What Oxaliplatin induced peripheral neuropathy and cold-modality QST have in common

In a recent study from Aalborg University in Denmark the effect of oxaliplatin on nerve function has been prospectively assessed throughout the treatment course. Patients (n=17) with Stage III colon cancer, but otherwise healthy, were tested before commencement of oxaliplatin-adjuvant chemotherapy, and prior to each new cycle.

Prior to each new treatment round, oxaliplatin-associated nerve damage was assessed using the Common Terminology Criteria for Adverse Events (CTCAE) scale. According to the department’s clinical guidelines, based on this scale, Oxaliplatin dosage was adjusted or ceased if the patients suffered moderate symptoms limiting activities of daily living or worse.

Peripheral nerve assessment included the following Quantitative Sensory Testing (QST) measures: Thermal thresholds – cold and warm sensation thresholds, cold and heat pain thresholds (tested with Medoc’s TSA-II), Vibration thresholds, and pinprick stimulation.

Large fibre perception threshold tracking (PTT) measures were tested: estimation of the Strength-Duration Time- Constant (SDTC), threshold electrotonus and rheobase.

Of the 17 patients, 16 completed all 12 treatment cycles. All patients showed oxaliplatin-induced peripheral neuropathy according to the CTCAE, and dosage was adjusted or stopped altogether accordingly. In the 12 months follow-up after termination of treatment CTCAE scores remained elevated pointing to prolonged oxaliplatin-induced effects on peripheral nerve function.

Even though Vibration thresholds were elevated after the 12th cycle, at 12 months follow-up they had normalized and were considered not to reflect the clinical manifestation of oxaliplatin induced peripheral neuropathy of which the patients complained, expressed in their CTCAE scores.

In the cold sensation range, cold sensation thresholds decreased and cold pain thresholds increased, narrowing the non-painful sensation range for cold stimuli and bringing along cold allodynia. While the cold pain thresholds remained elevated during follow-up, cold detection threshold normalized over this period. Similarly heat pain threshold significantly decreased during treatment and remained lower during follow-up. Of the PTT measures, rheobase increased during treatment and remained high during follow-up.

Based on these findings the authors concluded that tracking Cold Pain Thresholds and Rheobase may be an important tool and more sensitive in detecting potential long-term oxaliplatin peripheral nerve complications than the commonly used CTCAE.

Reference:

Szpejewska, J. E., Yilmaz, M., Falkmer, U. G., Arendt-Nielsen, L., & Mørch, C. D. (2022). New diagnostic measures of oxaliplatin-induced peripheral sensory neuropathy. Cancer Treatment and Research Communications, 31, 100543.