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DOI: 10.1055/s-0042-1750178
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 System
Funding 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.
Abstract
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.
Keywords
sinonasal mucosal melanoma - TNM - immunotherapy - immune checkpoint blockade - immune checkpoint inhibitors ipilimumabAuthors' Contributions
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.
Publication History
Received: 22 January 2022
Accepted: 22 April 2022
Article published online:
10 July 2022
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References
- 1 Lund VJ, Chisholm EJ, Howard DJ, Wei WI. Sinonasal malignant melanoma: an analysis of 115 cases assessing outcomes of surgery, postoperative radiotherapy and endoscopic resection. Rhinology 2012; 50 (02) 203-210
- 2 Amit M, Tam S, Abdelmeguid AS. et al. Patterns of treatment failure in patients with sinonasal mucosal melanoma. Ann Surg Oncol 2018; 25 (06) 1723-1729
- 3 Lund VJ. Sinonasal malignant melanoma. Adv Otorhinolaryngol 2020; 84: 185-196
- 4 Miglani A, Patel SH, Kosiorek HE, Hinni ML, Hayden RE, Lal D. Endoscopic resection of sinonasal mucosal melanoma has comparable outcomes to open approaches. Am J Rhinol Allergy 2017; 31 (03) 200-204
- 5 Hur K, Zhang P, Yu A, Kim-Orden N, Kysh L, Wrobel B. Open versus endoscopic approach for sinonasal melanoma: a systematic review and meta-analysis. Am J Rhinol Allergy 2019; 33 (02) 162-169
- 6 Meleti M, Leemans CR, de Bree R, Vescovi P, Sesenna E, van der Waal I. Head and neck mucosal melanoma: experience with 42 patients, with emphasis on the role of postoperative radiotherapy. Head Neck 2008; 30 (12) 1543-1551
- 7 Ajmani GS, Liederbach E, Kyrillos A, Wang CH, Pinto JM, Bhayani MK. Adjuvant radiation and survival following surgical resection of sinonasal melanoma. Am J Otolaryngol 2017; 38 (06) 663-667
- 8 Gore MR, Zanation AM. Survival in sinonasal melanoma: a meta-analysis. J Neurol Surg B Skull Base 2012; 73 (03) 157-162
- 9 Manton T, Tillman B, McHugh J, Bellile E, McLean S, McKean E. Sinonasal melanoma: a single institutional analysis and future directions. J Neurol Surg B Skull Base 2019; 80 (05) 484-492
- 10 Ganti A, Raman A, Shay A. et al. Treatment modalities in sinonasal mucosal melanoma: a national cancer database analysis. Laryngoscope 2020; 130 (02) 275-282
- 11 Dauer EH, Lewis JE, Rohlinger AL, Weaver AL, Olsen KD. Sinonasal melanoma: a clinicopathologic review of 61 cases. Otolaryngol Head Neck Surg 2008; 138 (03) 347-352
- 12 Khan MN, Kanumuri VV, Raikundalia MD. et al. Sinonasal melanoma: survival and prognostic implications based on site of involvement. Int Forum Allergy Rhinol 2014; 4 (02) 151-155
- 13 Roth TN, Gengler C, Huber GF, Holzmann D. Outcome of sinonasal melanoma: clinical experience and review of the literature. Head Neck 2010; 32 (10) 1385-1392
- 14 Houette A, Gilain L, Mulliez A, Mom T, Saroul N. Prognostic value of two tumour staging classifications in patients with sinonasal mucosal melanoma. Eur Ann Otorhinolaryngol Head Neck Dis 2016; 133 (05) 313-317
- 15 Umeda Y, Yoshikawa S, Kiniwa Y. et al. Real-world efficacy of anti-PD-1 antibody or combined anti-PD-1 plus anti-CTLA-4 antibodies, with or without radiotherapy, in advanced mucosal melanoma patients: a retrospective, multicenter study. Eur J Cancer 2021; 157: 361-372
- 16 Takayasu Y, Kubo N, Shino M. et al; Working Group on Head and Neck Tumors. Carbon-ion radiotherapy combined with chemotherapy for head and neck mucosal melanoma: prospective observational study. Cancer Med 2019; 8 (17) 7227-7235
- 17 Swegal W, Koyfman S, Scharpf J. et al. Endoscopic and open surgical approaches to locally advanced sinonasal melanoma: comparing the therapeutic benefits. JAMA Otolaryngol Head Neck Surg 2014; 140 (09) 840-845
- 18 Castelnuovo P, Lepera D, Turri-Zanoni M. et al. Quality of life following endoscopic endonasal resection of anterior skull base cancers. J Neurosurg 2013; 119 (06) 1401-1409
- 19 Turri-Zanoni M, Medicina D, Lombardi D. et al. Sinonasal mucosal melanoma: Molecular profile and therapeutic implications from a series of 32 cases. Head Neck 2013; 35 (08) 1066-1077
- 20 Amit M, Tam S, Abdelmeguid AS. et al. Mutation status among patients with sinonasal mucosal melanoma and its impact on survival. Br J Cancer 2017; 116 (12) 1564-1571
- 21 Hodi FS, O'Day SJ, McDermott DF. et al. Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med 2010; 363 (08) 711-723
- 22 D'Angelo SP, Larkin J, Sosman JA. et al. Efficacy and safety of nivolumab alone or in combination with ipilimumab in patients with mucosal melanoma: a pooled analysis. J Clin Oncol 2017; 35 (02) 226-235
- 23 Ribas A, Hamid O, Daud A. et al. Association of pembrolizumab with tumor response and survival among patients with advanced melanoma. JAMA 2016; 315 (15) 1600-1609
- 24 Ribas A, Puzanov I, Dummer R. et al. Pembrolizumab versus investigator-choice chemotherapy for ipilimumab-refractory melanoma (KEYNOTE-002): a randomised, controlled, phase 2 trial. Lancet Oncol 2015; 16 (08) 908-918
- 25 Robert C, Schachter J, Long GV. et al; KEYNOTE-006 investigators. Pembrolizumab versus ipilimumab in advanced melanoma. N Engl J Med 2015; 372 (26) 2521-2532
- 26 Li J, Kan H, Zhao L, Sun Z, Bai C. Immune checkpoint inhibitors in advanced or metastatic mucosal melanoma: a systematic review. Ther Adv Med Oncol 2020; 12: 1758835920922028
- 27 Rose AAN, Armstrong SM, Hogg D. et al. Biologic subtypes of melanoma predict survival benefit of combination anti-PD1+anti-CTLA4 immune checkpoint inhibitors versus anti-PD1 monotherapy. J Immunother Cancer 2021; 9 (01) e001642
- 28 Kim HJ, Chang JS, Roh MR. et al. Effect of radiotherapy combined with pembrolizumab on local tumor control in mucosal melanoma patients. Front Oncol 2019; 9: 835