A validation study of disease definitions for immune checkpoint inhibitor neurotoxicity

<h3></h3> Immune checkpoint inhibitors (ICIs) have transformed cancer outcomes. By targeting immune-cell- surface receptors, they augment the immune response to tumour cells but can cause range of immune-related (IR) toxicities. Neurological toxicity occurs in 1–12% and is much less frequent than other tissue IR-toxicity but carries a higher risk of long-term morbidity and mortality. Prompt and <b>c orrect</b> identification of IR-neurotoxicity is essential to accessing treatment, optimizing outcome, avoiding adverse effects of immunosuppression if not indicated and facilitating ongoing ICI therapy where appropriate. [1] Guidon et al suggest criteria for diagnosis of IR-neurotoxicity [2]: onset within 6–12 months of exposure, AND Improvement with corticosteroids SUPPORTED BY presence of neural antibodies, paraneoplastic neurological syndrome. The NHNN ICI neurotoxicity service has received 100 referrals between 2019–2023. Thirty-two individuals (32%) were diagnosed with IR-neurotoxicity on exhaustive assessment and close clinical follow up. Application of the published diagnostic definitions to this cohort reveals Se:84.4%,Sp:73.5%.,PPV:60%,NPV:90.9% With very low additive benefit from the supportive components. Given the relative rarity of IR-neurotoxicity with ICI (1% in monotherapy) we suggest careful clinical assessment superior to use of broad diagnostic definitions. The correct exclusion of IR-neurotoxicity (specificity) is VERY important, to avoid adverse effects of high-dose corticosteroids and discontinuation of effective anti-cancer immunotherapies.