Advances and trends in dermato-oncology

Abstract

The 6th Congress of the European Association of Dermato-Oncology, held in Athens, Greece (16–19 June 2010), focused on the most recent advances in the field of melanoma, epithelial skin cancers and other malignant skin tumors. Under the theme ‘transforming care through personalized medicine’, the scientific program reviewed and discussed the significant changes that are currently taking place in many aspects of skin cancer care, from risk prediction and prevention to the use of targeted treatments. This article highlights the key messages from selected presentations that feature the remarkable progress in our understanding of the pathogenesis of skin malignancies and the rapid ‘translation’ of this knowledge into new effective treatments in clinical practice.

The European Association of Dermatologic Oncology (EADO) organized the 6th EADO congress in Athens, Greece, from 16 to 19 June 2010. Nearly 600 participants from 35 countries participated in this international multidisciplinary scientific meeting. The scientific program of the congress focused on the advances and trends in the management of melanoma and skin cancer patients in the era of molecular medicine. Although melanoma was the primary focus of the program, an equal number of sessions were dedicated to cover the entire spectrum of skin cancers, including epithelial skin cancers, lymphoma, Merkel cell carcinoma and Kaposi sarcoma. During the 3 days of the congress, the scientific sessions reviewed in a step-wise fashion the diverse but interconnected aspects of these tumors, spanning from their epidemiology, biology and genetics, to the results of the most recent therapeutic trials [1]. In this article, we review selected presentations that best reflect the improved understanding of the biology of melanoma and skin tumors, and the changing landscape in their diagnosis and management.

Advances in melanoma & skin cancer: towards a molecular classification & targeted treatment

The meeting officially opened with a keynote address by Boris Bastian (Memorial Sloan–Kettering Cancer Center, NY, USA) on the molecular classification of melanocytic neoplasias. Melanoma can now be classified based on molecular characteristics that correspond to distinct clinical phenotypes. Tumors harboring BRAF mutations mainly affect younger patients with many nevi, and the primary tumor involves intermittently sun-exposed sites. On the other hand, melanomas harboring NRAS and KIT mutations mainly affect older patients with the primary tumor located on chronically sun-exposed sites, palms, soles, nail beds and mucosa. Of note, NRAS mutations are characteristic of giant congenital nevi (found in 80% of these nevi). GNAQ mutations predominate in blue nevi (70%) and uveal melanoma (50%), while HRAS mutations are found in 20% of Spitz nevi [2]. These findings may provide criteria for a more refined melanoma classification.

In his keynote address on the first day of the congress, Hensin Tsao (Massachusetts General Hospital, Harvard Medical School, MA, USA) expanded on the theme of the Congress by reviewing how our knowledge of the genetic basis of melanoma can be used to generate personalized evaluation and management of high-risk patients; that is, patients with a family history of melanoma, sun-sensitive phenotype and a high nevus count. CDKN2A mutations occur in 2.9% of individuals with multiple primary melanomas and in 1.2% of individuals with single primary melanoma [3,4]. Sun-sensitive individuals with fair eye, hair or skin color, genetically determined by variants of pigmentation genes such as melanocortin 1 receptor (MC1R), ASIP, tyrosinase (TYR), TYRP-1, oculocutaneous albinism (OCA2) and SLC24A4, are at an increased risk for melanoma. A high melanocytic nevus count is the strongest risk factor for cutaneous melanoma and genome-wide association studies have revealed new susceptibility loci at chromosomes 9p21 and 22q13 shared by both nevi and melanoma. Genetic risk testing may be offered to high-risk individuals, with drawbacks including the investigation of only a few loci (CDKN2A p16 coding region) and medium analytical validity. Tsao concluded that phenotype-based medicine (based on family history of melanoma, fair skin color and nevi number) is evolving to genotype-based medicine (based on mutations/polymorphisms of CDKN2A, MC1R, TYR, TYRP1 and ASIP genes).

In his keynote lecture, Axel Hauschild (University of Kiel, Germany) discussed targeted treatment modalities for skin cancer. As EGF receptor expression has been demonstrated in most squamous cell carcinomas (SCCs), a Phase II multicenter trial used an EGF receptor inhibitor (cetuximab 400 mg/m² followed by 250 mg/m² twice weekly) in 36 patients with advanced or metastatic SCC, with response in 32% of patients. As patched mutations result in the activation of the Sonic Hedgehog signaling pathway and basal cell carcinoma (BCC) growth, a Phase I trial of 33 patients with advanced BCC evaluated treatment with an oral Hedgehog signaling pathway inhibitor (GDC-0449), and showed a good efficacy and safety profile, with 54% of treated patients showing complete or partial responses. In addition, imatinib, which inhibits the PDGF signaling pathway, blocking tumor cell proliferation, has been used with impressive results in patients with dermatofibrosarcoma protuberans. Likewise, the molecular classification of melanoma will unravel distinct molecular subtypes of ‘melanomas’, which will be more likely to profit from targeted treatments [5,6]. The use of imatinib 400 mg/day in 35 stage IV melanoma patients with either c-Kit mutations or amplifications led to partial responses in 20% of patients and stable disease in 40% of patients. A Phase III trial of nilotinib (800 mg/day) versus dacarbazine (1000 mg/m²) for c-kit-mutated melanomas is currently underway. Phase I/II trials of the use of selective inhibitors of oncogenic mutant BRAF kinase (BRAFV600E) in patients with metastatic melanoma showed 63–70% partial response. A randomized Phase III trial on GSK2118436, a B-Raf inhibitor, versus dacarbazine in 670 previously untreated BRAF-mutant metastatic melanoma patients is designed to start in 2010. Based on encouraging results from a preliminary trial, a Phase III trial was recently initiated to evaluate adjuvant immunotherapy with MAGE-A3 in metastatic melanoma in 1300 patients.

Primary & secondary prevention of melanoma

Strategies for melanoma control include primary prevention of causal factors beginning as early as childhood, secondary prevention with screening and detection of melanoma at an early stage, and tertiary prevention aiming to halt progression of the tumor.

Cynthia Holterhues (Erasmus Medical Center, Rotterdam, The Netherlands) began the session by talking about the increasing incidence of cutaneous malignant melanoma in European countries with a higher incidence for women, but a higher mortality/incidence ratio for men. Although higher incidence rates are predicted for Scandinavia and The Netherlands, a higher mortality/incidence ratio is found in Eastern Europe. Existing data demonstrate a high percentage of stage III/IV melanoma in Ireland, Slovakia, Slovenia, Italy and Spain. David Whiteman (Queensland Institute of Medical Research, Queensland, Australia) presented melanoma development as a complex process influenced by environmental factors (UV radiation [UVR]), constitutional and somatic genotype and phenotypic characteristics (patient age and tumor location). Constitutional genotypes (MC1R, ASIP, MTAP, OCA and TYR1) are important determinants of risk within populations, and different somatic genotypes (BRAF, NRAS, TP53, CDKN2A and PTEN) reflect different causal pathways in melanoma. BRAF-mutant melanomas mainly affect younger patients, with a high nevus count, sun exposure early in life and trunk location, while p53-mutant melanomas affect older patients, with a low nevus count, accumulated sun exposure and head/neck location. Thus, melanomas should be analyzed according to anatomic site, histology and host phenotype for a better understanding of the complex pathways of melanoma pathogenesis.

Sabine Kruger-Krasagakis (University of Crete, Greece) discussed the supporting evidence of the role of vitamin D3 in melanomagenesis, that is, inhibition of tumor proliferation, apoptosis of human melanoma cell lines in vitro, and inhibition of melanoma migration, invasion and metastasis in vivo in mice. Higher vitamin D serum levels have been associated with lower Breslow thickness and are independently protective of relapse or death [7]. Almost 200 polymorphisms of the VDR gene have been found, but their association with melanoma risk has not been substantiated. Further research is needed to study the correlation of baseline 25(OH)₂D3 serum concentrations with melanoma progression, to investigate the protective role of dietary vitamin D intake and to decipher VDR protein signaling [7]. Veronique Bataille (Hemel Hempstead General Hospital, Hemel Hempstead, UK) elucidated the relationship between sunbed use and the formation of nevi and melanoma. A meta-analysis of case–control studies showed a slightly increased melanoma risk in sunbed users, with those with fair skin type I/II and exposure during early adulthood being at a significantly increased risk (odds ratio: 2.66; 95% CI: 1.66–6.09). The reported mean time between exposure to sunbeds and melanoma development was 7 years. In addition, sunbed use appears to be nevogenic, resulting in an increased count of common nevi (but not of large atypical nevi), which in turn is an important risk factor for melanoma.

Iris Zalaudek (Medical University of Graz, Austria), explained that nevi patterns depend on the individual’s age, skin type and genetic background. A dual concept of nevogenesis has been proposed by the correlation of age-related dermoscopic, clinical, epidemiologic and histopathologic features of acquired nevi [8]. Dermoscopically globular nevi (i.e., congenital melanocytic nevi, compound and dermal nevi) with dermal proliferations develop via an ‘endogenous’ pathway involving mutations of c-kit, c-met or N-ras (but not of BRAF) that may cause melanoblast migration arrest in the dermis. These nevi are stable and commonly persist throughout life. By contrast, reticular nevi (i.e., junctional nevi) with epidermal proliferations develop in response to ‘exogenous’ factors such as intermittent UVR exposure. These nevi are dynamic and their number increases before midlife but decreases thereafter. The prevalence of such nevi in non-chronically sun-exposed skin sites may be attributed to BRAF mutations in melanocytic stem cells at the dermoepidermal junction, caused by UVR exposure.

Melanoma thickness trends in France and the USA demonstrate an increase in thin melanomas (<1 mm) and a stable rate of new cases of thick melanomas over time. Jean-Jacques Grob (CHU de Marseille, Hopital Ste Maguerite, France) discussed pitfalls that may explain the failure to prevent thick melanomas. Patients at high risk of developing a melanoma are different from patients at high risk of dying of melanoma. Indeed, thick melanomas mainly affect elderly males over the age of 50 years with a small number of nevi and freckles, who do not readily respond to campaigns for screening. Although total body examination over 3 years reduces the risk of thick melanoma by 40%, it is not routinely performed by general practitioners.

Arthur Sober (Massachusetts General Hospital) discussed the controversial effect of sunscreens on melanoma as indicated by the lack of reliable positive protective effect on melanoma risk or even increased risk in relevant studies. The incorrect use of sunscreens, the use of low sun protection factor (SPF) index products, the absence of UVA filters in older sunscreen formulations and the reduced vitamin D production in sunscreen users might explain these findings. New approaches to photoprotection were presented by Veronique del Marmol (Hopital Erasme, Brussels, Belgium) and Marita Kosmadaki (A Sygros Hospital, Athens, Greece). After UV exposure, skin pigmentation/tanning (melaninogenesis) is mediated via the POMC/ACTH/MSH/MC1R signaling pathway. Synthetic α-MSH analogs (afamelanotide, subcutaneous use) induce tanning in both exposed and non-sun-exposed skin sites, and are photoprotective against UV damage. Afamelanotide is under study for erythropoietic protoporphyria, solar urticaria, polymorphic light eruption and skin cancer prevention in organ transplant recipient (OTR) patients (Phase II clinical study). Purchase of nonlicensed α-MSH analogs sold on the internet (melanotan I and II, and bremelanotide) may incur risks, as melanotan I has only been approved for use in erythropoietic protoporphyria and melanotan II has not been tested for human use, and it was recently associated with the development of eruptive nevi, while bremelanotide was withdrawn by the US FDA in 2007 owing to arterial hypertension. Topically applied DNA-repair enzymes (T4N5 liposome lotion, oxoguanine glycosylase 1, photolyase and T-oligos) have been studied for their use in photoprotection via their repairing role on UV-induced DNA damage.

Melanoma genetics, staging & screening

The symposium on melanoma genetics included a diverse list of topics, including the role of pigmentation genes in melanoma susceptibility presented by Maria Concetta Fragnoli (University of L’Aguila, Italy), and genetic determinants of disease progression and survival in melanoma presented by Julia Newton-Bishop (Leeds Institute of Molecular Medicine, Leeds, UK). Pigmentation genes associated with melanoma susceptibility include OCA2, ASIP, TYR, TYRP1 and SLC45A2/MATP, SLC24A5 and MC1R. MC1R is a well-established, low-penetrance gene of melanoma. CDKN2A mutation carriers with at least one MC1R variant have a twofold increased melanoma risk and an earlier age of tumor diagnosis compared with carriers of the CDKN2A mutation with no MC1R variants. In addition, melanoma risk increased with the number of MC1R variants, suggesting a gene dosage effect. Moreover, germline MC1R variants confer an increased risk for BRAF-mutated melanoma. Fragnoli presented results from her work showing that this MC1R/BRAF association is not modified by personal or melanoma characteristics including age, melanoma location or thickness, or nevus count. On the other hand, no association between germline MC1R variants and somatic BRAF mutations was found in melanoma patients from Australian and North Carolina populations. Key somatic genetic events, such as BRAF, NRAS and KIT are involved in melanoma pathogenesis but their effect on prognosis is not yet clear, as reported by Newton-Bishop. Reduced gene dosage across 9p21.3 (in coding regions impacting on CDKN2B, P14ARF and CDKN2A) was associated with increased tumor thickness, increased mitotic rate and presence of ulceration. DNA-repair genes (RAD51, RAD52 and TOP2A) are independent predictors of relapse-free survival. Germline biomarkers (IL-10, TYR, ASIP and MC1R) are currently under investigation and may help elucidate the effect of genes on melanoma survival.

A special session of the Congress was dedicated to the use of novel imaging techniques in the diagnosis and management of patients with melanoma. In vivo confocal microscopy in melanoma diagnosis was reviewed by Giovanni Pellacani (University of Modena and Reggio Emilia, Modena, Italy). It is a noninvasive in vivo imaging technique that comprises an 830-nm diode laser, and provides cytological and architectural analysis with a near histologic resolution and permits real-time evaluation. Drawbacks include the limited depth of laser light penetration (maximum 200 µm), the difficulty in examining particular body sites, the prolonged examination time (5–10 min per lesion) and the need for trained personnel.

Jeffrey Gershenwald (University of Texas, MD Anderson Cancer Center, TX, USA) reviewed evidence-based revisions to the 2009 American Joint Cancer Committee/Union Internationale Contre le Cancer melanoma staging system (7th edition) [9]. No major changes were recommended for tumor node metastasis and stage grouping criteria for stages I, II and III. Mitotic rate is an independent prognostic factor (included in T1b if at least one mitosis/mm²), all patients with microscopic nodal metastases, regardless of extent of tumor burden, are classified as stage III, and immunohistochemical detection of micrometastases is acceptable. For patients with distant metastases, the site of distant metastases and an elevated serum lactate dehydrogenase level continue to be the two dominant determinants of stage IV disease. The prognostic value of tumor-related factors such as tumor-infiltrating lymphocytes remains to be elucidated.

In the symposium on melanoma skin cancer screening, Ana Maria Forsea (Carol Davila University of Medicine and Pharmacy, Bucharest, Romania) presented data from Eastern Europe, where 55% of diagnosed melanomas are more than 2 mm thick owing to lack of education on skin cancer in the population, financial issues and difficulty in assessing medical facilities.

Adjuvant therapy in melanoma

The second day of the congress was dedicated to adjuvant therapy in metastatic melanoma. Survival in patients with stage IV disease is approximately 6–9 months, with only 25% of stage IV patients surviving 2 years and less than 5% surviving 5 years, posing an urgent need for new treatments. Claus Garbe (University of Tubingen Medical Center, Tubingen, Germany) discussed the biology of metastasis in melanoma. Melanoma cell dissemination in sentinel lymph nodes is a highly significant prognostic factor, with tumor burden in sentinel node being the most important prognostic factor in early melanoma. Tumor dormancy and inhibition of angiogenesis is dependent on IFN-γ secretion from Th1-cells. John Kirkwood (University of Pittsburgh School of Medicine, PA, USA) provided an overview on adjuvant therapies for melanoma, which include biologics (pegylated IFN, ipilimumab and bevacizumab), vaccines (MAGE-3 and granulocyte–macrophage colony-stimulating factor [GM-CSF]), small molecules (B-Raf inhibitors), chemotherapy (dacarbazine), immunotherapy (adoptive T cell, dendritic cell therapy, GM-CSF, IFN-α, vaccines, IL-2 and anti-CTLA4), and various combinations. Adjuvant therapies are recommended for stage IIB/C, stage III and fully resected stage IV melanoma [10]. Profiling of patients’ sera treated with high-dose IFN-α (HDI) for serum biomarkers of autoimmunity, baseline serum proinflammatory cytokine profile and T-cell STAT1 signaling may identify potential predictors of adjuvant therapeutic benefit. Baseline low serum C-reactive protein predicts clinical benefit with tremelimumab. Preliminary results of a Phase III study (E4697) in stage III–IV melanoma showed that there was no significant benefit on disease-free survival or overall survival with GM-CSF or with peptide vaccination (for HLA-A2⁺ patients). Combination of tremelimumab and HDI will be evaluated in Phase III trials. MAGE-A3 is a tumor-specific antigen used as adjuvant therapy. A Phase III trial to evaluate the use of adjuvant immunotherapy with MAGE-A3 antigen-specific cancer immunotherapeutic in stage IIIB/C MAGE-A3-positive melanoma is currently in progress. The advent of new agents designed to target specific molecules that are involved in melanoma pathogenesis (B-Raf and c-kit) is promising.

Brigitte Dreno (University Hospital Nantes, France) discussed prognostic factors of response to vaccine immunotherapy. The use of MELAN-A/MART-1- and MELOE-1-specific TIL increased relapse-free survival in melanoma patients. The presence of primary melanoma ulceration has been associated with clinical benefit after treatment with vaccination with tumor-specific antigenic peptides. Serum predictive markers include circulating tumor cell markers (MART-1, MAGE-A3, Mitf, PAX-3 and GalNac-T), markers of autoimmunity related with a better prognosis with low-dose IFN treatment, and the presence of CD16⁺CD8^- perforin⁺ cells associated with better prognosis following dendritic cell vaccination. In addition, increased tumor endothelial marker 8 (TEM-8) levels were associated with worse prognosis with dendritic cell vaccination. The use of gene microarray in melanoma lesions for MAGE-3 screening showed that the MAGE-3 signature is predictive of clinical outcome with MAGE-3 vaccination. The session shifted gears to anti-CTLA4 antibody treatment presented by Dirk Schadendorf (University Hospital Essen, Germany). The first study to show clinical benefit with anti-CTLA4 antibody in metastatic melanoma was published recently. Improved survival was shown with ipilimumab monotherapy (3 mg/m² intravenously every 3 weeks × four doses) compared with ipilimumab combined with gp100 or gp100 alone in patients with pretreated metastatic melanoma, M1c-stage, irrespective of lactate dehydrogenase levels. A Phase III study (CA184-024) in 500 patients with untreated advanced melanoma will be initiated in 2010 to study ipilimumab combined with dacarbazine versus dacarbazine alone. Selma Ugurel (University of Wuerzburg, Germany) presented data on biomarkers predicting therapy response. Serum proteins include S100B (to predict and monitor response to chemoimmunotherapy in metastatic malignant melanoma) and pretreatment serum VEGF and fibronectin (lower levels predict improved response and survival to high-dose IL-2 therapy for stage IV malignant melanoma). Microphthalmia-associated transcription factor gene amplification in melanoma tissue is a prognostic marker in metastatic melanoma (suggestive of disease progression) but not a predictive marker of response to chemotherapy. Immune response gene aberrations may be used to predict immunotherapy outcome, such as the CCR5 Δ32 polymorphism that was associated with worse survival with immunotherapy. B-Raf, a member of the Ras–Raf–Mek–Erk–MAPK pathway, is involved in degradation of the extracellular matrix, enhanced collagen attachment, loss of keratinocyte control, resistance to apoptosis and cell proliferation. BRAF mutation carriers show shorter survival. While a Phase II trial showed that BRAF mutation status was not predictive for treatment response to sorafenib, a Phase II trial of PLX4032, a B-Raf inhibitor selective for V600E, showed that the presence of BRAF V600E mutation was associated with better treatment response, thus providing a selection tool for personalized treatment. C-kit mutations have been found in distinct subtypes of melanoma (mucosal and acral melanomas and melanomas arising in chronically sun-damaged skin). Phase II trials of c-kit inhibitors, imatinib (600 mg/day) and sorafenib (800 mg/day), in stage IV melanoma showed no efficacy in patients with no c-kit mutations detected, and 100% efficacy in all four patients carrying c-kit mutations. A Phase III trial will provide evidence regarding individualized chemotherapy by test profile (ex vivo chemosensitivity profiling after pretreatment biopsy of lymph node metastases) compared with standard dacarbazine monochemotherapy. Helen Gogas (University of Athens, Greece) further discussed the selection of melanoma patients for adjuvant treatment based on predictor markers [11]. Low-dose IFN-α has been approved (3 million IU subcutaneously three-times per week for 18 months) for stage II as it has a positive effect on disease-free survival in stage II malignant melanoma. HDI has been approved for use in stages IIB/C and IIIA/B/C (high-risk patients). Potential biological factors that predict IFN responsiveness include tumor load (better response in stage IIB/C compared with stage IIIA/B/C) and primary tumor ulceration (suggesting a distinct biology for ulcerated melanoma). Earlier disease is generally more responsive to IFN than more advanced disease. The results of a Phase III trial of pegylated IFN in ulcerated melanoma are in the pipeline. The prolongation of overall survival is the aim of adjuvant IFN treatment but this goal is yet to be achieved.

Keith Flaherty (Massachusetts General Hospital) discussed targeting signal transduction pathways in melanoma. BRAF mutations are found in 6% of cancers and 60% of melanoma. PLX4032 is a selective BRAF inhibitor used in metastatic melanoma. GSK1120212 showed best-in-class activity among MEK inhibitors for BRAFV600E melanomas. Combination or sequential treatment with inhibitors of concomitantly activated oncogenic pathways, or with immunologic and antiangiogenic therapies, may enhance treatment outcomes.

Nonmelanoma skin cancers & cutaneous T-cell lymphoma

The third day of the congress focused on the biology, diagnosis and management of nonmelanoma skin cancers (NMSC). Myrto Trakatelli (Aristotle University, Papageorgiou Hospital, Thessaloniki, Greece) emphasized how the data on the epidemiology of NMSC is important for effective public health monitoring and preventive interventions in Europe. The increasing incidence of NMSC may be attributed to changes in sunbathing behavior (with increased sun-exposure patterns) and the increasing mean age of the population. The role of human papillomavirus (HPV) in the pathogenesis of cutaneous carcinoma (anogenital cancers, periungual SCC and epidermodysplasia verucciformis) was presented in detail by Gillian Murphy (Royal College of Surgeons, Beaumont Hospital, Dublin, Ireland). The integration of high-risk HPV DNA results in the disruption of the regulatory viral E2 gene (a repressor of viral early gene transcription), the degradation of cellular tumor-suppressor proteins (retinoblastoma protein and p53), the abnormal expression of viral E6 and E7 transforming genes, and the promotion of chromosome instability with consequent malignant transformation of the infected cells. β-HPV interact with DNA-repair mechanisms by directly binding XRCC1, leading to defective repair of UV-induced thymine dimers and permitting UV-induced mutations. A Zur Hausen (University Hospital Freiburg, Germany) discussed the emerging role of Merkel cell polyomavirus as a new human tumor virus in the pathogenesis of Merkel cell carcinoma.

Eggert Stockfleth (Skin Cancer Charite, Berlin, Germany) presented new agents in the pipeline for the treatment of actinic keratoses, including PEP005 (ingenol mebutate) gel applied for a total period of 3 days, imiquimod 3.75% in new dosing regimens applied once daily for 2 weeks, and a low-dose 0.5% fluorouracil/10% salicylic acid combination.

In a special session on skin cancer induced by immunosuppression, Jean Kanitakis (Ed Herriot Hospital Group, Lyon, France) presented data suggesting that skin cancers are the most frequent malignancies in OTRs (kidney, heart or liver) including mainly NMSC (95% of skin cancers), Bowen’s disease, Kaposi’s sarcomas (85–500-fold increase compared with the general population), melanomas (eight- to tenfold increase), Merkel cell carcinoma and cutaneous lymphomas. The pathogenesis of NMSC in OTRs involves UVR, genetic factors, immunosuppressive medications and β-HPV infection. Of note, skin cancer has been reported to arise from donor cells in a kidney transplant recipient. For SCC, excision is the treatment of choice in combination with oral retinoids and a dose decrease of immunosuppressive therapy. Switching to a mTOR inhibitor (sirolimus), which combines immunosuppressive and anti-tumor properties, has been recently been suggested as a valuable option to reduce the rate of NMSC and to decrease vascularization and growth of SCC in OTR. Prevention measures for NMSC in OTR include education concerning adequate sun protection, self-skin examination, regular dermatologic surveillance and low-dose long-term (3-year) chemoprevention with oral retinoids. Future perspectives include HPV vaccination and the use of α-MSH analogs for enhanced photoprotection. Claas Ulrich (Charite Universitatsmedizin, Berlin, Germany) presented results from a 2-year, prospective, case–control study that showed that regular sunscreen use in OTR resulted in reduction in the number of actinic keratoses and SCC, but interestingly had no effect on BCC. Vitamin D supplementation (1000 IU per day) is useful in OTR as serum 25-hydroxyvitamin D deficiency has been demonstrated in renal transplant patients.

Rudolf Stadler (Johannes Wesling Medical Center, Minden, Germany) discussed the guidelines for the treatment of cutaneous T-cell lymphoma (CTCL), emphasizing that early aggressive therapy does not increase the response rates or the overall survival rate, and that cytotoxic therapies should be minimized. Antonio Cozzio (University Hospital Zurich, Switzerland) reviewed treatment advances in CTCL. A Phase II trial of the histone deacetylase inhibitor, romidepsin, as monotherapy for patients with CTCL showed a 33% response rate, and side effects included transient hematologic abnormalities such as granulocytopenia and thrombocytopenia. Combination with denileukin diftitox, retinoids and cytotoxic agents may be used in order to enhance efficacy of HDI therapy. Phase II trials showed clinical efficacy and rapid onset of action for the antibody zanolimumab (HuMax–CD4) in refractory CTCL. Clinical response correlated with serum zanolimumab concentrations and the development of dermatitis as an adverse event.

The scientific program of the congress concluded with a session on clinical and therapeutic challenges in cutaneous oncology. Colin Fleming (Ninewells Hospital, Dundee, UK) emphasized new diagnostic and treatment modalities of lentigo maligna. Dermoscopy and confocal microscopy may help in the differential diagnosis from lentigo maligna melanoma or solar lentigenes. Isabel Longo (Hospital General Universitario Gregorio Maranon, Madrid, Spain) reviewed the management of cutaneous high-risk SCC The treatment of choice for the primary site is surgery. Radiotherapy should be considered when surgery is not indicated, in case of positive surgical margins, for tumors with perineural involvement, or for SCCs located on the lip or on ulcers. In case of nodal metastases, sentinel lymph node biopsy can be applied for staging high-risk SCC and may improve prognosis, as nodal disease is mostly curable. Proposed follow-up includes clinical examination and ultrasound of the regional lymph nodes every 3 months for 4 years.

Overall, the meeting was very productive with exciting new information on the diagnosis and management of skin cancer. In the era of molecular medicine, the field of cutaneous oncology has reached the point where scientific advances in the biology of skin tumors are rapidly ‘translated’ into new and effective treatment modalities. Still, many issues need to be further elucidated. The 7th EADO congress will be held in Nantes, France, 20–22 June 2011 (organizer: Brigitte Dreno), and information can be found online [101]. The abstracts of the 6th EADO Congress have been published as an electronic supplement of the journal Melanoma Research[102].

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.