Abstract
We have read with interest the report by Blevins et al. on three patients developing a rare but unpredictable and dreadful complication of antiangiogenic TKIs in advanced radioactive iodine (RAI)-refractory thyroid cancer (1). We fully agree with the authors' conclusions indicating that novel non-antiangiogenic—hence potentially safer drugs—should be explored in patients at high risk of aerodigestive fistula formation. Known risk factors for fistula formation include prior radiation, surgery and infiltration, or invasion of vital organs in the neck and mediastinum. In clinical practice, most of those treatments are delivered in the attempt to control tumor growth that is associated with the risk of vital organ invasion.
Since the treatment strategies for advanced thyroid cancer are mostly unsuccessful, at least in the long term, they result in multiple treatment procedures that are at the basis of increased probability of fistula formation associated with TKI. In this scenario, we wonder whether an alternative strategy should include an earlier use of antiangiogenic TKIs. In this context, one could envision to start with TKIs already before the appearance of signs and symptoms indicating aerodigestive tract invasion. Based on the impressive response rate reported with second-generation drugs (2), we propose to postpone local treatments such as surgery and radiation for neck and mediastinum manifestations after initial treatment with TKIs, thus reducing the risk of fistula formation and, possibly, prolonging the overall treatment effects. In addition, patients responding to TKIs might be in need of less extensive local salvage treatments with reduced local morbidity, thus paving the way for a safer use of second-line TKIs, if needed. Moreover, this would result in an earlier and thus potentially beneficial TKI exposure before the tumor acquires biological resistance due to its natural evolution or the exposure to previous treatments.