ACRT Journal

Introduction

Radiation therapy is utilized as an adjuvant therapy in over 60% of cancer patients. [1] It is estimated that by 2030, there will be over 2 million radiation-treated breast cancer survivors alone. [2] For breast cancer specifically, radiation therapy effectively reduces cancer recurrence and mortality. [3] Unfortunately, radiation therapy is associated with both systemic and local side effects. The local impact of radiation includes radiation dermatitis, radiationinduced fibrosis, hyperpigmentation, telangiectasias, fat necrosis, and poor wound healing. [4,5]

Deferoxamine (DFO) is an iron-chelating agent that has been approved by the US Food and Drug Administration (FDA) for the treatment of acute iron intoxication and chronic iron overload due to transfusion-dependent anemias. [6] Notably, FDA approval was granted for intramuscular, subcutaneous, and intravenous administration. Topical DFO has since been studied for the treatment of radiation induced fibrosis [4], diabetic wounds [7], and sickle cell related wounds [8]. The mechanism of action in the treatment of iron intoxication/overload is iron chelation. Whereas, the mechanism of action in the treatment of radiation induced fibrosis and wound healing is likely a combination of hypoxia-inducible factor-1α (HIF-1α) activation and stabilization, neovascularization, and a reduction in reactive oxygen species. [4,7] 

We present a patient that developed a non-healing radiation therapy associated wound with little improvement over five months, which then healed following two weeks of topical DFO treatment.

Methods

The patient is a 71-year-old female with inflammatory breast carcinoma diagnosed in 1981. Initial therapy included radiation and 6 cycles of chemotherapy with cyclophosphamide, doxorubicin, and fluorouracil. She did well for many years until she developed new malignant disease in the right axilla and left breast in July 2020. She underwent 6 cycles of combination chemotherapy and immunotherapy from August 2020 to January 2021, including carboplatin (5 of 6 cycles), docetaxel (2 of 6 cycles), and pembrolizumab (Keytruda). The planned number of chemotherapy cycles was limited by toxicities. In January 2021 she underwent left extended mastectomy with sentinel lymph node biopsy. Pathology showed primary triple negative breast cancer, and the left and right sentinel lymph node biopsies showed metastatic disease.  She underwent autologous breast reconstruction with a free flap from abdominal tissue in February 2021. After breast reconstruction she received 5000 cGy of radiation therapy over 25 fractions. After undergoing radiation therapy, in October of 2021, the patient developed a draining wound at the superior-medial aspect of the abdominal tissue flap measuring 0.5 cm² (Figure 1). The wound did not improve with local wound care and risk factor modification. Since there were no available alternatives, approval was obtained for treatment with a Deferoxamine Intradermal Delivery Patch (DIDP) through the FDA single patient investigative new drug pathway.

Figure 1: Radiation breast wound before and after treatment with topical deferoxamine.

Other medical history included hysterectomy (1985), mitral valve stenosis, tricuspid valve regurgitation, atrial fibrillation, and aortic stenosis treated with a total aortic valve replacement (2012). 

Treatment with DIDP was started on March 10, 2022. The patch was applied to the wound and the surrounding skin (Figure 2). The DIDP measured 7.5 x 6 cm and contained 1 mg DFO per 1 cm2, formulated to release DFO over 24 hours in a controlled manner. As such, the patch was changed daily by the patient at home and secured with an adhesive dressing. Treatment continued until the wound was healed. 

Figure 2: Deferoxamine Intradermal Delivery Patch applied to radiation breast wound.

Results

After two weeks of treatment the wound had healed (Figure 1). The patient was seen again five weeks after healing to ensure the wound had not recurred. Serum DFO levels were drawn on cessation of therapy and 5 weeks after. High powered liquid chromatography was performed by Frontage Laboratories, Inc. On cessation of therapy, serum level for DFO was < 1.00 ng/ml. Five weeks after cessation of therapy, serum DFO level was 1.39 ng/ml.

The “Radiation” and “Physical Well Being: Chest” instruments on the Breast-Q questionnaire were used before and after treatment. The patient reported improvements in both the appearance and quality of the skin (Tables 1 and 2).

Table 1: Adverse Effects of Radiation.

Table 2: Physical Well Being: Chest.