A Novel Approach to Reconstructing Unresectable Basal Cell Carcinoma of the Extremity
Armando A. Davila, MD1, Caryn Zagaynov, BS1, Allison Beckham, MD1, Walter Chang, MD2.
1Loma Linda University, Loma Linda, CA, USA, 2Fontana Medical Center, Southern California Permanente Medical Group, Fontana, CA, USA.
PURPOSE: Basal cell carcinoma (BCC) is the most prevalent skin malignancy with about 2 million cases per year in the US. BCC is caused by overactivation of the sonic hedgehog (Shh) signaling pathway, either by inhibition of the transmembrane protein Patched Homolog 1 (PTCH) or by activation of the transmembrane protein called Smoothened (SMO). In a cancerous cell, Hedgehog ligand binds to PTCH1, disinhibiting SMO, activating transcription factors leading to cell overgrowth.
While most cases of BCC are treated with surgical excision and closure, neglected malignancies can pose a reconstructive dilemma, particularly on the extremities. Resection can result in disfigurement, loss of function, or even amputation.
Vismodegib (Erivedge, Genentech) is the first targeted inhibitor of the Shh pathway and is taken orally. Specifically, Vismodegib is an antagonist for SMO which suppresses downstream activation of transcription factors. This novel drug has not been previously explored as it relates to extremity reconstruction.
METHODS: In several case reports, we will demonstrate how Erivedge can increase reconstructive options, and simplify the management of unresectable extremity malignancies.
RESULTS: Case 1: A 67-year-old male presented with a 9 by 12 centimeters BCC of the right lateral arm. He underwent radiation therapy for 3 months, however no reduction in size was achieved. Erivedge was administered for 7 months until a local excision and skin graft could be performed. Mapping biopsies were performed, which showed no residual BCC. He therefore continued conservative wound care until the wound healed.
Case 2: A 90-year-old female with advanced Alzheimer’s Dementia and multiple comorbidities presented with a 4 centimeter BCC of the left forearm. She could not cooperate with awake surgical treatment and was not a candidate for systemic anesthesia. She was started on Erivedge and saw compete resolution of her lesion in 3 months.
Case 3: A 65-year-old male presented with a 15 by 12 centimeter BCC involving a near circumferential portion of the right forearm. It involved the radial artery and was unresectable without amputation. He was started on Erivedge and after 3 months his lesion had significantly reduced in size. The patient was considered for resection and flow-through free flap for reconstruction of his radial artery. He passed away prior to free flap due to metastatic melanoma.
CONCLUSION: Vismodegib (Erivedge) is intended for the treatment of BCC that is locally invasive, metastatic, recurrent, patients not candidates for surgery or radiation therapy, or for cancer that is located where resection or radiation would cause substantial disfigurement or loss of function. Since the approval of Vismodegib, it has been shown to cause significant regression in BCC tumors in several studies. These case reports further demonstrate promising results for management of unresectable BCC in the extremities, creating scenarios where reconstruction becomes possible.
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