BACKGROUNDYKL‐40 is a growth factor for connective tissue cells and stimulates migration of endothelial cells. Cancer cells, macrophages, and neutrophils secrete YKL‐40. Its function in cancer is unknown. High serum YKL‐40 levels have been associated with a poor prognosis in patients with several solid tumors. The prognostic impact of serum YKL‐40 in metastatic melanoma was evaluated.METHODSYKL‐40 was measured in serial serum samples from 110 patients with metastatic melanoma obtained immediately before and during treatment and from 245 healthy subjects.RESULTSPatients had higher serum YKL‐40 values than healthy subjects (P < 0.001). Pretreatment serum YKL‐40 was elevated in 45% of the patients and correlated to site of metastases (P = 0.03) and poor performance status (P = 0.002). Multivariate Cox analysis showed that serum YKL‐40 (hazard ratio [HR] = 1.9; 95% confidence interval [CI], 1.2–2.8; P = 0.004) and serum lactate dehydrogenase (LDH) (HR = 1.9; 95% CI, 1.2–2.9; P = 0.004) were independent prognostic factors for survival. A combination variable of elevated serum YKL‐40 and LDH quadrupled the risk of early death (HR = 4.4; 95% CI, 2.5–7.7; P < 0.001) compared with patients with normal levels. The combination of YKL‐40 and LDH had a stronger prognostic impact than the American Joint Committee on Cancer (AJCC) Stage IV classification. Furthermore, serum samples were available from 12 patients during followup. In 9 of 11 patients a significant increase in serum YKL‐40 was observed together with disease progression. In one patient with a lasting complete response, serum YKL‐40 remained normal.CONCLUSIONSAn elevated serum YKL‐40 was an independent prognostic factor for poor survival in patients with metastatic melanoma. When combining serum YKL‐40 and LDH, patients could be separated into three prognostic groups based on the number of elevated biomarkers. The findings should be validated in an independent study. Cancer 2006. © 2006 American Cancer Society.

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Timing of CI did not significantly influence the incidence of in-field recurrences, CNS recurrences, or overall survival.

Introduction: Ipilimumab is effective in the treatment of metastatic malignant melanoma, but few biomarkers reliably predict treatment response. Methods: Patients were treated with Ipilimumab for metastatic malignant melanoma. Blood and serum samples were collected before and during treatment. Mononuclear cells in peripheral blood were subjected to immune phenotypic analyses and cytokine levels were measured in serum samples. Results were correlated with clinical data. Results: A total of 40 patients were included in the analyses. Clinical response were associated with an increase after one series of treatment in absolute lymphocyte count (ALC) (p D 0.008), absolute T cell count (p D 0.02) and the absolute number of activated T cells in peripheral blood (p D 0.003). A high frequency of myeloid derived suppressor cells (MDSC) and a higher level of IL6 were associated with treatment failure, though not significantly. Levels of IL6 in serum above the median showed a tendency to associate with reduced survival by the 4th treatment series. Finally, treatment with Ipilimumab led to a decreased frequency of FOXP3C regulatory T cells (p D 0.009). Conclusion: Ipilimumab leads to increased ALC, T cell count and T cell activation in malignant melanoma patients responding to treatment. A high baseline frequency of myeloid-derived suppressor cells and high levels of IL6 is associated with a reduced chance of responding to therapy.

This retrospective study documents that the implementation of targeted therapy has resulted in significantly improved treatment rates and overall survival in a complete national cohort of treated mRCC patients.