Fracture Toughness of Human Solid Cancers

Abstract

Human solid cancers typically are harder and firmer than surrounding normal tissue upon clinical palpation. This characteristic has been linked to the presence of abundant collagen in the tumor stroma, referred to as the desmoplastic reaction. Recent evidence indicates that tumor-associated desmoplastic stroma is critical to cancer’s growth and progression. However, how best to measure, interpret, and/or model the mechanical attributes of tumor microenvironment in vivo remain unclear. During routine sonographically-guided fine needle biopsy of solid tumors of the human thyroid gland, it was serendipitously observed by the lead author that the nature and strength of the haptic force feedback cues varied among tumors [See Movie:http://www.jbioleng.org/imedia/6538834542236038/supp1.mov]. Note the apparent ease with which the needle travels through a non-cancerous tumor. In contrast, a cancerous tumor offers substantial resistance to needle insertion and penetration. To further investigate this phenomenon and to assess the relationship between tumor hardness and cytological diagnosis, a clinical study was designed and implemented incorporating the principles of fracture mechanics with haptic modality. In this prospective study, 609 solid thyroid gland tumors were percutaneously probed using standard 25-gauge fine needles, their tissue toughness ranked on the basis of the nature and strength of the haptic force feedback cues, and subjected to standard fine needle biopsy. Ranked tumors were placed in one of two groups: Group 1 [N = 134]: tumors exhibiting penetration resistance with a distinctive force-feedback cue, as if cutting through an unripe pear; and Group 2 [N = 475]: tumors exhibiting no resistance, as if cutting through jelly. The results were dramatic: 64% of Group 1 tumors were cancerous while 95% of Group 2 tumors were noncancerous. This qualitative method, though subject to some operator bias, identifies a previously unreported in vivo approach for characterizing the fracture toughness of human solid tumors that can be correlated with malignancy. Our results when validated by quantitative measurement data are likely to provide a new framework for understanding the mechanical attributes of the tumor microenvironment. We anticipate our method to be a starting point for the development of a mechanical device that can quantify a tumor’s toughness in vivo using the principles of fracture mechanics. [Journal of Biological Engineering 2008;2:12 doi:10.1186/1754-1611-2-12]