Abstract P3-08-27: Imaging predictors for development of chemotherapy induced peripheral neuropathy
Authors: Win Hninyee , Gimber Lana , Segar Jennifer , Chu Michele , Ehsani Sima , Chalasani Pavani 
Published: March 2020

Background: Chemotherapy induced peripheral neuropathy (CIPN) can affect up to a third of patients undergoing chemotherapy. CIPN is thought to be caused by drug induced damage to the peripheral motor or sensory nervous system. Symptoms range from tingling and numbness to balance issues and falls. Based on severity of symptoms, chemotherapy (CTX) is delayed, reduced, or discontinued which can adversely affect outcomes. Currently there are no predictive biomarkers to identify those at risk of developing CIPN. Diffuse tensor imaging (DTI), a subtype of diffusion-weighted imaging (DWI), measured by routine magnetic resonance imaging (MRI) is being increasingly evaluated to assess nerve fiber trajectory. DTI allows for quantitative measurements such as fractional anisotropy (FA) and apparent diffusion coefficient (ADC) which have shown some promising but mixed results in evaluating peripheral neuropathy and CIPN in some studies. We conducted a pilot study to evaluate if quantitative DTI measurements, FA and ADC, at mid-calf and ankle can evaluate CTX induced nerve damage and predict development of CIPN.

Methods: We conducted a prospective study in patients with breast cancer who were treated with a taxane-based CTX regimen. Study was approved by our institutional review board and registered on clinicaltrials.gov (NCT03365895). Patients who were eligible to get CTX with a taxane based regimen (paclitaxel or docetaxel) were included. Patients with prior exposure to neurotoxic CTX, significant peripheral neuropathy at baseline, or history of diabetes were excluded. All patients completed pre and post CTX MRI of bilateral leg and ankles and a self-reported Functional Assessment of Cancer Therapy/Gynecological Oncology Group neurotoxic questionnaire (FACT-NTX). Patients were diagnosed with developing symptomatic neuropathy if the absolute increase in their FACT-NTX score was ≥3 at post treatment evaluation.

Results: Twenty patients consented however 6 were ineligible. Fourteen patients completed all the study procedures. Median age of the evaluable patients was 53 years (33-72 years); 11/14 had paclitaxel CTX. For all patients, median baseline FACT-NTX score was significantly lower (2.5) than post treatment score (5.5) (p=0.009). Based on FACT-NTX score changes, 64% of patients developed symptomatic neuropathy. For all patients, the minimum FA values post-chemotherapy at mid-calf and ankle (0.42 and 0.41 respectively) are significantly lower than baseline (0.54 and 0.49 respectively, p=&lt;0.0001 at mid-calf, p=0.03 at ankle) indicating change in nerve structure with CTX. There was no significant change in mean ADC measurements at mid-calf and ankle pre CTX (1.21 and 1.17 respectively) versus post CTX (1.29 and 1.9 respectively, p=0.14 for mid-calf, p=0.9 at ankle). In patients who developed neuropathy, the median minimum FA value at mid-calf at baseline was lower compared to those who did not (p=0.016).

Conclusions: Our study highlights the use of measuring minimum FA value at the mid-calf and ankle to evaluate for CIPN. Our results indicate that minimum FA value decreased with CTX induced nerve damage and a lower baseline measurement is likely predictive of developing CIPN. This suggests that minimum FA value can be used as a non-invasive imaging biomarker to help predict those at risk for CIPN and potentially be used to implement prevention strategies. Additional clinical trials are warranted to further evaluate this promising predictive biomarker.

Citation Format: Hninyee Win, Lana Gimber, Jennifer Segar, Michele Chu, Sima Ehsani, Pavani Chalasani. Imaging predictors for development of chemotherapy induced peripheral neuropathy [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P3-08-27.