Operational classification of cutaneous squamous cell carcinomas based on unsupervised clustering of real cases by experts

Author:

Gaudy‐Marqueste C.1,Grob J. J.1,Garbe C.2ORCID,Ascierto P. A.3,Arron S.4,Basset‐Seguin N.5,Bohne A. S.6,Lenoir C.7ORCID,Dummer R.8ORCID,Fargnoli M. C.9ORCID,Guminski A.1011,Hauschild A.6,Kaufmann R.12ORCID,Lallas A.13ORCID,del Marmol V.14,Migden M.15,Penicaud M.16,Rembielak A.1718,Stratigos A.19,Tagliaferri L.2021,Zalaudek I.22,Arance A.23,Badinand D.24,Bossi P.2526ORCID,Challapalli A.27ORCID,Clementi M.28,Di Stefani A.2930,Ferrándiz‐Pulido C.3132,Giuffrida R.33ORCID,Gravina G. L.34,Ha P.35,Heinzerling L.36,Mallet S.1,Paradisi A.2930,Mohr P.37,Piccerillo A.2930ORCID,Rutkowski D.38,Saiag P.39,Sollena P.2930,Trakatelli M.40ORCID,Wojcieszek P.41,Yom S. S.42,Zelin E.43ORCID,Peris K.2930ORCID,Malvehy J.44

Affiliation:

1. Dermatology and Skin Cancer Department Aix‐Marseille University, APHM Marseille France

2. Centre for Dermatooncology, Department of Dermatology Eberhard Karls University Tuebingen Germany

3. Department of Skin Cancer, Cancer Immunotherapy and Development Therapeutics Istituto Nazionale Tumori IRCCS Fondazione Pascale Naples Italy

4. Peninsula Dermatology Burlingame California USA

5. Dermatology Department Saint‐Louis Hospital Paris France

6. Department of Dermatology University Hospital Schleswig‐Holstein (UKSH), Campus Kiel Kiel Germany

7. Department of Dermatology, Hôpitaux Universitaires de Bruxelles Université Libre de Bruxelles Brussels Belgium

8. Skin Cancer Centre at University Hospital Zurich Zurich Switzerland

9. Dermatology, Department of Biotechnological and Applied Clinical Sciences University of L'Aquila L'Aquila Italy

10. Department of Medical Oncology Royan North Shore Hospital Sydney New South Wales Australia

11. Northern Clinical School University of Sydney Sydney New South Wales Australia

12. Department of Dermatology, Venereology and Allergology Frankfurt University Hospital Frankfurt Germany

13. First Department of Dermatology, School of Medicine, Faculty of Health Sciences Aristotle University Thessaloniki Greece

14. Department of Dermatology University Hospital Erasme, Universite'Libre de Bruxelles Brussels Belgium

15. Departments of Dermatology and Head and Neck Surgery UT MD Anderson Cancer Center Houston Texas USA

16. Department of Oto‐Rhino‐Laryngology and Head and Neck Surgery APHM, La Conception University Hospital Marseille France

17. Department of Clinical Oncology The Christie NHS Foundation Trust Manchester UK

18. Division of Cancer Sciences, School of Medical Sciences, Faculty of Biology, Medicine and Health The University of Manchester Manchester UK

19. 1st Department of Dermatology‐Venereology Andreas Sygros Hospital, National and Kapodistrian University of Athens Athens Greece

20. Dipartimento di Diagnostica per Immagini e Radioterapia Oncologica Fondazione Policlinico Universitario A. Gemelli‐IRCCS Rome Italy

21. Università Cattolica del Sacro Cuore Rome Italy

22. Dermatology Clinic, Maggiore Hospital University of Trieste Trieste Italy

23. Department of Medical Oncology and IDIBAPS Hospital Clínic Barcelona Spain

24. Department of Radiotherapy Oncology Hospital La Timone Marseille France

25. Department of Biomedical Sciences Humanitas University Milan Italy

26. IRCCS Humanitas Research Hospital Milan Italy

27. Department of Oncology, Bristol Haematology and Oncology Centre UHBW Bristol UK

28. Department of Biotechnological and Applied Clinical Sciences University of L'Aquila L'Aquila Italy

29. UOC Dermatologia, Dipartimento di Scienze Mediche e Chirurgiche Addominali ed Endocrino Metaboliche Fondazione Policlinico Universitario A. Gemelli – IRCCS Rome Italy

30. Dermatologia, Dipartimento di Medicina e Chirurgia Traslazionale Università Cattolica del Sacro Cuore Rome Italy

31. Department of Dermatology University Hospital Vall d'Hebron Barcelona Spain

32. Facultad de Medicina Universitat Autònoma de Barcelona Bellaterra Spain

33. Department of Clinical and Experimental Medicine Dermatology – University of Messina Messina Italy

34. Department of Biotechnological and Applied Clinical Sciences, Radiotherapy and Radiobiology Unit University of L'Aquila L'Aquila Italy

35. Department of Otolaryngology Head and Neck Surgery University of California San Francisco San Francisco California USA

36. Department of Dermatology and Allergy Ludwig‐Maximilian University Hospital, LMU Munich Germany

37. Department of Dermatology Elbe‐Kliniken Buxtehude Buxtehude Germany

38. Department of Dermatology Manchester Foundation Trust Manchester UK

39. Department of General and Oncologic Dermatology, Ambroise Paré Hospital, APHP, & EA 4340 “Biomarkers in Cancerology and Hemato‐Oncology” UVSQ, Université Paris‐Saclay Boulogne‐Billancourt France

40. Second Department of Dermatology Aristotle University Medical School, Papageorgiou General Hospital Thessaloniki Greece

41. Brachytherapy Department Maria Sklodowska‐Curie National Research Institute of Oncology (MSCNRIO) Gliwice Poland

42. Department of Radiation Oncology University of California San Francisco San Francisco California USA

43. Institute of Dermatology Santa Maria Della Misericordia University Hospital Udine Italy

44. Dermatology Department, Hospital Clinic of Barcelona IDIBAPS, University of Barcelona and CIBER de enfermedades Raras, ICIII Barcelona Spain

Abstract

AbstractBackgroundThere is currently no staging system for cutaneous squamous cell carcinoma (cSCC) that is adapted to decision‐making and universally used. Experts have unconscious ability to simplify the heterogeneity of clinical situations into a few relevant groups to drive their therapeutic decisions. Therefore, we have used unsupervised clustering of real cases by experts to generate an operational classification of cSCCs, an approach that was successful for basal cell carcinomas.ObjectiveTo generate a consensual and operational classification of cSCCs.MethodUnsupervised independent clustering of 248 cases of cSCCs considered difficult‐to‐treat. Eighteen international experts from different specialties classified these cases into what they considered homogeneous clusters useful for management, each with freedom regarding clustering criteria. Convergences and divergences between clustering were analysed using a similarity matrix, the K‐mean approach and the average silhouette method. Mathematical modelling was used to look for the best consensual clustering. The operability of the derived classification was validated on 23 new practitioners.ResultsDespite the high heterogeneity of the clinical cases, a mathematical consensus was observed. It was best represented by a partition into five clusters, which appeared a posteriori to describe different clinical scenarios. Applicability of this classification was shown by a good concordance (94%) in the allocation of cases between the new practitioners and the 18 experts. An additional group of easy‐to‐treat cSCC was included, resulting in a six‐group final classification: easy‐to‐treat/complex to treat due to tumour and/or patient characteristics/multiple/locally advanced/regional disease/visceral metastases.ConclusionGiven the methodology based on the convergence of unguided intuitive clustering of cases by experts, this new classification is relevant for clinical practice. It does not compete with staging systems, but they may complement each other, whether the objective is to select the best therapeutic approach in tumour boards or to design homogeneous groups for trials.

Funder

Sanofi

Publisher

Wiley

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