Can anticancer chemotherapy promote the progression of brain metastases?
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.
KeywordsBrain metastases Chemotherapy Survival Anticancer drug
AA, LMT, BM, CAV, AC, ML and JJM contributed to design and conceptualization of the study; AA, LMT, ARC, CAV and PC analyzed the data; AA, BM, ARC, LMT, AC, ML and JJM interpreted the data; AA, LMT, AC, ML, JJM and PC drafted the manuscript; AA, LMT, AC, ML and ARC wrote the manuscript; AA, BM, ARC, LMT, CAV, AC, ML, JJM and ARC contributed to manuscript revision for intellectual content. The guarantors, AA and ML are responsible for the overall content.
Compliance with Ethical Standards
Conflict of interest
AA, LMT, BM, JJM, CAV, PC, AC and ML declare that they have no conflict of interest.
This article does not contain any studies with human participants or animals performed by any of the authors. Informed consent was obtained from all individual participants included in the study.
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