Rachael Anforth1, Alexander Menzies2, Karen Byth3, Giuliana Carlos1, Shaun Chou4, Raghwa Sharma5, Richard A Scolyer6, Richard Kefford2, Georgina V Long2, Pablo Fernandez-Peñas7. 1. Department of Dermatology, Westmead Hospital, Westmead, Australia; Sydney Medical School, University of Sydney, Sydney, Australia. 2. Westmead Institute for Cancer Research, Westmead Hospital, Westmead, Australia; Sydney Medical School, University of Sydney, Sydney, Australia; Melanoma Institute Australia, Sydney, Australia. 3. Research and Education Network, Westmead Hospital, Westmead, Australia. 4. Department of Tissue Pathology and Diagnostic Oncology, Westmead Hospital, Westmead, Australia. 5. Department of Tissue Pathology and Diagnostic Oncology, Westmead Hospital, Westmead, Australia; Sydney Medical School, University of Sydney, Sydney, Australia; Faculty of Medicine, University of Western Sydney, Sydney, Australia. 6. Sydney Medical School, University of Sydney, Sydney, Australia; Melanoma Institute Australia, Sydney, Australia; Tissue Pathology and Diagnostic Oncology, Royal Prince Alfred Hospital, Sydney, Australia. 7. Department of Dermatology, Westmead Hospital, Westmead, Australia; Sydney Medical School, University of Sydney, Sydney, Australia. Electronic address: pablo.fernandezpenas@sydney.edu.au.
Abstract
BACKGROUND: BRAF inhibitors (BRAFi) cause paradoxical activation of the MAPK pathway in keratinocytes resulting in cutaneous squamous cell carcinoma (cuSCC). OBJECTIVE: We sought to examine the clinical factors involved in BRAFi-induced cuSCC development. METHODS: We studied 134 patients with BRAF-mutant metastatic melanoma treated with a BRAFi at Westmead Hospital, Sydney, Australia. Details of cuSCC development and associations with melanoma clinicopathologic features and treatment outcome were examined. RESULTS: In all, 32 (24%) patients developed 110 cuSCC after commencing treatment. In all, 61 (55%) cuSCC developed within the first 3 months. Age was the only independent risk factor for cuSCC development. After 3 months of therapy 4% of patients younger than 40 years developed cuSCC compared with 33% who were older than 60 years, and the hazard ratio of developing a cuSCC increased by 1.7 (95% confidence interval 1.3-2.3) per decade (P < .001). BRAFi cuSCC occurred more often in sun-protected areas (42%) compared with sporadic cuSCC (21%) (P < .001). cuSCC was not associated with progression-free survival. LIMITATIONS: The study was from a single center and patients were also at risk of sporadic cuSCC. CONCLUSION: Most BRAFi-induced cuSCC develop within 3 months of BRAFi therapy. The only independent risk factor is increasing age. cuSCC may present in anatomical locations with low ultraviolet exposure such that thorough dermatologic assessment is required.
BACKGROUND:BRAF inhibitors (BRAFi) cause paradoxical activation of the MAPK pathway in keratinocytes resulting in cutaneous squamous cell carcinoma (cuSCC). OBJECTIVE: We sought to examine the clinical factors involved in BRAFi-induced cuSCC development. METHODS: We studied 134 patients with BRAF-mutant metastatic melanoma treated with a BRAFi at Westmead Hospital, Sydney, Australia. Details of cuSCC development and associations with melanoma clinicopathologic features and treatment outcome were examined. RESULTS: In all, 32 (24%) patients developed 110 cuSCC after commencing treatment. In all, 61 (55%) cuSCC developed within the first 3 months. Age was the only independent risk factor for cuSCC development. After 3 months of therapy 4% of patients younger than 40 years developed cuSCC compared with 33% who were older than 60 years, and the hazard ratio of developing a cuSCC increased by 1.7 (95% confidence interval 1.3-2.3) per decade (P < .001). BRAFi cuSCC occurred more often in sun-protected areas (42%) compared with sporadic cuSCC (21%) (P < .001). cuSCC was not associated with progression-free survival. LIMITATIONS: The study was from a single center and patients were also at risk of sporadic cuSCC. CONCLUSION: Most BRAFi-induced cuSCC develop within 3 months of BRAFi therapy. The only independent risk factor is increasing age. cuSCC may present in anatomical locations with low ultraviolet exposure such that thorough dermatologic assessment is required.
Authors: Subashini Sharon Gnanendran; Lauren Maree Turner; James Austin Miller; Shelley Ji Eun Hwang; Andrew Charles Miller Journal: Curr Treat Options Oncol Date: 2020-03-19
Authors: Marius Tham; Hans-Jürgen Stark; Anna Jauch; Catherine Harwood; Elizabeth Pavez Lorie; Petra Boukamp Journal: Front Oncol Date: 2022-01-31 Impact factor: 6.244
Authors: Jayesh Desai; Hui Gan; Catherine Barrow; Michael Jameson; Victoria Atkinson; Andrew Haydon; Michael Millward; Stephen Begbie; Michael Brown; Ben Markman; William Patterson; Andrew Hill; Lisa Horvath; Adnan Nagrial; Gary Richardson; Christopher Jackson; Michael Friedlander; Phillip Parente; Ben Tran; Lai Wang; Yunxin Chen; Zhiyu Tang; Wendy Huang; John Wu; Dewan Zeng; Lusong Luo; Benjamin Solomon Journal: J Clin Oncol Date: 2020-03-17 Impact factor: 44.544