Quantitative Sensory Testing at Baseline and During Cycle 1 Oxaliplatin Infusion Detects Subclinical Peripheral Neuropathy and Predicts Clinically Overt Chronic Neuropathy in Gastrointestinal Malignancies

There is a need for early identification of patients who will develop chronic oxaliplatin neuropathy. We used quantitative sensory testing (QST), a noninvasive and commercially available test of nerve fiber function, to show that patients with a preexisting subclinical neuropathy and those in whom subclinical neurologic deficits develop with cycle 1 oxaliplatin infusion are at highest risk for the development of chronic clinically significant neuropathy. Purpose: Oxaliplatin neurotoxicity has a spectrum of manifestations from an often reversible acute neurotoxicity to a more irreversible stocking and glove chronic neuropathy that is associated with high morbidity. Quantitative sensory testing (QST) is a noninvasive psychometric testing method that can potentially be used in the clinic setting to measure subclinical neurologic changes early on to identify patients that will experience chronic oxaliplatin-induced peripheral neuropathy at 1 year. Patients and Methods: Thirty patients with gastrointestinal malignancies who were receiving oxaliplatin were recruited. QST and patient-reported outcomes were assessed at baseline; during infusion cycles 1, 2, 4, and 6; and at 1 year. National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 4.0, chronic neuropathy scores were assessed at the 1-year time point. The variables at each time point were evaluated for prediction of 1-year chronic neuropathy scores. Results: We found that patients with preexisting subclinical neuropathy were more likely to experience grades 2 and 3 chronic neuropathy than were those who did not have this condition (heat detection threshold, Spearman correlation coefficient (r(s)) = 0.39; P=.037; pellet retrieval time, r(s)=0.47; P=.024). Patients in whom thermal and cutaneous sensory deficits developed with cycle 1 infusion were also more likely to experience grades 2 and 3 neuropathy at 1 year (cold detection threshold, r(s)=0.50; P=.007; heat detection threshold, r(s)=0.39; P=.042; cutaneous detection threshold, r(s)=0.42; P=.043). Conclusion: QST provides a noninvasive, commercially available, and feasible clinical test to select patients, even before oxaliplatin treatment, who are likely to experience moderate to severe chronic peripheral neuropathy.