title: Tyrosine kinase inhibitor sunitinib therapy is effective in the treatment of bone metastasis from cancer of unknown primary: Identification of clinical and immunohistochemical biomarkers predicting survival.
abstract: Bone metastasis from cancer of unknown primary (BMCUP) brings poor survival prognosis and its management remains controversial. Sunitinib (SUTENT) proved effective in many sorts of solid tumors but has never been applied for patients with occult primary cancers, and there is no study to identify sensitive or resistant biomarkers for sunitinib therapy in CUP patients. An analysis was carried out to investigate the efficacy of sunitinib by multivariate survival analysis of 286 patients with BMCUP. We further carried out multivariate analysis to identify histological and clinical biomarkers that could predict sensitivity or resistance for sunitinib therapy. Of the 286 patients included from January 2011 to March 2016, sunitinib therapy proved effective to prolong survival in patients with BMCUP. Sensitive and resistant biomarkers were identified in histological specimen of patients receiving sunitinib therapy. Clinical factors were also identified that predict poor survival prognosis for sunitinib therapy. Sunitinib therapy proved effective to prolong survival in patients with BMCUP. Sensitive markers for sunitinib therapy include KDR positivity and early-developed treatment-induced hypertension. Resistance factors for sunitinib include VEGF positivity, CAIX positivity and squamous cell carcinoma pathology type. Prolonged symptom time and severe weight loss before therapy seemed to be associated with poor survival prognosis for sunitinib therapy.
authors.affiliation: Department of Orthorpedic Oncology, Changzheng Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Yifei
authors.initials: Y
authors.lastname: Ma
authors.affiliation: Department of Orthorpedic Oncology, Changzheng Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Wang
authors.initials: W
authors.lastname: Zhou
authors.affiliation: Department of Orthorpedic Oncology, Changzheng Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Shaohui
authors.initials: S
authors.lastname: He
authors.affiliation: Department of Orthorpedic Oncology, Changzheng Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Xu
authors.affiliation: Department of Orthorpedic Oncology, Changzheng Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Jianru
authors.initials: J
authors.lastname: Xiao
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use; D015415:Biomarkers; D001859:Bone Neoplasms / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality / Q000556:secondary*; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009382:Neoplasms, Unknown Primary / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D011379:Prognosis; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D000970:Antineoplastic Agents; D015415:Biomarkers; D047428:Protein Kinase Inhibitors
keywords: biomarkers; cancer of unknown primary; sunitinib