Melanoma Management最新文献

Giuseppe Argenziano speaks to Sebastian Dennis-Beron, Commissioning Editor: Giuseppe Argenziano is Full Professor and Head of the Dermatology Unit at the University of Campania, Naples, Italy. His main research field is dermato-oncology. He is an author of numerous scientific articles and books concerning dermoscopy, a new technique improving the clinicians detection of benign and malignant skin tumors. As a coordinator of a Skin Cancer Unit, he has established a successful tertiary, multidisciplinary, referral center particularly devoted to the diagnosis and management of patients with skin tumors. Over the past 20 years he has supervised over 100 foreign students and 40 residents in dermatology, established scientific collaborations with more than 200 colleagues from more than 30 nations, and organized more than 50 national and international scientific activities, courses and conferences (such as the Consensus Net Meeting on Dermoscopy and the First Congress of the International Dermoscopy Society). He is co-founder and past president of the International Dermoscopy Society; project leader for the development of a high diagnostic technology oncologic center at the Arcispedale Santa Maria Nuova IRCCS in Reggio Emilia; faculty member of the Master of Science in Dermoscopy and Preventive Dermato-oncology and has undertaken a short course in dermoscopy, two e-learning courses by the Medical University of Graz and by Cardiff University, respectively; and member of the Editorial Board of the Journal of the American Academy of Dermatology. Professor Argenziano has authored more than 400 full scientific articles and produced landmark primary publications and books in the field of dermoscopy. Over the past 20 years, he has been invited as speaker and/or chairman in more than 500 national and international conferences in the field of dermatology. His combined publications have received a sum total of more than 8000 citations with an h-index value of 46.

Melanoma is usually apparent on the skin and readily detected by trained medical providers using a routine total body skin examination, yet this malignancy is responsible for the majority of skin cancer-related deaths. Currently, there is no national consensus on skin cancer screening in the USA, but dermatologists and primary care providers are routinely confronted with making the decision about when to recommend total body skin examinations and at what interval. The objectives of this paper are: to propose rational, risk-based, data-driven guidelines commensurate with the US Preventive Services Task Force screening guidelines for other disorders; to compare our proposed guidelines to recommendations made by other national and international organizations; and to review the US Preventive Services Task Force's 2016 Draft Recommendation Statement on skin cancer screening.

Melanoma is the deadliest form of skin cancer and one of the few malignancies whose incidence is on the rise. The treatment of metastatic melanoma continues to be quite challenging, although in recent years, there has been significant progress. Current National Comprehensive Cancer Network guidelines list immunotherapy, chemotherapy, surgery and clinical trials as potential options for patients with metastatic disease but do not clearly recommend which is superior. Additionally, when utilizing combined modality treatment there are no clear guidelines for the optimal timing of surgery in the treatment of metastatic melanoma. In this paper we sought to compile the current evidence and on-going trials in order to provide a comprehensive review of the different options available and underway in regards to the treatment of metastatic melanoma. It is clear that with the responses now seen with systemic immunotherapies and targeted therapies, an expanded role for surgery is the logical next step.

Immunotherapy has radically transformed the management of metastatic malignant melanoma. Ipilimumab, a CTLA-4-targeted monoclonal antibody, was the first immunotherapeutic drug to reach a survival benefit compared with traditional chemotherapy. PD-1 targeted therapies, pembrolizumab and nivolumab, have demonstrated, in recent clinical trials, to be even more effective and safer. PD-1 and CTLA-4 blockade combination appears to improve the outcomes achieved so far, although increasing toxicity. However, many questions concerning the optimal timing of administration or the most adequate sequence of treatment are yet to be answered.

The extent and timing of regional lymphadenectomy and its role in patients with clinically localized primary melanoma has been the subject of considerable debate. While therapeutic lymphadenectomy for clinically positive nodes is uniformly accepted, the benefit of regional lymphadenectomy in patients with clinically uninvolved lymph nodes potentially harboring micrometastatic disease is less clear. Efforts to better select patients for complete regional lymphadenectomy after sentinel lymph node biopsy are underway. The future holds the promise of more stringent selection criteria and perhaps the identification of subgroups of patients for which a therapeutic benefit may be realized. Moreover, novel sensitive radiological techniques for detecting in vivo micrometastatic nodal disease may improve surgical precision, further decreasing potential morbidities of lymphadenectomy.

Advances in immune therapy have changed the landscape of advanced melanoma treatment. Intralesional therapy is an important type of immune therapy due to its efficacy and safety, especially in the setting of locoregional metastases. These therapies induce frequent responses in injected lesions as well as distant nontreated lesions through a 'bystander' effect of priming an antitumor immune response. The culmination of nearly a century of innovation has led to the approval of the first US FDA approved intralesional therapy for melanoma in talimogene laherparepvec. Numerous efforts to combine intralesional therapies with systemic immune checkpoint inhibitors are ongoing, whereby a synergistic effect may continue to improve outcomes for patients.

Administering dendritic cells (DC) loaded with tumor-associated antigens (TAA) ex vivo is a promising strategy for therapeutic vaccines in advanced melanoma. To date the induction of immune responses to specific TAA has been more impressive than clinical benefit because of TAA limitations, suboptimal DC and possibly immune-checkpoint inhibition. Various products, antigen-loading techniques, treatment schedules, routes of administration and adjunctive agents continue to be explored. Biologic heterogeneity suggests autologous tumor as the optimal TAA source to induce immune responses to the entire repertoire of unique patient-specific neoantigens. Many questions remain regarding the optimal preparation of DC and strategies for antigen loading. Effective DC vaccines should result in additive or synergistic effects when combined with checkpoint inhibitors.

Talimogene laherparepvec (T-VEC, Imlygic^®, Amgen, CA, USA) is an oncolytic herpes simplex type 1 virus used as intralesional therapy for unresectable metastatic melanoma in a cutaneous, subcutaneous or nodal location. Talimogene laherparepvec selectively replicates within and lyses tumor cells while producing granulocyte macrophage colony-stimulating factor, which may promote an immune mediated antitumor response. The US FDA approved T-VEC in late 2015 following Phase I-III trials that demonstrated safety and efficacy. Future directions for T-VEC include combination therapies with other systemic immunotherapies such as anti-CTLA-4 antibody and anti-PD-1 drugs. Current National Comprehensive Cancer Network (NCCN) practice guidelines have added T-VEC as a primary treatment for stage IIIB/C and stage IVM1a melanoma patients.