: A narrative review of published English-language literature on CIPN was performed, focusing on its known pathogenic mechanisms and its clinical manifestations including onset, duration of dysfunction, and effect size. The literature was also searched for existing evidence on the effects of the same agents on nerve regeneration and outcomes after peripheral nerve surgery. RESULTS: CIPN can manifest with sensory, motor, and/or autonomic dysfunction. Platinum-based compounds, taxanes, vinca alkaloids, antimetabolites, and proteasome inhibitors are implicated drug classes, all of which have distinct neurotoxicity profiles. CIPN phenotypes vary in timing, severity, and nerve modalities affected. Some agents are associated with a "coasting" phenomenon, where neuropathy persists even after the offending drug's discontinuation. The neurotoxic milieu induced by chemotherapy likely impairs nerve regeneration, but this has not been addressed in the literature. Data on neurotoxic chemotherapy agents were synthesized and used to create an index and risk-stratified decision tree based on inferred likelihood of CANF. CONCLUSION: Denervated patients on neurotoxic adjuvant chemotherapy regimens pose unique challenges to peripheral nerve surgeons. At least a cursory understanding of CIPN-implicated drugs, mechanisms of neurotoxicity, presentations, and the inferred risk of CANF is recommended before pursuing neurotization surgery. This index serves as a resource for peripheral nerve surgeons in this clinical conundrum.