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Effective use of Vismodegib as a neoadjuvant prior to Mohs surgery

Brian J Simmons BS

Department of Dermatology and Cutaneous Surgery, University of Miami Miller School of Medicine, Miami, USA

E-mail : bjsimmons@med.miami.edu

Fleta Netter Bray BS

Department of Dermatology and Cutaneous Surgery, University of Miami Miller School of Medicine, Miami, USA

Leyre A Falto-Aizpurua

Department of Dermatology and Cutaneous Surgery, University of Miami Miller School of Medicine, Miami, USA

Mohammed Alsaidan

Department of Dermatology, Salman bin Abdulaziz University, Riyadh, Kingdom of Saudi Arabia

Keyvan Nouri

Department of Dermatology and Cutaneous Surgery, University of Miami Miller School of Medicine, Miami, USA

DOI: 10.15761/GOD.1000124

Article
Article Info
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Figures & Data

Abstract

Importance

Basal Cell Carcinoma (BCC) represents a majority of skin cancers (80%), and can be locally invasive and difficult to treat in patients with Nevoid Basal Cell Carcinoma syndrome (Gorlin syndrome) or in patients with multiple BCCs in high-risk areas.

Observations

Long-term use of Vismodegib was tolerated well in the 2 patients in this case series and was able to shrink large BCCs by up to 80.5%.

Conclusions and Relevance

In Gorlin syndrome and high risk non-resectable BCCs, vismodegib can provide neoadjuvant treatment. In turn, allowing for Mohs surgery to be a viable option with smaller surgical defects with good cosmetic outcomes.

Introduction

Gorlin syndrome is an autosomal dominant disorder that usually presents with patients developing BCCs in adolescence or early adulthood. In addition, patients present with distinct faces with frontal or temporoparietal bossing, hypertelorism and mandibular prognathism. Other skeletal abnormalities can be seen along with benign odontogenickeratocyst of the jaw [1]. The condition is due to a defect in PTCH1 gene [2]. PTCH1 encodes the protein patched-1 that functions as a tumor suppressor. If the gene is mutated the cell cycle is not suppressed in turn leading to the high occurrence of BCCs.

Vismodegib acts as a competitive antagonist of the smoothened receptor part of the Sonic hedgehog-signaling pathway. In turn, leading to the inhibition of transcription factors leading to cell cycle arrest. This drug has been used in the treatment of metastatic BCCs and in controlling the occurrence of BCCs in Gorlin syndrome.

Report of a case series

Case 1

A 78-year-old Hispanic gentleman with a history of chronic sun exposure as a field worker and multiple skin cancers treated in the past including an extensive basal cell carcinoma (BCC) of the left-postaricular with extensive involvement of auditory canal and mastoid. Patient was started on 150mg/day vismodegib for his extensive BCCs by oncology. Patient was seen by a dermatologist for lesions on the lower eyelids bilaterally, which were subsequently biopsied and returned the diagnosis of Morpheaform BCC. Patient was referred to our Mohs surgery clinic for evaluation and resection of cancers after being on vismodegib treatment for 13 months shrinking the tumor from 2.0cm by 1.8cm to 1.0cm by 0.7cm (Figures 1a and 1b). tumor was resected using traditional Mohs surgery technique in 4 stages leaving a defect of 2cm by 1.6cm (Figure 1c). Patient was seen by oculoplastics for surgical defect reconstruction, without complications.

Figure 1. a. preoperative Morpheaform BCC of right lower eyelid patient 1; b. Close up preoperative BCC of right lower eyelid patient 1; c. post surgical defect after Mohs surgery patient 1; d. Preoperative Nodulocystic BCC of nasal bridge; e. Close up preoperative Nodulocystic BCC of nasal bridge patient 2; f. Post surgical defect after Mohs surgery patient 2

Case 2

A 47-year-old Hispanic gentleman, with a previous history of Nevoid Basal Cell Carcinoma syndrome (Gorlin) with multiple family members with extensive BCCs. Patient has had a growing nodule on the nose present for 7-8 years, which started to erode and bleed easily leading the patient to present for treatment. Lesion was previously treated in Cuba via surgical excision and postoperative radiation treatment. Biopsy confirmed diagnosis of BCC nodulocystic type. Patient was started on 150mg/daily treatment of vismodegib and has continued treatment for approximately 3 months. Lesion shrunk from initial size of 1.5 cm by 1.5cm to 1.2cm by 1.3cm (Figures 1d and 1e). Patient was referred for excision of lesion at our Mohs clinic where the lesion was excised using traditional Mohs technique in 1 stage leaving a 2cm by 1.5cm defect (Figure 1f) and was reconstructed at the Mohs surgery clinic. Patient will be followed for recurrence of BCCs on a regular basis while maintaining his vismodegib maintenance therapy for Gorlin syndrome.

Discussion

There are few studies looking at vismodegib as a neoadjuvant therapy [3-5]. This case series demonstrates that vismodegib can be used as a neoadjuvant to shrink large BCCs in patients with genetic predisposition for increased BCCs (Gorlins syndrome) and in patients with a history of locally invasive BCCs in high-risk areas. In turn, shrinking the tumors to allow for Moh’s surgery with smaller defects and better reconstructive outcomes. The study by Ally et al.[5] found that surgical defects could be decreased on average 27% if at least 3 months on neoadjuvant treatment was done. Although only 2 patients were included in our case series, lesions shrunk by 80.5% and 30.7% respectively. This in turn lead to a smaller surgical defect than would have occurred with the initial untreated lesions. Thus, showing the potential for neoadjuvant vismodegib treatment for large BCCs in difficult to treat patients or in patients with genetic predispositions where recurrence is high.

References

  • Kimonis VE, Goldstein AM, Pastakia B, Yang ML, Kase R, et al. (1997) Clinical manifestations in 105 persons with nevoid basal cell carcinoma syndrome. Am J Med Genet 69: 299-308. [Crossref]
  • Johnson RL, Rothman AL, Xie J, Goodrich LV, Bare JW, et al. (1996) Human homolog of patched, a candidate gene for the basal cell nevus syndrome. Science 272: 1668-1671. [Crossref]
  • Chang AL, Atwood SX, Tartar DM, Oro AE (2013) Surgical excision after neoadjuvant therapy with vismodegib for a locally advanced basal cell carcinoma and resistant basal carcinomas in Gorlin syndrome. JAMA Dermatol 149: 639-641. [Crossref]
  • Aldabagh B, Yu J, Perkocha LA, Arron S (2013) Histologic changes in basal cell carcinoma after treatment with vismodegib. Dermatol Surg 39: 1703-1705.
  • Ally MS, Aasi S, Wysong A, Teng C, Anderson E, et al. (2014) An investigator-initiated open-label clinical trial of vismodegib as a neoadjuvant to surgery for high-risk basal cell carcinoma. J Am Acad Dermatol 71: 904-911. [Crossref]

Editorial Information

Editor-in-Chief

Torello Lotti
University of Rome "G.Marconi" Rome

Article Type

Case Report

Publication history

Received: January 30, 2015
Accepted: February 13, 2015
Published: February 15, 2015

Copyright

©2015 Brian J Simmons. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Citation

Simmons BJ, Bray FN, Falto-Aizpurua LA, Alsaidan M, Nouri K (2015) Effective use of Vismodegib as a neoadjuvant prior to Mohs surgery. Glob Dermatol, 2: DOI: 10.15761/GOD.1000124.

Corresponding author

Brian James Simmons

Department of Dermatology and Cutaneous Surgery, University of Miami Miller School of Medicine, 1475 NW 12th Ave. Miami, FL 33136, USA, Tel: 305-243-3996; Fax: 305-243-4184.

E-mail : bjsimmons@med.miami.edu

Figure 1. a. preoperative Morpheaform BCC of right lower eyelid patient 1; b. Close up preoperative BCC of right lower eyelid patient 1; c. post surgical defect after Mohs surgery patient 1; d. Preoperative Nodulocystic BCC of nasal bridge; e. Close up preoperative Nodulocystic BCC of nasal bridge patient 2; f. Post surgical defect after Mohs surgery patient 2