Swiss Recommendations for Cutaneous Basal Cell Carcinoma

Basal cell carcinoma (BCC) is the most common nonmelanoma skin cancer in Switzerland and worldwide. Most BCCs can be treated in a curative setting. However, patients can develop locally destructive and, rarely, metastatic tumors that require a different treatment approach. The clinical subtype of individual lesions provides prognostic information and influences management decisions. Surgical excision, topical therapies, and radiotherapy are highly effective in the majority of subtypes as well as in low- and high-risk diseases. For patients with low-risk diseases and superficial tumors not amenable to surgery, several nonsurgical alternatives are available. Systemic therapy is indicated for high-risk BCCs, which are not amenable to either surgery or radiotherapy. Hedgehog pathway inhibitors (HHI) are currently approved. Other therapeutic options such as immune checkpoint inhibitors show promising results in clinical trials. This first version of Swiss recommendations for diagnosis and management of BCC was prepared through extensive literature review and an advisory board consensus of expert dermatologists and oncologists in Switzerland. The present guidelines recommend therapies based on a multidisciplinary team approach and rate of recurrence for individual lesions. Based on the risk of recurrence, two distinct groups have been identified: low-risk (easy-to-treat) and high-risk (difficult-to-treat) tumors. Based on these classifications, evidence-based recommendations of available therapies are presented herein

Swiss Recommendations for Cutaneous Basal Cell Carcinoma.

Basal cell carcinoma (BCC) is the most common nonmelanoma skin cancer in Switzerland and worldwide. Most BCCs can be treated in a curative setting. However, patients can develop locally destructive and, rarely, metastatic tumors that require a different treatment approach. The clinical subtype of individual lesions provides prognostic information and influences management decisions. Surgical excision, topical therapies, and radiotherapy are highly effective in the majority of subtypes as well as in low- and high-risk diseases. For patients with low-risk diseases and superficial tumors not amenable to surgery, several nonsurgical alternatives are available. Systemic therapy is indicated for high-risk BCCs, which are not amenable to either surgery or radiotherapy. Hedgehog pathway inhibitors (HHI) are currently approved. Other therapeutic options such as immune checkpoint inhibitors show promising results in clinical trials. This first version of Swiss recommendations for diagnosis and management of BCC was prepared through extensive literature review and an advisory board consensus of expert dermatologists and oncologists in Switzerland. The present guidelines recommend therapies based on a multidisciplinary team approach and rate of recurrence for individual lesions. Based on the risk of recurrence, two distinct groups have been identified: low-risk (easy-to-treat) and high-risk (difficult-to-treat) tumors. Based on these classifications, evidence-based recommendations of available therapies are presented herein

A multifaceted perspective on skin cancer prevention

Solar ultraviolet radiation has been acknowledged as the main culprit for the three major types of skin cancer which are among the most numerous (basal cell carcinoma [BCC], squamous cell carcinoma [SCC]) and most dangerous (cutaneous malignant melanoma) malignancies in Caucasian populations. The present thesis comprises six individual projects providing a multifaceted perspective on the prevention of these tumours. Project I evaluated a school-based sun safety education programme developed by the Swiss Cancer Leagues. Primary school students in the Canton of Zurich (North-Eastern Switzerland) were asked to answer a questionnaire regarding their sun-related knowledge, behaviour, and sunburn experience shortly before and one year after the intervention (repeated cross- sectional assessment). Based on the data from more than 3000 students, the sun safety education programme was effective in sustainably improving children’s sun-related knowledge and possibly to some extent in decreasing sunburn rates, but had no obvious impact on the examined sun protective behaviours (use of sunscreen, seeking shade). Project II represents a systematic review of cross-sectional and interventional studies on sun-related knowledge, attitudes, and protective behaviours of outdoor workers. The 52 relevant publications identified through an electronic search of medical literature databases (PubMed, Embase, PsycINFO) and an extensive hand search suggested that outdoor workers’ sun protective behaviours are largely inadequate and sunburn rates are high (50-80% per season). However, there is evidence that sun safety education in outdoor occupational settings is effective in increasing workers’ protective behaviours and presumably also in reducing sunburn incidence. Project III investigated sun protective behaviour and sunburn experience of vacationers spending holidays in the tropics or subtropics. The 1165 standardised face-to-face interviews conducted among air passengers waiting in the departure or baggage claim area at the Airport Basel-Mulhouse (Switzerland/France) and among vacationers waiting for pre-travel health advice at the Travel Clinic of the Swiss Tropical and Public Health Institute Basel (Switzerland) revealed that almost all respondents used sunscreen at the holiday destination. Nevertheless, wearing a sunhat and protective clothing as well as seeking shade were clearly less common sun protection methods. The assessed sunburn rate among the 324 interviewed returning air passengers was alarmingly high, with 44% having suffered from sunburn during their holiday stay. Project IV comprehensively analysed the content and quality of 2103 print media articles pertaining to skin cancer prevention and related topics (solaria, vitamin D) published in Germany and Switzerland over a one-year period (2012-2013). Whereas skin cancer secondary prevention received little press attention, primary prevention was a frequently covered media topic. However, the delivered information was generally rather superficial. By far the most common and often sole sun protection recommendation made was the use of sunscreen. In total, 27% of all analysed articles contained misleading or erroneous statements which were mostly related to the use of sunscreen and vitamin D issues. Projects V and VI are based on data derived from the Clinical Practice Research Datalink, a large, well-validated primary care database established in the United Kingdom (UK). Project V estimated BCC incidence in the UK and characterised affected patients regarding lifestyle factors and comorbidities. The calculated age-standardised BCC incidence in adults rose from 119 to 165 per 100 000 person-years between the years 2000 and 2011. According to the matched case-control analysis including 57 121 BCC cases and 57 121 BCC-free controls, BCC risk was slightly increased in alcohol drinkers, but reduced in smokers and in individuals with a body mass index outside the normal range. BCC was associated with various comorbidities related to iatrogenic or non-iatrogenic immunosuppression. Project VI explored whether patients regularly exposed to systemic nonsteroidal anti- inflammatory drugs (NSAIDs) are at a reduced risk of nonmelanoma skin cancer (NMSC). The matched case-control analysis comprised 65 398 BCC cases, 65 398 BCC-free controls, 7864 SCC cases, and 31 456 SCC-free controls. Overall, NSAID use was not negatively associated with BCC, but when looking exclusively at users of single NSAID substances there was a suggestion of a reduced BCC risk in regular users of aspirin and ibuprofen. SCC risk was slightly decreased in regular users of any NSAIDs, with the strongest risk reduction observed in current users of coxibs. These findings provide evidence that patients predisposed to NMSC may benefit from chemoprevention with NSAIDs

Swiss clinical practice guidelines on field cancerization of the skin.

Actinic keratosis (AK) affects millions of people worldwide, and its prevalence continues to increase. AK lesions are caused by chronic ultraviolet radiation exposure, and the presence of two or more AK lesions along with photodamage should raise the consideration of a diagnosis of field cancerization. Effective treatment of individual lesions as well as field cancerization is essential for good long-term outcomes. The Swiss Registry of Actinic Keratosis Treatment (REAKT) Working Group has developed clinical practice guidelines for the treatment of field cancerization in patients who present with AK. These guidelines are intended to serve as a resource for physicians as to the most appropriate treatment and management of AK and field cancerization based on current evidence and the combined practical experience of the authors. Treatment of AK and field cancerization should be driven by consideration of relevant patient, disease, and treatment factors, and appropriate treatment decisions will differ from patient to patient. Prevention measures and screening recommendations are discussed, and special considerations related to management of immunocompromised patients are provided

Silencing of ASC in Cutaneous Squamous Cell Carcinoma.

Apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) is an important adaptor protein for inflammasome activation, mediating the secretion of protumorigenic innate cytokines. However, ASC is also known to trigger apoptosis in tumor cells, acting as a tumor-suppressor gene, which is lost in several human cancers. The aim of this study was to evaluate the clinical significance of ASC in human cutaneous squamous cell carcinoma (SCC). Initially, ASC expression was immunohistochemically evaluated in non-metastic and metastatic SCC. While ASC expression does not correlate with metastatic potential, it correlates with the degree of dedifferentiation. Using methylation specific PCR we were able to demonstrate ASC silencing by promotor specific methylation and impaired inflammasome function in methylated cell lines, linking epigenetic modifications to innate immune activation in keratinocytes. Interestingly, upon ASC restoration by treatment with demethylating agents, we were able to restore AIM2 and NLRP3 activation. In summary, loss of ASC driven tumor development is counterbalanced in the identical cell by the inhibition of pro-tumorigenic inflammation in the tumor cell itself

Structured Expert Consensus on Actinic Keratosis:Treatment Algorithm Focusing on Daylight PDT

BACKGROUND: A practical and up-to-date consensus among experts is paramount to further improve patient care in actinic keratosis (AK). OBJECTIVES: To develop a structured consensus statement on the diagnosis, classification, and practical management of AK based on up-to-date information. METHODS: A systematic review of AK clinical guidelines was conducted. This informed the preparation of a 3-round Delphi procedure followed by a consensus meeting, which combined the opinions of 16 clinical experts from 13 countries, to construct a structured consensus statement and a treatment algorithm positioning daylight photodynamic therapy (dl-PDT) among other AK treatment options. RESULTS: The systematic review found deficiencies in current guidelines with respect to new AK treatments such as ingenol mebutate and dl-PDT. The Delphi panel established consensus statements across definition, diagnosis, classification, and management of AK. While the diagnosis of AK essentially rests on the nature of lesions, treatment decisions are based on several clinical and nonclinical patient factors and diverse environmental attributes. Participants agreed on ranked treatment preferences for the management of AK and on classifying AK in 3 clinical situations: isolated AK lesions requiring lesion-directed treatment, multiple lesions within a small field, and multiple lesions within a large field, both requiring specific treatment approaches. Different AK treatment options were discussed for each clinical situation. CONCLUSIONS: The results provide practical recommendations for the treatment of AK, which are readily transferable to clinical practice, and incorporate the physician's clinical judgement. The structured consensus statement positioned dl-PDT as a valuable option for patients with multiple AKs in small or large fields

European Dermatology Forum guidelines on topical photodynamic therapy 2019 Part 2: emerging indications – field cancerization, photorejuvenation and inflammatory/infective dermatoses

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Electrochemotherapy for solid tumors: literature review and presentation of a novel endoscopic approach

Background: Electrochemotherapy (ECT) is a minimally invasive and safe treatment gaining positive and long-lasting antitumoral results that are receiving the attention of the scientific community. It is a local treatment that combines the use of electroporation and the administration of cytotoxic drugs to induce cell death in the target tissue. ECT is largely used for the treatment of cutaneous and subcutaneous lesions, and good results have been reported for the treatment of deep visceral tumors. The latest literature review is provided. Moreover, in line with its development for the treatment of visceral tumors in this article, we describe a novel approach of ECT: endoscopic treatment of colorectal cancer. Endoscopic ECT application was combined with systemic chemotherapy in the treatment of obstructing rectal cancer without prospective surgery. A good response after ECT was described: concentric involvement of the rectum was reduced, and no stenosing lesions were detected. Conclusions: Clinical studies have demonstrated that ECT is a very effective treatment for tumors of different histologic types and localizations. Endoscopic treatment for gastrointestinal cancer is an innovative application of ECT. The combination of systemic treatment and ECT was safe and highly effective in the treatment of colorectal cancer, especially when obstructive, giving the patient a significant gain in quality of life