The Macroscopic Growth Laws of Brain Metastases
B. Ocaña-Tienda, J. Pérez-Beteta, D. Molina-García, J. Jiménez-Sánchez, O. Leon-Triana, A. Ortiz de Mendivil, B. Asenjo, D. Albillo, L. Pérez-Romasanta, M. Valiente, L. Zhu, P. García- Gómez, E. González-Del Portillo, M. Llorente, N. Carballo, E. Arana, V. M. Pérez-García
medrxiv (submitted for publication, 2022)
Abstract
Tumor growth is the result of the interplay of complex biological pro- cesses in a huge number of individual cells in a changing environment. Effective simple mathematical laws have been shown to describe tumor growth in vitro, or in animal models with bounded-growth dynam- ics accurately. However, results for human cancers in patients are scarce. The study mined a dataset of 1133 brain metastases (BMs) with longitudinal imaging follow-up, treated with radiosurgery (SRS) to find growth laws for untreated BMs, relapsing treated BMs, and radiation necrosis (RN). Untreated BMs showed sustained growth accel- eration, most likely related to the underlying evolutionary dynamics. Relapsing BM growth was slower, most probably due to a reduction in tumor heterogeneity after SRS, which may limit the evolutionary possibilities of the tumor. RN lesions had significantly larger growth exponents than relapsing BMs, providing a way to differentiate them from true progression. This may help in solving a problem of clinical relevance, since the first condition may resolve spontaneously, and not require further work-up, while the second requires therapeutic action.