Future of radiation therapy for malignant melanoma in an era of newer, more effective biological agents

• Type of Material: Article
• Authors: Mohammad Khan, Emory University; Niloufer Khan, Case Western Reserve University School of Medicine; Alex Almasan, Cleveland Clinic; Roger Macklis, Cleveland Clinic
• Language: English
• Date: 2011-01-01
• Publisher: Dove Medical Press
• Publication Version: Final Published Version
• Copyright Statement: © 2011 Khan et al, publisher and licensee Dove Medical Press Ltd.
• License: Creative Commons Attribution-Noncommercial 3.0 Unported
• Final Published Version (URL): http://dx.doi.org/10.2147/OTT.S20257
• Title of Journal or Parent Work: OncoTargets and Therapy
• ISSN: 1178-6930
• Volume: 4
• Start Page: 137
• End Page: 148
• Grant/Funding Information: We would like to thank Mr Gaurav Choudhary (Case Western Reserve University) for help with illustrations and the National Institutes of Health for partial support to AA.
• Keywords: GAMMA-KNIFE RADIOSURGERY; Oncology; POSTOPERATIVE RADIOTHERAPY; CUTANEOUS MELANOMA; brachytherapy; Biotechnology & Applied Microbiology; Life Sciences & Biomedicine; systemic agents; Science & Technology; radiosurgery; BRAIN METASTASES; hypofractionation radiotherapy; METASTATIC MELANOMA; melanoma cell cycle; BIOTECHNOLOGY & APPLIED MICROBIOLOGY; 2 CM; targeted biologic agents; HIGH-RISK MELANOMA; EXCISION MARGINS; ADJUVANT THERAPY; CELL-PROLIFERATION; ONCOLOGY
• Research Categories: Health Sciences, General; Health Sciences, Oncology; Health Sciences, Radiology

Abstract

The incidence of melanoma is rising. The primary initial treatment for melanoma continues to be wide local excision of the primary tumor and affected lymph nodes. Exceptions to wide local excision include cases where surgical excision may be cosmetically disfiguring or associated with increased morbidity and mortality. The role of definitive or adjuvant radiotherapy has largely been relegated to palliative measures because melanoma has been viewed as a prototypical radiotherapy-resistant cancer. However, the emerging clinical and radiobiological data summarized here suggests that many types of effective radiation therapy, such as radiosurgery for melanoma brain metastases, plaque brachytherapy for uveal melanoma, intensity modulated radiotherapy for melanoma of the head and neck, and adjuvant radiotherapy for selected highrisk, node-positive patients can improve outcomes. Similarly, although certain chemotherapeutic agents and biologics have shown limited responses, long-term control for unresectable tumors or disseminated metastatic disease has been rather disappointing. Recently, several powerful new biologics and treatment combinations have yielded new hope for this patient group. The recent identification of several clinically linked melanoma gene mutations involved in mitogenactivated protein kinase (MAPK) pathway such as BRAF, NRAS, and cKIT has breathed new life into the drive to develop more effective therapies. Some of these new therapeutic approaches relate to DNA damage repair inhibitors, cellular immune system activation, and pharmacological cell cycle checkpoint manipulation. Others relate to the investigation of more effective targeting and dosing schedules for underutilized therapeutics, such as radiotherapy. This paper summarizes some of these new findings and attempts to give some context to the renaissance in melanoma therapeutics and the potential role for multimodality regimens, which include certain types of radiotherapy as aids to locoregional control in sensitive tissues.