title: Changes of ferritin and CRP levels in melanoma patients treated with adjuvant interferon-α (EORTC 18952) and prognostic value on treatment outcome.
abstract: Adjuvant therapy with interferon-α (IFN) only benefits a small subgroup of melanoma patients and a predictive marker selecting responders does not exist. IFN induces increased ferritin and decreased C-reactive protein (CRP) levels; however, an association with treatment effect was not studied. Serum was collected from patients participating in the European Organization for Research and Treatment of Cancer 18 952 trial comparing adjuvant treatment with IFN to observation. Serial ferritin and CRP levels were determined using enzyme-linked immunosorbent assays, before treatment and up to 24 months. Ferritin levels are influenced by sex and age; therefore ratios of serial ferritin and CRP values with corresponding pretreatment values were calculated. Cox regression model and landmark method at end of induction and 6 months were used to evaluate the association between ferritin, CRP and distant metastasis-free survival (DMFS). Baseline ferritin levels were comparable in the two treatment groups (P=0.92). However, ferritin ratios were significantly higher in IFN-treated patients (N=96) compared with untreated patients (N=21) at end of induction (mean: 2.88 vs. 0.75; P=0.0003) and at 6 months (mean: 3.18 vs. 1.02; P=0.009). In the IFN arm, higher ferritin ratios at end of induction and at 6 months were not associated with improved outcome (respectively, P=0.66 and 0.86). Concerning CRP ratios, no differences between the treatment groups, neither an association with DMFS, were observed. Administration of IFN in melanoma patients induced increase in ferritin levels but not in CRP levels. Ferritin and CRP ratios have no prognostic value regarding DMFS.
authors.affiliation: Laboratory Experimental Surgical Oncology, Section Surgical Oncology, Department of Surgery, Erasmus MC, Rotterdam 3015 GE, The Netherlands. m.bouwhuis@erasmusmc.nl
authors.forename: Marna G
authors.initials: MG
authors.lastname: Bouwhuis
authors.forename: Sandra
authors.initials: S
authors.lastname: Collette
authors.forename: Stefan
authors.initials: S
authors.lastname: Suciu
authors.forename: Els R
authors.initials: ER
authors.lastname: de Groot
authors.forename: Wim H
authors.initials: WH
authors.lastname: Kruit
authors.forename: Timo L M
authors.initials: TL
authors.lastname: Ten Hagen
authors.forename: Lucien A
authors.initials: LA
authors.lastname: Aarden
authors.forename: Alexander M M
authors.initials: AM
authors.lastname: Eggermont
authors.forename: Antonius J G
authors.initials: AJ
authors.lastname: Swaak
mesh_terms: D000367:Age Factors; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000378:metabolism*; D017024:Chemotherapy, Adjuvant; D018572:Disease-Free Survival; D004797:Enzyme-Linked Immunosorbent Assay; D005060:Europe; D005260:Female; D005293:Ferritins / Q000097:blood*; D006801:Humans; D007370:Interferon Type I / Q000627:therapeutic use*; D008197:Lymph Node Excision; D008297:Male; D008545:Melanoma / Q000097:blood / Q000188:drug therapy* / Q000276:immunology / Q000556:secondary / Q000601:surgery; D008875:Middle Aged; D009367:Neoplasm Staging; D016016:Proportional Hazards Models; D011994:Recombinant Proteins; D018570:Risk Assessment; D012307:Risk Factors; D012737:Sex Factors; D012878:Skin Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology / Q000601:surgery; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D015415:Biomarkers; D007370:Interferon Type I; D011994:Recombinant Proteins; D002097:C-Reactive Protein; D005293:Ferritins