Marieke W J Louwman’s research while affiliated with The Netherlands Organisation for Health Research Development and other places

Background Patients with haematologic malignancies are at increased risk of developing skin cancer and often experience worse skin cancer-related outcomes. However, there is a lack of nationwide, population-based data with long-term follow-up on the incidence and risks of different skin cancer types across all haematologic malignancies. Objectives To assess population-based risk estimates for cutaneous squamous cell carcinoma (CSCC), malignant melanoma (MM), Merkel cell carcinoma (MCC), and basal cell carcinoma (BCC) among patients with haematologic malignancies, stratified by skin cancer type and haematologic malignancy subgroup. These estimates can serve as a base for surveillance guidelines and patient education. Methods This nationwide population-based epidemiologic cohort study used data on 210,794 patients diagnosed with a haematologic malignancy between 1989 and 2020 from the Netherlands Cancer Registry (NCR). In addition, data on each type of histopathologically confirmed skin cancer per patient after haematologic malignancy diagnosis was retrieved from the NCR. Patients with a history of skin cancer prior to their haematologic malignancy were excluded. Cumulative incidences, standardized incidence ratio’s (SIRs), and absolute excess risks for each of the four skin cancers were calculated and stratified by haematologic malignancy subgroup, age, sex, follow-up, and primary treatment. Results The overall 10-year cumulative incidence of developing a first skin cancer was 2.6% for CSCC, 0.5% for MM, 0.05% for MCC, and 4.8% for BCC. Compared to the general population, nearly all haematologic malignancy subgroups showed more than a twofold increased risk of CSCC, MM, MCC and BCC. Patients with chronic lymphocytic leukemia (CLL) showed the highest risks for each of the four skin cancers, with SIRs of 4.4 for CSCC, 2.7 for MM, 9.3 for MCC, and 2.6 for BCC. These elevated risks persisted for more than 30 years after haematologic malignancy diagnosis. Conclusions Patients with all types of haematologic malignancies, and especially those with CLL, have a lifetime increased risk of developing different types of skin cancer. These findings highlight the importance of creating awareness among patients and care providers about this increased risk and promoting sun-protective measures and regular skin self-examinations in this high-risk population.

Early-stage cutaneous melanoma patients generally have a favorable prognosis, yet a significant proportion of metastatic melanoma cases arise from this group, highlighting the need for improved risk stratification using novel prognostic biomarkers. The Dutch Early-Stage Melanoma (D-ESMEL) study introduces a robust, population-based methodology to develop an absolute risk prediction model for stage I/II melanoma, incorporating clinical, imaging, and multi-omics data to identify patients at increased risk for distant metastases. Utilizing the Netherlands Cancer Registry and Dutch Nationwide Pathology Databank, we collected primary tumor samples from early-stage melanoma patients, with and without distant metastases during follow-up. Our study design includes a discovery set of metastatic cases and matched controls to identify novel prognostic factors, followed by a validation cohort using a nested case–control design to validate these factors and to build a risk prediction model. Tissue sections underwent Hematoxylin & Eosin (H&E) staining, RNA sequencing (RNAseq), DNA sequencing (DNAseq), immunohistochemistry (IHC), and multiplex immunofluorescence (MxIF).The discovery set included 442 primary melanoma samples (221 case–control sets), with 46% stage I and 54% stage II melanomas. The median time to distant metastasis was 3.4 years, while controls had a median follow-up time of 9.8 years. The validation cohort included 154 cases and 154 controls from a random population-based selection of 5,815 patients. Our approach enabled the collection of a large number of early-stage melanoma samples from population-based databases with extensive follow-up and a sufficient number of metastatic events. This methodology in prognostic cancer research holds the potential to impact clinical decision-making through absolute risk prediction.

Purpose Sinonasal mucosal melanoma (SNMM) is a rare malignancy, characterised by high (local) recurrence rates and poor survival. Comprehensive understanding of tumour etiology is currently lacking, which complicates adequate tumour treatment. Besides examining trends in incidence, this study aims to assess the association between clinical characteristics, treatment practices and patient outcomes, with the objective of establishing a baseline from which SNMM management can be enhanced. Methods All newly diagnosed SNMM cases in The Netherlands between 2001 and 2021 were included using data from The Netherlands Cancer Registry (NCR). Results A total of 320 patients were included. The annual incidence rate for the overall population was stable over the inclusion period with an annual percentage change (APC) of only − 0.01%. The 5-year overall survival (OS) and relative survival (RS) were 24.5 and 32.4%, respectively. Relative survival did not increase over time. The addition of adjuvant radiotherapy to surgery was not associated with a higher OS and RS compared to surgery alone. Conclusion Sinonasal mucosal melanoma is a rare disease with stable incidence rates in the Netherlands between 2001 and 2021. There has been no improvement in survival over the course of the inclusion period. The study reaffirms that adjuvant radiotherapy does not seem to improve patient outcomes. Given the generally poor outcomes for SNMM patients, novel therapeutic options ought to be considered in order to improve care.

Novel systemic therapies for advanced melanoma improve survival, but carry potential serious side effects and high costs. This study aimed to assess the timing and use of systemic therapies in the months before death. Patients diagnosed with advanced melanoma (July 2017–June 2020) who died before July 2020 were selected from the Netherlands Cancer Registry. We evaluated the timing of systemic therapies within 30 days and 3 months before death, and studied patient and tumor characteristics associated with systemic therapy use between diagnosis and death. Out of 1097 patients 68% received systemic therapy. Almost 25% and 10% started a new therapy within 90 days and within 30 days before death, respectively. Female sex, elevated LDH, BRAF mutation, poor ECOG performance status (≥3), and high comorbidity index reduced the odds of receiving immune therapy. Poor performance status and high comorbidity decreased the odds for both therapies. A considerable number of patients started systemic therapy shortly before death, emphasizing the importance of considering potential benefits and drawbacks through shared decision‐making.

Background Although patients with melanoma of unknown primary (MUP) have a better prognosis than similar-staged melanoma patients with known primary, the occurrence of brain metastases (BM) entails a serious complication. This study provides an overview of the incidence, treatment patterns, and overall survival (OS) of adult patients with BM-MUP in the Netherlands.MethodsBM-MUP cases were retrieved from the Netherlands Cancer Registry. Patient, disease and treatment-related characteristics were summarised using descriptive statistics. Overall survival (OS) was calculated by the Kaplan–Meier method, and the impact of prognostic factors on OS was assessed using Cox proportional hazard regression analyses.ResultsAmong 1779 MUP patients, 450 were identified as BM-MUP (25.3%). Of these patients, 381 (84.7%) presented with BM along with other metastases, while 69 (15.3%) had BM only. BM-MUP patients were predominantly male (68.2%), and had a median age of 64 years at diagnosis (interquartile range 54–71 years). Over time, the proportion of BM along other metastatic sites increased, and the occurrence of BM decreased (p = 0.01). 1-Year OS improved for the total population, from 30.0% (95% confidence interval (CI): 19.8–40.9%) in 2011–2012 to 43.6% (95%CI: 34.5–52.3%) in 2019–2020, and median OS more than doubled from 4.2 months (95%CI: 3.3–6.2 months) to 9.8 months (95%CI: 7.0–13.2 months). Patient’s age, localisation of BM, presence of synchronous liver metastasis and treatment were identified as independent predictors of OS.Conclusion Notwithstanding the progress made in OS for patients with BM-MUP in the past decade, their overall prognosis remains poor, and further efforts are needed to improve outcomes.