{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T11:45:13Z","timestamp":1789472713553,"version":"build-2803163510"},"reference-count":58,"publisher":"Harborside Press, LLC","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,7,26]]},"abstract":"<jats:p><jats:bold>Background:<\/jats:bold>Prognostic parameters in sentinel node (SN)\u2013positive melanoma are important indicators to identify patients at high risk of recurrence who should be candidates for adjuvant therapy. We aimed to evaluate the presence of melanoma cells beyond the SN capsule\u2014extranodal extension (ENE)\u2014as a prognostic factor in patients with positive SNs.<jats:bold>Methods:<\/jats:bold>Data from 1,047 patients with melanoma and positive SNs treated from 2001 to 2020 at the Istituto Nazionale dei Tumori in Milano, Italy, were retrospectively investigated. Kaplan-Meier survival and crude cumulative incidence of recurrence curves were estimated. A multivariable logistic model was used to investigate the association between ENE and selected predictive factors. Cox models estimated the effect of the selected predictors on survival endpoints.<jats:bold>Results:<\/jats:bold>Median follow-up was 69 months. The 5-year overall survival rate was 62.5% and 71.7% for patients with positive SNs with and without ENE, respectively. The 5-year disease-free survival rate was 54.0% and 64.0% for patients with positive SNs with and without ENE, respectively. The multivariable logistic model showed that age, size of the main metastatic focus in the SN, and number<jats:strike>s<\/jats:strike>of metastatic non-SNs were associated with ENE (all<jats:italic>P<\/jats:italic>&lt;.0001). The multivariable Cox regression models showed the estimated prognostic effects of ENE associated with age, ulceration, size of the main metastatic focus in the SN, and number of metastatic non-SNs (all<jats:italic>P<\/jats:italic>&lt;.0001) on disease-free survival and overall survival.<jats:bold>Conclusions:<\/jats:bold>ENE was a significant prognostic factor in patients with positive-SN melanoma. This parameter may be useful in clinical practice as a selection criterion for adjuvant treatment in patients with stage IIIA disease with a tumor burden &lt;1 mm in the SN. We recommend its inclusion as an independent prognostic determinant in future updates of melanoma guidelines.<\/jats:p>","DOI":"10.6004\/jnccn.2020.7693","type":"journal-article","created":{"date-parts":[[2021,10,20]],"date-time":"2021-10-20T17:47:55Z","timestamp":1634752075000},"source":"Crossref","is-referenced-by-count":5,"title":["Survival in Patients With Sentinel Node\u2013Positive Melanoma With Extranodal Extension"],"prefix":"10.6004","author":[{"given":"Andrea","family":"Maurichi","sequence":"first","affiliation":[{"name":"1Melanoma and Sarcoma Surgical Unit,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Barretta","sequence":"additional","affiliation":[{"name":"2Clinical Epidemiology and Trial Organization Unit,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberto","family":"Patuzzo","sequence":"additional","affiliation":[{"name":"1Melanoma and Sarcoma Surgical Unit,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosalba","family":"Miceli","sequence":"additional","affiliation":[{"name":"2Clinical Epidemiology and Trial Organization Unit,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gianfranco","family":"Gallino","sequence":"additional","affiliation":[{"name":"1Melanoma and Sarcoma Surgical Unit,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilaria","family":"Mattavelli","sequence":"additional","affiliation":[{"name":"1Melanoma and Sarcoma Surgical Unit,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Consuelo","family":"Barbieri","sequence":"additional","affiliation":[{"name":"1Melanoma and Sarcoma Surgical Unit,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Leva","sequence":"additional","affiliation":[{"name":"1Melanoma and Sarcoma Surgical Unit,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martina","family":"Angi","sequence":"additional","affiliation":[{"name":"1Melanoma and Sarcoma Surgical Unit,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco Baldo","family":"Lanza","sequence":"additional","affiliation":[{"name":"1Melanoma and Sarcoma Surgical Unit,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"Spadola","sequence":"additional","affiliation":[{"name":"1Melanoma and Sarcoma Surgical Unit,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mara","family":"Cossa","sequence":"additional","affiliation":[{"name":"3Department of Pathology,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Nesa","sequence":"additional","affiliation":[{"name":"3Department of Pathology,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Umberto","family":"Cortinovis","sequence":"additional","affiliation":[{"name":"4Plastic and Reconstructive Surgical Unit, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Sala","sequence":"additional","affiliation":[{"name":"4Plastic and Reconstructive Surgical Unit, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorenza","family":"Di Guardo","sequence":"additional","affiliation":[{"name":"5Melanoma Medical Oncology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Milan, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolina","family":"Cimminiello","sequence":"additional","affiliation":[{"name":"5Melanoma Medical Oncology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Milan, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michele","family":"Del Vecchio","sequence":"additional","affiliation":[{"name":"5Melanoma Medical Oncology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Milan, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara","family":"Valeri","sequence":"additional","affiliation":[{"name":"3Department of Pathology,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mario","family":"Santinami","sequence":"additional","affiliation":[{"name":"1Melanoma and Sarcoma Surgical Unit,"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"4047","reference":[{"key":"ref321","doi-asserted-by":"crossref","first-page":"2211","DOI":"10.1056\/NEJMoa1613210","article-title":"Completion dissection or observation for sentinel-node metastasis in melanoma","volume":"376","author":"Faries","year":"2017","journal-title":"N Engl J Med"},{"key":"ref71","doi-asserted-by":"crossref","first-page":"1824","DOI":"10.1056\/NEJMoa1709030","article-title":"Adjuvant nivolumab versus 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