TREATMENT OF METASTATIC MELANOMA Edited by Rachael Morton Treatment of Metastatic Melanoma Edited by Rachael Morton Published by InTech Janeza Trdine 9, 51000 Rijeka, Croatia Copyright © 2011 InTech All chapters are Open Access distributed under the Creative Commons Attribution 3.0 license, which permits to copy, distribute, transmit, and adapt the work in any medium, so long as the original work is properly cited. After this work has been published by InTech, authors have the right to republish it, in whole or part, in any publication of which they are the author, and to make other personal use of the work. Any republication, referencing or personal use of the work must explicitly identify the original source. As for readers, this license allows users to download, copy and build upon published chapters even for commercial purposes, as long as the author and publisher are properly credited, which ensures maximum dissemination and a wider impact of our publications. Notice Statements and opinions expressed in the chapters are these of the individual contributors and not necessarily those of the editors or publisher. No responsibility is accepted for the accuracy of information contained in the published chapters. The publisher assumes no responsibility for any damage or injury to persons or property arising out of the use of any materials, instructions, methods or ideas contained in the book. Publishing Process Manager Sandra Bakic Technical Editor Teodora Smiljanic Cover Designer Jan Hyrat Image Copyright photopixel, 2011. Used under license from Shutterstock.com First published September, 2011 Printed in Croatia A free online edition of this book is available at www.intechopen.com Additional hard copies can be obtained from orders@intechweb.org Treatment of Metastatic Melanoma, Edited by Rachael Morton p. cm. ISBN 978-953-307-574-7 free online editions of InTech Books and Journals can be found at www.intechopen.com Contents Preface IX Part 1 Treatment Options for Cutaneous Melanoma 1 Chapter 1 Cutaneous Metastases from Malignant Melanoma: Clinical Features and New Therapeutic Perspectives 3 Paola Savoia, Paolo Fava and Maria Grazia Bernengo Part 2 Surgical Treatment of Melanoma 15 Chapter 2 Impact of Sentinel Node Biopsy on Outcome in Melanoma 17 Justin Kelly and MJ Kerin Chapter 3 Management of Head and Neck Melanoma 29 James H F Shaw and Michael Fay Chapter 4 Diagnosis and Treatment Options for Brain Metastasis of Melanoma 47 Khan K. Chaichana and Kaisorn L. Chaichana Part 3 Targeted Chemotherapy and Immunotherapy 71 Chapter 5 Chemotherapy 73 Aylin Türel Ermertcan, Ferdi Öztürk and Kamer Gündüz Chapter 6 Chemocentric Chemoimmunotherapy: A New Concept in Melanoma Immunotherapy 91 Paul Howell, Soroosh Radfar, Yixiang Wang and Hung Khong Chapter 7 Melanoma Immunomodulation: A War of Attrition 115 Bently P. Doonan, Jessica D. Hathaway and Azizul Haque Chapter 8 Simultaneous Knockdown of Mutant BRAF and Expression of INK4A in Melanoma Cells Leads to Potent Growth Inhibition and Apoptosis 149 Jianli Dong and Chet L. Schwab VI Contents Chapter 9 Promising Experimental Therapies for Metastatic Melanoma 183 Bao Lam, Patrick A. Ott and Anna C. Pavlick Part 4 Electrochemotherapy 207 Chapter 10 The Role of Electrochemotherapy in the Treatment of Malignant Melanoma 209 Mecker G. Möller, Slawomir Salwa, Declan M. Soden and Gerald C. O’Sullivan Chapter 11 Pulse Power Ablation of Melanoma with Nanosecond Pulsed Electric Fields 231 Stephen J. Beebe, Wentia E. Ford, Wei Ren and Xinhua Chen Part 5 Photodynamic Therapy 269 Chapter 12 Can Photodynamic Therapy Be an Alternative Method in Melanoma Treatment? 271 Anna Choromańska, Julita Kulbacka, Agnieszka Chwiłkowska, Nina Skołucka, Andrzej Gamian and Jolanta Saczko Part 6 Clinical Trials 295 Chapter 13 Update on Clinical Trials for Malignant Melanoma 297 Raffaele Califano, Ruth Board, Aidalena Z Abidin, Louise Carter, Laura Cove-Smith, Bihani Kularatne and Paul Lorigan Part 7 Treatment of Oral and Uveal Melanoma 319 Chapter 14 Oral Malignant Melanoma 321 Thomas Mücke, Anna Borgmann, Klaus-Dietrich Wolff and David Andrew Mitchell Chapter 15 Choroidal Melanoma 337 Raquel Correa, Mario Lobato and José Antonio Medina Preface The National Cancer Institute in the United States estimates that more than 70,000 new cases of melanoma will be diagnosed in the US in 2011 with the disease causing approximately 8,790 deaths. The highest incidence of cutaneous melanoma is seen in Australia and New Zealand where it represents 9.5% of all cancers. Here the risk of being diagnosed by age 85 is 1 in 15 for men and 1 in 24 for women. The risk of melanoma increases with exposure to ultra-violet radiation, increased numbers of dysplastic naevi, immunosuppression, a history of melanoma in a first degree relative, fair skin with light eye or hair colour, and a previous history of melanoma or non- melanoma skin cancer. The classification of cutaneous melanoma is according to the American Joint Cancer Committee (AJCC)/UICC melanoma staging system (2009). The diagnosis of melanoma is confirmed by surgical excision and histological examination of the biopsy specimen, with superficial spreading melanoma the most common histological type. The staging of melanoma is based on tumour characteristics that include Breslow thickness, Clark level of invasion, tumour mitotic rate and ulceration (stage I/II); the involvement of lymph nodes (stage III); and the involvement of distant sites such as skin or other organs (stage IV). While the five-year survival for patients with stage I or II melanoma ranges from 53-97% depending on sub-stage, patients diagnosed with stage IV disease have a considerably worse outcome. In disease localized to the primary tumor site and/or lymph nodes, surgery remains the mainstay of treatment of this malignancy. Many improvements in surgical techniques have occurred in the last decade, including sentinel node biopsy for the staging of patients with of cutaneous melanoma of intermediate thickness. Adjuvant radiotherapy to regional lymph node fields is often recommended after surgery for patients at high risk of relapse. Isolated limb perfusion, electrochemotherapy, and photodynamic therapy continue to be evaluated for treatment of stage IV disease. However, the greatest excitement in new treatment has been with the targeted therapies for genetic mutations. In particular, there have been promising results with partial and complete tumor responses in stage IV disease from early phase trials of the B-RAF kinase inhibitors. This book provides an insight into the current therapeutic treatment options for patients with metastatic melanoma and is relevant to clinicians and researchers X Preface worldwide. In addition, an update on current clinical trials for melanoma treatment has been included, and two chapters have been included in which the treatment of oral and uveal melanoma is discussed. Rachael Morton, MScMed(Clin Epi)(Hons) Research Fellow, Sydney Medical School, The University of Sydney Executive Member, Australia and New Zealand Melanoma Trials Group (ANZMTG) [...]... survival in patients with metastatic melanoma Cancer 2007; 110: 1791-1795 Olsen G.Some views on the treatment of melanomas of the skin.Arch Chir Neerl 1970;22(2):79-90 Quaglino P, Mortera C, Osella-Abate S, Barberis M, Illengo M, Rissone M, Savoia P & Bernengo MG Electrochemotherapy with intravenous bleomycin in the local 14 Treatment of Metastatic Melanoma treatment of skin melanoma metastases.Ann Surg... of melanoma including frozen section analysis of the sentinel node, imprint cytology of the sentinel node, targeted assessment of the regional lymph node basin, the use of risk stratification algorithms of histological factors of the primary tumour and microRNAs 2 Impact of sentinel node biopsy on outcome in melanoma The key to survival for patients with melanoma is early detection and treatment of metastatic. .. ulceration of cutaneous tumours, local infectious complications and to ensure an acceptable quality of life 10 Treatment of Metastatic Melanoma 7.4 Radiotherapy The effectiveness of radiotherapy in the treatment of melanoma metastases is still debated A poor response was historically observed on in vitro cultures from melanoma cells treated with external-beam radiation (Barranco, Romsdahl & Humphrey 1971) So,... interleukin-2 treatment of 72 melanoma patients and response upon the first chemotherapy during follow-up Cancer Immunol Immunother 2010; Dec 21 WHO From Handbook for Reporting Results of Cancer Treatment, vol 48; Geneva, 1997 Wolf IH, Richtig E, Kopera D & Kerl H Locoregional cutaneous metastases of malignant melanoma and their management Dermatol Surg 2004; 30: 244-247 Part 2 Surgical Treatment of Melanoma. .. aims of this book chapter are 1 to examine the impact of sentinel node biopsy on outcome in melanoma, 2 determine the effect, if any, of stage migration in melanoma 3 to clarify the impact of the different clinical sites on outcome, 4 to ascertain the reasons behind a lack of universal adoption of sentinel node biopsy in melanoma and 5 to critically assess other emerging strategies in the management of. .. controlled study of electrochemotherapy in the local treatment of skin metastases of melanoma J Cutan Med Surg 2006 May-Jun; 10(3): 115-121 Gibson SC, Byrne DS & Mc Kay AJ Ten-year experience of carbon dioxide laser ablation as treatment for cutaneous recurrence of malignant melanoma Br J Surg 2004; 91: 893895 Gimbel MI, Delman KA & Zager JS Therapy for unresectable recurrent and in-transit extremity melanoma. .. patients with melanoma, 5- and 10-year KaplanMeier survival probabilities for scalp/neck melanoma were 83.1% and 76.2%, respectively, compared with 92.1% and 88.7%, respectively, for melanoma of the other sites, including extremities, trunk, face, and ears They found that patients with melanoma of the scalp/neck had an 84% greater chance of melanoma- related death compared with those with melanomas of the... the peripheral blood was observed (Brossart et al 1995), associating the rate of positivity with stage of the disease There is accumulating evidence to support the use of targeted ultrasound assessment of the regional nodal basin at the time of diagnosis of the primary tumour, thus enhancing routine 24 Treatment of Metastatic Melanoma clinical palpation It is possible to identify deposits as small as... site of metastatic involvement after the primary melanoma diagnosis In about one third of cases, patients develop skin involvement after evidences of regional lymph nodal metastatic disease The finding of concomitant distant cutaneous, visceral and nodal metastases account for more than 10% of cases, whereas skin involvement after visceral dissemination is rare, and occurs only in about the 3% of patients... 18 Treatment of Metastatic Melanoma Grover, and Sanders 2004) The status of the regional lymph node basin has been widely shown to be the most important prognostic indicator for patients diagnosed with cutaneous melanoma (Balch et al 2001) The disease-free survival and overall survival is dependent on the initial disease burden, thus melanomas less than 1mm rarely metastasise while at least 25% of melanomas . TREATMENT OF METASTATIC MELANOMA Edited by Rachael Morton Treatment of Metastatic Melanoma Edited by Rachael Morton Published. features of local recurrences that are defined as the reappearance of melanoma in or contiguous with an excision scar or graft and bearing an in situ component. Treatment of Metastatic Melanoma. Therapies for Metastatic Melanoma 183 Bao Lam, Patrick A. Ott and Anna C. Pavlick Part 4 Electrochemotherapy 207 Chapter 10 The Role of Electrochemotherapy in the Treatment of Malignant Melanoma