title: The occurrence of non-melanoma malignant skin lesions and non-cutaneous squamous-cell carcinoma among metastatic melanoma patients: an observational cohort study in Denmark.
abstract: BACKGROUND
  Inhibitors of mutant BRAF are emerging as standard of care in patients with metastatic melanoma who carry relevant oncogenic mutations. However, BRAF inhibitors are found to induce cutaneous squamous cell carcinoma (cuSCC). Population-based background rates of cuSCC and non-cutaneous squamous cell carcinoma (non-cuSCC) in the metastatic melanoma population may contextualize safety signals from randomized clinical trials or the clinics. However, these background rates are lacking.
  
  
  METHODS
  We conducted a historical cohort study to evaluate the background rates of new-onset non-melanoma skin lesions and non-cuSCC among 2,814 metastatic malignant melanoma patients diagnosed in 1997-2010, identified through the Danish Cancer Registry and the National Pathology Registry. Patients were excluded if they had a history of cancer before the metastatic melanoma diagnosis, other than skin cancers. We determined the incidence of non-melanoma malignant skin lesions and non-cuSCC that occurred post metastatic melanoma diagnosis, censoring patients at death, emigration, or December 31, 2011 (end of study period), whichever came first.
  
  
  RESULTS
  The median age at metastatic melanoma diagnosis was 64 years. Over 40% of patients died within one year of metastatic diagnosis and ~70% died within 5 years. The percentages of patients with prior history or prevalent disease at metastatic melanoma diagnosis included: 8.6% with cuSCC or basal cell carcinoma (BCC), 3.9% with actinic keratosis (AK), and 0.7% with Bowen's disease. No patients had past or current non-cuSCC per study exclusion criterion. The incidence of non-melanoma skin lesions during the 6 months post-metastatic melanoma diagnosis was as follows: BCC, 1.8% (42.5 per 1000 person-years [PY]); AK, 0.8% (18.6 per 1000 PY); cuSCC, 0.1% (1.7 per 1000 PY); Bowen's disease, 0.04% (0.8 per 1000 PY); and keratoacanthoma (KA), 0%. Non-cuSCC was observed in 3 patients (0.1%; 2.5 per 1000 PY) at 3 sites: bronchi, heart and lung.
  
  
  CONCLUSIONS
  CuSCC and non-cuSCC were rare events among metastatic melanoma patients.
authors.affiliation: Worldwide Epidemiology, R&D, GlaxoSmithKline, 1250 South Collegeville Rd, Collegeville, PA, 19426, USA. haojie.li@gmail.com.
authors.forename: Haojie
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Clinical Epidemiology, Aarhus University Hospital, Olof Palmes Allé 43 - 45, Aarhus N, DK-8200, Denmark.
authors.forename: Lars
authors.initials: L
authors.lastname: Pedersen
authors.affiliation: Department of Clinical Epidemiology, Aarhus University Hospital, Olof Palmes Allé 43 - 45, Aarhus N, DK-8200, Denmark.
authors.forename: Mette
authors.initials: M
authors.lastname: Nørgaard
authors.affiliation: Department of Clinical Epidemiology, Aarhus University Hospital, Olof Palmes Allé 43 - 45, Aarhus N, DK-8200, Denmark.
authors.forename: Sinna P
authors.initials: SP
authors.lastname: Ulrichsen
authors.affiliation: Department of Clinical Epidemiology, Aarhus University Hospital, Olof Palmes Allé 43 - 45, Aarhus N, DK-8200, Denmark.
authors.forename: Sandra K
authors.initials: SK
authors.lastname: Thygesen
authors.affiliation: Worldwide Epidemiology, R&D, GlaxoSmithKline, 5 Moore Drive, Research Triangle Park, NC, 27709-3398, USA.
authors.forename: Jeanenne J
authors.initials: JJ
authors.lastname: Nelson
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002280:Basal Cell Carcinoma / Q000150:complications / Q000453:epidemiology / Q000473:pathology*; D002294:Carcinoma, Squamous Cell / Q000150:complications / Q000453:epidemiology / Q000473:pathology*; D015331:Cohort Studies; D003718:Denmark; D005260:Female; D006801:Humans; D055623:Keratosis, Actinic / Q000150:complications / Q000453:epidemiology / Q000473:pathology*; D008297:Male; D008545:Melanoma / Q000150:complications / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D008875:Middle Aged; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D012307:Risk Factors; D012878:Skin Neoplasms / Q000150:complications / Q000453:epidemiology / Q000473:pathology*; D000096142:Cutaneous Malignant Melanoma
chemical_list: C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf
keywords: Actinic keratosis (AK); Basal-cell carcinoma (BCC); Bowen’s disease; Cutaneous melanoma; Cutaneous squamous-cell carcinoma (cuSCC); Danish Cancer Registry; Incidence; National Pathology Registry; Non-cutaneous squamous-cell carcinoma (non-cuSCC); Population-based; keratoacanthoma (KA)