The strengths of our study are a relatively large sample size and the robustness of the YKL-40 protein to TWS119 601514-19-6 multiple thawing/ refreezing cycles and to delays in processing of plasma samples, for up to 3 hours. Moreover, there is no circadian variability in plasma YKL-40, and the YKL-40 ELISA has a low long-term CV. These characteristics make our results reliable, and the YKL-40 analysis is attractive in the clinical setting where plasma YKL-40 may be used as a factor in risk stratification of patients with mCRC and selection of treatment. Our study had some limitations, firstly it was a retrospective biomarker exploratory study, and may suffer from multiple comparison data fitting. Secondly, the NORDIC VII Study did not meet its endpoint, i.e. it failed to show a significant benefit of adding cetuximab to NORDIC FLOX regimen in first-line treatment of patients with mCRC. It was therefore not possible to estimate whether plasma YKL-40 could be a predictive biomarker for response to cetuximab treatment. In conclusion, plasma YKL-40 is a new, independent prognostic biomarker in patients with mCRC treated with first-line oxaliplatin-based therapy, with or without cetuximab. Furthermore, our results show that changes in plasma YKL-40 during treatment may be useful for monitoring cancer progression. The predictive value of plasma YKL-40 could not be clarified. Patients with palpable regional lymphatic involvement with melanoma carry a risk of relapse and death that approaches 70% at 5 years. The development of local or regional recurrence after initial surgical management portends an even poorer prognosis. In the Melanoma Surgical Trial, a local recurrence was associated with 5 and 10 year survival rates of 9–11% and 5%, respectively. Neoadjuvant therapy has been demonstrated to improve outcome in the management of patients with multiple different solid tumors. A further significant advantage of the neoadjuvant approach in relation to translational investigations of new agents is the ability to evaluate the clinical and pathologic responses, and the access to tumor tissue before and after neoadjuvant therapy. This allows a direct assessment of the antitumor mechanisms that may enable selective application of therapeutic agents to those patients most likely to benefit. Ipilimumab is a human immunoglobulin-G k antiCTLA-4 monoclonal antibody. It was approved by the U.S. FDA for the treatment of advanced inoperable melanoma in March 2011 at a dose of 3 mg/kg given every 3 weeks for 4 doses, based on the results of a phase III trial. Prior data suggested a dose dependent effect of ipilimumab from 0.3 mg/kg to 10 mg/ kg, where 10 mg/kg appeared to have the greatest efficacy, but the rate of high-grade immune related adverse events was also dose dependent. Based on these and other data, ipilimumab at 10 mg/kg was taken forward for phase II and phase III studies including the CA184024 trial in metastatic disease combined with dacarbazine and the adjuvant trials EORTC18071 and E1609.