cNF affect up to 99% of patients with neurofibromatosis 1 (NF1) and are a major source of social/emotional distress. Treatment options for cNF are limited and drug development has been hampered by the inability to accurately detect small changes in tumor size. Calipers, the current standard for cNF measurement, can only assess a subset of cNF that are above the skin surface, cannot assess deep portions of tumor, and are subject to inter-rater variability. A reliable measurement technique for cNF is a critical gap for development of therapies for these tumors.

We are recruiting participants with NF1 to a study assessing the intra-and inter-rater reliability of various measurement techniques for cNF. Six cNF on each NF1 participant were assessed independently by three different examiners using calipers, 3D photography, and HFUS.  Photographs and ultrasound images were processed using manufacturer provided software, and tumors were measured via manual outlining of tumors by up to three assessors. Linear and volumetric assessments were compared using intraclass correlation coefficient (ICC) to determine the intra-and inter-rater reliability of each measurement technique. 

Five patients have participated to date. Reproducibility of image acquisition and measurement was excellent within and across examiners (ICC > 0.90 for HFUS and 3D camera techniques).  Acquisition of images was rapid (less than 30 seconds) and examiners found these devices easy to use. Both systems require no action from the patient and are easily tolerated. 

HFUS and 3D photography are feasible, reliable,non-invasive methods for measurement of cNF. These methods are currently being evaluated as potential methods to assess changes in cNF size over time. This information will ultimately inform clinical trial design and facilitate the development of interventional treatments for cNF.