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International Multicenter Study of Clinical Outcomes of Sinonasal Melanoma Shows Survival Benefit for Patients Treated with Immune Checkpoint Inhibitors and Potential Improvements to the Current TNM Staging SystemFunding This work was supported by the Rhinology and Laryngology Research Fund, Royal College of Surgeons and the UCL/UCLH Biomedical Research Centre (BRC). Additional support was provided by the National Institutes of Health/National Institute on Deafness and Other Communication Disorders.
Objectives Sinonasal mucosal melanoma (SNMM) is an extremely rare and challenging sinonasal malignancy with a poor prognosis. Standard treatment involves complete surgical resection, but the role of adjuvant therapy remains unclear. Crucially, our understanding of its clinical presentation, course, and optimal treatment remains limited, and few advancements in improving its management have been made in the recent past.
Methods We conducted an international multicenter retrospective analysis of 505 SNMM cases from 11 institutions across the United States, United Kingdom, Ireland, and continental Europe. Data on clinical presentation, diagnosis, treatment, and clinical outcomes were assessed.
Results One-, three-, and five-year recurrence-free and overall survival were 61.4, 30.6, and 22.0%, and 77.6, 49.2, and 38.3%, respectively. Compared with disease confined to the nasal cavity, sinus involvement confers significantly worse survival; based on this, further stratifying the T3 stage was highly prognostic (p < 0.001) with implications for a potential modification to the current TNM staging system. There was a statistically significant survival benefit for patients who received adjuvant radiotherapy, compared with those who underwent surgery alone (hazard ratio [HR] = 0.74, 95% confidence interval [CI]: 0.57–0.96, p = 0.021). Immune checkpoint blockade for the management of recurrent or persistent disease, with or without distant metastasis, conferred longer survival (HR = 0.50, 95% CI: 0.25–1.00, p = 0.036).
Conclusions We present findings from the largest cohort of SNMM reported to date. We demonstrate the potential utility of further stratifying the T3 stage by sinus involvement and present promising data on the benefit of immune checkpoint inhibitors for recurrent, persistent, or metastatic disease with implications for future clinical trials in this field.
Keywordssinonasal mucosal melanoma - TNM - immunotherapy - immune checkpoint blockade - immune checkpoint inhibitors ipilimumab
M.L., Y.T., M.T.-Z., M.F., J. L., N.C., P.H.H., M.H., P.B., P.C., D.M.B., V.J.L., and E.Y.H. were responsible for conception and design.
M.L., Y.T., M.T.-Z., M.F., J.L., N.C., P.H.H., M.H., P.B., P. C., D.M.B., V.J.L., and E.Y.H. were responsible for the development of methodology.
M.L., Y.T., M.T.-Z., M.F., J.L., D. M., V.R., W.V., D.L., R.S., K.W.P., V.H.S., A.F., C.F., F.S., S.B., T.F., F.M.V., P. O'F., P. S., S.W., S.A.H., S.U., J.H., R.D., C.T.F., P.R., S.G., J.J., P.J. A., M.D., D.T., A.T., T.Z., G.R., C. S., J.E.J., J.L., E.W.W., C.S., P.D.L., R. W., J.P. O'N., A.S., R.P.K., T.Z., M. R. Jr., G.G., N.L., Q.T. L., R.B.W., Z.M.P., J. N., P.H.H., M.H., J.L., F.F., P.N., P. B., P.C., A.J., D.C., M.D.F., D.M.B., V.J. L., and E.Y.H. were responsible for acquisition of data.
M.L., Y.T., M.T.-Z., M.F., J.L., N.C., P.H.H., M.H., P.B., P.C., D.M.B., V.J.L., and E.Y.H. were responsible for analysis and interpretation of data.
M.L., Y.T., M.T.-Z., M.F., J.L., N.C., D.M., D.T., A.E.T., J.E.J., J.L., C.S., R.W., P.H.H., A.S., M.H., P.B., P.C., D.M.B., V.J. L., and E.Y.H. were Writing, review, and/or revision of the manuscript.
M.L., V.J.L., and E.Y.H. were responsible for study supervision.
* These authors contributed equally to this article.
Received: 22 January 2022
Accepted: 22 April 2022
Article published online:
10 July 2022
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