Identifying optimized assessment of nerve damage during chemotherapy.

Tiffany Li The University of Sydney, Sydney, NSW, Australia info_outline Tiffany Li, Hannah C Timmins, Fawaz Mayez Mahfouz, David Mizrahi, Lisa Horvath, Michelle L. Harrison, Peter S. Grimison, Michael Friedlander, Gavin M. Marx, Frances M. Boyle, David Wyld, Robert Henderson, Tracy King, Sally E. Baron-Hay, Matthew C Kiernan, Claudia Rutherford, David Goldstein, Susanna B Park

Authors Tiffany Li The University of Sydney, Sydney, NSW, Australia info_outline Tiffany Li, Hannah C Timmins, Fawaz Mayez Mahfouz, David Mizrahi, Lisa Horvath, Michelle L. Harrison, Peter S. Grimison, Michael Friedlander, Gavin M. Marx, Frances M. Boyle, David Wyld, Robert Henderson, Tracy King, Sally E. Baron-Hay, Matthew C Kiernan, Claudia Rutherford, David Goldstein, Susanna B Park Organizations The University of Sydney, Sydney, NSW, Australia, Chris O'Brien Lifehouse, Camperdown, Australia, Chris O’Brien Lifehouse, Sydney, NSW, Australia, Chris O'Brien Lifehouse, Sydney, NSW, Australia, Prince of Wales Hospital, Randwick, NSW, Australia, Northern Hematology and Oncology Group, Wahroonga, NSW, Australia, The Mater Hospital, North Sydney, NSW, Australia, University of Queensland, Brisbane, QLD, Australia, Royal Brisbane & Women's Hospital, Brisbane, QLD, Australia, Royal Prince Alfred Hospital, Sydney, NSW, Australia, Royal North Shore Hospital, St Leonards, NSW, Australia, Department of Medical Oncology, Sydney, NSW, Australia Abstract Disclosures Research Funding National Health and Medical Research Council (NHMRC) Cancer Institute NSW Background: Chemotherapy-induced peripheral neurotoxicity (CIPN) is a significant and persisting toxicity of anticancer treatments, impacting dose delivery and quality of life. There is a lack of consensus on the optimal method of CIPN assessment in clinical settings. This study compared the validity and responsiveness of patient reported outcome measures (PROMs) against neurological, neurophysiological and sensory assessment approaches of CIPN. Methods: A multi-centre dual study design evaluated patients treated with neurotoxic chemotherapy across two cohorts: patients commencing treatment assessed prospectively and patients who completed treatment assessed cross-sectionally. CIPN was assessed via PROMs (EORTC-CIPN20, FACT/GOG-Ntx, PRO-CTCAE), neurological and neurophysiological assessment (Total Neuropathy Score, sural and tibial compound nerve amplitudes) and sensory functional measures (Grating orientation, Von Frey monofilament and 2-Point discrimination tasks). Convergent and known-groups validity were assessed cross-sectionally following treatment completion and responsiveness was evaluated prospectively during treatment. Neurological, neurophysiological, and sensory outcome measure scores were compared between high and low CIPN symptom reporters. Results: A total of 1,033 patients were recruited, incorporating 1,623 assessments. PROMs demonstrated superior ability to identify CIPN (convergent validity; α = 0.75-0.85, all P < 0.001), to discriminate between CIPN severity (known-groups validity; all P < 0.001) and to detect changes in CIPN development (responsiveness; Cohen’s d = 0.65-0.83) compared to neurological, neurophysiological and sensory assessment approaches. These other measures did not achieve threshold for convergent validity (α< 0.7). and did not demonstrate acceptable responsiveness (Cohen’s d < 0.5). Neurological, neurophysiological, and sensory outcome measures were significantly impaired in patients who were high CIPN symptom reporters compared to low (all P < 0.05). Conclusions: PROMs represent a valid method of CIPN assessment, with preferential measurement properties over other approaches to assessing neuropathy. Adoption of PROMs in clinical practice will allow for accurate representation and early recognition of CIPN, leading to reduced long term morbidity in this key long-term toxicity in cancer survivors.