In 83 patients with lung metastases from thyroid cancer treated on multi-targeted antiangiogenic TKIs, the prevalence and impact of pulmonary cavitation was relatively low, at 12%. Only two patients developed pneumothorax while on treatment with TKI and the incidence risk difference of developing pneumothorax was not significant in those patient that developed cavitation and those who did not develop cavitation while on TKI .Our findings suggest that these TKIs do not increase significantly cavitation risk in this population, however the interpretation is limited due to small sample size.
The multi-targeted antiagiogenic TKIs lenvatinib, sorafenib, vandetanib, and cabozantinib each target multiple pathways and are under investigation for use in various thyroid cancer subtypes. Lenvatinib is being investigated for treatment of differentiated thyroid cancer and is a multi-targeted TKI of the VEGFR1-VEGFR3, fibroblast growth factor receptor 1 through 4 (FGFR1-FGFR4), platelet-derived growth factor receptor α (PDGFRα), the rearranged during transfection (RET) proto-oncogene, and v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog signaling networks.4 The drug is under investigation for treatment of anaplastic thyroid cancer. Sorafenib is also approved for differentiated thyroid cancer and is an oral dual-action inhibitor of Raf-kinase and multiple tyrosine kinases including VEGFR2, VEGFR3, PDGFR, and c-kit.2. These two targeted agents were by far the most common ones used in our cohort. Vandetanib and cabozantinib have both demonstrated clinical activity in medullary thyroid cancer. Vandetanib is an inhibitor of the RET kinase, VEGFR, and epidermal growth factor receptor signaling and.18 cabozantinib is a TKI of the hepatocyte growth factor (MET) receptor, VEGFR2, and RET.19
A few studies in patients with lung cancer have reported a rate of cavitation as high as 24% with antiangiogenic agents.10 If these agents indeed increase the risk of pulmonary cavitation, this risk would be problematic in patients with metastatic thyroid cancer, as the lung is the most common site of distant metastases and antiangiogenic TKIs are frequently used for to treat thyroid cancer. It has been suggested that all antiangiogenics have the potential to induce pulmonary nodule necrosis and cavitation, increasing risk of rupture and pneumothorax.20 Antiangiogenic agents that target VEGFRs could cause cavitation of lung lesions and increase risk of pneumothorax.9,10,21 However, among our cases, only 10 (12%) patients had evidence of cavitation, and only two developed pneumothorax, leading to drug discontinuation. We could speculate the thyroid cancer itself, not the antiangiogenic agents, increases the risk of cavitation and pneumothorax however in view of lack of comparators, such as patients with metastatic thyroid cancer who are not on TKIs we can’t be sure. Furthermore, the cavitation that did occur in our cohort had no significant effect on survival.
Our study has limitations inherent to retrospective analyses, which are subject to selection bias. In addition, the small sample size may be explain the lack of difference we observed between patients with lesions that cavitate and those without cavitation, in addition we don’t have a meaningful comparison with other subgroups, e.g., according to specific drug used or according to cancer type, or patients who were not on TKI and had metastatic disease to the lung.