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.

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Serum YKL-40 may be an early biomarker of relapse and survival in patients with AJCC stage I and II melanoma. Serum YKL-40 may also be useful for patient stratification and follow-up in clinical trials. Our results need confirmation in an independent study.

Purpose: We did a phase I dose-escalation trial to evaluate the feasibility and safety of intratumoral injections of C Cure 709, an allogeneic, continuous CTL cell line that, restricted by HLA-A2, recognizes MART-1-positive tumor cells through transduction with aT-cell receptor encoding gene. Experimental Design: Cells were administered intratumorally in four dose levels ranging from 10 8 to 10 9 cells/d on days 1, 4, 7, 10, 14, and 28 of each treatment cycle to patients with metastatic melanoma. Main inclusion criteria were HLA-A2 tissue type, MART-1-positive tumor cells, and metastases suitable for ultrasound-guided injections. Patients were assessed for toxicity and response. Three to six patients were treated per dose level. Patients without progressive disease were offered up to three treatment cycles. Results: Fifteen patients received a total of 24 treatment cycles with a total of 266 injections of C Cure 709.Toxicity was minor to moderate and most common injection site reactions were fever, fatigue, nausea/vomiting, and arthralgia/myalgia. Side effects disappeared in general within 24 hours. Toxicity was not dose dependent. One patient obtained a partial response, encompassing both metastases used and not used for intratumoral injections. Remaining patients did not achieve an overall response. In addition, we observed local regression of metastases used for injection in two patients and of metastases not used for injection in one patient. Conclusion: Intratumoral injections of C Cure 709 are feasible, safe, and capable of inducing tumor regression. Further investigation in a phase II setting is warranted.