title: Tumor-free osteosclerotic lesions in patients treated for metastatic melanoma using BRAF inhibitors.
abstract: BRAF inhibitors (vemurafenib and dabrafenib) are commonly prescribed in BRAF-mutant metastatic melanoma and allow improvement of the overall survival and progression-free survival. They are, however, accompanied by many adverse effects which mainly affect the skin. We observed on computed tomographic scans in three different patients after 3 months of treatment, the onset of osteosclerotic lesions. In parallel, the computed tomographic scans showed a significant reduction in all of the previously identified metastases in all patients. The occurrence of such bone modifications under treatment was reported previously in others cancers, such as inoperable non-small-cell lung cancers under epidermal growth factor receptor inhibitors, as the 'osteoblastic bone flare phenomenon'. However, it had never been reported in melanoma patients treated with targeted therapies, and the results of two performed bone biopsies are reported here. This phenomenon is generally believed to indicate a better response under treatment, whereas in our study, the patients experienced, after a short partial response, a severe cerebral relapse leading to death. Finally, although its physiopathological mechanisms are poorly understood, the occurrence of tumor-free osteosclerotic lesions in patients under BRAF inhibitors should not be misinterpreted as a progression of the disease.
authors.affiliation: Departments of aDermatology bRadiology, Centre Hospitalier Lyon-Sud, Pierre Benite cUniversité Claude Bernard Lyon 1, Villeurbanne dCancer Research Center of Lyon, Lyon, France.
authors.forename: Lea
authors.initials: L
authors.lastname: Bottlaender
authors.forename: Marie
authors.initials: M
authors.lastname: Perier-Muzet
authors.forename: Véronique
authors.initials: V
authors.lastname: Lapras
authors.forename: Luc
authors.initials: L
authors.lastname: Thomas
authors.forename: Stephane
authors.initials: S
authors.lastname: Dalle
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects*; D006801:Humans; D007093:Imidazoles / Q000009:adverse effects*; D007211:Indoles / Q000009:adverse effects*; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000235:genetics / Q000556:secondary; D008875:Middle Aged; D009154:Mutation; D010026:Osteosclerosis / Q000139:chemically induced* / Q000000981:diagnostic imaging; D010091:Oximes / Q000009:adverse effects*; D048493:Proto-Oncogene Proteins B-raf / Q000037:antagonists & inhibitors / Q000235:genetics; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D013449:Sulfonamides / Q000009:adverse effects*; D014057:Tomography, X-Ray Computed; D000077484:Vemurafenib
chemical_list: D000970:Antineoplastic Agents; D007093:Imidazoles; D007211:Indoles; D010091:Oximes; D013449:Sulfonamides; D000077484:Vemurafenib; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; C561627:dabrafenib