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J Neurol Surg B Skull Base 2023; 84(04): 307-319
DOI: 10.1055/s-0042-1750178
Original Article

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

Matt Lechner‡   *
1   UCL Cancer Institute, University College London, London, United Kingdom
2   UCL Division of Surgery and Interventional Science, University College London, London, United Kingdom
3   Department of ENT, Barts Health NHS Trust, London, United Kingdom
,
Yoko Takahashi‡   *
4   Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, Texas, United States
,
Mario Turri-Zanoni‡   *
5   Unit of Otorhinolaryngology—Head and Neck Surgery, Department of Biotechnology and Life Sciences, University of Insubria, Varese, Italy
,
Marco Ferrari
6   Section of Otorhinolaryngology—Head and Neck Surgery, Department of Neurosciences, University of Padova, Padova, Italy
,
Jacklyn Liu
1   UCL Cancer Institute, University College London, London, United Kingdom
,
Nicholas Counsell
7   Cancer Research UK and UCL Cancer Trials Centre, University College London, London, United Kingdom
,
Davide Mattavelli
8   Unit of Otorhinolaryngology—Head and Neck Surgery, Department of Medical and Surgical Specialties, Radiological Sciences, and Public Health, University of Brescia, Brescia, Italy
,
Vittorio Rampinelli
8   Unit of Otorhinolaryngology—Head and Neck Surgery, Department of Medical and Surgical Specialties, Radiological Sciences, and Public Health, University of Brescia, Brescia, Italy
,
William Vermi
8   Unit of Otorhinolaryngology—Head and Neck Surgery, Department of Medical and Surgical Specialties, Radiological Sciences, and Public Health, University of Brescia, Brescia, Italy
,
Davide Lombardi
8   Unit of Otorhinolaryngology—Head and Neck Surgery, Department of Medical and Surgical Specialties, Radiological Sciences, and Public Health, University of Brescia, Brescia, Italy
,
Rami Saade
4   Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, Texas, United States
9   Department of Otolaryngology—Head and Neck Surgery, Lebanese American University, Beirut, Lebanon
,
Ki Wan Park
10   Rhinology and Endoscopic Skull Base Surgery, Department of Otolaryngology—Head and Neck Surgery, Stanford University School of Medicine, Palo Alto, California, United States
,
Volker H. Schartinger
11   Department of Otorhinolaryngology, Medical University of Innsbruck, Innsbruck, Austria
,
Alessandro Franchi
12   Department of Translational Research, University of Pisa, Pisa, Italy
,
Carla Facco
13   Unit of Pathology, ASST Sette Laghi, University of Insubria, Varese, Italy
,
Fausto Sessa
13   Unit of Pathology, ASST Sette Laghi, University of Insubria, Varese, Italy
,
Simonetta Battocchio
14   Pathology Unit, Department of Molecular and Translational Medicine, University of Brescia, ASST Spedali Civili, Brescia, Italy
,
Tim R. Fenton
15   Cancer Sciences Unit, Faculty of Medicine, University of Southampton, United Kingdom
,
Francis M. Vaz
16   Royal National ENT Hospital and Head and Neck Centre, University College London Hospitals NHS Trust, London, United Kingdom
,
Paul O'Flynn
16   Royal National ENT Hospital and Head and Neck Centre, University College London Hospitals NHS Trust, London, United Kingdom
,
David Howard
16   Royal National ENT Hospital and Head and Neck Centre, University College London Hospitals NHS Trust, London, United Kingdom
,
Paul Stimpson
16   Royal National ENT Hospital and Head and Neck Centre, University College London Hospitals NHS Trust, London, United Kingdom
,
Simon Wang
17   Department of Oncology, Haematology and Bone Marrow Transplantation with Section Pneumology, Hubertus Wald Tumorzentrum, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
,
S. Alam Hannan
16   Royal National ENT Hospital and Head and Neck Centre, University College London Hospitals NHS Trust, London, United Kingdom
,
Samit Unadkat
16   Royal National ENT Hospital and Head and Neck Centre, University College London Hospitals NHS Trust, London, United Kingdom
,
Jonathan Hughes
18   Head and Neck Centre, University College London Hospitals NHS Trust, London, United Kingdom
,
Raghav Dwivedi
18   Head and Neck Centre, University College London Hospitals NHS Trust, London, United Kingdom
,
Cillian T. Forde
16   Royal National ENT Hospital and Head and Neck Centre, University College London Hospitals NHS Trust, London, United Kingdom
,
Premjit Randhawa
16   Royal National ENT Hospital and Head and Neck Centre, University College London Hospitals NHS Trust, London, United Kingdom
,
Simon Gane
16   Royal National ENT Hospital and Head and Neck Centre, University College London Hospitals NHS Trust, London, United Kingdom
,
Jonathan Joseph
16   Royal National ENT Hospital and Head and Neck Centre, University College London Hospitals NHS Trust, London, United Kingdom
,
Peter J. Andrews
16   Royal National ENT Hospital and Head and Neck Centre, University College London Hospitals NHS Trust, London, United Kingdom
,
Manas Dave
19   Division of Dentistry, University of Manchester, Manchester, United Kingdom
,
Jason C. Fleming
21   Liverpool Head & Neck Centre, University of Liverpool, Liverpool, United Kingdom
,
David Thomson
20   Department of Clinical Oncology, The Christie NHS Foundation Trust, Manchester, United Kingdom
21   Liverpool Head & Neck Centre, University of Liverpool, Liverpool, United Kingdom
,
Tianyu Zhu
22   CAS Key Laboratory of Computational Biology, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Shanghai, People's Republic of China
,
Andrew Teschendorff
22   CAS Key Laboratory of Computational Biology, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Shanghai, People's Republic of China
,
Gary Royle
1   UCL Cancer Institute, University College London, London, United Kingdom
,
Christopher Steele
1   UCL Cancer Institute, University College London, London, United Kingdom
,
Joaquin E. Jimenez
23   Department of Otolaryngology, University of Pittsburgh Medical Center, Pittsburgh, United States
,
Jan Laco
24   The Fingerland Department of Pathology, Charles University Faculty of Medicine and University Hospital Hradec Kralove, Czech Republic
,
Eric W. Wang
23   Department of Otolaryngology, University of Pittsburgh Medical Center, Pittsburgh, United States
25   Center for Cranial Base Surgery, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, United States
,
Carl Snyderman
23   Department of Otolaryngology, University of Pittsburgh Medical Center, Pittsburgh, United States
25   Center for Cranial Base Surgery, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, United States
,
Peter D. Lacy
26   Department of Otolaryngology—Head and Neck Surgery, Beaumont Hospital, Dublin, Ireland
,
Robbie Woods
26   Department of Otolaryngology—Head and Neck Surgery, Beaumont Hospital, Dublin, Ireland
,
James P. O'Neill
26   Department of Otolaryngology—Head and Neck Surgery, Beaumont Hospital, Dublin, Ireland
27   The Royal College of Surgeons in Ireland, Dublin, Ireland
,
Anirudh Saraswathula
28   Department of Otolaryngology—Head and Neck Surgery, Johns Hopkins School of Medicine, Baltimore, United States
,
Raman Preet Kaur
28   Department of Otolaryngology—Head and Neck Surgery, Johns Hopkins School of Medicine, Baltimore, United States
,
Tianna Zhao
29   Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States
,
Murugappan Ramanathan Jr.
28   Department of Otolaryngology—Head and Neck Surgery, Johns Hopkins School of Medicine, Baltimore, United States
29   Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States
,
Gary L. Gallia
28   Department of Otolaryngology—Head and Neck Surgery, Johns Hopkins School of Medicine, Baltimore, United States
29   Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States
30   Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States
,
Nyall R. London Jr.
28   Department of Otolaryngology—Head and Neck Surgery, Johns Hopkins School of Medicine, Baltimore, United States
29   Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States
31   Sinonasal and Skull Base Tumor Program—Head and Neck Surgery Branch, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, Maryland, United States
,
Quynh-Thu Le
32   Department of Radiation Oncology, Stanford University School of Medicine, Palo Alto, California, United States
,
Robert B. West
32   Department of Radiation Oncology, Stanford University School of Medicine, Palo Alto, California, United States
,
Zara M. Patel 
10   Rhinology and Endoscopic Skull Base Surgery, Department of Otolaryngology—Head and Neck Surgery, Stanford University School of Medicine, Palo Alto, California, United States
,
Jayakar V. Nayak
10   Rhinology and Endoscopic Skull Base Surgery, Department of Otolaryngology—Head and Neck Surgery, Stanford University School of Medicine, Palo Alto, California, United States
,
Peter H. Hwang
10   Rhinology and Endoscopic Skull Base Surgery, Department of Otolaryngology—Head and Neck Surgery, Stanford University School of Medicine, Palo Alto, California, United States
,
Mario Hermsen
33   Department of Head and Neck Oncology, Instituto de Investigación Sanitaria del Principado de Asturias, Oviedo, Spain
,
Jose Llorente
33   Department of Head and Neck Oncology, Instituto de Investigación Sanitaria del Principado de Asturias, Oviedo, Spain
,
Fabio Facchetti
14   Pathology Unit, Department of Molecular and Translational Medicine, University of Brescia, ASST Spedali Civili, Brescia, Italy
,
Piero Nicolai
6   Section of Otorhinolaryngology—Head and Neck Surgery, Department of Neurosciences, University of Padova, Padova, Italy
,
Paolo Bossi
34   Medical Oncology, Department of Medical and Surgical Specialities, Radiological Sciences, and Public Health, University of Brescia, Brescia, Italy
,
Paolo Castelnuovo
5   Unit of Otorhinolaryngology—Head and Neck Surgery, Department of Biotechnology and Life Sciences, University of Insubria, Varese, Italy
,
Amrita Jay
35   Department of Histopathology, University College London Hospitals NHS Trust, London, United Kingdom
,
Dawn Carnell
18   Head and Neck Centre, University College London Hospitals NHS Trust, London, United Kingdom
,
Martin D. Forster
1   UCL Cancer Institute, University College London, London, United Kingdom
,
Diana M. Bell
36   Disease Team Alignment: Head and Neck, City of Hope Medical Center, Duarte, California, United States
,
Valerie J. Lund
16   Royal National ENT Hospital and Head and Neck Centre, University College London Hospitals NHS Trust, London, United Kingdom
,
Ehab Y. Hanna
4   Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, Texas, United States
› Author Affiliations 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.
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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 ipilimumab

Authors' 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.


Supplementary Material



Publication History

Received: 22 January 2022

Accepted: 22 April 2022

Article published online:
10 July 2022

© 2022. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

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