P12.02.A BRIDGING DISCIPLINES: TOTAL NEUROPATHY SCORE AND HIGH-RESOLUTION ULTRASOUND FOR THE EVALUATION OF IMMUNE-RELATED NEUROTOXICITY IN THE PARTICIPATE TRIAL
Authors: I Mäurer, N A Leistner, C Schönherr, S Hartinger, J Hammersen, B Heiling, M Dannemann, N Page, M A Mäurer, S Goetze, S M Lang, S Foller, C Senft, M Schwab
Journal: Neuro-Oncology (2024)

Abstract BACKGROUND Neuromuscular immune-related adverse events (irAEs) are the most prevalent neurological complication of immune checkpoint inhibitors (ICIs). An increase in the cross-sectional area of various nerves (CSA) has been observed in both chemotherapy-induced and immunotherapy-related neuropathies, as determined by the ultrasound pattern sum score (UPSS), using neuromuscular high-resolution ultrasound (HRUS). With no widely accepted biomarkers for neurological irAEs, HRUS offers a promising avenue for the expansion of diagnostics and monitoring. However, existing data are mainly limited to small retrospective studies without pre-treatment assessments or valid distinction between treatment effects and pre-existing conditions. MATERIAL AND METHODS The ongoing prospective, cross-sectional PARTICIPATE trial aims to demonstrate the diagnostic relevance of HRUS for the detection of neurotoxicity in patients treated with ICIs. Furthermore, the trial serves to identify those patients who will particularly benefit from pre-treatment TNS and HRUS screening. Comparative analysis contrasting HRUS measurements between patients receiving other systemic therapies and ICIs will be conducted to delineate immune-related patterns of peripheral neurotoxicity. The presented study includes data collected from individuals who have undergone both a baseline and at least one follow-up HRUS examination. RESULTS This preliminary analysis includes 30 patients diagnosed with lung cancer (N=17), melanoma (N=10), or renal cell carcinoma (N=3), with a median age of 62.5 years at diagnosis (range: 37-83). Among them, 23 patients received ICIs, while 7 patients in the control group underwent radiochemotherapy, chemotherapy, or targeted therapy alone. Prior to the initiation of systemic treatment, TNS revealed the presence of pre-existing neurological pathologies in 70% of patients. Initial HRUS detected significant nerve swelling in one patient (UPSS=5), while 15 patients exhibited slight (UPSS=1-4), and 13 patients had no increase in CSA at baseline assessment. Notably, 87% of participants with increased TNS at the baseline assessment presented focal nerve swelling in HRUS. Finally, significant increases in TNS and UPSS were observed in a patient with a history of multiple nerve compression syndromes who developed immune-related neuropathy during nivolumab treatment. CONCLUSION Initial findings indicate that the combined assessment via TNS and neuromuscular HRUS is a promising modality for cancer patients, with the potential to differentiate between immune-related neuropathies and the worsening of pre-existing neurological comorbidities. The forthcoming data from the PARTICIPATE study will demonstrate the utility of longitudinal neuromonitoring, including neuromuscular ultrasound, in identifying distinct patterns of peripheral neurotoxicity.