Can anticancer chemotherapy promote the progression of brain metastases?

Aymeric Amelot, Louis-Marie Terrier, Bertrand Mathon, Ann-Rose Cook, Jean-Jacques Mazeron, Charles-Ambroise Valery, Philippe Cornu, Marc Leveque, Alexandre Carpentier

Brain metastases natural history from one primary tumor type might be accelerated or favored by using certain systemic chemotherapy. A great deal was described in mice and suggested in human with antiangiogenic drugs, but little is known about the metastatic progression generated by the perverse effect of anticancer drugs. A total of 413 patients who underwent treatment for brain metastasis (2013-2016) were included. The identification of all previous anticancer drugs received by patients from primary tumor diagnosis to brain metastases diagnosis was collated. The median value for the time of first appearance of brain metastasis in all patients was 13.1 months (SD 1.77). The values of brain metastasis-free survival (bMFS) for each primary cancer were: 50.9 months (SD 8.8) for breast, 28.5 months (SD 11.4) for digestive, 27.7 months (SD 18.3) for melanoma, 12.3 months (SD 8.3) for kidney, 1.5 months (SD 0.1) for lung and 26.9 months (SD 18.3) for others (p < 0.009). Through Cox multivariate proportional hazard model, we identified that the only independent factors associated with short bMFS were: lung primary tumor [odd ratio (OR) 0.234, CI 95% 0.16-0.42; p < 0.0001] and mitotic spindle inhibitor (taxanes) chemotherapy [OR 0.609, CI 95% 0.50-0.93; p < 0.001]. Contrariwise, breast primary tumor [odd ratio (OR) 2.372, CI 95% 1.29-4.3; p < 0.005] was an independent factor that proved a significantly longer bMFS. We suggest that anticancer drugs, especially taxane and its derivatives, could promote brain metastases, decreasing free survival. Mechanisms are discussed but still need to be determined.