Effective treatment of anlotinib in giant delayed pulmonary metastasis of osteosarcoma: a case report and literature review.

Tumor relapse and pulmonary metastasis, especially unresectable lesions, are the major cause of poor prognosis of patients with osteosarcoma. Anlotinib, a novel small-molecule tyrosine kinase inhibitor (TKI), has been proved to have desirable anti-tumor effects via blocking VEGFR2 and PDGFRβ phosphorylation in several tumors, including non-small cell lung cancer and soft tissue sarcoma. In this study, we presented a case of giant delayed pulmonary metastasis of osteosarcoma which was effectively treated by anlotinib. CT scan of this patient showed a giant neoplasm with the size of 1,366 cm3 in the left lung, clinically diagnosed as pulmonary metastasis of osteosarcoma. Due to refusing to chemotherapy and not eligible for surgery of the giant neoplasm, anlotinib was recommended. As a result, the tumor volume decreased more than 82% during 24-week anlotinib administration, from 1,366 to 247 cm3. Unfortunately, disease progression was observed at 27-week. Although argon-helium cryoablation (AHC) was performed followed by apatinib administration, the patient was dead in 16 weeks after disease progression. The progression-free survival (PFS) and overall survival since anlotinib administration of this patient was 27 weeks and 43 weeks, respectively. The toxicity included hypertension, fatigue and hand-foot skin syndrome in grade 1-2, which were controllable and well tolerated. Meanwhile, immunohistochemical staining showed that the expression of VEGFR2 and PDGFRβ was decreased significantly and the whole exon sequencing revealed that c-MYC was duplicated, which was potentially associated with anlotinib resistance. Anlotinib had promising anti-tumor efficiency in the treatment of delayed pulmonary metastatic osteosarcoma. However, the potential mechanism of anlotinib resistance and the subsequent therapy after resistance were still challengeable and needed further investigation.