Vismodegib as a Neoadjuvant Treatment to Mohs Surgery for Aggressive Basal Cell Carcinoma
March 2015 | Volume 14 | Issue 3 | Original Article | 219 | Copyright © March 2015
Joseph Alcalay MD,a Gil Tauber MD,b Eyal Fenig MD,c and Emmilia Hodak MDb
aMohs Surgery Unit, Assuta Medical Center, Tel-Aviv, Israel and School of Health Sciences, Ariel University, Israel
bDepartment of Dermatology, Beilinson Hospital, Rabin Medical Center, Petah-Tikva, Israel
cRadiotherapy Unit, Davidoff Center, Rabin Medical Center, Petah-Tikva, Israel
BACKGROUND: Vismodegib, a hedgehog pathway inhibitor has been recently introduced as an oral therapy for locally advanced and metastatic basal cell carcinoma. Although treatment of patients with basal cell carcinoma with vismodegib has been associated with partial or complete clinical response, it is still unclear if it is also associated with histological cure.
PATIENTS: Two patients with 3 large and aggressive basal cell carcinomas were treated with Vismodegib for 6 months. The treatment was followed by Mohs micrographic surgery.
RESULTS: Two tumors disappeared clinically and one was reduced dramatically in its size following treatment with vismodegib. Mohs surgery in all three tumors revealed residual islands of BCC although margins were cleared at the end of surgery.
CONCLUSIONS: Neoadjuvant therapy with vismodegib for 6 months prior to Mohs surgery was effective in reducing the size of primary and recurrent aggressive basal cell carcinoma. However, residual tumor nests were found during surgery. Further larger studies are needed to evaluate the efficacy of Vismodegib as a neoadjuvant treatment prior to Mohs surgery.
J Drugs Dermatol
Basal cell carcinoma (BCC) is the most common cancer amongst men and women.1 The majority of non-superficial BCCs are treatable either by surgery or radiotherapy. Some BCC’s especially while neglected, become aggressive with potential local destruction, disfiguring and a rare chance of metastases.2 When a BCC becomes locally aggressive the role of surgery and or radiotherapy becomes less efficient. In these cases surgery can result in loss of function of vital structures such as the nose, eyelids, ears and lips and also in severe cosmetic defect. More than 90% of patients with BCC have a mutation in the hedgehog (Hh) signaling pathway.3 Recently, Vismodegib (Erivedge, Roche) was found to be a potent inhibitor of the Hh pathway and was approved for the treatment of locally advanced and metastatic BCC’s that are not amendable for surgery or radiotherapy.4,5 We report 2 patients with three aggressive BCC’s in whom Vismodegib served as a useful neoadjuvant therapy prior to Mohs micrographic surgery.
Two patients with three locally aggressive BCC’s received Vismodegib for 6 months prior to Mohs surgery.
Patient 1. A 70-year-old woman was referred for Mohs surgery because of growing tumor on the nose for 10 years. A large “bunch of grapes” like tumor was seen on the lower half of the nose. (Figure 1). She also had a large BCC on the forehead (Figure1). An attempt to decrease the size of the tumors prior to Mohs surgery was initiated. Treatment with Vismodegib 150 mg per day was initiated. At the end of 6 months treatment, the tumor on the forehead had completely disappeared clinically, and the tumor of the nose was reduced dramatically more than 60% of its original size (Figure 1). One month after session of the oral treatment the patient underwent Mohs surgery in the forehead and nose. Margins were marked at the clinical border of the atrophic scar in the forehead, and at the clinical border of the tumor on the nose. Despite clinical elimination of the forehead tumor, remnants of tumor were found in the debulking stage (Figure 2). The forehead defect was closed primarily after one stage. The tumor of the nose required 2 stages of Mohs surgery to clean the tumor. The surgical defect was closed by full-thickness graft from the preauicular area (Figure 2). Follow-up for 6 months after surgery revealed no recurrences.
Patient 2. A 70-year-old male had a recurrent nodular BCC on the left upper lip-cheek junction. Two operations were performed before he showed up with a 2cm subcutaneous firm nodule which caused retraction of the left upper lip (Figure 3a, b). Biopsy revealed BCC. We decided to try to shrink the tumor with