To be the leading Dutch Skin Cancer Center by: providing excellent outcome-driven integrated multidisciplinary care pathways ranging from prevention to innovative therapies for individual (complex) patients with skin cancer.
Patient management is evidence based and driven by innovation based on basic and translational research. The public health impact of skin cancer care is evaluated to secure future sustainability.
The ACE includes excellent complementary research groups, but they need to collaborate more closely in the future to fully profit from the existing knowledge and broaden the scope of the skin cancer research. Fundamental: In collaboration with Duke University, University of Munich and Medical University of South Caroline (NIH R01) the possible manipulation of the melanoma vasculature to improve chemotherapy is studied.
Our goals are to develop
- biomarkers for disease progression;
- introduce stratified treatments and
- to expand our successful platform of 3D grown metastatic melanoma organoids.
Epidemiology: an internationally recognized center for the 'epidemiology of skin cancer'. We use big data from IKNL, Rotterdam Study, DIS and PALGA to develop prediction models, burden of disease concepts, discrete choice experiments, health economics and health services research. Internationally, we collaborate with other cohorts such as Nurses Health Study, Framingham and DeCODE in the genetic epidemiology of skin color, aging and cancer. Translational: Bioprofiling of melanoma and developing 3D organoid is being done in detail for stage III melanomas. This endeavor can be expanded to low risk primary melanoma using the established biobank ROSCAN.
Non-invasive diagnostics of skin tumors, in particular melanoma, based on Raman spectroscopy is being developed in a Ducth consortium. Together with Nottingham University, the Raman technique will be introduced in the Mohs procedure. Clinical: to be a reference center for phase II-III trials in skin cancer. In line with biobanking and value based health care, we want to create cohorts (multiple cohort RCTs) to evaluate treatment.
The participating departments contribute substantially to students in Medicine in bachelor year 2 and Master year 1. In BSc year 2, a program on 'Head & Neck' is offered. In the MSc the educational program regular teachings and self learning courses are facilitated in master s second year.
The MSc program also comprises internships in which all ACE departments participate. Several departments participate in two partly overlapping Minors "From head to hands" and "Hoofdzaken" and the minor "Oncology". Each of the departments supervises (multiple) Research Master students annually.
The PhD education is located within MolMed and NIHES. The ACE hosts about 5 international PhD/Master students and 8 international clinical fellows. Each of the collaborating clinical departments provides residency programs and provide skin cancer programs for residents. In postgraduate education, we have successfully organized a Skin cancer congress in Spa (Belgium) and FACE IT course. From 2017 onwards, a multidisciplinary congress 'Cells to Surgery' will be organized in Rotterdam. The departments provide international fellowship in collaboration with their Dutch or European Society (www.dafprs.nl and EADV Mohs fellowship).
Societal Relevance to Research, Education and Patient Care
Valorization: RiverD International is a spin-out of Erasmus MC and has a close working relationship with Erasmus MC, which has resulted in 10 patent families. Its Raman technology has become an accepted standard for non-invasive skin analysis. Public Health: The ACE is involved with setting up the KWF sun avoidance campaigns. We provide the epidemiological data of skin cancer in the Netherlands and are affiliated with IKNL.
The shift of low value care for low risk BCC and its surveillance from dermatology to GP is being studied. Guidelines: Several partners participated in working groups of the existing skin cancer guidelines such as BCC, SCC and melanoma. Erasmus MC is the reference center for micrographic Mohs surgery this treatment is now included in the national BCC and PCC guidelines. The occurrence on multiple BCC's is integrated in the recent guidelines.
The Rotterdam criteria for the pathological assessment of the melanoma sentinel node is incorporated in European guidelines.
Viability of Research, Education and Patient Care
The Skin Cancer Center is a advanced knowledge sharing ACE, but the ambition is to enhance the cross discipline activities. Many of the departments have internal procedures to keep research, education and clinic viable, but a cross discipline approach is lacking and needs to be developed.
In research, several ACE related research groups are already collaborating intensely, but some are less involved because of interest in different tumor types, research questions and methodology. However, we have started discussing and active seeking future collaborative projects.
The many existing multidisciplinary clinics and working groups involve residents and provide the opportunity to share knowledge between discipline and across ages. One skin cancer working group might further enhance this. Departments identify and stimulate young talent both in clinic and research and several involved departments starting discussing the future faculty needs for the ACE to fully blossom. A shared HR policy and vision needs to be developed.
Key and relevant publications of the last five years
- Hollestein LM, et al. Trends of cutaneous melanoma in The Netherlands: increasing incidence rates among all Breslow thickness categories and rising mortality rates since
- Flohil SC, et al. Incidence, prevalence and future trends of primary basal cell carcinoma in the Netherlands. Acta Derm Venereol. 2011 Jan;91(1):24-30.
- Joosse A, et al. Superior outcome of women with stage I/II cutaneous melanoma: pooled analysis of four European Organisation for Research and Treatment of Cancer phase III trials. J Clin Oncol. 2012 Jun 20;30(18):2240-7.
- Joosse A, et al. Sex is an independent prognostic indicator for survival and relapse/progression-free survival in metastasized stage III to IV melanoma: a pooled analysis of five European organisation for research and treatment of cancer randomized controlled trials. J Clin Oncol. 2013 Jun 20;31(18):2337-46
- Verkouteren JA, et al. Predicting the Risk of a Second Basal Cell Carcinoma. J Invest Dermatol. 2015 Nov;135(11):2649-56.
- Jacobs LC, et al. IRF4, MC1R and TYR genes are risk factors for actinic keratosis independent of skin color. Hum Mol Genet. 2015 Jun 1;24(11):3296-303.
- Das AM, Eggermont AM, ten Hagen TL. A ring barrier-based migration assay to assess cell migration in vitro. Nat Protoc. 2015 Jun;10(6):904-15.
- Das AM, Koljenović S, Oude Ophuis CM, van der Klok T, Galjart B, Nigg AL, van Cappellen WA, Noordhoek Hegt V, Dinjens WN,
- Oude Ophuis CM, van Akkooi AC, Hoekstra HJ, Bonenkamp JJ, van Wissen J, Niebling MG, de Wilt JH, van der Hiel B, van de Wiel B, Koljenović S, Grünhagen DJ, Verhoef C. Risk Factors for Positive Deep Pelvic Nodal Involvement in Patients with Palpable Groin Melanoma Metastases: Can the Extent of Surgery be Safely Minimized? : A Retrospective, Multicenter Cohort Study. Ann Surg Oncol. 2015 Dec;22 Suppl 3:S1172-80.
- Kruiswijk F, Hasenfuss SC, Sivapatham R, Baar MP, Putavet D, Naipal KA, van den Broek NJ, Kruit W, van der Spek PJ, van Gent DC, Brenkman AB, Campisi J, Burgering BM, Hoeijmakers JH, de Keizer PL. Targeted inhibition of metastatic melanoma through interference with Pin1-FOXM1 signaling. Oncogene. 2016 Apr 28;35(17):2166-77.
PhD theses of the last five years
- Holterhues (2011) Burden of Melanoma
- Flohil (2012) Basal cell carcinoma in The Netherlands
- Joosse (2013) Gender differences in melanoma progression and survival
- Hollestein (2013) Burden and chemoprevention of skin cancer
- van der Leest (2015) Multiple cutaneous (pre)-malignancies
- Van der Ploeg (2014) Tumor load in lymph node positive melanoma
- Van Akkooi (2011). Sentinel Node (SN) Tumor Load Assessment in Melanoma: Dilemmas and Clinical Management
- Jacobs (2015) Genetic determinants of skin color, aging, and cancer
- Middelburg (2014) Photodynamic Therapy of skin using porphyrin precursors
- De Vijlder (2013) New insights into photodynamic therapy using porphyrin pre-cursors