A Fibroblast-Derived Human Growth Factor Preparation for the Management of Acute Radiodermatitis: A Case Report

Georgia Vadarli Plastic Surgery Consultancy Private Practice, Thessaloniki, Greece; Maria Angelo-Khattar American Academy of Anti-Aging Medicine (A4M), Dubai, United Arab Emirates Abstract: Radiotherapy is a commonly used modality in breast cancer management. Amongst the consequences of treatment are acute and/or chronic skin changes, which often lead to itching, pain, and a diminished aesthetic appearance, all of which greatly impact the patient’s quality of life. Management of radiation-induced skin effects has not as yet been standardized, with various protocols being applied by different radiotherapy departments. This case study outlines the management of a grade 3 acute radiodermatitis in a female with a synergistic preparation of anti-inflammatory cytokines and growth factors derived from human fibroblasts. The treatment resulted in the total resolution of the radiation-induced skin reaction, with a minimally visible residual scar. Keywords: radiotherapy, acute radiodermatitis, growth factors, cytokines

Introduction

It is estimated that radiotherapy (RT) is administered in more than half of patients diagnosed with cancer. The goal of the treatment is to deliver optimal results with the least possible untoward effects.1 Nonetheless, it has been reported that even with the most advanced radiotherapy procedures, approximately 95% of patients will experience substantial skin reactions in the treatment area.2,3 These untoward effects on the skin, secondary to radiotherapy, may be acute or chronic. Acute radiodermatitis is a burn injury, which generally appears within one to four weeks after treatment initiation and persists for the radiotherapy duration. Chronic or late-onset reactions may appear in several years post-therapy. The severity of radiodermatitis has been graded by the National Cancer Institute (USA) into four levels: Grade 1 (mild erythema or desquamation), grade 2 (moderate erythema and moist desquamation confined to skin folds and creases), grade 3 (confluent moist desquamation greater than 1.5cm diameter which is not confined to skin folds possibly with pitting oedema) and grade 4 (skin necrosis or ulceration of full thickness of the dermis).4,5 At present, there is no unanimous agreement regarding recommendations to prevent or treat radiodermatitis despite the publication of general guidelines by several multidisciplinary groups.6–8 In fact, substantial variations exist regarding patient instructions, specified by various radiotherapy units.9 Nonetheless, it is generally agreed that maintaining a clean and dry irradiated area and diligent moisturization of the treated area with the use of steroid creams and skin barrier preparations are beneficial in mitigating the skin response to radiation. Since the primary reasons for acute radiodermatitis skin reactions are inflammation, a reduction in the number of stem cells and skin-cell necrosis and death,10 it stands to reason that treatment of radiodermatitis wounds with anti-inflammatory cytokines and growth factors may be beneficial in modulating the inflammatory response and regulating an orderly wound-healing reaction. It is a well-established fact that growth factors and cytokines are integral to each of the three phases of normal wound healing, namely inflammation, proliferation, and matrix remodeling. Levels of growth factors, such as PDGF, EFG, TGF-Beta and FGF, are reduced in chronic pressure and dermal ulcers than acute wounds.11,12 Each of these growth factors has a specific role in the promotion of wound healing. TGF-Beta stimulates collagen and glycosaminoglycan formation, increases fibronectin synthesis, inhibits matrix degradation and facilitated cell chemotaxis. Platelet-derived growth factor stimulates angiogenesis and is a potent activator for cells of mesenchymal origin. Epidermal growth factor is responsible for the regeneration of the epidermis and fibroblast growth factor stimulates fibroblasts and angiogenesis. Exogenous application of a synergistic complex of anti-inflammatory cytokines and growth factors may be of potential benefit in the regenerative process leading to orderly wound healing of radiodermatitis.