Ultrasound in Detecting Taxane-Induced Neuropathy in Patients With Breast Cancer

PRIMARY OBJECTIVES:

I. To compare tibial motor nerve ultrasound cross-sectional area (CSA) between taxane-induced peripheral neuropathy (TIPN) patients and historical data among healthy adults.

SECONDARY OBJECTIVES:

I. To compare sural sensory nerve ultrasound CSA between TIPN patients and historical data among healthy adults.

II. To determine if the above changes in nerve CSA correlate with NCS changes in the same TIPN patients.

III. To determine if the above changes in nerve CSA correlate with changes on a self-reported neuropathy scale (Quality of Life Questionnaire - Chemotherapy-Induced Peripheral Neuropathy 20 \[QLQ-CIPN20\]) in the same TIPN patients.

IV. To determine if the above changes in nerve CSA correlate with intraepidermal nerve fiber (IENF) density changes on skin biopsy in the same TIPN patients.

TERTIARY OBJECTIVES:

I. To assess activated mast cells in skin biopsies in TIPN patients in relation to severity of symptoms and above findings.

II. To assess serum inflammatory markers in TIPN patients in relation to severity of symptoms and above findings.

OUTLINE:

Patients undergo peripheral nerve ultrasound. Patients also undergo skin biopsy.

After completion of study, patients are followed up for 30 days.

• Biopsy (Procedure), also known as Bx: Undergo skin biopsy
• Questionnaire Administration (Other): Ancillary studies
• Ultrasound Tomography (Diagnostic test): Undergo peripheral nerve ultrasound

Primary outcomes

• Tibial Nerve Cross-sectional Area [Up to 30 days]: Will be determined by ultrasound in the tibial nerve. Will be compared to the historical data from healthy patients using two-sample t-test (two-sample t-test selected as primary data from the historical control patients is available and will be used for analysis). Will also compare the nerve cross-sectional area in our study sample to that in the historical diabetic neuropathy patients and historical oxaliplatin neuropathy patients using one-sample t-test. The general linear model will be used to evaluate any factors (e.g., age) that may be associated with the nerve cross-sectional area. Due

Secondary outcomes

• Amplitude of Nerve Response - Ankle [Up to 30 days]: Spearman's rank correlation coefficient will be used to examine the associations between nerve cross-sectional area (tibial cross-sectional area) and nerve conduction studies (amplitude of nerve response - ankle).
• Conduction Velocity of Nerve Response - Tibial [Up to 30 days]: Spearman's rank correlation coefficient will be used to examine the associations between nerve cross-sectional area (tibial cross-sectional area) and nerve conduction studies (conduction velocity of nerve response - tibial).
• Distal Latency of Nerve Response - Ankle [Up to 30 days]: Spearman's rank correlation coefficient will be used to examine the associations between nerve cross-sectional area (tibial cross-sectional area) and nerve conduction studies (distal latency of nerve response - ankle).
• Nerve Fiber Density in the Skin [Up to 30 days]: Spearman's rank correlation coefficient will be used to examine the association between nerve cross-sectional area and distal intraepidermal nerve fiber density.
• Self-reported Neuropathy Score [Up to 30 days]: Will be assessed by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire - Chemotherapy-Induced Peripheral Neuropathy 20. Spearman's rank correlation coefficient will be used to examine the associations between the cross-sectional area and the self-reported neuropathy scale.
• Sural Nerve Cross-sectional Area [Up to 30 days]: Will be determined by ultrasound of the sural nerve. Spearman's rank correlation coefficient will be used to examine the associations between nerve cross-sectional area and nerve conduction studies. The general linear model will be also used to evaluate the association after adjusting for one or two risk factors (e.g., age). Nerve cross-sectional area will be treated as the dependent variable.

Other outcomes

• Serum Levels of Inflammatory Molecules [Up to 30 days]: Spearman's rank correlation coefficient will be used to assess the associations between activated mast cells in skin biopsies, serum inflammatory markers, severity of symptoms, and primary outcome and secondary outcomes in taxane-induced peripheral neuropathy patients.
• The Number of Activated Mast Cells [Up to 30 days]: Spearman's rank correlation coefficient will be used to assess the associations between activated mast cells in skin biopsies, serum inflammatory markers, severity of symptoms, and primary outcome and secondary outcomes in taxane-induced peripheral neuropathy patients.

Sex: Female

Inclusion Criteria:

* Breast cancer (any stage)
* Previously or currently receiving taxane-based chemotherapy
* Clinical symptoms of peripheral neuropathy noted in medical record and suspected to be secondary to taxane-based therapy
* Ability and willingness to understand and sign an informed consent

Exclusion Criteria:

* Self-reported or documented history of pre-existing peripheral neuropathy prior to initiation of taxane chemotherapy
* Unable to provide history

Participant flow

Outcome results

• Tibial Nerve Cross-sectional Area (Primary), Mean, mm^2: Case 13.0 +/- 3.6; Control 14.0 +/- 4.3
• Amplitude of Nerve Response - Ankle (Secondary), Number, Spearman correlation coefficient: Case 0.15
• Conduction Velocity of Nerve Response - Tibial (Secondary), Number, Spearman correlation coefficient: Case 0.15
• Distal Latency of Nerve Response - Ankle (Secondary), Number, Spearman correlation coefficient: Case -0.23
• Nerve Fiber Density in the Skin (Secondary), Number, Spearman correlation coefficient: Case -0.12
• Self-reported Neuropathy Score (Secondary), Number, Spearman correlation coefficient: Case -0.18
• Sural Nerve Cross-sectional Area (Secondary), Number, Spearman correlation coefficient: Case 0.30
• Serum Levels of Inflammatory Molecules (Other pre specified)
• The Number of Activated Mast Cells (Other pre specified)

Adverse events

Time frame: 1 month

Other adverse events by term

• Study Protocol and Statistical Analysis Plan (PDF, 2018-05-09)
• Informed Consent Form (PDF, 2019-01-22)

• Roy Strowd, Principal investigator, Wake Forest University Health Sciences

NIH grants: P30CA012197