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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

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
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
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.
TNM, immune checkpoint blockade, immune checkpoint inhibitors ipilimumab, immunotherapy, sinonasal mucosal melanoma
2193-6331
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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. and Hanna, Ehab Y. (2022) 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. Journal of Neurological Surgery Part B Skull Base. (doi:10.1055/s-0042-1750178).

Record type: Article

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.

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SNMM_JNS_author_accepted_2022 - Accepted Manuscript
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Accepted/In Press date: 22 April 2022
e-pub ahead of print date: 10 July 2022
Published date: 10 July 2022
Additional Information: Funding Information: We would like to acknowledge the invaluable support from Prof. Tariq Enver and the UCL Cancer Institute. We would also like to thank Josep Linares, Dr. Naomi Guppy, and David Allan from HSL Labs/UCL Advanced Diagnostics. Publisher Copyright: © 2022 Thieme Medical Publishers, Inc.. All rights reserved.
Keywords: TNM, immune checkpoint blockade, immune checkpoint inhibitors ipilimumab, immunotherapy, sinonasal mucosal melanoma

Identifiers

Local EPrints ID: 471232
URI: http://eprints.soton.ac.uk/id/eprint/471232
ISSN: 2193-6331
PURE UUID: 810e26b3-db6e-4e40-ad0f-d9fb9ade78ce
ORCID for Tim R. Fenton: ORCID iD orcid.org/0000-0002-4737-8233

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Date deposited: 01 Nov 2022 17:33
Last modified: 17 Mar 2024 07:32

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Contributors

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

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