Cost-of-Illness of Skin Cancer: A Systematic Review.

BACKGROUND: Skin cancer's rising incidence demands understanding of its economic impact. The current understanding is fragmented because of the various methodological approaches applied in skin cancer cost-of-illness studies. OBJECTIVE: This study systematically reviews melanoma and keratinocyte carcinoma cost-of-illness studies to provide an overview of the applied methodological approaches and to identify the main cost drivers. METHODS: This systematic review was conducted adhering to the 2020 PRISMA guidelines. PubMed, Embase, and Web of Science were searched from December 2022 until December 2023 using a search strategy with entry terms related to the concepts of skin cancer and cost of illness. The records were screened on the basis of the title and abstract and subsequently on full text against predetermined eligibility criteria. Articles published before 2012 were excluded. A nine-item checklist adapted for cost-of-illness studies was used to assess the methodological quality of the articles. RESULTS: This review included a total of 45 studies, together evaluating more than half a million patients. The majority of the studies (n = 36) focused on melanoma skin cancer, a few (n = 3) focused on keratinocyte carcinomas, and 6 studies examined both. Direct costs were estimated in all studies, while indirect costs were only estimated in nine studies. Considerable heterogeneity was observed across studies, mainly owing to disparities in study population, methodological approaches, included cost categories, and differences in healthcare systems. In melanoma skin cancer, both direct and indirect costs increased with progressing tumor stage. In advanced stage melanoma, systemic therapy emerged as the main cost driver. In contrast, for keratinocyte carcinoma no obvious cost drivers were identified. CONCLUSIONS: A homogeneous skin cancer cost-of-illness study design would be beneficial to enhance between-studies comparability, identification of cost drivers, and support evidence-based decision-making for skin cancer.

Skin cancers are the most frequent cancers in fair-skinned populations, but we can prevent them.

Cancers of the skin are the most commonly occurring cancers in humans. In fair-skinned populations, up to 95% of keratinocyte skin cancers and 70-95% of cutaneous melanomas are caused by ultraviolet radiation and are thus theoretically preventable. Currently, however, there is no comprehensive global advice on practical steps to be taken to reduce the toll of skin cancer. To address this gap, an expert working group comprising clinicians and researchers from Africa, America, Asia, Australia, and Europe, together with learned societies (European Association of Dermato-Oncology, Euromelanoma, Euroskin, European Union of Medical Specialists, and the Melanoma World Society) reviewed the extant evidence and issued the following evidence-based recommendations for photoprotection as a strategy to prevent skin cancer. Fair skinned people, especially children, should minimise their exposure to ultraviolet radiation, and are advised to use protective measures when the UV index is forecast to reach 3 or higher. Protective measures include a combination of seeking shade, physical protection (e.g. clothing, hat, sunglasses), and applying broad-spectrum, SPF 30 + sunscreens to uncovered skin. Intentional exposure to solar ultraviolet radiation for the purpose of sunbathing and tanning is considered an unhealthy behaviour and should be avoided. Similarly, use of solaria and other artificial sources of ultraviolet radiation to encourage tanning should be strongly discouraged, through regulation if necessary. Primary prevention of skin cancer has a positive return on investment. We encourage policymakers to communicate these messages to the general public and promote their wider implementation.

European consensus-based interdisciplinary guideline for diagnosis and treatment of basal cell carcinoma-update 2023.

Basal cell carcinoma (BCC) is the most common malignant tumour in white populations. Multidisciplinary experts from European Association of Dermato-Oncology (EADO), European Dermatology Forum, European Society for Radiotherapy and Oncology (ESTRO), Union Européenne des Médecins Spécialistes, and the European Academy of Dermatology and Venereology developed updated recommendations on diagnosis and treatment of BCC. BCCs were categorised into 'easy-to-treat' (common) and 'difficult-to-treat' according to the new EADO clinical classification. Diagnosis is based on clinico-dermatoscopic features, although histopathological confirmation is mandatory in equivocal lesions. The first-line treatment of BCC is complete surgery. Micrographically controlled surgery shall be offered in high-risk and recurrent BCC, and BCC located on critical anatomical sites. Topical therapies and destructive approaches can be considered in patients with low-risk superficial BCC. Photodynamic therapy is an effective treatment for superficial and low-risk nodular BCCs. Management of 'difficult-to-treat' BCCs should be discussed by a multidisciplinary tumour board. Hedgehog inhibitors (HHIs), vismodegib or sonidegib, should be offered to patients with locally advanced and metastatic BCC. Immunotherapy with anti-PD1 antibodies (cemiplimab) is a second-line treatment in patients with a progression of disease, contraindication, or intolerance to HHI therapy. Radiotherapy represents a valid alternative in patients who are not candidates for or decline surgery, especially elderly patients. Electrochemotherapy may be offered when surgery or radiotherapy is contraindicated. In Gorlin patients, regular skin examinations are required to diagnose and treat BCCs at an early stage. Long-term follow-up is recommended in patients with high-risk BCC, multiple BCCs, and Gorlin syndrome.

Dermatologist versus artificial intelligence confidence in dermoscopy diagnosis: Complementary information that may affect decision-making.

In dermatology, deep learning may be applied for skin lesion classification. However, for a given input image, a neural network only outputs a label, obtained using the class probabilities, which do not model uncertainty. Our group developed a novel method to quantify uncertainty in stochastic neural networks. In this study, we aimed to train such network for skin lesion classification and evaluate its diagnostic performance and uncertainty, and compare the results to the assessments by a group of dermatologists. By passing duplicates of an image through such a stochastic neural network, we obtained distributions per class, rather than a single probability value. We interpreted the overlap between these distributions as the output uncertainty, where a high overlap indicated a high uncertainty, and vice versa. We had 29 dermatologists diagnose a series of skin lesions and rate their confidence. We compared these results to those of the network. The network achieved a sensitivity and specificity of 50% and 88%, comparable to the average dermatologist (respectively 68% and 73%). Higher confidence/less uncertainty was associated with better diagnostic performance both in the neural network and in dermatologists. We found no correlation between the uncertainty of the neural network and the confidence of dermatologists (R = -0.06, p = 0.77). Dermatologists should not blindly trust the output of a neural network, especially when its uncertainty is high. The addition of an uncertainty score may stimulate the human-computer interaction.

Checkpoint Inhibitors in Combination With Stereotactic Body Radiotherapy in Patients With Advanced Solid Tumors: The CHEERS Phase 2 Randomized Clinical Trial.

Importance: Although immune checkpoint inhibitors (ICIs) targeting programmed cell death 1 (PD-1) and PD-1 ligand 1 have improved the outcome for many cancer types, the majority of patients fails to respond to ICI monotherapy. Hypofractionated radiotherapy has the potential to improve the therapeutic ratio of ICIs. Objective: To assess the addition of radiotherapy to ICIs compared with ICI monotherapy in patients with advanced solid tumors. Design, Setting, and Participants: This open-label, multicenter, randomized phase 2 trial was conducted in 5 Belgian hospitals and enrolled participants between March 2018 and October 2020. Patients 18 years or older with locally advanced or metastatic melanoma, renal cell carcinoma, urothelial carcinoma, head and neck squamous cell carcinoma, or non-small cell lung carcinoma were eligible. A total of 99 patients were randomly assigned to either the control arm (n = 52) or the experimental arm (n = 47). Of those, 3 patients (1 in the control arm vs 2 in the experimental arm) withdrew consent and thus were not included in the analysis. Data analyses were performed between April 2022 and March 2023. Interventions: Patients were randomized (1:1) to receive anti-PD-1/PD-1 ligand 1 ICIs alone as per standard of care (control arm) or combined with stereotactic body radiotherapy 3 × 8 gray to a maximum of 3 lesions prior to the second or third ICI cycle, depending on the frequency of administration (experimental arm). Randomization was stratified according to tumor histologic findings and disease burden (3 and fewer or more than 3 cancer lesions). Main Outcomes and Measures: The primary end point was progression-free survival (PFS) as per immune Response Evaluation Criteria in Solid Tumors. Key secondary end points included overall survival (OS), objective response rate, local control rate, and toxic effects. Efficacy was assessed in the intention-to-treat population, while safety was evaluated in the as-treated population. Results: Among 96 patients included in the analysis (mean age, 66 years; 76 [79%] female), 72 (75%) had more than 3 tumor lesions and 65 (68%) had received at least 1 previous line of systemic treatment at time of inclusion. Seven patients allocated to the experimental arm did not complete the study-prescribed radiotherapy course due to early disease progression (n = 5) or intercurrent illness (n = 2). With a median (range) follow-up of 12.5 (0.7-46.2) months, median PFS was 2.8 months in the control arm compared with 4.4 months in the experimental arm (hazard ratio, 0.95; 95% CI, 0.58-1.53; P = .82). Between the control and experimental arms, no improvement in median OS was observed (11.0 vs 14.3 months; hazard ratio, 0.82; 95% CI, 0.48-1.41; P = .47), and objective response rate was not statistically significantly different (22% vs 27%; P = .56), despite a local control rate of 75% in irradiated patients. Acute treatment-related toxic effects of any grade and grade 3 or higher occurred in 79% and 18% of patients in the control arm vs 78% and 18% in the experimental arm, respectively. No grade 5 adverse events occurred. Conclusions and Relevance: This phase 2 randomized clinical trial demonstrated that while safe, adding subablative stereotactic radiotherapy of a limited number of metastatic lesions to ICI monotherapy failed to show improvement in PFS or OS. Trial Registration: ClinicalTrials.gov Identifier: NCT03511391.

Impact of the COVID-19 Pandemic on the Incidence and Thickness of Cutaneous Melanoma in Belgium.

(1) Background: COVID-19 had a major impact on cancer diagnostics and treatment. Delays in diagnosis of cutaneous melanoma were particularly feared, given the impact on survival and morbidity that comes with advanced stages. Moreover, its incidence in Belgium has been rapidly increasing in recent decades. This Belgian population-level study quantifies the pandemic effect on the number of melanoma diagnoses and Breslow thickness in 2020 and 2021. (2) Methods: In using an automated algorithm, the number of cutaneous melanoma diagnoses and Breslow thickness were extracted from all pathology protocols from 2017-2021 by the Belgian Cancer Registry. Monthly variations, as well as year-to-year differences, were studied. (3) Results: Annual incidence of cutaneous melanoma fell by 1% in 2020, compared to 2019, mainly due to a diagnostic deficit in March, April, and May 2020. An 8% incidence increase occurred in 2021, primarily reflecting an increase in the number of the thinnest melanomas (≤1 mm). Both the mean and median Breslow thicknesses were higher in spring 2020, resulting from an underrepresentation of thinner tumors. However, no particulars stood out on a full-year basis in either 2020 or 2021. (4) Conclusions: Considering the expected incidence increase, we estimate almost 210 melanoma diagnoses were missed in Belgium in 2020, corresponding to 6% of the expected number. This deficit occurred mainly during the first COVID-19 wave. Despite some rebound, the 2021 total was still 3% short of the expected number, leaving around 325 diagnoses remaining pending in 2020 and 2021, corresponding to a two-year deficit of 4.35%. Fortunately, mainly thin melanomas were missed, without any detectable shift toward thicker tumors later in 2020 and or 2021.

A critical re-evaluation of Mohs micrographic surgery for a facial basal cell carcinoma in older adults: Should we waive this treatment in certain patients?

BACKGROUND: Skin cancer incidences are increasing. Treatment for basal cell carcinomas (BCCs) can be questioned in certain patients. Treatment options are various, but Mohs micrographic surgery (MMS) has the highest cure rate. It is, however, time-consuming and results in high logistical burden and treatment costs for both patients and society. OBJECTIVES: This study critically re-evaluates MMS for facial BCCs in older adults. The main objective is to examine all clinical, tumour and patient characteristics in relation to safety and survival to detect a subgroup in which MMS was not the best choice. The overall aim is to identify characteristics that support clinical decision-making in daily practice. METHODS: Patients that received MMS between November 1998 and December 2012 were included. Only patients >75 years with a facial BCC were withheld for analysis. This is a retrospective cohort study, since evaluating the outcome of MMS in accordance with life expectancy is the main objective. Patient charts were evaluated towards comorbidities, complications and survival. RESULTS: This cohort comprises 207 patients. Median survival was 7.85 years. The age-adjusted Charlson comorbidity index (aCCI) was divided into low/medium scores (aCCI < 6) and high scores (aCCI ≥ 6). Median survival was 11.58 years in the low aCCI group and 3.60 years in the high aCCI group (p < 0.001). There was a very strong association between high aCCI and survival (HR, 6.25; 95% CI, 3.83-10.21). Other characteristics were not associated with survival. CONCLUSIONS: Clinicians should assess the aCCI in older patients presenting with a facial BCC before deciding if MMS is an eligible treatment option. High aCCI has shown to be an indicator for low median survival, even in MMS patients with usually high functional status. MMS should be waived as treatment in older patients with high aCCI scores in favour of other, less intensive and less expensive treatment options.

The therapeutic dilemma of basal cell carcinoma in older adults: A review of the current literature.

Skin cancer is known to be a significant health care threat due to the massively increasing numbers of diagnoses. In 2019, 4 million basal cell carcinoma (BCC) cases were diagnosed globally, making BCC the most frequent of all cancers worldwide in fair skinned populations. Given the increasing life-expectancy for all countries worldwide (by 2050, the world's population of people aged 60 years and older will have doubled), the incidence of BCC is expected to keep increasing in the future. Management of BCCs is challenging, especially among older adults, as mortality due to BCCs is extremely rare, whereas locally destructive growth can cause significant morbidity in certain cases. Therapeutic management in this population is further hampered because of the presence of comorbidities, frailty, and the heterogeneity of these aspects in older patients, leading to treatment dilemmas. A literature review was conducted to identify relevant patient, tumour, and treatment related factors that should be considered in the decision making for BCC treatment in older adults. This narrative review synthesizes all aspects concerning BCC treatment in older adults and aims to make some specific suggestions considering BCC treatment in older adults that can be used in daily practice. We found that nodular BCC was found to be the most common subtype in older adults, most frequently located in the head and neck region. In non-facial BCCs, current literature has shown no significant impact on the quality of life (QoL) in older patients. Besides comorbidity scores, functional status should guide clinicians in treatment decisions. Taking all aspects into account when making treatment decisions is of great importance. When treating superficial BCCs on difficult-to-reach lesions in older adults, a clinician-administered treatment should be suggested because of possible impaired mobility in these patients. Based on current literature, we recommend assessing the comorbidities, the functional status, and frailty in older patients with BCC to evaluate life expectancy. In patients with low-risk BCCs and a limited life expectancy (LLE), an active surveillance or watchful waiting strategy can be suggested.

Can Multispectral Dermoscopy Help In Distinguishing Blue Color?

INTRODUCTION: The interpretation of colors is essential in the dermoscopic evaluation of skin lesions. The same blue color on white dermoscopy may indicate blood or pigment deep in the dermis. Contrary to white dermoscopy, multispectral dermoscopy uses different wavelengths of light to illuminate a lesion and is able to decompose the dermoscopic image into individual maps that allow to more clearly visualize specific skin structures such as pigment distribution (pigment map) and vasculature (blood map). These maps are called skin parameter maps. OBJECTIVES: The aim of this research is to investigate whether skin parameter maps can be used to objectively identify and distinguish the presence of pigment and blood, by using blue naevi and angiomas as models for respectively pigment and blood. METHODS: We retrospectively analyzed 24 blue naevi and 79 angiomas. The skin parameter maps of each of the lesions were independently reviewed by 3 expert dermoscopists, in the absence of the regular white-light dermoscopic image. RESULTS: All the observers provided high levels of diagnostic accuracy for blue naevus and angioma based on skin parameter maps alone, and the dermoscopic diagnosis was considered substantially reliable because of the 79% of diagnostic K agreement. Percentages of blue naevi and angiomas that showed respectively deep pigment and blood were very high at 95.8% and 97.5%. There was a percentage of lesions that counterintuitively showed blood in blue naevi (37.5%) and deep pigment in angiomas (28.8%). CONCLUSIONS: Skin parameter maps based on multispectral images can help to objectify the presence of deep pigment or blood in blue naevi and angiomas. The application of these skin parameter maps could help in the differential diagnosis between pigmented and vascular lesions.

Angiosarcoma Mimicking Rhinophyma.

This case report describes a man in his 60s who was referred to the department of dermatology for further evaluation of a lesion on the nose.

Preoperative assessment of cutaneous melanoma thickness by multispectral dermoscopy.

Preoperative assessment of Breslow thickness by means of sonography and clinical and dermoscopic criteria in white light dermoscopy has been reported, but up until now, the use of multispectral dermoscopy has not been investigated. Aim of this research is to determine whether multispectral dermoscopy and more specifically pigment maps can be used as a predictive marker for Breslow thickness in melanoma. Pigment maps are generated in real time from multispectral dermoscopic images and help to visualize the presence of pigment in a lesion. Multispectral images of 110 melanomas were collected, using a digital handheld multispectral dermatoscope, and assessed independently by five observers for the presence or absence of deep pigment compared with the surrounding skin. According to histopathological examination, the mean Breslow thickness of all 110 melanomas was 1.04 mm (ranging from 0.1 to 14 mm). The group of melanomas where deep pigment was visualized on the multispectral image (n = 78) had a significantly higher Breslow thickness (1.19 mm) than the group where no deep pigment was observed (n = 32, mean Breslow 0.68 mm) (P = 0.025). This study is unique in preoperative assessment of tumour thickness by means of multispectral dermoscopy. Our data indicate that the presence of deep pigment as visualized in digital dermoscopic skin parameter maps identifies a group of thicker melanomas. Further prospective research is needed to validate these pigment maps, generated by multispectral dermoscopy as a measure to predict invasiveness in melanoma.

Truth or dare: switching BRAF/MEK inhibitors after acute interstitial nephritis in a patient with metastatic melanoma - A case report and review of the literature.

INTRODUCTION: The introduction of BRAF/MEK inhibitors has significantly improved overall survival of patients with BRAF V600-mutant advanced or metastatic melanoma. Most patients treated with BRAF/MEK inhibitors will experience adverse events during the course of their treatment. Kidney impairment, however, was rarely reported in the pivotal trials. To date, there are only three cases of biopsy-proven acute interstitial nephritis associated with dabrafenib and trametinib reported in the literature. CASE REPORT: A 50-year-old man diagnosed with metastatic melanoma was hospitalized in August 2021, 5 months after treatment initiation with dabrafenib and trametinib. He presented with acute kidney injury, with serum creatinine of 3.34 mg/dL and eGFR of 20.3 mL/min/m². Kidney biopsy revealed acute interstitial nephritis. MANAGEMENT & OUTCOME: He was treated with methylprednisolone 16 mg qd, and both dabrafenib and trametinib were permanently discontinued, with recuperation of his kidney function. Another BRAF/MEK inhibitor combination, encorafenib and binimetinib, was introduced, with preserved kidney function and excellent disease control. DISCUSSION: We report the first case of biopsy-proven interstitial nephritis in a patient treated with dabrafenib and trametinib, with successful introduction of another BRAF/MEK inhibitor combination. Although rare, clinicians should be aware of the risk of renal adverse events associated with BRAF/MEK inhibitors. Renal biopsy is mandatory in the absence of a clear explanation or rapid recovery of renal failure. In case of proven interstitial nephritis, corticosteroids should be initiated. Switching to another BRAF/MEK inhibitor combination can be considered for patients with complete recovery of renal function and limited treatment options.

Study protocol of the BASINEL Study: a pragmatic randomised controlled trial investigating treatment versus no treatment of low-risk basal cell carcinomas in older persons.

INTRODUCTION: Basal cell carcinomas (BCCs) represent 70% of all skin cancers. These tumours do not metastasise but are locally invasive if left untreated. There is a high incidence of BCC in the elderly, and clinicians frequently face important treatment dilemmas. The approach to BCC in the elderly should be investigated thoroughly. METHODS AND ANALYSIS: Data on health-related quality of life (HrQoL), survival and complication rate will be examined in a treatment and a non-treatment arm (1:1 allocation). In the non-treatment arm, in vivo biological behaviour of low-risk BCCs in elderly patients will be examined. The main objective is to combine tumour characteristics with demographic data, in order to determine whether treatment will positively affect the patients' HrQoL within a predetermined time frame. A monocentric randomised controlled trial (RCT) was designed at the Ghent University Hospital. The study population consists of patients with the minimum age of 75 years and a new diagnosis of (a) low-risk BCC(s). Patients in the treatment arm will receive standard care. Patients in the non-treatment arm will be closely monitored: the tumour will be intensively evaluated using multispectral dermoscopy, reflectance confocal microscopy and high-definition optical coherence tomography. All patients will be asked to fill in a questionnaire concerning their HrQoL at consecutive time points. Patient-reported side effects will be evaluated via an additional questionnaire.Primary outcomes will include the difference in HrQoL and the difference in complication risks (treatment vs non-treatment) at different time points of the study. Secondary endpoints are the evolution of the BCCs in the non-treatment arm and the long-term survival in both study arms. Tertiary endpoint is the treatment effectiveness in the treatment arm. The sample size calculation was performed and resulted in a target sample size of 272 patients in this study with a 1:1 allocation. ETHICS AND DISSEMINATION: Subjects can withdraw from participating in this study at any time for any reason without any consequences. Approval for this study was received from the Ethics Committee of the Ghent University Hospital on 26 August 2021.The results of this RCT will be submitted for publication in one or more international, peer-reviewed medical journals, regardless of the nature of the study results. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov (NCT05110924).

Skin Cancer Detection Using Infrared Thermography: Measurement Setup, Procedure and Equipment.

Infrared thermography technology has improved dramatically in recent years and is gaining renewed interest in the medical community for applications in skin tissue identification applications. However, there is still a need for an optimized measurement setup and protocol to obtain the most appropriate images for decision making and further processing. Nowadays, various cooling methods, measurement setups and cameras are used, but a general optimized cooling and measurement protocol has not been defined yet. In this literature review, an overview of different measurement setups, thermal excitation techniques and infrared camera equipment is given. It is possible to improve thermal images of skin lesions by choosing an appropriate cooling method, infrared camera and optimized measurement setup.

Clinical Relevance of Serum Kyn/Trp Ratio and Basal and IFNγ-Upregulated IDO1 Expression in Peripheral Monocytes in Early Stage Melanoma.

Immune escape is an early phenomenon in cancer development/progression. Indoleamine 2,3-dioxygenase 1 (IDO1) is a normal endogenous mechanism of acquired peripheral immune tolerance and may therefore be tumor-promoting. This study investigated the clinical relevance of IDO1 expression by immune cells in the lymph nodes and blood and of the serum kynurenine/tryptophan (Kyn/Trp) ratio in 65 systemic treatment naïve stage I-III melanoma patients. Blood samples were collected within the first year of diagnosis. Patients had a median follow-up of 61 months. High basal IDO1 expression in peripheral monocytes and low IFNγ-induced IDO1 upregulation correlated with worse outcome independent from disease stage. Interestingly studied factors were not interrelated. During follow-up, the risk of relapse was 9% (2/22) in the subgroup with high IFNγ-induced IDO1 upregulation in monocytes. In contrast, if IDO1 upregulation was low, relapse occurred in 30% (3/10) of patients with low basal IDO1 expression in monocytes and in 61.5% (8/13) in the subgroup with high basal IDO1 expression in monocytes (Log-Rank test, p=0.008). This study reveals some immune features in the blood of early stage melanoma that may be of relevance for disease outcome. These may offer a target for sub-stratification and early intervention.