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. 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 Takahashi  4 , Mario Turri-Zanoni  5 , Marco Ferrari  6 , Jacklyn Liu  1 , Nicholas Counsell  7 , Davide Mattavelli  8 , Vittorio Rampinelli  8 , William Vermi  8 , Davide Lombardi  8 , Rami Saade  4   9 , Ki Wan Park  10 , Volker H Schartinger  11 , Alessandro Franchi  12 , Carla Facco  13 , Fausto Sessa  13 , Simonetta Battocchio  14 , Tim R Fenton  15 , Francis M Vaz  16 , Paul O'Flynn  16 , David Howard  16 , Paul Stimpson  16 , Simon Wang  17 , S Alam Hannan  16 , Samit Unadkat  16 , Jonathan Hughes  18 , Raghav Dwivedi  18 , Cillian T Forde  16 , Premjit Randhawa  16 , Simon Gane  16 , Jonathan Joseph  16 , Peter J Andrews  16 , Manas Dave  19 , Jason C Fleming  20 , David Thomson  21   20 , Tianyu Zhu  22 , Andrew Teschendorff  22 , Gary Royle  1 , Christopher Steele  1 , Joaquin E Jimenez  23 , Jan Laco  24 , Eric W Wang  23   25 , Carl Snyderman  23   25 , Peter D Lacy  26 , Robbie Woods  26 , James P O'Neill  26   27 , Anirudh Saraswathula  28 , Raman Preet Kaur  28 , Tianna Zhao  29 , Murugappan Ramanathan Jr  28   29 , Gary L Gallia  28   29   30 , Nyall R London Jr  28   29   31 , Quynh-Thu Le  32 , Robert B West  32 , Zara M Patel  10 , Jayakar V Nayak  10 , Peter H Hwang  10 , Mario Hermsen  33 , Jose Llorente  33 , Fabio Facchetti  14 , Piero Nicolai  6 , Paolo Bossi  34 , Paolo Castelnuovo  5 , Amrita Jay  35 , Dawn Carnell  18 , Martin D Forster  1 , Diana M Bell  36 , Valerie J Lund  16 , Ehab Y Hanna  4
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

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

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.

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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
Fig. 1
Kaplan–Meier curve of overall survival.
Fig. 2
Fig. 2
Kaplan–Meier curve of disease-free survival.
Fig. 3
Fig. 3
Kaplan–Meier curve of T Staging.
Fig. 4
Fig. 4
Kaplan–Meier curve of sinus (maxillary, frontal, ethmoid, and/or sphenoid) involvement of the primary tumor.
Fig. 5
Fig. 5
Kaplan–Meier curve of a modified T-staging system, where T3 has been stratified by sinus involvement.
Fig. 6
Fig. 6
Kaplan–Meier curve of a modified T-staging system, where T3 with sinus involvement has been combined with T4a.
Fig. 7
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
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
Fig. 9
Kaplan–Meier curve of checkpoint inhibition compared with biochemotherapy or neither for the management of recurrent/persistent distantly metastatic disease.
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Grants and funding

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.