Clinico‐morphological features of BRAF inhibition–induced proliferative skin lesions in cancer patients. Issue 1 (3rd September 2014)

• Record Type: Journal Article
• Authors: Belum, Viswanath Reddy; Rosen, Alyx C.; Jaimes, Natalia; Dranitsaris, George; Pulitzer, Melissa P.; Busam, Klaus J.; Marghoob, Ashfaq A.; Carvajal, Richard D.; Chapman, Paul B.; Lacouture, Mario E.
• Is Part Of: Cancer. Volume 121:Issue 1(2015)
• Page Start: 60
• Page End: 68
• Publication Date: 2014-09-03
• Subjects: BRAF -- dabrafenib -- keratoacanthoma -- risk factors -- skin neoplasms -- squamous cell carcinoma -- vemurafenib -- verrucous lesion -- XL281; Cancer -- Periodicals; Cancer -- Cytopathology -- Periodicals; 616.99405
• DOI: 10.1002/cncr.28980
• Languages: English
• ISSNs: 0008-543X

Abstract

Abstract : BACKGROUND: The use of BRAF inhibitors may lead to the development of cutaneous toxicities such as rashes, photosensitivity, alopecia, palmoplantar erythrodysesthesia, and proliferative skin lesions, including keratoacanthomas (KAs) and cutaneous squamous cell carcinomas (cuSCCs). The latter are noteworthy for their potential to exhibit malignant features, and they may necessitate invasive treatment. Their prompt identification is of primary importance for directing supportive care efforts and maintaining dose intensity while minimizing the morbidity associated with supportive care interventions. Because such lesions are less familiar to oncologists, this study was designed to characterize their clinico‐morphological features, which have not been hitherto described. METHODS: The clinical and dermoscopic characteristics and risk factors of new‐onset proliferative skin lesions (benign verrucous lesions and KAs/cuSCCs) developing after the initiation of treatment with vemurafenib, dabrafenib, and XL281 were analyzed; the histopathological diagnoses were ascertained. RESULTS: The majority of the lesions were benign verrucous lesions (78%, n = 87), whereas KAs/cuSCCs represented 22% (n = 25). The median times to biopsy for the initial verrucous lesions and KAs/cuSCCs were 4.8 and 10.5 weeks, respectively. The clinico‐morphological features significant for KAs/cuSCCs included a larger size ( P < .001), a nodular appearance ( P < .001), a central keratin plug ( P < .001), a central ulceration or crust ( P = .04), an adherent scale ( P = .02), an erythematous halo ( P = .03), and a scaly ring (collarette; P < .001) at the periphery. CONCLUSIONS: Our findings represent the first detailed description of the clinico‐morphological characteristics that permit distinction between the benign and malignant skin lesions induced by BRAF inhibitors. They are valuable for the recognition of lesions that require intervention and/or a dermatology referral versus those that permit provisional monitoring. Cancer 2015;121:60–68 . © 2014 American Cancer Society . Abstract : Despite improved cancer outcomes with BRAF inhibitors, the characterization and management of the associated adverse events exemplify the challenges of survivorship care. Published studies involving BRAF inhibitors reflect an adverse event profile that is characterized by proliferative skin lesions (keratoacanthomas/cutaneous squamous cell carcinomas and verrucous lesions), maculopapular rashes, and hyperkeratosis. With regulatory approval and expanding use of vemurafenib and dabrafenib, oncologists will encounter proliferative skin lesions more often. Recognition of their key identifying features and appropriate management are crucial for ensuring consistent dosing of life‐saving anticancer therapy, maintenance of health‐related quality of life, and lower morbidity associated with adverse event management.