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: Lechner Matt , Takahashi Yoko , Turri-Zanoni Mario , Ferrari Marco , Liu Jacklyn , Counsell Nicholas , Mattavelli Davide , Rampinelli Vittorio , Vermi William , Lombardi Davide , Saade Rami , Park Ki Wan , Schartinger Volker H. , Franchi Alessandro , Facco Carla , Sessa Fausto , Battocchio Simonetta , Fenton Tim R. , Vaz Francis M. , O'Flynn Paul , Howard David , Stimpson Paul , Wang Simon , Hannan S. Alam , Unadkat Samit , Hughes Jonathan , Dwivedi Raghav , Forde Cillian T. , Randhawa Premjit , Gane Simon , Joseph Jonathan , Andrews Peter J. , Dave Manas , Fleming Jason C. , Thomson David , Zhu Tianyu , Teschendorff Andrew , Royle Gary , Steele Christopher , Jimenez Joaquin E. , Laco Jan , Wang Eric W. , Snyderman Carl , Lacy Peter D. , Woods Robbie , O'Neill James P. , Saraswathula Anirudh , Kaur Raman Preet , Zhao Tianna , Ramanathan Murugappan , Gallia Gary L. , London Nyall R. , Le Quynh-Thu , West Robert B. , Patel Zara M. , Nayak Jayakar V. , Hwang Peter H. , Hermsen Mario , Llorente Jose , Facchetti Fabio , Nicolai Piero , Bossi Paolo , Castelnuovo Paolo , Jay Amrita , Carnell Dawn , Forster Martin D. , Bell Diana M. , Lund Valerie J. , Hanna Ehab Y. 
Published: July 2022

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.