Isabelle Hoorens

Background/Objectives: Keratinocyte carcinoma (KC) treatment is guided primarily by tumor characteristics, but sociodemographic factors may also influence care. We examined associations of age, sex, marital status, and educational level with treatment selection. Methods: Adults with actinic keratosis or KC were recruited in four Belgian and Dutch settings between 2020 and September 2023. Treatment was categorized as topical/non-invasive therapy, Mohs micrographic surgery (MMS), or standard surgical excision (reference). Multinomial regression adjusted for histologic group, tumor size, location, recruiting center, and an age-independent Charlson comorbidity component. The primary analysis included 681 participants, with additional sensitivity analyses. Results: The model converged normally. Age (global p = 0.023) and educational level (p = 0.002) were associated with treatment selection; sex and marital status were not. Each additional decade of age was associated with lower odds of MMS versus standard excision (adjusted odds ratio [aOR] 0.755, 95% confidence interval [CI] 0.595–0.959). Low versus high education was associated with lower odds of topical/non-invasive treatment versus standard excision (aOR 0.123, 95% CI 0.034–0.450), but not with MMS (aOR 0.533, 95% CI 0.232–1.222). Conclusions: Age and educational level were associated with KC treatment selection after clinical and center adjustment. These associations do not establish inequitable care because relevant patient-, clinician-, and pathway-level determinants were not captured.

Spatial transcriptomics (ST) has revolutionized our understanding of tumour biology but inherently lacks information on the upstream somatic driver mutations. We developed a spatially-aware graph convolutional neural network approach (SPOT-Mut) that infers mutated (sub)clones directly from ST data. SPOT-Mut was trained on virtual ST slides with clones simulated from a large collection of existing RNA and matched DNA sequencing data. SPOT-Mut was first evaluated for predicting mutations in TP53 , the most frequently mutated gene in human cancer. Precision and recall values exceeded 95% in most analysed cancer types and the model was validated on ST and matched DNA sequencing data from serial slices obtained from cutaneous SCC samples. SPOT-Mut was then trained on 62 frequently mutated driver genes, resulting in highly performing somatic mutation prediction models for 40 driver genes, including KRAS , KEAP1 , CTNNB1 and APC . With the increasing availability of ST data and upcoming atlases, SPOT-Mut potentiates the localization of (sub)clonal alterations in TP53 and other common driver mutations.

Keratinocyte carcinoma (KC) represents 90% of all skin cancers and despite its relatively low mortality, may affect patients' health-related quality of life (HRQoL). This Belgian/Dutch cross-sectional study measured the impact of KC on HRQoL using generic instruments and a disease-specific questionnaire. HRQoL was measured using the disease-specific Basal and Squamous Cell Carcinoma Quality of Life (BaSQoL) questionnaire, consisting of five domains. Sub-scores range from 0 to 3, with a higher score meaning higher impact on HRQoL. Additionally, the generic instruments EuroQol 5-Dimension 5-level (EQ-5D-5 L), visual analog scale (VAS), 15-dimensions (15D) and the time trade-off (TTO) technique were employed. Scores range from 0 to 1, with 0 meaning death and 1 meaning perfect health. HRQoL scores were stratified by patients with single and multiple KC. Generalized linear models assessed differences in mean HRQoL scores across KC groups, adjusting for relevant covariates. The study included 715 patients; 332 with single KC and 383 with multiple KC. The BaSQoL subscores for single and multiple KC patients ranged from 0.44 to 0.52 for the 'appearance' subdomain to 1.16 and 1.27 for the 'other people' subdomain, indicating a low-to-moderate impact on HRQoL. Patients with multiple KC showed significantly higher impact on BaSQoL 'worries' subdomain (p = 0.002) and worse perceived health on the EQ-5D-5 L (p = 0.004) compared to patients with single KC. No significant differences were observed in VAS, 15D or TTO between single and multiple KC. Findings suggest, both with disease-specific and generic instruments, a moderate to low impact of KC on HRQoL.

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.

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.