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

Author:

Lechner Matt123,Takahashi Yoko4,Turri-Zanoni Mario5,Ferrari Marco6,Liu Jacklyn1,Counsell Nicholas7,Mattavelli Davide8,Rampinelli Vittorio8,Vermi William8,Lombardi Davide8,Saade Rami49,Park Ki Wan10,Schartinger Volker H.11,Franchi Alessandro12,Facco Carla13,Sessa Fausto13,Battocchio Simonetta14,Fenton Tim R.15,Vaz Francis M.16,O'Flynn Paul16,Howard David16,Stimpson Paul16,Wang Simon17,Hannan S. Alam16,Unadkat Samit16,Hughes Jonathan18,Dwivedi Raghav18,Forde Cillian T.16,Randhawa Premjit16,Gane Simon16,Joseph Jonathan16,Andrews Peter J.16,Dave Manas19,Fleming Jason C.20,Thomson David2120,Zhu Tianyu22,Teschendorff Andrew22,Royle Gary1,Steele Christopher1,Jimenez Joaquin E.23,Laco Jan24,Wang Eric W.2325,Snyderman Carl2325,Lacy Peter D.26,Woods Robbie26,O'Neill James P.2627,Saraswathula Anirudh28,Kaur Raman Preet28,Zhao Tianna29,Ramanathan Murugappan2829,Gallia Gary L.282930,London Nyall R.282931,Le Quynh-Thu32,West Robert B.32,Patel Zara M.10ORCID,Nayak Jayakar V.10,Hwang Peter H.10,Hermsen Mario33,Llorente Jose33,Facchetti Fabio14,Nicolai Piero6,Bossi Paolo34,Castelnuovo Paolo5,Jay Amrita35,Carnell Dawn18,Forster Martin D.1,Bell Diana M.36,Lund Valerie J.16,Hanna Ehab Y.4

Affiliation:

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

Abstract

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.

Publisher

Georg Thieme Verlag KG

Subject

Neurology (clinical)

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