Comparison of clinicopathological features and treatment outcomes for cutaneous melanomas of the head and neck and melanomas arising at other sites: Implications for systemic therapy

Andrew T Li; Jessie X Xu; Tyler R Blah; Serigne N Lo; Robyn Pm Saw; Alexander Hr Varey; Alexander Van Akkooi; Matteo S Carlino; Ines Pires da Silva; Alexander M Menzies; Kerwin F Shannon; Georgina V Long; Richard A Scolyer; John F Thompson; Sydney Ch'ng

doi:10.1016/j.jaad.2024.06.107

Comparison of clinicopathological features and treatment outcomes for cutaneous melanomas of the head and neck and melanomas arising at other sites: Implications for systemic therapy

J Am Acad Dermatol. 2024 Sep 6:S0190-9622(24)02768-3. doi: 10.1016/j.jaad.2024.06.107. Online ahead of print.

Authors

Affiliations

¹ Melanoma Institute Australia, The University of Sydney, North Sydney, NSW, Australia; Royal Prince Alfred Hospital, Camperdown, NSW, Australia; Faculty of Medicine and Health, The University of Sydney, Sydney, NSW, Australia; Victorian Melanoma Service, The Alfred Hospital, Melbourne, VIC, Australia.
² Melanoma Institute Australia, The University of Sydney, North Sydney, NSW, Australia; Royal Prince Alfred Hospital, Camperdown, NSW, Australia.
³ Faculty of Medicine and Health, The University of Sydney, Sydney, NSW, Australia.
⁴ Melanoma Institute Australia, The University of Sydney, North Sydney, NSW, Australia; Faculty of Medicine and Health, The University of Sydney, Sydney, NSW, Australia.
⁵ Melanoma Institute Australia, The University of Sydney, North Sydney, NSW, Australia; Royal Prince Alfred Hospital, Camperdown, NSW, Australia; Faculty of Medicine and Health, The University of Sydney, Sydney, NSW, Australia; Mater Hospital, Sydney, NSW, Australia.
⁶ Melanoma Institute Australia, The University of Sydney, North Sydney, NSW, Australia; Faculty of Medicine and Health, The University of Sydney, Sydney, NSW, Australia; Westmead and Blacktown Hospitals, Sydney, NSW, Australia.
⁷ Melanoma Institute Australia, The University of Sydney, North Sydney, NSW, Australia; Mater Hospital, Sydney, NSW, Australia; Westmead and Blacktown Hospitals, Sydney, NSW, Australia; Charles Perkins Centre, The University of Sydney, Sydney, NSW, Australia.
⁸ Melanoma Institute Australia, The University of Sydney, North Sydney, NSW, Australia; Faculty of Medicine and Health, The University of Sydney, Sydney, NSW, Australia; Mater Hospital, Sydney, NSW, Australia; Royal North Shore Hospital, St Leonards, NSW, Australia.
⁹ Melanoma Institute Australia, The University of Sydney, North Sydney, NSW, Australia; Royal Prince Alfred Hospital, Camperdown, NSW, Australia; Mater Hospital, Sydney, NSW, Australia.
¹⁰ Melanoma Institute Australia, The University of Sydney, North Sydney, NSW, Australia; Faculty of Medicine and Health, The University of Sydney, Sydney, NSW, Australia; Mater Hospital, Sydney, NSW, Australia; Charles Perkins Centre, The University of Sydney, Sydney, NSW, Australia; Royal North Shore Hospital, St Leonards, NSW, Australia.
¹¹ Melanoma Institute Australia, The University of Sydney, North Sydney, NSW, Australia; Royal Prince Alfred Hospital, Camperdown, NSW, Australia; Faculty of Medicine and Health, The University of Sydney, Sydney, NSW, Australia; Charles Perkins Centre, The University of Sydney, Sydney, NSW, Australia; NSW Health Pathology, Sydney, NSW, Australia.
¹² Melanoma Institute Australia, The University of Sydney, North Sydney, NSW, Australia; Royal Prince Alfred Hospital, Camperdown, NSW, Australia; Faculty of Medicine and Health, The University of Sydney, Sydney, NSW, Australia; Mater Hospital, Sydney, NSW, Australia; Faculty of Health and Medical Sciences, The University of Western Australia, Perth, WA, Australia.
¹³ Melanoma Institute Australia, The University of Sydney, North Sydney, NSW, Australia; Royal Prince Alfred Hospital, Camperdown, NSW, Australia; Faculty of Medicine and Health, The University of Sydney, Sydney, NSW, Australia; Mater Hospital, Sydney, NSW, Australia; Chris O'Brien Lifehouse Cancer Centre, Camperdown, NSW, Australia. Electronic address: sydney.chng@sydney.edu.au.

PMID: 39243946
DOI: 10.1016/j.jaad.2024.06.107

Abstract

Background: Melanoma is increasingly recognized as a heterogeneous disease, with conflicting evidence regarding whether cutaneous head and neck melanoma (CHNM) represents a distinct entity.

Objective: Comparison of clinicopathological features and treatment outcomes of CHNM and cutaneous melanomas of other sites (CMOS).

Methods: Patients with CHNM and CMOS diagnosed between 2000 and 2018 were included. Locoregional control, distant metastasis-free survival, melanoma-specific survival (MSS), and overall survival (OS) were described using the Kaplan-Meier method. Cox regression analyses were performed to examine associations between prognostic factors and outcomes. Additional analyses of survival from time of stage IV disease diagnosis were undertaken, stratified by receipt of BRAF-targeted therapy and immune checkpoint inhibitor immunotherapy.

Results: Of 3007 CHNM and 10,637 CMOS patients, CHNM had more adverse pathological features (median age 65.9 vs 58.5, P < .001; median Breslow thickness 1.7 mm vs 1.2 mm, P < .001; and ulceration 21.2% vs 18.2%, P < .001). CHNM had worse locoregional control (hazard ratio (HR) 1.17, P < .001) and distant metastasis-free survival (HR 1.25, P < .001) but there were no significant differences in MSS or OS. Among stage IV patients who received immune checkpoint inhibitor, CHNM had better MSS (HR 0.56, P = .001) and OS (HR 0.57, P < .001) on multivariable analyses.

Limitations: Retrospective study, offset by prospective data collection.

Conclusion: CHNM is associated with a distinct clinicopathological and prognostic profile.

Keywords: anatomic subsites; head and neck; immunotherapy; melanoma; melanoma survival; prognostic factors; targeted therapy.