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Development of individualized surgical treatments for malignant melanoma

Doctoral thesis
Authors Valerio Belgrano
Date of public defense 2019-06-04
ISBN 978-91-7833-349-3
Publisher Göteborgs universitet
Publication year 2019
Published at Institute of Clinical Sciences, Department of Surgery
Language en
Links hdl.handle.net/2077/59551
Keywords Melanoma, sentinel node, isolated limb perfusion, immune-humanized xenograft mouse models, translational research
Subject categories Surgery

Abstract

Background: Cutaneous melanoma is a malignancy with an increasing incidence worldwide, especially in northern Europe. The aim of this thesis is to scrutinize the results achieved by traditional surgery and the opportunities offered by translational research for the more advanced stages of the disease. Paper I analysed outcomes of sentinel node biopsy (SNB) performed on 769 con-secutive patients with cutaneous melanoma. Breslow thickness was the only pre-dictive factor for a positive SN. The 5-year melanoma specific survival (MSS) was 81% and in multivariate analysis the negative prognostic factors for survival were SN-status, followed by Breslow thickness and ulceration. Paper II reported on 290 consecutive patients who underwent 380 isolated limb perfusion (ILP), of which 90 were re-ILPs. The results between the 1st, the 2nd and the 3-5th were compared. Patients with a complete response at the first treat-ment were likely to have the same response at re-ILP without any increase in the risk for local toxicity or complications. Paper III BRAF mutational status as a predictive factor for response was studied in 98 patients who underwent ILP. In this consecutive series, 32 patients had a BRAF V600E/K mutation and 66 patients were BRAF wild type, and no significant correlation for response or survival was found. Paper IV was a translational study based on patient-derived xenograft models including 21 cutaneous melanoma biopsies transplanted into either NOG or IL-2 transgenic NOG (hIL2-NOG) mice. It was shown that the models reliably could be used to predict the effect of tumour-infiltrating lymphocytes against the tumours. Conclusions: The surgical approach and therapies for patients with cutaneous melanoma are becoming more targeted and personalized. A specialised multidisci-plinary approach can improve the understanding of the disease, support the deci-sion-making process towards the most advantageous treatment options for each individual patient at a specific time.

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