Figure 11. The cancer punctuated equilibrium model of colon tumor evolution better explains the variability of colorectal polyp growth.

CTC images from the initial (a) and final (b) scans from a patient with polyp that had an annual volumetric growth rate of 59% that was followed over 2.1 years prior to polypectomy. Black arrows point to the polyp that was followed longitudinally. (c) and (d) are possible evolutionary trajectories for a growing polyp. Shading under the line represent levels of intratumoral heterogeneity with punctuation events creating the greatest amount of heterogeneity. Tumorigenesis may begin with a punctuation event or periods of stasis and gradualism, a second punctuation event may provide enough molecular diversity allowing for malignant transformation. (e) and (f) are CTC images from the initial and final scans from a patient with polyp that had an annual volumetric growth rate of −33% that was followed over 0.9 years prior to polypectomy. (g) and (h) are possible evolutionary trajectories for a regressing polyp. Tumor regression may occur with the emergence of a negative or immunogenic phenotype acquired during a period of gradualism or via a punctuation event.

From Sievers CK, Grady WM, Halberg RB, et al. New insights into the earliest stages of colorectal tumorigenesis. Expert Rev Gastroenterol Hepatol 2017;11:723-9; with permission.