Skin cancer in Europe today and challenges for tomorrow.

One in every three cancers diagnosed is a skin cancer. Europe has the global lead in the number of UV-attributable cancer cases with the highest number of melanoma cases worldwide and the second highest number of keratinocyte cancers (KC). Further increases are expected in Europe for the coming decades. Projected increases are highest for KC with increases in incidence around 40% and increases in mortality around 50%, with KC mortality in males approximating melanoma mortality in females. The two main drivers for this skin cancer epidemic are ageing of the population but especially UV exposure. In conclusion, skin cancer represents a major challenge in the cancer field in Europe today and will continue to do so in the coming decades. This calls for a European skin cancer action plan intended to reduce avoidable UV exposure and to prepare the healthcare system to safeguard early diagnosis and treatment of skin cancer.

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.

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.

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.

Checkpoint inhibition in combination with an immunoboost of external beam radiotherapy in solid tumors (CHEERS): study protocol for a phase 2, open-label, randomized controlled trial.

BACKGROUND: While the introduction of checkpoint inhibitors (CPIs) as standard of care treatment for various tumor types has led to considerable improvements in clinical outcome, the majority of patients still fail to respond. Preclinical data suggest that stereotactic body radiotherapy (SBRT) could work synergistically with CPIs by acting as an in situ cancer vaccine, thus potentially increasing response rates and prolonging disease control. Though SBRT administered concurrently with CPIs has been shown to be safe, evidence of its efficacy from large randomized trials is still lacking. The aim of this multicenter randomized phase II trial is to assess whether SBRT administered concurrently with CPIs could prolong progression-free survival as compared to standard of care in patients with advanced solid tumors. METHODS/DESIGN: Ninety-eight patients with locally advanced or metastatic disease will be randomized in a 1:1 fashion to receive CPI treatment combined with SBRT (Arm A) or CPI monotherapy (Arm B). Randomization will be stratified according to tumor histology (melanoma, renal, urothelial, head and neck squamous cell or non-small cell lung carcinoma) and disease burden (≤ or > 3 cancer lesions). The recommended SBRT dose is 24Gy in 3 fractions, which will be administered to a maximum of 3 lesions and is to be completed prior to the second or third CPI cycle (depending on CPI treatment schedule). The study's primary endpoint is progression-free survival as per iRECIST. Secondary endpoints include overall survival, objective response, local control, quality of life and toxicity. Translational analyses will be performed using blood, fecal and tissue samples. DISCUSSION: The CHEERS trial will provide further insights into the clinical and immunological impact of SBRT when combined with CPIs in patients with advanced solid tumors. Furthermore, study results will inform the design of future immuno-radiotherapy trials. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT03511391 . Registered 17 April 2018.

A randomized controlled phase II clinical trial on mRNA electroporated autologous monocyte-derived dendritic cells (TriMixDC-MEL) as adjuvant treatment for stage III/IV melanoma patients who are disease-free following the resection of macrometastases.

BACKGROUND: Autologous monocyte-derived mRNA co-electroporated dendritic cells with mRNA encoding CD40 ligand (CD40L), CD70 and a constitutively activated TLR4 (caTLR4) (referred to as TriMixDC-MEL) have anti-tumor activity in advanced melanoma patients. We investigated the safety and activity of adjuvant TriMixDC-MEL in stage III/IV melanoma patients. MATERIALS AND METHODS: Forty-one patients were randomly assigned to treatment with TriMixDC-MEL (n = 21) and standard follow-up (n = 20). "Cross-over" was allowed at the time of non-salvageable recurrence. The primary endpoint was the percentage of patients alive and disease-free at 1-year. For a subset of patients, (formalin-fixed paraffin-embedded), tumor tissue samples were available for mRNA expression profiling and PD-L1 immunohistochemical staining. RESULTS: Baseline characteristics were well balanced. One-year after randomization, 71% of patients in the study arm were alive and free of disease compared to 35% in the control arm. After a median follow-up of 53 months (range 3-67), 23 patients experienced a non-salvageable melanoma recurrence (TriMixDC-Mel arm n = 9 and control arm n = 14).The median time to non-salvageable recurrence was superior in the TriMixDC-MEL arm (median 8 months (range 1-6) vs. not reached; log-rank p 0.044). TriMixDC-MEL-related adverse events (AE) consisted of transient local skin reactions, flu-like symptoms and post-infusion chills. No grade ≥ 3 AE's occurred. The mRNA expression profiling revealed four genes (STAT2, TPSAB1, CD9 and CSF2) as potential predictive biomarkers. CONCLUSION: TriMixDC-MEL id/iv as adjuvant therapy is tolerable and may improve the 1-year disease-free survival rate. Combination of optimized autologous monocyte-derived DC-formulations warrants further investigation in combination with currently approved adjuvant therapy options.

Enhanced visualization of blood and pigment in multispectral skin dermoscopy.

BACKGROUND AND OBJECTIVES: Dermoscopy has proven its value in the diagnosis of skin cancer and, therefore, is well established in daily dermatology practice. Up until now, analogue white light dermoscopy is the standard. Multispectral dermoscopy is based on illumination of the skin with narrowband light sources with different wavelengths. Each of these wavelengths is differently absorbed by skin chromophores, such as pigment or (de)oxygenated blood. Multispectral dermoscopy could be a way to enhance the visualization of vasculature and pigment. We illustrate possible additional information by such "skin parameter maps" in some cases of basal cell carcinoma and Bowen's disease. METHODS: Using a new digital multispectral dermatoscope, skin images at multiple wavelengths are collected from different types of skin lesions. These particular images together with the knowledge on skin absorption properties, result in so called "skin parameter maps". RESULTS: A "pigment contrast map," which shows the relative concentration of primarily pigment, and a "blood contrast map" which shows the relative concentration of primarily blood were created. Especially, the latter is of importance in diagnosing keratinocyte skin cancer hence vascular structures are a characteristic feature, as further illustrated in the study. CONCLUSIONS: Skin parameter maps based on multispectral images can give better insight in the inner structures of lesions, especially in lesions with characteristic blood vessels such as Bowen's disease and basal cell carcinoma. Skin parameter maps can be used complementary to regular dermoscopy and could potentially facilitate diagnosing skin lesions.

Immune checkpoint blockade for organ transplant patients with advanced cancer: how far can we go?

PURPOSE OF REVIEW: Checkpoint inhibitors (CPIs) provide impressive response rates among immunocompetent patients with various solid tumors. So far, organ transplant recipients have been excluded from clinical studies due to the putative risk of allograft rejection however 48 cases of liver and renal transplant patients treated with CPI were already described in literature. RECENT FINDINGS: Here we discuss 19 cases of liver and 29 cases of renal transplant patients who received CPI for advanced cancer. Disease control rate [stable disease, complete response (CR) and partial response (PR) together] was 35% (21% for liver and 45% for kidney transplant patients). Graft rejection was seen in 37% of liver and 45% and kidney transplant patients. Significantly, our analysis shows that an 'ideal' response occurs in 21% of all patients (antitumor response accompanied with durable graft tolerance). SUMMARY: We believe that transplant patients can be treated with CPI in a controlled setting and for well informed patients. To obtain a durable antitumor immune response while avoiding rejection, to be able to adjust immunosuppression and to have the opportunity to develop biomarkers for tumor response and transplant rejection, these patients should be treated according to a clinical care path or a prospective clinical trial.

A phase II trial of stereotactic body radiotherapy with concurrent anti-PD1 treatment in metastatic melanoma: evaluation of clinical and immunologic response.

BACKGROUND: Antibodies blocking programmed cell death 1 (PD-1) have encouraging responses in patients with metastatic melanoma. Response to anti-PD-1 treatment requires pre-existing CD8+ T cells that are negatively regulated by PD-1-mediated adaptive immune resistance. Unfortunately, less than half of melanoma tumours have these characteristics. Combining anti-PD-1 treatment with other immunomodulating treatments to activate CD8+ T cells is therefore of vital importance to increase response rates and long-term survival benefit in melanoma patients. Both preclinical and retrospective clinical data support the hypothesis that radiotherapy increases the response rates to anti-PD-1 treatment by stimulating the accumulation and activation of CD8+ T cells in the tumour microenvironment. Combining radiotherapy with a PD-1 blocking antibody might therefore increase response rates and even induce long-term survival. The current phase II study will be testing these hypotheses and aims to improve local and distant tumour responses by exploiting the pro-immunogenic effects of radiotherapy in addition to anti-PD-1 treatment. METHODS: The trial will be conducted in patients with metastatic melanoma. Nivolumab or pembrolizumab, both antibodies that target PD-1, will be administrated according to the recommended dosing schedule. Prior to the 2nd cycle, radiotherapy will be delivered in three fractions of 8 Gy to the largest FDG-avid metastatic lesion. The primary endpoint is the proportion of patients with a partial or complete response in non-irradiated metastases according to RECIST v1.1. Secondary endpoints include response rate according to immune related response criteria, metabolic response, local control and survival. To identify peripheral blood biomarkers, peripheral blood mononuclear cells and serum samples will be collected prospectively before, during and after treatment and subjected to flow cytometry and cytokine measurement. DISCUSSION: The current phase II trial aims at exploring the suggested benefits of combining anti-PD-1 treatment and radiotherapy. The translational focus on immunologic markers might be suitable for predicting efficacy and monitoring the effect so to improve patient selection for future clinical applications. ClinicalTrials.gov Identifier NCT02821182.

A phase I/II trial of fixed-dose stereotactic body radiotherapy with sequential or concurrent pembrolizumab in metastatic urothelial carcinoma: evaluation of safety and clinical and immunologic response.

BACKGROUND: Current first-line standard of therapy for metastatic urothelial carcinoma is platinum-based combination chemotherapy. Pembrolizumab in phase III has demonstrated a promising overall response rate of 21.1% in patients with progression or recurrence after platinum-based chemotherapy. Preclinical and clinical evidence suggests that radiotherapy has a systemic anti-cancer immune effect and can increase the level of PD-L1 and tumor infiltrating lymphocytes in the tumor microenvironment. These findings gave rise to the hypothesis that the combination of radiotherapy with anti-PD1 treatment could lead to a synergistic effect, hereby enhancing response rates. METHODS: The phase I part will assess the dose limiting toxicity of the combination treatment of stereotactic body radiotherapy (SBRT) with four cycles of pembrolizumab (200 mg intravenously, every 3 weeks) in patients with metastatic urothelial carcinoma. The dose of both pembrolizumab and SBRT will be fixed, yet the patients will be randomized to receive SBRT either before the first cycle of pembrolizumab or before the third cycle of pembrolizumab. SBRT will be delivered (24 Gy in 3 fractions every other day) to the largest metastatic lesion. Secondary objectives include response rate according to RECIST v1.1 and immune related response criteria, progression-free survival and overall survival. The systemic immune effect triggered by the combination therapy will be monitored on various time points during the trial. The PD-L1/TIL status of the tumors will be analyzed via immunohistochemistry and response rates in the subgroups will be analyzed separately. A Simon's two-stage optimum design is used to select the treatment arm associated with the best response rate and with acceptable toxicity to proceed to the phase II trial. In this phase, 13 additional patients will be accrued to receive study treatment. DISCUSSION: The progress made in the field of immunotherapy has lead to promising breakthroughs in various solid malignancies. Unfortunately, the majority of patients do not respond. The current trial will shed light on the toxicity and potential anti-tumor activity of the combination of radiotherapy with anti-PD1 treatment and may identify potential new markers for response and resistance to therapy. Trial registration this trial is registered on clinicaltrials.gov (NCT02826564).

Chronic and Invasive Fungal Infections in a Family with CARD9 Deficiency.

Chronic mucocutaneous or invasive fungal infections are generally the result of primary or secondary immune dysfunction. Patients with autosomal recessive CARD9 mutations are also predisposed to recurrent mucocutaneous and invasive fungal infections with Candida spp., dermatophytes (e.g., Trichophyton spp.) and phaeohyphomycetes (Exophiala spp., Phialophora verrucosa). We study a consanguineous family of Turkish origin in which three members present with distinct clinical phenotypes of chronic mucocutaneous and invasive fungal infections, ranging from chronic mucocutaneous candidiasis (CMC) in one patient, treatment-resistant cutaneous dermatophytosis and deep dermatophytosis in a second patient, to CMC with Candida encephalitis and endocrinopathy in a third patient. Two patients consented to genetic testing and were found to have a previously reported homozygous R70W CARD9 mutation. Circulating IL-17 and IL-22 producing T cells were decreased as was IL-6 and granulocyte/macrophage colony-stimulating factor (GM-CSF) secretion upon stimulation with Candida albicans. Patients with recurrent fungal infections in the absence of known immunodeficiencies should be analyzed for CARD9 gene mutations as the cause of fungal infection predisposition.

Burden of skin cancer in Belgium and cost-effectiveness of primary prevention by reducing ultraviolet exposure.

Skin cancer (melanoma- and non-melanoma skin cancer) is one of the most rapidly increasing cancers worldwide. This study analysed the current and future economic burden of skin cancer in Belgium and the cost-effectiveness of primary prevention of skin cancer. A retrospective bottom-up cost-of-illness study was performed, together with a Markov model in order to analyse the cost-effectiveness and the budget impact analysis of primary prevention of skin cancer in Belgium. Total prevalence of skin cancer in Belgium was estimated to triple in the next 20years. The total economic burden of skin cancer in 2014 in Belgium was estimated at €106 million, with a cumulative cost of €3 billion in 2034. The majority of this total cost was due to melanoma (65%). Over a period of 50years, both a sensitisation campaign and a total ban on sunbed use would lead to a gain in quality-adjusted life-years and cost-savings. For every euro invested in the campaign, €3.6 would be saved on the long-term for the healthcare payer. Policy makers and clinicians should promote UV protection strategies, as they were estimated to be dominant strategies.

Clinical significance of plasmacytoid dendritic cells and myeloid-derived suppressor cells in melanoma.

BACKGROUND: Immune markers in the peripheral blood of melanoma patients could provide prognostic information. However, there is currently no consensus on which circulating cell types have more clinical impact. We therefore evaluated myeloid-derived suppressor cells (MDSC), dendritic cells (DC), cytotoxic T-cells and regulatory T-cells (Treg) in a series of blood samples of melanoma patients in different stages of disease. METHODS: Flow cytometry was performed on peripheral blood mononuclear cells of 69 stage I to IV melanoma patients with a median follow-up of 39 months after diagnosis to measure the percentage of monocytic MDSCs (mMDSCs), polymorphonuclear MDSCs (pmnMDSCs), myeloid DCs (mDCs), plasmacytoid DCs (pDCs), cytotoxic T-cells and Tregs. We also assessed the expression of PD-L1 and CTLA-4 in cytotoxic T-cells and Tregs respectively. The impact of cell frequencies on prognosis was tested with multivariate Cox regression modelling. RESULTS: Circulating pDC levels were decreased in patients with advanced (P = 0.001) or active (P = 0.002) disease. Low pDC levels conferred an independent negative impact on overall (P = 0.025) and progression-free survival (P = 0.036). Even before relapse, a decrease in pDC levels was observed (P = 0.002, correlation coefficient 0.898). High levels of circulating MDSCs (>4.13%) have an independent negative prognostic impact on OS (P = 0.012). MDSC levels were associated with decreased CD3+ (P < 0.001) and CD3 + CD8+ (P = 0.017) T-cell levels. Conversely, patients with high MDSC levels had more PD-L1+ T-cells (P = 0.033) and more CTLA-4 expression by Tregs (P = 0.003). pDCs and MDSCs were inversely correlated (P = 0.004). The impact of pDC levels on prognosis and prediction of the presence of systemic disease was stronger than that of MDSC levels. CONCLUSION: We demonstrated that circulating pDC and MDSC levels are inversely correlated but have an independent prognostic value in melanoma patients. These cell types represent a single immunologic system and should be evaluated together. Both are key players in the immunological climate in melanoma patients, as they are correlated with circulating cytotoxic and regulatory T-cells. Circulating pDC and MDSC levels should be considered in future immunoprofiling efforts as they could impact disease management.

A short dermoscopy training increases diagnostic performance in both inexperienced and experienced dermatologists.

Dermoscopy is a clinical tool known to improve the early detection of melanoma and other malignancies of the skin, but only for experienced users. Our aim was to evaluate the effect of short (3-hour) dermoscopy training sessions in both residents and practicing dermatologists. The training improved diagnostic accuracy for both melanocytic and nonmelanocytic neoplasms of the skin and the observed effect was the highest for residents but was also significant for more experienced practicing dermatologists.

Efficacy of products to remove eggs of Pediculus humanus capitis (Phthiraptera: Pediculidae) from the human hair.

Head lice infestations are very common in children aged between 3 and 12 yr old. The eggs of the head louse are difficult to remove and remain firmly attached to the hair even after any head louse treatment. Solid in vitro and in vivo evidence to support the use of any of the proposed products to facilitate nit removal is scarce. The objective of the current study was to determine the efficacy of several products to remove eggshells from human hair using an objective measurement procedure. Water and ordinary hair conditioner significantly facilitated the removal of nits in vitro. We found no difference between ordinary conditioner and products specifically marketed for the purpose of nit removal. Other products such as formic acid solution and almond oil did not have a beneficial effect.

Clinicopathologically Defined Naevus Subtypes and Melanoma Risk.

Early detection of melanoma is a major determinant in disease outcome and drives the number of (over)excised naevi in clinical practice. This study aimed to evaluate demographic features and melanoma risk of clinically suspicious, mainly flat naevus subtypes. Based on the methodology of ex vivo dermoscopy and derm dotting, the 12 most prevalent naevus subtypes were identified in a collection of over 7000 naevi excised for medical reason. Dermoscopical, histopathological and clinical features of these subtypes were described. In addition, the association with melanoma history, histopathological atypia and melanoma occurrence within naevi was compared. Nearly half of the naevi removed for medical reasons were of the hypermelanotic subtype with no or mild histopathological atypia and low melanoma association, suggesting overtreatment in daily practice. Contrarily, the subtypes atypical lentiginous naevus and orange pulverocytic flat naevus were associated with higher proportions of (severe) atypia and melanoma (history). We believe these subtypes may reflect different tumoural and/or (germline) genetic entities with different melanoma risk. The data from this study may direct further prospective research on specific naevus subtypes in order to obtain better insights in associated clinical/genetic factors and melanoma risk.

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.

The impact of basal cell carcinoma on the quality-of-life in older patients.

Basal cell carcinoma (BCC) is the most frequent malignant tumour worldwide and incidences are rising rapidly. BCC grow locally, but can invade surrounding tissues. Little is known concerning their impact on the health-related quality of life (HrQoL), and limited available data reports contradicting results. Measuring HrQoL in BCC patients should be done using disease-specific questionnaires such as the Basal and Squamous cell carcinoma Quality of Life (BaSQoL) questionnaire. The aim of this study was to assess the BCC-related HrQoL by examining all relevant patient, tumour and treatment characteristics to identify the main factors for the BCC-related impact. Specific attention for older BCC patients wass brought forward because of the often complex decisions in this subgroup. Patients ≥ 18 years with a history of BCC were asked to fill in the BaSQoL questionnaire, consisting of 5 subdomains. Multivariable analyses were done using a generalized additive model (GAM) because of the need for incorporation of non-linear functions. The study obtained approval of the Ethics Committee of the Ghent University Hospital (EC/2019/1352). Informed consent was obtained from all subjects. All experiments were performed in accordance with relevant guidelines and regulations. Four hundred patients with a median age of 66 were enrolled. Mean BaSQoL subscores were 0.78 (SD 0.63) for 'behaviour', 1.01 (SD 0.73) for 'diagnosis&treatment', 0.90 (SD 0.73) for 'worries', 0.40 (SD 0.63) for 'appearance' and 1.20 (SD 0.75) for 'other people', illustrating the low to moderate impact of BCC on the HrQoL. A GAM with subsequent ANOVA testing was done for all relevant variables. In 4 out of 5 BaSQoL subdomains 'age' showed a significant correlation ('behaviour' p = 0.007; 'diagnosis&treatment' p = 0.026; 'worries' p = 0.003; 'appearance' p = 0.008). Lower BaSQoL scores were seen in older patients, meaning less BCC-impact on their HrQoL. There was a clear non-linear correlation between BaSQoL scores and age, illustrating that the impact of BCC on the HrQoL shows a rapid decrease starting around the age of 70. This study is the first to illustrate the relation between the BCC-related HrQoL and the age of patients with the use of a disease-specific HrQoL instrument. We found a lower BaSQoL score in older adults, with a specific age group of interest starting around the age of 70-75. This is an argument for a potential wait-and-see strategy for BCC in these patients.