Electrochemotherapy, a local treatment for squamous cell carcinoma in patients with recessive dystrophic epidermolysis bullosa

Abstract

Epidermolysis Bullosa (EB) is a rare group of diseases caused by genetic variants in skin structural proteins. EB is characterized by varying degrees of skin fragility, blisters and impaired wound healing, and is classified based on the ultrastructural levels of skin cleavage-simplex, junctional, dystrophic, and Kindler Syndrome. Squamous cell carcinoma (SCC) is the most severe complication and most common cause of death of patients with EB, particularly in those with recessive dystrophic Epidermolysis Bullosa (RDEB). To date, the first line of treatment of SCC in patients with RDEB is surgery, despite the high risk of recurrence. Radiotherapy and systemic therapy have been avoided due to its skin toxicity. Recently, electrochemotherapy (ECT) has been proposed as a potential treatment. We report eight sessions of ECT using bleomycin for treatment of SCC in five patients with EB. After 8 weeks all patients showed an objective response. Four patients (seven ECT sessions) had a complete response. The treatment was well tolerated, with mild adverse effects, such as local pain, erythema, and ulceration. Our results demonstrate that ECT is a potential treatment for SCC in patients with RDEB.

Therapies for cutaneous squamous cell carcinoma in recessive dystrophic epidermolysis bullosa: a systematic review of 157 cases

“…In many cases, chemotherapy was poorly tolerated and disease progression often occurred, resulting in patient death. However, when chemotherapeutic agents were delivered to tumor cells after electroporation, complete responses were observed in 6 patients (46.2%) [ 49 , 50 ]. The dimension of cSCCs that responded completely to electrochemotherapy ranged from 3 to 15 cm.…”

“…By inducing membrane permeability with short, intense electric pulses (electroporation), hydrophilic drugs such as bleomycin can gain direct access to the cytosol and demonstrate higher cytotoxicity by several 100-fold [ 48 ]. Among the 18 cases treated with electrochemotherapy, the clinical outcomes of 13 patients were further described: 2 demonstrated disease progression [ 18 , 27 ], 4 partial response [ 19 , 20 , 49 , 50 ], 6 patients complete response [ 49 , 50 ], and 1 stable disease [ 27 ]. Adverse events related to electrochemotherapy were primarily limited to pain, erythema, and ulceration [ 27 , 49 , 50 ].…”

“…Among the 18 cases treated with electrochemotherapy, the clinical outcomes of 13 patients were further described: 2 demonstrated disease progression [ 18 , 27 ], 4 partial response [ 19 , 20 , 49 , 50 ], 6 patients complete response [ 49 , 50 ], and 1 stable disease [ 27 ]. Adverse events related to electrochemotherapy were primarily limited to pain, erythema, and ulceration [ 27 , 49 , 50 ].…”

Intralesional Treatments for Invasive Cutaneous Squamous Cell Carcinoma

“…ECT has also been used as a neoadjuvant setting in cSCCs located on the lower lip, in recurrent cSCCs on the scalp, in aesthetically compromised areas like the nose, and in cSCCs in particular conditions like recessive dystrophic epidermolysis bullosa and linear porokeratosis [ 117 , 118 , 119 , 120 , 121 , 122 , 123 ].…”

Managing squamous cell carcinoma in recessive dystrophic <i>epidermolysis bullosa</i> with electrochemotherapy

“…Even though ECT is mainly applied as palliative care for metastases, it may also be used for primary tumors that are unresectable due to size and location 10,11 . ECT has been proposed as a new treatment modality for EB-SCCs, due to its effectiveness and favorable safety profile 4,12,13 .…”