Oral Hedgehog Pathway Inhibition as a Means for Ocular Salvage in Locally Advanced Intraorbital Basal Cell Carcinoma

Abstract

BACKGROUND Basal cell cancer is the most common cutaneous malignancy. It rarely presents with locally advanced or metastatic disease. Rare presentations such as intraorbital invasion remain a difficult clinical problem with significant potential morbidity. There is no review of sonic hedgehog pathway inhibitors (HPIs) for intraorbital basal cell cancer, and evidence regarding optimal management is limited. OBJECTIVE To evaluate the evidence for the management of intraorbital basal cell cancer with HPIs. METHODS A search to identify evidence for treatment intraorbital basal cell cancers with HPIs to date was performed in PubMed database and OVID using the phrases “basal cell cancer/carcinoma/BCC,” “intraorbital,” “orbital,” “ocular,” “periocular,” “vismodegib,” “GDC-0449,” “sonidegib,” and “LDE224,” in various combinations with Boolean operators “AND” and “OR.” RESULTS Rigorous clinical trials have previously reported the use of vismodegib and sonidegib in locally advanced and metastatic basal cell carcinoma (BCC). However, specific descriptions of treatment of intraorbital tumors are rarely presented in detail adequate for analysis. Twenty-two cases of intraorbital BCC treated with vismodegib have been described in the literature, and no cases using sonidegib were identified. These vary in quality, but highlight important questions regarding optimal treatment duration, follow-up, and adjunctive therapies. Reports describing locally advanced BCC in various facial and periocular locations, but without specific mention of intraorbital invasion, were excluded. CONCLUSION Vismodegib is an attractive eye and vision-sparing option in patients with locally advanced intraorbital basal cell cancer whose other options often include exenteration, radiation, or other radical surgery.

Systemic hedgehog inhibitors to treat locally advanced basal cell carcinomas of the head–neck region: A retrospective study

“… 3 , 4 Sonidegib, is a selective hedgehog pathway inhibitor (HHI) approved in 2015 for patients with laBCC that are ineligible for surgery and/or radiation therapy. 5 To date, clinical trials and case reports regarding its efficacy and tolerability, also during COVID‐19 pandemic period, 6 have already been reported 7 , 8 ; the aim of this study is to report the efficacy of sonidegib in treating laBCCs localized in critical structures as the head–neck region, highlighting also the cosmetic results reported in patients achieving the complete remission of the tumor. This retrospective analysis included patients with head–neck laBCCs treated with sonidegib at the Non‐Melanoma Skin Cancer Unit of the University of Federico II in Naples from February 2020 to December 2020.…”

Treatment of Advanced Basal Cell Carcinoma with Hedgehog Pathway Inhibitors: A Multidisciplinary Expert Meeting

“…In cases with a limited number of lesions (i.e., 1-2), it is not difficult to establish an effective treatment plan according to the localization of the tumour. Indeed, if neglected, BCC in the periorificial areas of the face, especially the periocular region or the nose, can lead to severe consequences [15]. Surgery is generally contraindicated when it would cause severe deformities and when lesions relapse after multiple surgeries [16].…”

Effective systemic treatment of advanced periocular basal cell carcinoma with sonidegib

“…Indeed, targeted therapy for periocular and orbital tumors is becoming an exploding and hot topic for ophthalmologists and oncologists [1][2][3][4][5]. Sonidegib (Odomzo®) is an oral hedgehog pathway inhibitor (HPI) and that it is indicated for the treatment of adults with locally advanced basal cell carcinomas (BCCs) [2,6,7].…”