title: Lack of elevation of serum S100B in patients with metastatic melanoma as a predictor of outcome after induction with an autologous vaccine of proliferating tumor cells and dendritic cells.
abstract: Serum levels of S100B and/or lactate dehydrogenase (LDH) are putative tumor markers in melanoma. Early changes in such markers may correlate with a positive immune response to vaccine therapy. In patients with metastatic melanoma, S100B and LDH serum levels were measured at baseline, and 1 week after 3 weekly subcutaneous injections of investigational, patient-specific vaccines consisting of autologous dendritic cells loaded with antigens from irradiated proliferating autologous tumor cells, and suspended in granulocyte macrophage colony-stimulating factor. There was a poor correlation between S100B and LDH levels at baseline (p = 0.324). Fourteen (14) patients with measurable disease had higher S100B (p = 0.0456) and LDH (p = 0.0013) levels than 31 patients who lacked measurable disease at that time. Fourteen (14) deceased patients (median survival, 13 months) had a mean baseline S100B of 0.62 mug/L (95% confidence interval [CI] 0.00-1.66) and LDH of 815 U/L (95% CI 222-1408); 31 surviving patients (median follow-up, 35.4 months) had mean S100B of 0.07 mug/L (95% CI 0.00-0.23; p = 0.006) and LDH of 442 U/L (95% CI 296-588; p = 0.002). Elevated baseline levels of LDH and S100B were each predictive of inferior progression-free survival (PFS) and overall survival (OS) (both p < 0.0001), but S100B was a better predictor for PFS than LDH. Changes in LDH between baseline and week 4 were not predictive of survival, but an increase in S100B predicted for inferior OS ( p = 0.039). Both LDH and S100B are predictive tumor markers in patients with metastatic melanoma. This is the first study to examine the changes in serum levels of LDH and S100B in response to an autologous tumor-cell vaccine.
authors.affiliation: Hoag Cancer Center, Newport Beach, CA, USA.
authors.forename: Patric M
authors.initials: PM
authors.lastname: Schiltz
authors.forename: Robert O
authors.initials: RO
authors.lastname: Dillman
authors.forename: Catharina M
authors.initials: CM
authors.lastname: Korse
authors.forename: James M
authors.initials: JM
authors.lastname: Cubellis
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Lee
authors.forename: Gijsbert C
authors.initials: GC
authors.lastname: De Gast
mesh_terms: D014408:Biomarkers, Tumor / Q000097:blood; D019496:Cancer Vaccines / Q000276:immunology* / Q000627:therapeutic use*; D049109:Cell Proliferation; D003713:Dendritic Cells / Q000276:immunology*; D006801:Humans; D006836:Hydro-Lyases / Q000097:blood; D007167:Immunotherapy; D008545:Melanoma / Q000097:blood / Q000276:immunology* / Q000473:pathology / Q000628:therapy*; D009362:Neoplasm Metastasis / Q000276:immunology / Q000473:pathology / Q000628:therapy; D009414:Nerve Growth Factors / Q000097:blood* / Q000276:immunology*; D011379:Prognosis; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins / Q000097:blood* / Q000276:immunology*; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: D014408:Biomarkers, Tumor; D019496:Cancer Vaccines; D009414:Nerve Growth Factors; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins; C579160:S100B protein, human; D006836:Hydro-Lyases; C045581:lactate dehydratase