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Uveal melanoma (UM) is the most frequent primary ocular cancer in adults, accounting for 5% of all melanomas. Despite effective treatments for the primary tumour, up to 50% of UM patients will develop metastasis, leading to a very poor prognosis and a median overall survival of 6 to 12 months, with no major improvements in the last 30 years. There is no standard oncological treatment available for metastatic UM patients, and BRAF/MEK and immune checkpoint inhibitors show disappointing results when compared to cutaneous melanoma (CM). Recent advances in biology, however, identified specific gene and chromosome alterations, potentially permitting an actively tailored surveillance strategy, and dedicated clinical studies. Being a rare cancer, UM patients have to overcome issues such as identifying referral centres, having access to information, and partnering with oncologists for specific management strategies and research priorities. Here, we describe how the European Rare Adult solid Cancer Network (EURACAN) will help in addressing these challenges and accelerating international collaborations to enhance the development of innovative treatments in UM. [ABSTRACT FROM AUTHOR]

Cutaneous squamous cell carcinoma (cSCC) is one of the most common cancers in Caucasian populations, accounting for 20% of all cutaneous malignancies. A unique collaboration of multi-disciplinary experts from the European Dermatology Forum (EDF), the European Association of Dermato-Oncology (EADO) and the European Organization of Research and Treatment of Cancer (EORTC) was formed to make recommendations on cSCC diagnosis and management, based on a critical review of the literature, existing guidelines and the expert’s experience. The diagnosis of cSCC is primarily based on clinical features. A biopsy or excision and histologic confirmation should be performed in all clinically suspicious lesions in order to facilitate the prognostic classification and correct management of cSCC. The first line treatment of cutaneous SCC is complete surgical excision with histopathological control of excision margins. The EDF–EADO–EORTC consensus group recommends a standardised minimal margin of 5 mm even for low-risk tumours. For tumours, with histological thickness of >6 mm or in tumours with high risk pathological features, e.g. high histological grade, subcutaneous invasion, perineural invasion, recurrent tumours and/or tumours at high risk locations an extended margin of 10 mm is recommended. As lymph node involvement by cSCC increases the risk of recurrence and mortality, a lymph node ultrasound is highly recommended, particularly in tumours with high-risk characteristics. In the case of clinical suspicion or positive findings upon imaging, a histologic confirmation should be sought either by fine needle aspiration or by open lymph node biopsy. In large infiltrating tumours with signs of involvement of underlying structures, additional imaging tests, such as CT or MRI imaging may be required to accurately assess the extent of the tumour and the presence of metastatic spread. Current staging systems for cSCC are not optimal, as they have been developed for head and neck tumours and lack extensive validation or adequate prognostic discrimination in certain stages with heterogeneous outcome measures. Sentinel lymph node biopsy has been used in patients with cSCC, but there is no conclusive evidence of its prognostic or therapeutic value. In the case of lymph node involvement by cSCC, the preferred treatment is a regional lymph node dissection. Radiation therapy represents a fair alternative to surgery in the non-surgical treatment of small cSCCs in low risk areas. It generally should be discussed either as a primary treatment for inoperable cSCC or in the adjuvant setting. Stage IV cSCC can be responsive to various chemotherapeutic agents; however, there is no standard regimen. EGFR inhibitors such as cetuximab or erlotinib, should be discussed as second line treatments after mono- or polychemotherapy failure and disease progression or within the framework of clinical trials. There is no standardised follow-up schedule for patients with cSCC. A close follow-up plan is recommended based on risk assessment of locoregional recurrences, metastatic spread or development of new lesions. [ABSTRACT FROM AUTHOR]

Background: Acquired resistance to BRAF inhibitors (BRAFi) is a near-universal phenomenon caused by numerous genetic and non-genetic alterations. In this study, we evaluated the spectrum, onset, pattern of progression, and subsequent clinical outcomes associated with specific mechanisms of resistance., Methods: We compiled clinical and genetic data from 100 patients with 132 tissue samples obtained at progression on BRAFi therapy from 3 large, previously published studies of BRAFi resistance. These samples were subjected to whole-exome sequencing and/or polymerase chain reaction-based genetic testing., Results: Among 132 samples, putative resistance mechanisms were identified in 58%, including NRAS or KRAS mutations (20%), BRAF splice variants (16%), BRAF(V600E/K) amplifications (13%), MEK1/2 mutations (7%), and non-mitogen-activated protein kinase pathway alterations (11%). Marked heterogeneity was observed within tumors and patients; 18 of 19 patients (95%) with more than one progression biopsy had distinct/unknown drivers of resistance between samples. NRAS mutations were associated with vemurafenib use (p = 0.045) and intracranial metastases (p = 0.036), and MEK1/2 mutations correlated with hepatic progression (p = 0.011). Progression-free survival and overall survival were similar across resistance mechanisms. The median survival after disease progression was 6.9 months, and responses to subsequent BRAF and MEK inhibition were uncommon (2 of 15; 13%). Post-progression outcomes did not correlate with specific acquired BRAFi-resistance mechanisms., Conclusions: This is the first study to systematically characterise the clinical implications of particular acquired BRAFi-resistance mechanisms in patients with BRAF-mutant melanoma largest study to compile the landscape of resistance. Despite marked heterogeneity of resistance mechanisms within patients, NRAS mutations correlated with vemurafenib use and intracranial disease involvement., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Merkel cell carcinoma (MCC) is a rare tumour of the skin of neuro-endocrine origin probably developing from neuronal mechanoreceptors. A collaborative group of multidisciplinary experts form the European Dermatology Forum (EDF), The European Association of Dermato-Oncology (EADO) and the European Organization of Research and Treatment of Cancer (EORTC) was formed to make recommendations on MCC diagnosis and management, based on a critical review of the literature, existing guidelines and expert's experience. Clinical features of the cutaneous/subcutaneous nodules hardly contribute to the diagnosis of MCC. The diagnosis is made by histopathology, and an incisional or excisional biopsy is mandatory. Immunohistochemical staining contributes to clarification of the diagnosis. Initial work-up comprises ultrasound of the loco-regional lymph nodes and total body scanning examinations. The primary tumour should be excised with 1-2cm margins. In patients without clinical evidence of regional lymph node involvement, sentinel node biopsy is recommended, if possible, and will be taken into account in a new version of the AJCC classification. In patients with regional lymph node involvement radical lymphadenectomy is recommended. Adjuvant radiotherapy might be considered in patients with multiple affected lymph nodes of extracapsular extension. In unresectable metastatic MCC mono- or poly-chemotherapy achieve high remission rates. However, responses are usually short lived. Treatment within clinical trials is regarded as a standard of care in disseminated MCC., (Copyright © 2015 Elsevier Ltd. All rights reserved.)