July 2021

Optimal biomechanical parameters for measuring sclerotic chronic graft-versus-host disease

Authors: Laura X. Baker 1, 2, Fuyao Chen 1, 2, 3, 4, Austin Cronin 1, 2, 3, Heidi Chen 5, Arved Vain 6, Madan Jagasia 5, Eric R. Tkaczyk 1, 2, 3

Author information:

  1. Dermatology Service and Research Service, Department of Veterans Affairs Tennessee Valley, Healthcare System, Nashville TN;
  2. Vanderbilt Dermatology Translational Research Clinic, Vanderbilt University Medical Center, Nashville, TN;
  3. Department of Biomedical Engineering, Vanderbilt University, Nashville, TN;
  4. Yale School of Medicine, New Haven, CT;
  5. Vanderbilt-Ingram Cancer Center, Nashville, TN;
  6. University of Tartu, Institute of Physics, Tartu, Estonia

Journal: JID Innovations - June 2021, Journal Pre-proof (DOI: 10.1016/j.xjidi.2021.100037)

Skin biomechanical parameters (dynamic stiffness, frequency, relaxation time, creep, and decrement) measured using a myotonometer (MyotonPRO) could inform management of sclerotic disease.

To determine which biomechanical parameter(s) can accurately differentiate sclerotic chronic graft-versus-host disease (cGVHD) patients from post-hematopoietic cell transplant (post-HCT) controls, 15 sclerotic cGVHD patients and 11 post-HCT controls were measured with the myotonometer on 18 anatomic sites.

Logistic regression and two machine learning algorithms, LASSO regression and random forest, were developed to classify subjects. In univariable analysis, frequency had the highest overfit-corrected area under the receiver operating characteristic curve (AUC 0.91). Backward stepwise selection and random forest machine learning identified frequency and relaxation time as the optimal parameters for differentiating sclerotic cGVHD patients from post-HCT controls. LASSO regression selected the combination of frequency and relaxation time (overfit-corrected AUC 0.87). Discriminatory ability was maintained when only the sites accessible while the patient is supine (12 sites) were used.

We report the distribution of values for these highly discriminative biomechanical parameters, which could inform assessment of disease severity in future quantitative biomechanical studies of sclerotic cGVHD.

In conclusion, this study shows that a brief clinical protocol measuring the frequency and relaxation time of patients’ skin can effectively differentiate sclerotic cGVHD patients from post-HCT controls. A larger follow-up study is needed for model validation.