Effectiveness, safety and utilization of vismodegib in locally advanced basal cell carcinoma under real-world conditions in Germany - The non-interventional study NIELS.

BACKGROUND: Basal cell carcinoma (BCC) can arise by the uncontrolled proliferation of cells from multiple epidermal compartments due to aberrant activation of the Hedgehog (Hh) signalling pathway. Vismodegib, a small-molecule inhibitor of this pathway, is approved for treatment of patients with locally advanced (la) BCC inappropriate for surgery or radiotherapy or patients with symptomatic metastatic (m) BCC. OBJECTIVES: The aim of this non-interventional study was to assess effectiveness with a special focus on duration of response (DOR), safety and utilization of vismodegib for treatment of laBCC in daily practice in Germany. METHODS: This non-interventional study (NIS) observed treatment of laBCC with vismodegib according to the German label in clinical practice. All available patients who had received at least one dose of vismodegib between commercial availability of vismodegib in Germany (02 August 2013) and 3 years before end of study (31 March 2016) could be included and were documented retrospectively and/or prospectively for up to 3 years. Primary effectiveness variable was DOR. Assessment of tumour response was carried out by the treating physicians. Exploratory variables included utilization of vismodegib, decision makers for therapy and method of tumour response evaluation. All statistical analyses were descriptive. RESULTS: Between September 2015 and March 2019, 66 patients were observed at 26 German centres. The objective response rate (ORR) was 74.2% and the disease control rate (DCR) was 90.9%. The median DOR was 15.9 months (95% CI: 9.2; 25.7; n = 49 patients with response). The median progression-free survival (PFS) was 19.1 months and the median time to response (TTR) 2.7 months. A total of 340 adverse events were reported in 63 (95.5%) patients; no new safety signals were identified. CONCLUSIONS: The NIS NIELS shows effectiveness and safety of vismodegib in patients with laBCC. It confirms the transferability of the results of the pivotal trial into routine clinical practice.

Response durability after cessation of immune checkpoint inhibitors in patients with metastatic Merkel cell carcinoma: a retrospective multicenter DeCOG study.

BACKGROUND: Immune checkpoint inhibitors (ICI) have led to a prolongation of progression-free and overall survival in patients with metastatic Merkel cell carcinoma (MCC). However, immune-mediated adverse events due to ICI therapy are common and often lead to treatment discontinuation. The response duration after cessation of ICI treatment is unknown. Hence, this study aimed to investigate the time to relapse after discontinuation of ICI in MCC patients. METHODS: We analyzed 20 patients with metastatic MCC who have been retrospectively enrolled at eleven skin cancer centers in Germany. These patients have received ICI therapy and showed as best overall response (BOR) at least a stable disease (SD) upon ICI therapy. All patients have discontinued ICI therapy for other reasons than disease progression. Data on treatment duration, tumor response, treatment cessation, response durability, and tumor relapse were recorded. RESULTS: Overall, 12 of 20 patients (60%) with MCC relapsed after discontinuation of ICI. The median response durability was 10.0 months. Complete response (CR) as BOR to ICI-treatment was observed in six patients, partial response (PR) in eleven, and SD in three patients. Disease progression was less frequent in patients with CR (2/6 patients relapsed) as compared to patients with PR (7/11) and SD (3/3), albeit the effect of initial BOR on the response durability was below statistical significance. The median duration of ICI therapy was 10.0 months. Our results did not show a correlation between treatment duration and the risk of relapse after treatment withdrawal. Major reasons for discontinuation of ICI therapy were CR (20%), adverse events (35%), fatigue (20%), or patient decision (25%). Discontinuation of ICI due to adverse events resulted in progressive disease (PD) in 71% of patients regardless of the initial response. A re-induction of ICI was initiated in 8 patients upon tumor progression. We observed a renewed tumor response in 4 of these 8 patients. Notably, all 4 patients showed an initial BOR of at least PR. CONCLUSION: Our results from this contemporary cohort of patients with metastatic MCC indicate that MCC patients are at higher risk of relapse after discontinuation of ICI as compared to melanoma patients. Notably, the risk of disease progression after discontinuation of ICI treatment is lower in patients with initial CR (33%) as compared to patients with initial PR (66%) or SD (100%). Upon tumor progression, re-induction of ICI is a feasible option. Our data suggest that the BOR to initial ICI therapy might be a potential predictive clinical marker for a successful re-induction.

The evolving field of Dermato-oncology and the role of dermatologists: Position Paper of the EADO, EADV and Task Forces, EDF, IDS, EBDV-UEMS and EORTC Cutaneous Lymphoma Task Force.

BACKGROUND: The incidence of skin cancers has been increasing steadily over the last decades. Although there have been significant breakthroughs in the management of skin cancers with the introduction of novel diagnostic tools and innovative therapies, skin cancer mortality, morbidity and costs heavily burden the society. OBJECTIVE: Members of the European Association of Dermato-Oncology, European Academy of Dermatology and Venereology, International Dermoscopy Society, European Dermatology Forum, European Board of Dermatovenereology of the European Union of Medical Specialists and EORTC Cutaneous Lymphoma Task Force have joined this effort to emphasize the fundamental role that the specialist in Dermatology-Venereology has in the diagnosis and management of different types of skin cancer. We review the role of dermatologists in the prevention, diagnosis, treatment and follow-up of patients with melanoma, non-melanoma skin cancers and cutaneous lymphomas, and discuss approaches to optimize their involvement in effectively addressing the current needs and priorities of dermato-oncology. DISCUSSION: Dermatologists play a crucial role in virtually all aspects of skin cancer management including the implementation of primary and secondary prevention, the formation of standardized pathways of care for patients, the establishment of specialized skin cancer treatment centres, the coordination of an efficient multidisciplinary team and the setting up of specific follow-up plans for patients. CONCLUSION: Skin cancers represent an important health issue for modern societies. The role of dermatologists is central to improving patient care and outcomes. In view of the emerging diagnostic methods and treatments for early and advanced skin cancer, and considering the increasingly diverse skills, knowledge and expertise needed for managing this heterogeneous group of diseases, dermato-oncology should be considered as a specific subspecialty of Dermatology-Venereology.

[Cutaneous squamous cell carcinoma]. / Kutanes Plattenepithelkarzinom.

Cutaneous squamous cell carcinoma (cSCC) is one of the most common cancers of the Caucasian population and accounts for 20% of all skin tumours. An S3 guideline of the German Guideline Program in Oncology has been available since 2019. The diagnosis is based on the clinical examination. Excision and histological confirmation is required for all clinically suspicious lesions to allow prognostic assessment and correct treatment. The therapy of first choice is complete excision with histological control of the surgical margin. In cSCC with risk factors such as tumor thickness >6 mm, sentinel lymph node biopsy may be discussed, but there is currently no clear evidence of its prognostic and therapeutic relevance. Adjuvant radiation therapy may be considered in cases of high risk of recurrence and should be tested in cases of inoperable tumors. The indication for electrochemotherapy should also be considered in the treatment of local or locoregional recurrence. The immune checkpoint inhibitor cemiplimab is approved for the treatment of inoperable or metastasized cSCC. In case of contraindications, chemotherapeutic agents, epidermal growth factor receptor (EGFR) inhibitors or palliative radiotherapy can be used. Since the evidence is low in these cases, a systemic therapy should be used preferentially within clinical studies. Follow-up care should be risk-adapted and includes a dermatological control, supplemented by ultrasound examinations in high-risk patients.

Prognostic factors in 161 patients with mucosal melanoma: a study of German Central Malignant Melanoma Registry.

BACKGROUND: Mucosal melanoma is a rare malignancy which represents approximately 1% of all melanomas. It is shown that mucosal melanomas have a different biology and less favourable prognosis than its cutaneous counterpart. OBJECTIVES: Predictive and prognostic factors of survival for mucosal melanoma have not yet been elucidated. The aim of this study was to investigate risk factors affecting the course of mucosal melanoma patients followed in our clinic. METHODS: One hundred and sixty-one patients with mucosal melanoma prospectively documented in the German Central Malignant Melanoma Registry (CMMR) were included in this study. Gender, age, localization, stage at first medical examination, tumour thickness and mutational status were documented. The American Joint Committee on Cancer (AJCC), 7th edition was used to define tumour stage. Kaplan-Meier survival curves were evaluated compared with the log-rank test. Multivariate Cox proportional hazard models were used to identify significant independent prognostic factors. RESULTS: According to the localization, patients were categorized in 44.7% oral-nasal, 28.6% genital, 20.5% anorectal and 6.2% visceral. Genital mucosal melanomas had the most favourable 5-year OS rate (58.6%) followed by visceral (58.3%) and oral-nasal (39.3%). Anorectal melanomas had the worst OS time (median: 21 ± 4.8 months) and 5-year survival rate (22.7%). Patients <60 years had a better survival than the older group (P = 0.013). Tumour stage at the time of the first medical examination was also a significant factor for survival (P = 0.001). Gender and mutational status were found to have no effect on survival. Age (<60 years vs. ≥60 years; HR = 2.1) and stage at first medical examination (Stage I vs. Stage IV; HR = 8.2) are shown to be significant independent prognostic factors on multivariate Cox regression analysis, but not localization. CONCLUSION: In this study, we observed that older age and advanced stage have significant negative effects on the survival of mucosal melanoma. Thus, the AJCC staging system is applicable for mucosal melanoma.

The more the better? An appraisal of combination therapies for actinic keratosis.

Actinic keratoses (AK) are common precancerous lesions of the skin. Numerous interventions exist for the treatment of AK, including lesion- and field-directed approaches. In daily practice, different treatment modalities are often combined to maximize clearance rates. However, whether a combination therapy is preferable to monotherapy in terms of efficacy and safety has been subject of intense debate. In this review, we summarize the current knowledge on the efficacy and safety of local combination therapies for the treatment of patients with AK. Combination approaches of cryosurgery followed by photodynamic therapy (PDT), laser-assisted PDT, PDT in combination with topical interventions and microneedling-assisted PDT have shown slightly better efficacy results with similar tolerability compared to the respective monotherapy. However, the individual usage of combination therapies should be checked on a case-by-case basis and take into account individual patient- and lesion-specific aspects as more resources are needed and because the individual monotherapies are already highly effective.

Late recurrence of melanoma after 10 years - Is the course of the disease different from early recurrences?

BACKGROUND: It is known that melanoma can metastasize and recur many years after the first diagnosis. Although predictive and prognostic factors for melanoma are well defined, there is still insufficient information about the factors affecting the recurrence period and the effect of the recurrence time to survival. OBJECTIVES: This study investigates the course of melanoma to show prognostic factors comparing early and late recurrence patients. The main objective is to uncover the effect of the recurrence time on the progression of the disease. METHODS: In this retrospective study, late recurrence (LR) was defined as melanoma recurrence 10 years after the first diagnosis and early recurrence (ER) was defined as recurrence within 10 years. Gender, age, localization of primary tumour, time to first metastasis, survival rates, histological subtype, stage, tumour thickness, invasion level, ulceration and regression of the primary melanoma were documented. Survival curves were evaluated using the Kaplan-Meier and compared with the log-rank test. Multivariate Cox proportional hazard models were used to identify significant independent prognostic factors for melanoma-specific survival (MSS). RESULTS: A total of 1537 melanoma patients were analysed. Early metastasis was developed in 1438 patients (93.6%), and 99 patients (6.4%) developed late metastasis. Late recurrence patients were younger (P < 0.001) and had fewer ulcerated (P = 0.005), fewer head/neck localized (P = 0.009) and thinner (P < 0.001) melanomas than ER patients. The MSS time (mean ± SD) was nearly identical for LR (31 ± 4.4 months 95% CI [22.3-39.7]) and ER (32 ± 1.9 months [28.3-35.7]). Multivariate regression analysis revealed male gender (hazard ratio [HR = 1.4, P < 0.001), truncal tumour localization (HR = 1.7, P < 0.001), tumour thickness (HR = 1.4, P < 0.045) and ulceration (HR = 1.3, P < 0.008) as significant independent prognostic factors for MSS. CONCLUSION: Although ER and LR patients are found to have different clinicopathologic features, the time of the first recurrence after diagnosis do not seem to have an effect on the survival.

Advanced cutaneous squamous cell carcinoma: real world data of patient profiles and treatment patterns.

BACKGROUND: Cutaneous squamous cell carcinoma (cSCC) is one of the most common types of cancer in the Caucasian population, with an increasing incidence. cSCC is mostly a local invasive disease that can be treated surgically in the majority of the cases. However, in the case of advanced cSCC (acSCC), a multimodality approach also involving systemic therapies needs to be considered. METHODS: One hundred and ninety-five patients diagnosed with acSCC (stages III and IV) treated in our centre between 2011 and 2018 were included. Patient and tumour characteristics along with treatment patterns were documented and analyzed. Descriptive analysis was performed and survival rates were estimated according to Kaplan-Meier and compared with the Log-rank test. Follow-up was defined as the time between diagnosis of advanced disease and last contact or death. All causes of death were considered as events. RESULTS: The median follow-up was 21 months [IQR = (10.0; 21.0)]. The median age at time of advanced disease diagnosis was 78 years [IQR = (72; 84)], with 40.5% of the patients in stage III and 59.5% in stage IV. One hundred and forty-five patients had resectable tumours. In this group the median overall survival (mOS) was 59 months (95% CI: 28.2-89.8), significantly higher than the mOS in patients with inoperable tumour [n = 50; mOS: 19 months (96% CI: 7-31, P <0.0001)]. Patients receiving immunotherapy (n = 20) showed a statistically significant better survival compared to those treated with other systemic therapies (n = 37; mOS not reached vs. mOS: 22 months (95% CI: 6.5-43.5), P = 0.034). For patients without systemic therapy, a combination of surgery and radiotherapy provided better outcomes compared to radiotherapy alone or best supportive care (P <0.001). CONCLUSION: Surgical complete resection should be the first therapeutic option for patients with acSCC. For patients with inoperable tumour, first-line immunotherapy should be preferably considered.

Efficacy of photodynamic therapy combined with topical interventions for the treatment of actinic keratosis: a meta-analysis.

BACKGROUND: Photodynamic therapy (PDT) is a highly effective treatment option for patients with actinic keratoses (AK). However, efficacy can be reduced by insufficient illumination or hyperkeratotic nature of lesions. OBJECTIVES: To investigate if PDT combined with a topical intervention is superior to monotherapy in terms of efficacy and tolerability. METHODS: A systematic literature research was conducted in Medline, Embase and CENTRAL. Pertinent trial registers were hand-searched for eligible randomized controlled trials (RCTs) until 20 August 2018. Results were pooled using a random effects model to calculate relative risks (RR) or mean differences. The risk of bias was assessed with the Cochrane Risk of Bias Tool. The quality of evidence was estimated for each outcome of interest according to GRADE. RESULTS: Out of 1800 references initially identified, 10 RCTs with a total sample size of n = 277 were included. Four studies investigated a combination of PDT with imiquimod cream, three with 5-fluorouracil cream and one each with ingenol mebutate gel, tazarotene gel and calcipotriol ointment, respectively. Patients treated with a combination showed higher participant complete (RR 1.63; 95% CI 1.15-2.33; P = 0.007) and partial clearance rates (RR 1.19; 95% CI 0.84-1.67; P = 0.33). Similarly, the lesion-specific clearance was higher for PDT plus topical intervention compared to monotherapy (RR 1.48; 95% CI 1.04-2.11; P = 0.03). A subgroup analysis was performed for PDT combined with imiquimod, revealing an increased participant complete clearance rate compared to monotherapy (RR 1.57, 95% CI 1.09-2.25, P = 0.02). PDT-induced pain and local skin reactions after treatment were poorly reported. The studies were estimated at high risk for performance and detection bias. CONCLUSION: The combination of PDT with another topical drug intervention does improve AK clearance rates compared to either monotherapy alone. This study highlights that the sequential application of two field-directed treatments represents an efficient approach in patients with multiple AK and field cancerization.

Incidence and characteristics of thick second primary melanomas: a study of the German Central Malignant Melanoma Registry.

BACKGROUND: Fast-growing melanomas are thought to be responsible for the stable incidence of thick melanomas. It has been suggested that campaigns for early diagnosis are unlikely to have a major impact on prognosis as rapid vertical growth rather than diagnostic delay is the major determinant for thick melanomas. OBJECTIVE: We investigated the impact of follow-up examinations on the incidence of thick second primary melanomas (SPMs) and analysed their clinic-pathologic characteristics. METHODS: We analysed a single-centre cohort of 2253 patients of the German Central Malignant Melanoma Registry with prospectively documented follow-up examinations. RESULTS: Primary tumour and patient characteristics were well balanced between patients with and without SPMs except for age (median 61 years, interquartile range [IQR] 51-67 vs. 56 years, IQR 43-67; P = 0.005). Metachronous SPMs occurred in 107 patients (4.7% of total) were thinner than the respective first primary melanoma (FPM) (median Breslow thickness of invasive melanomas 0.40 mm, IQR 0.28-0.75 vs. 0.80 mm, IQR 0.50-2.00; P < 0.001) and less often ulcerated (0.9% vs. 15.0%; P < 0.001). Melanomas >2.00 mm occurred in 2.8% of SPMs as compared to 23.4% of FPMs (P < 0.001). Thick SPMs (>1.00 mm; 14.0%) despite close-meshed follow-up examinations were frequently associated with atypical clinical presentation and uncommon histopathologic subtypes. One-third (5/15) of thick SPMs were clinically misdiagnosed as non-melanocytic lesions, most of them as basal cell carcinomas (n = 4). CONCLUSIONS: Regular total body skin examinations enable a highly efficient detection of early-stage melanomas and reduction of thick melanomas as compared to first primary melanomas. Our data indicate that fast-growing melanomas without opportunity of early detection are rare and cannot explain the stable incidence of thick melanomas. This highlights the importance of close-meshed total body skin examinations in patient groups that are at high risk of first or multiple primary melanomas.

Time trends in incidence and mortality of cutaneous melanoma in Germany.

OBJECTIVES: To characterize incidence and mortality trends of cutaneous melanoma (CM) in Germany to extrapolate these data until 2030. METHODS: We evaluated data from the Centre for Cancer Registry Data (1999-2012) and from the Saarland Cancer Registry (1970-2012). Age-standardized (according to the European Standard Population, WHO 1976) incidence and mortality rates [age-standardized incidence rates (ASIRs) and age-standardized mortality rates (ASMRs)] and crude incidence and mortality rates [crude incidence rates (CIRs) and crude mortality rates (CMRs)] were analysed. RESULTS: In entire Germany, ASIRs increased by 55% to 19.2 and CIRs by 77% to 26.0 new cases per 100 000 from 1999 to 2012. ASMRs remained stable, whereas CMR increased by 58% to 4.1 for males and by 30% to 3.0 for females per 100 000. In the Federal State of Saarland, ASIRs increased more than four-fold to 13.1, CIRs increased six-seven fold to 18.5/100 000 from 1970 to 2012. In the same period, ASMRs increased three-fold in males and two-fold in females to 2.5 and 1.6, whereas CMRs increased 5.5-fold in males and 3.5-fold in females to 3.9 and 3.2/100 000, mainly caused by steep increases of CIRs and CMRs in age groups ≥60 years. Projected CIRs will rise to 44-46 for males and 38-40 for females in 2030. Steepest increases were extrapolated for patients ≥60 years, especially for males, but are also expected for age groups of 40-59 years. In contrast, CIRs are anticipated to stabilize for subjects <40 years. CONCLUSIONS: There is a constant increase in incidence and mortality rates for CM in Germany. As the German population is ageing and the current population has already accumulated high levels of UV exposure, a further increase in melanoma incidence is projected for the future without signs of levelling-off.

Local interventions for actinic keratosis in organ transplant recipients: a systematic review.

BACKGROUND: Actinic keratosis (AK) in organ transplant recipients (OTRs) has a high risk of progressing to invasive squamous cell carcinoma of the skin. Thus, early and consequent treatment of AKs is warranted in OTRs. OBJECTIVES: To summarize the current evidence for nonsystemic treatments of AKs in OTRs. METHODS: We performed a systematic literature search in MEDLINE, Embase and the Cochrane Central Register of Controlled Trials (CENTRAL) and hand-searched pertinent trial registers up to 22 August 2018. Randomized controlled trials (RCTs) evaluating nonsystemic interventions for AKs in OTRs were included. The risk of bias was estimated using the Cochrane Risk of Bias Tool. RESULTS: Of 663 records initially identified, eight RCTs with 242 OTRs were included in a qualitative synthesis. Most studies evaluated methyl aminolaevulinate photodynamic therapy (MAL-PDT), followed by ablative fractional laser (AFXL) and diclofenac sodium 3% in hyaluronic acid, imiquimod 5% cream and 5-fluorouracil 5% cream (5-FU). MAL-PDT showed the highest rates of participant complete clearance (40-76·4%), followed by imiquimod (27·5-62·1%), diclofenac (41%) and 5-FU (11%). Similar results were observed for lesion-specific clearance rates. Treatment with AFXL alone revealed low lesion clearance (5-31%). Local skin reactions were most intense in participants treated with a combination of AFXL and daylight MAL-PDT. There were no therapy-related transplant rejections or worsening of graft function in any trial. The overall risk of bias was high. CONCLUSIONS: Limited evidence is available for the treatment of AKs in OTRs. MAL-PDT is currently the best-studied intervention. Lesion-specific regimens may not be sufficient to achieve disease control. Field-directed regimens are preferable in this high-risk population.

Acral lentiginous melanoma: a skin cancer with unfavourable prognostic features. A study of the German central malignant melanoma registry (CMMR) in 2050 patients.

BACKGROUND: Acral lentiginous melanoma (ALM) is one of the four major subtypes in cutaneous melanoma (CM). Although ALM has a poorer prognosis than other CM subtypes, the prognostic factors associated with ALM have only been verified in small-sized cohorts because of the low incidence of ALM worldwide. OBJECTIVES: To investigate the clinical characteristics of ALM and to evaluate their prognostic values based on a large dataset from the Central Malignant Melanoma Registry (CMMR) of the German Dermatologic Society. METHODS: The Kaplan-Meier method was used to estimate the potential influence of clinical and histological parameters on ALM disease-specific survival (DSS) curves, which were compared using the log-rank test. A Cox proportional hazards model was used to identify independent prognostic factors for DSS. RESULTS: In total, 2050 patients with ALM were identified from 58 949 patients with CM recorded by the CMMR with follow-up data. In multivariate analyses, age (P = 0·006), ulceration (P = 0·013), tumour thickness (P < 0·001) and tumour spread (P < 0·001) turned out to be significant prognostic factors for DSS in ALM whereas sex, nevus association and level of invasion were not independent factors. CONCLUSIONS: ALM has the same prognostic factors as other subtypes of melanoma. Unfavourable prognosis probably derives from the delay in diagnosis in comparison with other melanoma subtypes.

[Cutaneous squamous cell carcinoma]. / Kutanes Plattenepithelkarzinom.

Squamous cell carcinoma (SCC) of the skin accounts for 20 % of non-melanoma skin cancer and is one of the most frequent types of cancer in Caucasian populations. Diagnosis is based on the clinical features and should be histopathologically confirmed to adequately address the prognosis and treatment. Complete surgical excision with histopathological control of excision margins is the gold standard in the treatment of primary SCC. Sentinel lymph node biopsies (SLNB) can be considered in SCC with a tumor thickness of >6 mm but there is currently no evidence concerning prognostic and therapeutic effects. Radiotherapy can be discussed as an alternative to surgery for inoperable tumors or as adjuvant therapy for a high risk of recurrence. In SCC with distant metastases various chemotherapeutic agents are used; however, there is no standard regimen. The epidermal growth factor receptor (EGFR) inhibitors and immune checkpoint blockers can be discussed as treatment options, preferentially in clinical trials. There is no standard follow-up schedule for patients with SCC. A risk-adapted follow-up is recommended based on the risk of metastatic spread or development of new lesions primarily by dermatological control and supplemented by ultrasound investigations in high risk patients.

Ultraviolet exposure and risk of melanoma and basal cell carcinoma in Ulm and Dresden, Germany.

BACKGROUND: There is a perpetuating increase in melanoma and basal cell carcinoma (BCC) incidence in Europe. Few studies are evaluating various risk factors for both tumours. OBJECTIVES: This pre-planned additional analysis directly compared occupational and past-time ultraviolet exposure behaviour, and examined the effects of sun sensitivity between melanoma and sporadic BCC, and assessed its importance for the two entities. PATIENTS/METHODS: The study included 503 patients (melanoma, n = 291 and BCC, n = 212), and 329 controls from Germany. In all, 244 (49%) of the cases and 165 (50%) of the controls were male (median age melanoma, 55 years; BCC, 69 years; and controls, 57 years). Selection of important risk factors was performed by backward elimination in a polytomous logistic regression. RESULTS: When directly comparing melanoma and sporadic BCC, actinic elastosis (OR 48.83; 95% CI 17.87, 133.40) and site were associated with a higher risk of melanoma, whereas mountaineering in childhood, sunburn 20 years before diagnosis, farming full time, sunbed use in general, seborrheic keratosis, actinic cheilitis, actinic keratosis and age were associated with a higher risk of sporadic BCC. Gardening 20 years before melanoma, hair colour and solar lentigo were risk factors for both entities. A re-evaluation of the data excluding lentiginous melanoma entities (i.e. acro-lentiginous and lentigo-maligna melanoma) resulted in selection of the same factors. However, compared to controls, atopy evolved as a protective factor for melanoma (OR 0.29; 95% CI 0.15, 0.57) and BCC (OR 0.41; 95% CI 0.17, 0.99), respectively, but was associated with a higher risk of sporadic BCC compared to melanoma. CONCLUSION: The odds for having clinical actinic elastosis was lower in BCC compared to melanoma. In contrast, various factors associated with chronic UV exposure and age had higher odds for sporadic BCC, rather than melanoma. Further research is required to set the context for these findings, especially regarding, atopy in non-lentiginous vs. lentiginous forms of melanoma, and possible molecular pathways involved.

[Cutaneous squamous cell carcinoma: a review with consideration of special patient groups]. / Kutanes Plattenepithelkarzinom unter Berücksichtigung besonderer Patientengruppen.

The incidence of non-melanoma skin cancer (NMSC) is increasing. Squamous cell carcinoma of the skin (SCC) is a tumor of the elderly. Due to the increasing life expectancy, SCC will become more and more frequent in the future. Generally SCC has a favorable prognosis. Standard therapy is microscopically- controlled excision. Therapy of advanced and metastatic SCC is still challenging. Patients with regional lymph node metastasis have ten-year survival rates less than 20%; patients with distant metastases less than 10%. Immunosuppression has been shown to be one of the key prognostic factors for metastasis. The article reviews SCC and focusses on patients being at risk for an unfavorable course.

[Targeted therapies for melanoma]. / Zielgerichtete und immunologische Therapieansätze beim malignen Melanom.

Since the discovery of activating mutations in the BRAF oncogene and also stimulation of immune mediated antitumor response in melanoma, there has been remarkable progress in the development of targeted therapies for unresectable and metastatic melanoma. This article addresses the latest developments of BRAF/MEK/ERK pathway signaling. In addition, the development of drugs to attack alternative mutations in melanoma, such as NRAS and KIT is described. Strategies for the management of BRAF inhibitor resistance, such as with combination therapy, are outlined. Antitumor immune therapies with monoclonal antibodies such as ipilimumab which acts by promoting T-cell activation or antibody blockade of programmed death-1 (PD-1) led to a long term response in metastatic melanoma. Results of latest clinical studies including the toxicity profile are described. Due to selective kinase inhibitors and immune checkpoint blockade, the therapy of unresectable metastatic melanoma has greatly improved and long-term survival of patients with metastatic melanoma seems a real possibility.

Serum markers lactate dehydrogenase and S100B predict independently disease outcome in melanoma patients with distant metastasis.

BACKGROUND: Established prognostic factors are of limited value to predict long-term survival and benefit from metastasectomy in advanced melanoma. This study aimed to identify prognostic factors in patients with distant metastasis. METHODS: We analysed overall survival of 855 institutional melanoma patients with distant metastasis by bivariate Kaplan-Meier survival probabilities and multivariate Cox hazard regression analysis. RESULTS: Serum lactate dehydrogenases (LDH), S100B, the interval between initial diagnosis and occurrence of distant metastasis, the site of distant metastases, and the number of involved distant sites were significant independent prognostic factors in both bivariate and multivariate analyses. Visceral metastases other than lung (hazard ratio (HR) 1.8), elevated S100B (HR 1.7) and elevated LDH (HR 1.6) had the highest negative impact on survival. Complete metastasectomy was likewise an independent prognostic factor in multivariate analysis. This treatment was associated with favourable survival for patients with normal LDH and S100B values (5-year survival, 37.2%). CONCLUSION: The serum markers LDH and S100B were both found to be prognostic factors in melanoma patients with distant metastasis. Furthermore, complete metastasectomy had an independent favourable prognostic impact in particular for the patient subgroup with normal LDH and S100B values.