Vismodegib for Preservation of Visual Function in Patients with Advanced Periocular Basal Cell Carcinoma: The VISORB Trial

The oncologist

article

Alon Kahana¹  Christine C. Nelson¹  Denise S. Kim¹  Shannon S. Joseph¹  Paul L. Swiecicki²  Francis P. Worden²  Shelby P. Unsworth¹  Christopher A. Andrews¹  May P. Chan²  Scott C. Bresler²  Christopher K. Bichakjian²  Alison B. Durham²  Hakan Demirci¹  Victor M. Elner¹ 

[1] Department of Ophthalmology and Visual Sciences, Kellogg Eye Center, University of Michigan;Rogel Comprehensive Cancer Center, University of Michigan;Ophthalmic and Facial Plastic Surgery;Department of Ophthalmology, Oakland University William Beaumont School of Medicine;Section on Hematology and Oncology, Department of Internal Medicine, University of Michigan;Department of Pathology, University of Michigan;Department of Dermatology, University of Michigan

关键词: Basal cell;    Cancer;    Patched;    Smoothened;    SMO;    PTCH;    Hedgehog;    Orbit;    Orbital;    Tumor;    Cancer;    Lacrimal;    Epiphora;    Visual function;   

DOI  :  10.1002/onco.13820

学科分类：地质学

来源: AlphaMed Press Incorporated

【 摘 要 】

Background Basal cell carcinoma (BCC) is a common skin cancer often curable by excision; however, for patients with BCC around the eye, excision places visual organs and function at risk. In this article, we test the hypothesis that use of the hedgehog inhibitor vismodegib will improve vision-related outcomes in patients with orbital and extensive periocular BCC (opBCC). Materials and Methods In this open-label, nonrandomized phase IV trial, we enrolled patients with globe- and lacrimal drainage system–threatening opBCC. To assess visual function in the context of invasive periorbital and lacrimal disease, we used a novel Visual Assessment Weighted Score (VAWS) in addition to standard ophthalmic exams. Primary endpoint was VAWS with a score of 21/50 (or greater) considered successful, signifying globe preservation. Tumor response was evaluated using RECIST v1.1. Surgical specimens were examined histologically by dermatopathologists. Results In 34 patients with opBCC, mean VAWS was 44/50 at baseline, 46/50 at 3 months, and 47/50 at 12 months or postsurgery. In total, 100% of patients maintained successful VAWS outcome at study endpoint. Compared with baseline, 3% (95% confidence interval [CI], 0.1–15.3) experienced major score decline (5+ points), 14.7% (95% CI, 5 to 31.1) experienced a minor decline (2–4 points), and 79.4% experienced a stable or improved score (95% CI, 62.1–91.3). A total of 56% (19) of patients demonstrated complete tumor regression by physical examination, and 47% (16) had complete regression by MRI/CT. A total of 79.4% (27) of patients underwent surgery, of which 67% (18) had no histologic evidence of disease, 22% (6) had residual disease with clear margins, and 11% (3) had residual disease extending to margins. Conclusion Vismodegib treatment, primary or neoadjuvant, preserves globe and visual function in patients with opBCC. Clinical trail identification number .NCT02436408. Implications for Practice Use of the antihedgehog inhibitor vismodegib resulted in preservation of end-organ function, specifically with regard to preservation of the eye and lacrimal apparatus when treating extensive periocular basal cell carcinoma. Vismodegib as a neoadjuvant also maximized clinical benefit while minimizing toxic side effects. This is the first prospective clinical trial to demonstrate efficacy of neoadjuvant antihedgehog therapy for locally advanced periocular basal cell carcinoma, and the first such trial to demonstrate end-organ preservation.

【 授权许可】

CC BY|CC BY-NC