The impact of normal tissue density on tumor growth and evolution in a 3D whole-tumor model of lung cancer

Serial low-dose computed tomography (LDCT) scans in patients who are diagnosed with lung cancer during screening offer a history of the densities of tumors and the tissues that surround them during carcinogenesis and cancer progression. We built a CT-scan-resolution computational model to explore how variations in lung tissue density impact tumor growth and evolution in non-small cell lung cancer (NSCLC). Our findings indicate that tumors spread more rapidly through denser tissues when they upregulate glycolysis whilst tumors spread more rapidly through sparser tissues when they upregulate angiogenesis. We used data and images from the National Lung Screening Trial to calibrate our model for untreated lung cancer growth in patients and observed consistency with model predictions in low-density environments. SignificanceOur lung lesion model supports prior studies that find tumors tend to evolve toward angiogenic or glycolytic phenotypes. We demonstrate that these evolutionary strategies may be driven by the surrounding normal tissue density and may be observable on imaging.