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      Baseline relative eosinophil count as a predictive biomarker for ipilimumab treatment in advanced melanoma

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          Abstract

          As diverse therapeutic options are now available for advanced melanoma patients, predictive markers that may assist treatment decision are needed. A model based on baseline serum lactate dehydrogenase (LDH), peripheral blood relative lymphocyte counts (RLC) and eosinophil counts (REC) and pattern of distant metastasis, has been recently proposed for pembrolizumab-treated patients. Here, we applied this model to advanced melanoma patients receiving chemotherapy ( n = 116) or anti-CTLA-4 therapy ( n = 128). Visceral involvement, LDH and RLC were associated with prognosis regardless of treatment. Instead, when compared to chemotherapy-treated patients with REC < 1.5%, those with REC ≥ 1.5% had improved overall survival when receiving anti-CTLA-4 [Hazard Ratio (HR) = 0.56 (0.4–0.93)] but not chemotherapy [HR = 1.13, (0.74–1.74)], and the treatment-by-REC interaction was significant for both overall ( p = 0.04) and progression free survival ( p = 0.009). These results indicate baseline REC ≥ 1.5% as a candidate predictive biomarker for benefit from anti-CTLA-4. Further studies are needed to confirm these findings in patients receiving immune-modulating agents.

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          To revise the staging system for cutaneous melanoma on the basis of data from an expanded American Joint Committee on Cancer (AJCC) Melanoma Staging Database. The melanoma staging recommendations were made on the basis of a multivariate analysis of 30,946 patients with stages I, II, and III melanoma and 7,972 patients with stage IV melanoma to revise and clarify TNM classifications and stage grouping criteria. Findings and new definitions include the following: (1) in patients with localized melanoma, tumor thickness, mitotic rate (histologically defined as mitoses/mm(2)), and ulceration were the most dominant prognostic factors. (2) Mitotic rate replaces level of invasion as a primary criterion for defining T1b melanomas. (3) Among the 3,307 patients with regional metastases, components that defined the N category were the number of metastatic nodes, tumor burden, and ulceration of the primary melanoma. (4) For staging purposes, all patients with microscopic nodal metastases, regardless of extent of tumor burden, are classified as stage III. Micrometastases detected by immunohistochemistry are specifically included. (5) On the basis of a multivariate analysis of patients with distant metastases, the two dominant components in defining the M category continue to be the site of distant metastases (nonvisceral v lung v all other visceral metastatic sites) and an elevated serum lactate dehydrogenase level. Using an evidence-based approach, revisions to the AJCC melanoma staging system have been made that reflect our improved understanding of this disease. These revisions will be formally incorporated into the seventh edition (2009) of the AJCC Cancer Staging Manual and implemented by early 2010.
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              Baseline Biomarkers for Outcome of Melanoma Patients Treated with Pembrolizumab.

              Biomarkers for outcome after immune-checkpoint blockade are strongly needed as these may influence individual treatment selection or sequence. We aimed to identify baseline factors associated with overall survival (OS) after pembrolizumab treatment in melanoma patients.
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                Author and article information

                Journal
                Oncotarget
                Oncotarget
                Oncotarget
                ImpactJ
                Oncotarget
                Impact Journals LLC
                1949-2553
                3 October 2017
                1 August 2017
                : 8
                : 45
                : 79809-79815
                Affiliations
                1 Medical Oncology of Melanoma Unit, Division of Medical Oncology of Melanoma and Sarcoma, European Institute of Oncology, Milan, Italy
                2 Division of Epidemiology and Biostatistics, European Institute of Oncology, Milan, Italy
                3 Division of Surgery of Melanoma and Sarcoma, European Institute of Oncology, Milan, Italy
                4 IV Oncology Division, Istituto Dermopatico dell’Immacolata IRCCS, Rome, Italy
                Author notes
                Correspondence to: Pier Francesco Ferrucci pier.ferrucci@ 123456ieo.it
                Article
                19748
                10.18632/oncotarget.19748
                5668095
                29108362
                5129f7fd-96fb-4281-9bb3-96023126716b
                Copyright: © 2017 Ferrucci et al.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License 3.0 (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 17 May 2017
                : 30 June 2017
                Categories
                Clinical Research Paper

                Oncology & Radiotherapy
                eosinophil,predictive,biomarker,ipilimumab,melanoma
                Oncology & Radiotherapy
                eosinophil, predictive, biomarker, ipilimumab, melanoma

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