Andrea Maurichi1, Rosalba Miceli2, Hanna Eriksson3,4, Julia Newton-Bishop5, Jérémie Nsengimana5, May Chan5, Andrew J Hayes6,7, Kara Heelan6,7, David Adams8, Roberto Patuzzo1, Francesco Barretta2, Gianfranco Gallino1, Catherine Harwood9, Daniele Bergamaschi9, Dorothy Bennett10, Konstantinos Lasithiotakis11,12, Paola Ghiorzo13, Bruna Dalmasso13, Ausilia Manganoni14, Francesca Consoli14, Ilaria Mattavelli1, Consuelo Barbieri1, Andrea Leva1, Umberto Cortinovis15, Vittoria Espeli16, Cristina Mangas16, Pietro Quaglino17, Simone Ribero17, Paolo Broganelli17, Giovanni Pellacani18, Caterina Longo19,20, Corrado Del Forno21, Lorenzo Borgognoni22, Serena Sestini22, Nicola Pimpinelli23, Sara Fortunato23, Alessandra Chiarugi24, Paolo Nardini24, Elena Morittu25, Antonio Florita25, Mara Cossa12, Barbara Valeri12, Massimo Milione12, Giancarlo Pruneri12, Odysseas Zoras26, Andrea Anichini27, Roberta Mortarini27, Mario Santinami1. 1. Melanoma and Sarcoma Unit, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Istituto Nazionale dei Tumori di Milano, Milan, Italy. 2. Medical Statistics, Biometry and Bioinformatics Unit, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Milan, Italy. 3. Department of Oncology, Theme Cancer, Karolinska University Hospital, Stockholm, Sweden. 4. Department of Oncology and Pathology, Karolinska Institutet, Stockholm, Sweden. 5. Leeds Institute of Medical Research at St James's, University of Leeds, Leeds, United Kingdom. 6. Sarcoma Unit, Royal Marsden National Health Service (NHS) Foundation Trust, London, United Kingdom. 7. Skin Unit, Royal Marsden NHS Foundation Trust, London, United Kingdom. 8. Experimental Cancer Genetics, Wellcome Trust Sanger Institute, Hinxton, United Kingdom. 9. Queen Mary University of London, London, United Kingdom. 10. Molecular and Clinical Sciences Research Institute, St George's, University of London, London, United Kingdom. 11. York Teaching Hospital NHS Foundation Trust, York, United Kingdom. 12. Department of Pathology, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Milan, Italy. 13. University Hospital of Genoa, Genoa, Italy. 14. University Hospital of Brescia, Brescia, Italy. 15. Plastic and Reconstructive Surgical Unit, Department of Surgery, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Milan, Italy. 16. Istituto Oncologico Svizzera Italiana, Ospedale Regionale Bellinzona e Valli, Bellinzona, Switzerland. 17. University Hospital of Turin, Turin, Italy. 18. University Hospital of Modena, Modena, Italy. 19. Department of Dermatology, University of Modena and Reggio Emilia, Modena, Italy. 20. Azienda Unità Sanitaria Locale - IRCCS di Reggio Emilia, Centro Oncologico ad Alta Tecnologia Diagnostica-Dermatologia, Reggio Emilia, Italy. 21. University Hospital of Pavia, Pavia, Italy. 22. Ospedale S. Maria Annunziata, Tuscan Cancer Institute, Florence, Italy. 23. Division of Dermatology, University of Florence, Florence, Italy. 24. Institute for Cancer Research and Prevention, Florence, Italy. 25. Scientific Directorate, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Milan, Italy. 26. University Hospital of Heraklion, Heraklion, Greece. 27. Immunobiology of Human Cancers Unit, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Milan, Italy.
Abstract
PURPOSE: Thin melanomas (T1; ≤ 1 mm) constitute 70% of newly diagnosed cutaneous melanomas. Regional node metastasis determined by sentinel node biopsy (SNB) is an important prognostic factor for T1 melanoma. However, current melanoma guidelines do not provide clear indications on when to perform SNB in T1 disease and stress an individualized approach to SNB that considers all clinicopathologic risk factors. We aimed to identify determinants of sentinel node (SN) status for incorporation into an externally validated nomogram to better select patients with T1 disease for SNB. PATIENTS AND METHODS: The development cohort comprised 3,666 patients with T1 disease consecutively treated at the Istituto Nazionale Tumori (Milan, Italy) between 2001 and 2018; 4,227 patients with T1 disease treated at 13 other European centers over the same period formed the validation cohort. A random forest procedure was applied to the development data set to select characteristics associated with SN status for inclusion in a multiple binary logistic model from which a nomogram was elaborated. Decision curve analyses assessed the clinical utility of the nomogram. RESULTS: Of patients in the development cohort, 1,635 underwent SNB; 108 patients (6.6%) were SN positive. By univariable analysis, age, growth phase, Breslow thickness, ulceration, mitotic rate, regression, and lymphovascular invasion were significantly associated with SN status. The random forest procedure selected 6 variables (not growth phase) for inclusion in the logistic model and nomogram. The nomogram proved well calibrated and had good discriminative ability in both cohorts. Decision curve analyses revealed the superior net benefit of the nomogram compared with each individual variable included in it as well as with variables suggested by current guidelines. CONCLUSION: We propose the nomogram as a decision aid in all patients with T1 melanoma being considered for SNB.
PURPOSE: Thin melanomas (T1; ≤ 1 mm) constitute 70% of newly diagnosed cutaneous melanomas. Regional node metastasis determined by sentinel node biopsy (SNB) is an important prognostic factor for T1 melanoma. However, current melanoma guidelines do not provide clear indications on when to perform SNB in T1 disease and stress an individualized approach to SNB that considers all clinicopathologic risk factors. We aimed to identify determinants of sentinel node (SN) status for incorporation into an externally validated nomogram to better select patients with T1 disease for SNB. PATIENTS AND METHODS: The development cohort comprised 3,666 patients with T1 disease consecutively treated at the Istituto Nazionale Tumori (Milan, Italy) between 2001 and 2018; 4,227 patients with T1 disease treated at 13 other European centers over the same period formed the validation cohort. A random forest procedure was applied to the development data set to select characteristics associated with SN status for inclusion in a multiple binary logistic model from which a nomogram was elaborated. Decision curve analyses assessed the clinical utility of the nomogram. RESULTS: Of patients in the development cohort, 1,635 underwent SNB; 108 patients (6.6%) were SN positive. By univariable analysis, age, growth phase, Breslow thickness, ulceration, mitotic rate, regression, and lymphovascular invasion were significantly associated with SN status. The random forest procedure selected 6 variables (not growth phase) for inclusion in the logistic model and nomogram. The nomogram proved well calibrated and had good discriminative ability in both cohorts. Decision curve analyses revealed the superior net benefit of the nomogram compared with each individual variable included in it as well as with variables suggested by current guidelines. CONCLUSION: We propose the nomogram as a decision aid in all patients with T1 melanoma being considered for SNB.
Authors: Alexander M M Eggermont; Christian U Blank; Mario Mandala; Georgina V Long; Victoria Atkinson; Stéphane Dalle; Andrew Haydon; Mikhail Lichinitser; Adnan Khattak; Matteo S Carlino; Shahneen Sandhu; James Larkin; Susana Puig; Paolo A Ascierto; Piotr Rutkowski; Dirk Schadendorf; Rutger Koornstra; Leonel Hernandez-Aya; Michele Maio; Alfonsus J M van den Eertwegh; Jean-Jacques Grob; Ralf Gutzmer; Rahima Jamal; Paul Lorigan; Nageatte Ibrahim; Sandrine Marreaud; Alexander C J van Akkooi; Stefan Suciu; Caroline Robert Journal: N Engl J Med Date: 2018-04-15 Impact factor: 91.245
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Authors: Andrea Maurichi; Rosalba Miceli; Hanna Eriksson; Julia Newton-Bishop; Jérémie Nsengimana; May Chan; Andrew J Hayes; Kara Heelan; David Adams; Roberto Patuzzo; Francesco Barretta; Gianfranco Gallino; Catherine Harwood; Daniele Bergamaschi; Dorothy Bennett; Konstantinos Lasithiotakis; Paola Ghiorzo; Bruna Dalmasso; Ausilia Manganoni; Francesca Consoli; Ilaria Mattavelli; Consuelo Barbieri; Andrea Leva; Umberto Cortinovis; Vittoria Espeli; Cristina Mangas; Pietro Quaglino; Simone Ribero; Paolo Broganelli; Giovanni Pellacani; Caterina Longo; Corrado Del Forno; Lorenzo Borgognoni; Serena Sestini; Nicola Pimpinelli; Sara Fortunato; Alessandra Chiarugi; Paolo Nardini; Elena Morittu; Antonio Florita; Mara Cossa; Barbara Valeri; Massimo Milione; Giancarlo Pruneri; Odysseas Zoras; Andrea Anichini; Roberta Mortarini; Mario Santinami Journal: J Clin Oncol Date: 2020-07-23 Impact factor: 50.717