The skin department in our center has a strong focus on skin oncology. Management of skin cancers involves 4 departments of APHP.Centre (Internal medicine, Imaging and Pathology, Biology and Oncology) that collaborate together. It is an important center dedicated to skin oncology in the Great Paris area and at the national level. Our physicians, surgeons and biologists are mainly dedicated to skin cancer patients care and altogether 25 beds are dedicated to onco-dermatology. This program has managed 811 new cases of skin cancer during the last 3 years. It involves 2 sites of the APHP.5 sites (HEGP, Cochin) which are characterized by both medical and surgical strengths. The Dermatology department is also constitutive center of reference for genodermatoses predisposing to cutaneous cancer (CRMR MAGEC).
All these activities are structured around 2 weekly cancer multidisciplinary team meetings including members of the skin cancer program (Tuesday and Thursday). These meetings follow the INCA national guidelines, and ESMO guidelines. One is dedicated to primary cutaneous cancers while the second is devoted to metastatic tumors.
Therefore, an important feature of our site is that it is able to provide
- All state of art therapeutic: surgery, radiotherapy, stereotaxic radiotherapy, specific units dedicated to chemotherapy, targeted treatments as well as immunotherapy. Specific collaborations allow high level management of immune related events
- All current diagnostic tools: dermatopathology, molecular biology platform, all imaging procedures including PET scans and MRI.
Physicians, surgeons, pathologists and biologists of this program are strongly involved in clinical and translational research.
Clinical research is mainly performed with 7 therapeutic ongoing clinical trials (4 phaseIII – IIIb) see annex 2. A strong interaction with in-site physicians highly renowned in the diagnosis and treatment of skin cancers has been developed through several trials conducted during the last years and national ongoing trials. S. Aractingi, S Guégan, N Kramkimel, members of this program are involved at national level in national clinical research groups mainly in the Société Française de Dermatology.
Translational research involves 5 senior researchers in an Inserm labelled team (Skin Biology, Institut Cochin, UMRS 1016). This research team is led by Selim Aractingi. One of the main translational research fields of the team are about cutaneous melanocytic tumors and skin carcinomas.
Congenital melanocytic nevus is a benign melanocytic tumor with an increased risk of melanoma transformation. One research project aims at better characterizing certain cells subpopulations namely large CMN propagating cells in terms of signaling pathways, and identifying various inhibitors that have an impact on melanocytes proliferation and tumor maintenance.
A project, funded by PHRC, addresses the question of whether the presence of rare isolated melanoma cells in the peri-tumoral healthy tissue could have a prognostic significance in melanoma patients (DISSEMELA) using various state-of-the-art detection methods such as digital droplet PCR.
Two other projects aim at better characterizing genetic signatures involved in cutaneous and mucous membranes carcinomas that are non UV induced (GENOSKIN) using whole genome sequencing, as well as transcriptomic profile using RNA sequencing. This project has received a Leo foundation grant.
The Skin Cancer Program medical team is widely involved in the university teaching of skin conditions in Paris Descartes University and in several national teaching degrees/master’s degrees in the field of oncology :
- DIU d’onco-gériatrie et hématologie
- DIU transplantation d’organe
- DU de Cancérologie Clinique
- DESC/FST d’oncologie médicale
Based on our skillness we would like to improve
- Inclusion in therapeutic trials with an inclusion rate of 10 to 20% of patients
- Development of translational research, particularly studies of microenvironment and biomarkers of immunotherapies or targeted therapies
- Implementation of skin cancer screening
The following publications highlight the strength of skin cancer program physicians and researchers:
- Delanoy N, Michot JM, Comont T, Kramkimel N, Lazarovici J, Dupont R, Champiat S, Chahine C, Robert C, Herbaux C, Besse B, Guillemin A, Mateus C, Pautier P, Saïag P, Madonna E, Maerevoet M, Bout JC, Leduc C, Biscay P, Quere G, Nardin C, Ebbo M, Albigès L, Marret G, Levrat V, Dujon C, Vargaftig J, Laghouati S, Croisille L, Voisin AL, Godeau B, Massard C, Ribrag V, Marabelle A, Michel M, Lambotte O. Haematological immune-related adverse events induced by anti-PD-1 or anti-PD-L1 immunotherapy: a descriptive observational study. Lancet Haematol. 2019 Jan;6(1):e48-e57.
- Rouillé T, Aractingi S, Kadlub K, Fraitag S, How-Kit S, Daunay A, Hivelin M, Moguelet P, Picard A, Fontaine RH, Guégan S. Local inhibition of MEK/AKT prevents cellular growth in human congenital melanocytic nevi. J Invest Dermatol. 2019 Sep;139(9):2004-2015.
- Ramspott JP, Bekkat F, Bod L, Favier M, Terris B, Salomon A, Djerroudi L, Zaenker KS, Richard Y, Molinier-Frenkel V, Castellano F, Avril MF, Prévost-Blondel A. Emerging Role of IL-4-Induced Gene 1 as a Prognostic Biomarker Affecting the Local T-Cell Response in Human Cutaneous Melanoma. J Invest Dermatol. 2018 Dec;138(12):2625-2634.
- Mignard C, Deschamps Huvier A, Gillibert A, Duval Modeste AB, Dutriaux C, Khammari A, Avril MF, Kramkimel N, Mortier L, Marcant P, Lesimple T, Gaudy-Marqueste C, Lesage C, Machet L, Aubin F, Meyer N, Beneton N, Jeudy G, Montaudié H, Arnault JP, Visseaux L, Trabelsi S, Amini-Adle M, Maubec E, Le Corre Y, Lipsker D, Wierzbicka-Hainaut E, Litrowski N, Stefan A, Brunet-Possenti F, Leccia MT, Joly P. Efficacy of Immunotherapy in Patients with Metastatic Mucosal or Uveal Melanoma. J Oncol. 2018 Dec 2;2018:1908065.
- Denis D, Seta V, Regnier-Rosencher E, Kramkimel N, Chanal J, Avril MF, Dupin N. A fifth subtype of Kaposi’s sarcoma, classic Kaposi’s sarcoma in men who have sex with men: a cohort study in Paris. J Eur Acad Dermatol Venereol. 2018 Aug;32(8):1377-1384.
- Frazao A, Colombo M, Fourmentraux-Neves E, Messaoudene M, Rusakiewicz S, Zitvogel L, Vivier E, Vély F, Faure F, Dréno B, Benlalam H, Bouquet F, Savina A, Pasmant E, Toubert A, Avril MF, Caignard A. Shifting the Balance of Activating and Inhibitory Natural Killer Receptor Ligands on BRAFV600E Melanoma Lines with Vemurafenib. Cancer Immunol Res. 2017 Jul;5(7):582-593
- Heidelberger V, Goldwasser F, Kramkimel N, Jouinot A, Franck N, Arrondeau J, Guégan S, Mansuet-Lupo A, Alexandre J, Damotte D, Avril MF, Dupin N, Aractingi S. Clinical parameters associated with anti-programmed death-1 (PD-1) inhibitors-induced tumor response in melanoma patients. Invest New Drugs. 2017; 35(6):842-847.
- Heidelberger V, Goldwasser F, Kramkimel N, Jouinot A, Huillard O, Boudou-Rouquette P, Chanal J, Arrondeau J, Franck N, Alexandre J, Blanchet B, Leroy K, Avril MF, Dupin N, Aractingi S. Sarcopenic overweight is associated with early acute limiting toxicity of anti-PD1 checkpoint inhibitors in melanoma patients. Invest New Drugs. 2017 Aug;35(4):436-441.
- Garlan F, Blanchet B, Kramkimel N, Puszkiel A, Golmard JL, Noe G, Dupin N, Laurent-Puig P, Vidal M, Taly V, Thomas-Schoemann A. Circulating Tumor DNA Measurement by Picoliter Droplet-Based Digital PCR and Vemurafenib Plasma Concentrations in Patients with Advanced BRAF-Mutated Melanoma. Target Oncol. 2017 Jun;12(3):365-371.
- Desnoyer A, Dupin N, Assoumou L, Carlotti A, Gaudin F, Deback C, Peytavin G, Marcelin AG, Boué F, Balabanian K, Pourcher V; ANRS 154 LENAKAP trial group. Expression pattern of the CXCL12/CXCR4-CXCR7 trio in Kaposi sarcoma skin lesions. Br J Dermatol. 2016 Dec;175(6):1251-1262
- Guégan S, Kadlub N, Picard A, Rouillé T, Charbel C, Coulomb-L’Hermine A, How-Kit A, Fraitag S, Aractingi S, Fontaine RH. Varying proliferative and clonogenic potential in NRAS-mutated congenital melanocytic nevi according to size. Exp Dermatol. 2016; 25:789-96.
- Puszkiel A, White-Koning M, Dupin N, Kramkimel N, Thomas-Schoemann A, Noé G, Chapuis N, Vidal M, Goldwasser F, Chatelut E, Blanchet B. Plasma vemurafenib exposure and pre-treatment hepatocyte growth factor level are two factors contributing to the early peripheral lymphocytes depletion in BRAF-mutated melanoma patients. Pharmacol Res. 2016 Nov;113(Pt A):709-718.
- Herms F, Kramkimel N, Regnier-Rosencher E, Carlotti A, Chanal J, Boitier F, Aractingi S, Dupin N, Avril MF. Age and clear eyes are associated with an increased risk of cutaneous squamous cell carcinomas in vemurafenib-treated melanoma patients. Melanoma Res. 2016 Oct;26(5):487-91.
- Denis D, Régnier-Rosencher E, Kramkimel N, Jafari A, Avril MF, Dupin N. First-line treatment with paclitaxel for non-HIV-related Kaposi sarcoma: experience in 10 cases. Br J Dermatol. 2016 Apr;174(4):905-8.
- Charbel C, Fontaine RH, Kadlub N, Coulomb-L’hermine A, Rouillé T, How-Kit A, Moguelet P, Tost J, Picard A, Aractingi S, Guégan S. Clonogenic cell subpopulations maintain congenital melanocytic nevi. J Invest Dermatol. 2015; 135:824-33.
- Charbel C, Fontaine RH, Malouf GG, Picard A, Kadlub N, El-Murr N, How-Kit A, Su X, Coulomb-L’hermine A, Tost J, Mourah S, Aractingi S, Guégan S. NRAS Mutation Is the Sole Recurrent Somatic Mutation in Large Congenital Melanocytic Nevi. J Invest Dermatol. 2014; 134:1067-74.