. 2022 Jul 10;84(4):307-319.

doi: 10.1055/s-0042-1750178. eCollection 2023 Aug.

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

2

3}, Yoko Takahashi⁴, Mario Turri-Zanoni⁵, Marco Ferrari⁶, Jacklyn Liu¹, Nicholas Counsell⁷, Davide Mattavelli⁸, Vittorio Rampinelli⁸, William Vermi⁸, Davide Lombardi⁸, Rami Saade^{4

9}, Ki Wan Park¹⁰, Volker H Schartinger¹¹, Alessandro Franchi¹², Carla Facco¹³, Fausto Sessa¹³, Simonetta Battocchio¹⁴, Tim R Fenton¹⁵, Francis M Vaz¹⁶, Paul O'Flynn¹⁶, David Howard¹⁶, Paul Stimpson¹⁶, Simon Wang¹⁷, S Alam Hannan¹⁶, Samit Unadkat¹⁶, Jonathan Hughes¹⁸, Raghav Dwivedi¹⁸, Cillian T Forde¹⁶, Premjit Randhawa¹⁶, Simon Gane¹⁶, Jonathan Joseph¹⁶, Peter J Andrews¹⁶, Manas Dave¹⁹, Jason C Fleming²⁰, David Thomson^{21

20}, Tianyu Zhu²², Andrew Teschendorff²², Gary Royle¹, Christopher Steele¹, Joaquin E Jimenez²³, Jan Laco²⁴, Eric W Wang^{23

25}, Carl Snyderman^{23

25}, Peter D Lacy²⁶, Robbie Woods²⁶, James P O'Neill^{26

27}, Anirudh Saraswathula²⁸, Raman Preet Kaur²⁸, Tianna Zhao²⁹, Murugappan Ramanathan Jr^{28

29}, Gary L Gallia^{28

29

30}, Nyall R London Jr^{28

29

31}, Quynh-Thu Le³², Robert B West³², Zara M Patel¹⁰, Jayakar V Nayak¹⁰, Peter H Hwang¹⁰, Mario Hermsen³³, Jose Llorente³³, Fabio Facchetti¹⁴, Piero Nicolai⁶, Paolo Bossi³⁴, Paolo Castelnuovo⁵, Amrita Jay³⁵, Dawn Carnell¹⁸, Martin D Forster¹, Diana M Bell³⁶, Valerie J Lund¹⁶, Ehab Y Hanna⁴

Affiliations

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.
⁴ Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, Texas, United States.
⁵ Unit of Otorhinolaryngology-Head and Neck Surgery, Department of Biotechnology and Life Sciences, University of Insubria, Varese, Italy.
⁶ Section of Otorhinolaryngology-Head and Neck Surgery, Department of Neurosciences, University of Padova, Padova, Italy.
⁷ Cancer Research UK and UCL Cancer Trials Centre, University College London, London, United Kingdom.
⁸ Unit of Otorhinolaryngology-Head and Neck Surgery, Department of Medical and Surgical Specialties, Radiological Sciences, and Public Health, University of Brescia, Brescia, Italy.
⁹ Department of Otolaryngology-Head and Neck Surgery, Lebanese American University, Beirut, Lebanon.
¹⁰ Rhinology and Endoscopic Skull Base Surgery, Department of Otolaryngology-Head and Neck Surgery, Stanford University School of Medicine, Palo Alto, California, United States.
¹¹ Department of Otorhinolaryngology, Medical University of Innsbruck, Innsbruck, Austria.
¹² Department of Translational Research, University of Pisa, Pisa, Italy.
¹³ Unit of Pathology, ASST Sette Laghi, University of Insubria, Varese, Italy.
¹⁴ Pathology Unit, Department of Molecular and Translational Medicine, University of Brescia, ASST Spedali Civili, Brescia, Italy.
¹⁵ Cancer Sciences Unit, Faculty of Medicine, University of Southampton, United Kingdom.
¹⁶ Royal National ENT Hospital and Head and Neck Centre, University College London Hospitals NHS Trust, London, United Kingdom.
¹⁷ Department of Oncology, Haematology and Bone Marrow Transplantation with Section Pneumology, Hubertus Wald Tumorzentrum, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
¹⁸ Head and Neck Centre, University College London Hospitals NHS Trust, London, United Kingdom.
¹⁹ Division of Dentistry, University of Manchester, Manchester, United Kingdom.
²⁰ Liverpool Head & Neck Centre, University of Liverpool, Liverpool, United Kingdom.
²¹ Department of Clinical Oncology, The Christie NHS Foundation Trust, Manchester, United Kingdom.
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.
²³ Department of Otolaryngology, University of Pittsburgh Medical Center, Pittsburgh, United States.
²⁴ The Fingerland Department of Pathology, Charles University Faculty of Medicine and University Hospital Hradec Kralove, Czech Republic.
²⁵ Center for Cranial Base Surgery, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, United States.
²⁶ Department of Otolaryngology-Head and Neck Surgery, Beaumont Hospital, Dublin, Ireland.
²⁷ The Royal College of Surgeons in Ireland, Dublin, Ireland.
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.
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.
³² Department of Radiation Oncology, Stanford University School of Medicine, Palo Alto, California, United States.
³³ Department of Head and Neck Oncology, Instituto de Investigación Sanitaria del Principado de Asturias, Oviedo, Spain.
³⁴ Medical Oncology, Department of Medical and Surgical Specialities, Radiological Sciences, and Public Health, University of Brescia, Brescia, Italy.
³⁵ Department of Histopathology, University College London Hospitals NHS Trust, London, United Kingdom.
³⁶ Disease Team Alignment: Head and Neck, City of Hope Medical Center, Duarte, California, United States.

PMID: 37405239
PMCID: PMC10317567
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

Matt Lechner et al. J Neurol Surg B Skull Base. 2022.

. 2022 Jul 10;84(4):307-319.

doi: 10.1055/s-0042-1750178. eCollection 2023 Aug.

Authors

Affiliations

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.
⁴ Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, Texas, United States.
⁵ Unit of Otorhinolaryngology-Head and Neck Surgery, Department of Biotechnology and Life Sciences, University of Insubria, Varese, Italy.
⁶ Section of Otorhinolaryngology-Head and Neck Surgery, Department of Neurosciences, University of Padova, Padova, Italy.
⁷ Cancer Research UK and UCL Cancer Trials Centre, University College London, London, United Kingdom.
⁸ Unit of Otorhinolaryngology-Head and Neck Surgery, Department of Medical and Surgical Specialties, Radiological Sciences, and Public Health, University of Brescia, Brescia, Italy.
⁹ Department of Otolaryngology-Head and Neck Surgery, Lebanese American University, Beirut, Lebanon.
¹⁰ Rhinology and Endoscopic Skull Base Surgery, Department of Otolaryngology-Head and Neck Surgery, Stanford University School of Medicine, Palo Alto, California, United States.
¹¹ Department of Otorhinolaryngology, Medical University of Innsbruck, Innsbruck, Austria.
¹² Department of Translational Research, University of Pisa, Pisa, Italy.
¹³ Unit of Pathology, ASST Sette Laghi, University of Insubria, Varese, Italy.
¹⁴ Pathology Unit, Department of Molecular and Translational Medicine, University of Brescia, ASST Spedali Civili, Brescia, Italy.
¹⁵ Cancer Sciences Unit, Faculty of Medicine, University of Southampton, United Kingdom.
¹⁶ Royal National ENT Hospital and Head and Neck Centre, University College London Hospitals NHS Trust, London, United Kingdom.
¹⁷ Department of Oncology, Haematology and Bone Marrow Transplantation with Section Pneumology, Hubertus Wald Tumorzentrum, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
¹⁸ Head and Neck Centre, University College London Hospitals NHS Trust, London, United Kingdom.
¹⁹ Division of Dentistry, University of Manchester, Manchester, United Kingdom.
²⁰ Liverpool Head & Neck Centre, University of Liverpool, Liverpool, United Kingdom.
²¹ Department of Clinical Oncology, The Christie NHS Foundation Trust, Manchester, United Kingdom.
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.
²³ Department of Otolaryngology, University of Pittsburgh Medical Center, Pittsburgh, United States.
²⁴ The Fingerland Department of Pathology, Charles University Faculty of Medicine and University Hospital Hradec Kralove, Czech Republic.
²⁵ Center for Cranial Base Surgery, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, United States.
²⁶ Department of Otolaryngology-Head and Neck Surgery, Beaumont Hospital, Dublin, Ireland.
²⁷ The Royal College of Surgeons in Ireland, Dublin, Ireland.
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.
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.
³² Department of Radiation Oncology, Stanford University School of Medicine, Palo Alto, California, United States.
³³ Department of Head and Neck Oncology, Instituto de Investigación Sanitaria del Principado de Asturias, Oviedo, Spain.
³⁴ Medical Oncology, Department of Medical and Surgical Specialities, Radiological Sciences, and Public Health, University of Brescia, Brescia, Italy.
³⁵ Department of Histopathology, University College London Hospitals NHS Trust, London, United Kingdom.
³⁶ Disease Team Alignment: Head and Neck, City of Hope Medical Center, Duarte, California, United States.

PMID: 37405239
PMCID: PMC10317567
DOI: 10.1055/s-0042-1750178

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: TNM; immune checkpoint blockade; immune checkpoint inhibitors ipilimumab; immunotherapy; sinonasal mucosal melanoma.

PubMed Disclaimer

Conflict of interest statement

Conflict of Interest NL receives research funding from Merck Inc., not related to this manuscript and was a consultant for CoolTech Inc. and holds stock in Navigen Pharmaceuticals, both of which are unrelated to this manuscript. All other authors declare no potential relevant conflicts of interest.

Figures

**Fig. 1**
Kaplan–Meier curve of overall survival.

**Fig. 2**
Kaplan–Meier curve of disease-free survival.

**Fig. 3**
Kaplan–Meier curve of T Staging.

**Fig. 4**
Kaplan–Meier curve of sinus (maxillary, frontal, ethmoid, and/or sphenoid) involvement of the primary tumor.

**Fig. 5**
Kaplan–Meier curve of a modified T-staging system, where T3 has been stratified by sinus involvement.

**Fig. 6**
Kaplan–Meier curve of a modified T-staging system, where T3 with sinus involvement has been combined with T4a.

**Fig. 7**
( a ) Kaplan–Meier overall survival curve of surgery only versus surgery and adjuvant radiotherapy for the treatment of disease at presentation. ( b ) Kaplan–Meier local recurrence-free survival curve of surgery only versus surgery and adjuvant radiotherapy for the treatment of disease at presentation.

**Fig. 8**
Kaplan–Meier curve of checkpoint inhibition compared with biochemotherapy or neither for the management of recurrent/persistent disease with or without distant metastasis.

**Fig. 9**
Kaplan–Meier curve of checkpoint inhibition compared with biochemotherapy or neither for the management of recurrent/persistent distantly metastatic disease.

See this image and copyright information in PMC

Cited by

Survivorship in Tumors of the Sinonasal Tract: The Need for Improved Awareness, Patient Education, and an Emphasis on Multi-Disciplinary Care.
Liu J, Tang A, Rehman U, Nilsen ML, Snyderman CH, London NR Jr, Lund VJ, Lechner M. Liu J, et al. Cancers (Basel). 2025 May 15;17(10):1666. doi: 10.3390/cancers17101666. Cancers (Basel). 2025. PMID: 40427163 Free PMC article. Review.
Adjuvant Therapy with Immune Checkpoint Inhibitors after Carbon Ion Radiotherapy for Mucosal Melanoma of the Head and Neck: A Case-Control Study.
Mizoguchi N, Kano K, Okuda T, Koge H, Shima S, Tsuchida K, Takakusagi Y, Kawashiro S, Yoshida M, Kitani Y, Hashimoto K, Furukawa M, Shirai K, Kamada T, Yoshida D, Katoh H. Mizoguchi N, et al. Cancers (Basel). 2024 Jul 23;16(15):2625. doi: 10.3390/cancers16152625. Cancers (Basel). 2024. PMID: 39123353 Free PMC article.
Treatment and related morbidity of nasal cavity and paranasal sinus cancers.
Smaadahl N, Hool SL, Reinhardt P, Mose L, Hohenberger R, Giger R, Schanne DH, Anschuetz L. Smaadahl N, et al. Front Oncol. 2024 Sep 26;14:1422892. doi: 10.3389/fonc.2024.1422892. eCollection 2024. Front Oncol. 2024. PMID: 39391250 Free PMC article.
Resectable Sinonasal Mucosal Melanoma in the Immunotherapy Era: Upfront Surgery vs. Neoadjuvant Therapy.
Salem AF, Chen MM, Williams MD, Swanson DM, McQuade JL, Amaria RN, Hanna EY, Bishop AJ, Farooqi AS, Guadagnolo BA, Su SY, Mitra D. Salem AF, et al. Head Neck. 2025 Jul;47(7):1848-1856. doi: 10.1002/hed.28098. Epub 2025 Feb 5. Head Neck. 2025. PMID: 39906003
Skull Base Tumors: Therapeutic Challenges and Multi-Disciplinary Care.
Choby G. Choby G. Cancers (Basel). 2024 Jan 31;16(3):620. doi: 10.3390/cancers16030620. Cancers (Basel). 2024. PMID: 38339370 Free PMC article.

See all "Cited by" articles

References

1. Lund V J, Chisholm E J, Howard D J, Wei W I. Sinonasal malignant melanoma: an analysis of 115 cases assessing outcomes of surgery, postoperative radiotherapy and endoscopic resection. Rhinology. 2012;50(02):203–210. - PubMed
1. Amit M, Tam S, Abdelmeguid A S. Patterns of treatment failure in patients with sinonasal mucosal melanoma. Ann Surg Oncol. 2018;25(06):1723–1729. - PubMed
1. Lund V J. Sinonasal malignant melanoma. Adv Otorhinolaryngol. 2020;84:185–196. - PubMed
1. Miglani A, Patel S H, Kosiorek H E, Hinni M L, Hayden R E, Lal D. Endoscopic resection of sinonasal mucosal melanoma has comparable outcomes to open approaches. Am J Rhinol Allergy. 2017;31(03):200–204. - PubMed
1. 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. - PubMed

LinkOut - more resources

Full Text Sources
Miscellaneous
- NCI CPTAC Assay Portal

Save citation to file

Email citation

Add to Collections

Add to My Bibliography

Your saved search

Create a file for external citation management software

Your RSS Feed

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

Affiliations

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

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

Similar articles

Cited by

References

LinkOut - more resources

Full Text Sources

Miscellaneous

Abstract

Conflict of interest statement

Figures

Similar articles

Cited by

References

Related information

LinkOut - more resources

Full Text Sources

Miscellaneous