Severe skin radiodermatitis fully healed with the use of platelet gel and a hyperbaric chamber

Introduction

Despite the continuous development of new chemotherapy agents and immunotherapy drugs capable of targeting malignancies, radiotherapy still represents a key strategy for the treatment of aggressive cancer. For instance, breast cancer patients undergo radiotherapy of the involved field to reduce the risk of relapse, as do patients with lymphomas. However, radiotherapy is associated with the development of severe complications, such as secondary acute myeloid leukaemia and myelodysplasia, chronic skin infection and in some cases even skin cancers. Less aggressive complications include radiodermatitis. This skin disorder is due to exposure to x- or γ-rays causing ionization of tissue water, leading to skin changes resembling burn injuries. The lesions are aesthetically quite disfiguring and can lead to significant psychosocial stress, particularly for women. We report here the first case of severe radiodermatitis with successful restitution ab integro by repeated administration of platelet gel.

Case report

A 45-year old woman was diagnosed in 1989 with an intraductal adenocarcinoma of her right breast and was treated with quadrantectomy followed by 45 Gy fractionated radiotherapy. At the age of 54 (in 1998) she relapsed and a total mastectomy was performed. At the same time a breast prosthesis in silicon was inserted. Comorbid illness included recurrent gastritis, colon diverticulosis and kidney stones.

At the age of 60 (in 2004) she complained of severe swelling of her breast around the insertion area of the prosthesis and required syringe-aspiration of bloody serous fluid several times. The prosthesis was removed and the wound closed using standard surgery. However, at the age of 67 (in 2011) the patient developed a necrotic lesion on her right breast, which was consistent with an ALK-negative anaplastic large cell lymphoma. She underwent six cycles of standard chemotherapy with cyclophosphamide, doxorubicin, etoposide, vincristine and prednisone (CHOEP regimen) with intrathecal methotrexate, followed by a second course of fractionated radiotherapy with 45 Gy. However 6 months later (in June 2012) she developed a cutaneous relapse of her lymphoma, for which she was given two courses of gemcitabine, dexamethasone and cisplatin (GDP), followed by two cycles of romidepsin chemotherapy. In October 2012, due to disease progression, she was treated with four courses of ifosfamide, carboplatin, and etoposide (ICE) followed by an autologous peripheral blood stem cell transplant, using carmustine, etoposide, cytarabine and melphalan (BEAM) as the conditioning regimen. This was followed by three cycles of brentuximab vedotin monoclonal antibody therapy (the last cycle administered in May 2013).

In June 2012 the patient developed a severe wound (6×10 cm) on her right chest, with associated grade 4 radiodermatitis according to the NCI CTCA classification (Figure 1A). Plastic surgery with skin debridement was attempted without any major improvement. In October 2013, platelet gel for wound treatment became available and 10–15 mL of platelet-rich plasma (PRP) with added fibrin and CaCl₂ was applied locally every 2–3 weeks. At the same time, the patient commenced hyperbaric chamber therapy (32 treatment sessions in total). Signs of skin recovery were visible after 4 months of combined treatment. The administration of platelet gel was, therefore, continued every second week (40 applications in total) together with hyperbaric chamber treatment (50 treatment sessions in total) leading to complete resolution of the woman’s radiodermatitis/wound within 10 months (Figure 1B). The patient is currently stable with a Karnofsky score of 100% and her lymphoma remains in complete remission. Her radiodermatitis has now fully recovered.

Figure 1.

Radiodermatitis of the right breast.

(A) florid lesion with scanty signs of active tissue granulation; (B) the same area after 10 months of treatment with platelet gel (10–15 mL every second week).

Discussion

This type of anaplastic large cell lymphoma in women with breast implants has recently been recognised as a separate entity by the Food and Drug Administration, and may be considered separately in the next World Health Organization classification of malignant lymphomas¹. This finding raises several ethical and clinical issues, not least the need for careful review and close follow up of patients treated with breast implants. Moreover, we recently came across a similar case (personal communication) of a young adolescent who developed a diffuse large B-cell lymphoma 12 years after the insertion of a bioabsorbable polylactic screw for the treatment of a flat foot. Although we cannot prove the link between the silicon-like prosthesis and development of a non-Hodgkin’s lymphoma, we believe that physicians should consider this possibility and should be encouraged to report similar cases.

To the best of our knowledge this is the first case of platelet gel treatment of severe skin radiodermatitis, with successful skin recover. It is worth highlighting that our patient was diagnosed with two different malignancies, was treated with two courses of radiotherapy and several courses of chemotherapy, and that normally such patients are less likely to respond to treatment. Platelet-rich plasma is a unique source of growth factors (e.g. platelet-derived growth factor, fibroblast growth factor, transforming growth-β, epidermal growth factor, vascular endothelial growth factor) and other molecules able to help tissue growth². The addition of CaCl₂ to platelet-rich plasma activates the same into platelet gel, which has already been reported as a valid approach to wound healing^3,4. Only two other similar reports exist in the literature although in neither was hyperbaric chamber therapy associated with the use of platelet gel^5,6.

Conclusions

Further, prospective studies are warranted to investigate the role of platelet gel administration in radiodermatitis and to clarify the combined role of hyperbaric chamber treatment. The possibility of using cord blood platelet gel should also be considered and, when possible, tested^2,7,8.