Introduction
Kaposi’s sarcoma is a multifocal neoplasm of lymphatic endothelium-derived cells infected with human herpesvirus-8. Four main types of Kaposi’s sarcoma are described: the classic subtype, originally described by Kaposi, the endemic subtype, observed in Sub-Saharan Africa, the epidemic subtype, associated with HIV infection, and the iatrogenic subtype, associated with long-term pharmacologic immunodepression. Notwithstanding the subtype, immunosuppression is considered the leading factor for development, progression, and relapse of the disease [1,2].
Electrochemotherapy with bleomycin represents a valid option for the treatment of Kaposi’s sarcoma in a palliative setting, with good results, especially in the local control of sarcomatous lesions [3]. We present the case of a female patient with classic (or Mediterranean) Kaposi’s sarcoma known since 2013 and who had a satisfactory response to electrochemotherapy with bleomycin for the treatment of sarcomatous lesions of the left lower limb.
Case report
An 83-year-old woman was referred to the attention of the surgical oncology group at our Institution for the initiation of palliative electrochemotherapy for her sarcomatous lesions in the left leg and foot. Her medical history included well-controlled essential hypertension and chronic hepatitis C virus infection; she had undergone open cholecystectomy for acute calculous cholecystitis at young adult age.
The diagnosis of Kaposi’s sarcoma was made in 2013 on histological examination of some nodular subcutaneous lesions on the left lower limb. The patient was treated with external radiotherapy directed at the lesions of the foot and subsequently with intralesional vincristine. Given the poor results of this approach, she was started on systemic chemotherapy with intravenous vinblastine. After an initial response, the disease progressed, with evidence of left inguinal lymphadenopathy and multiple lung nodulations. The chemotherapy regimen was changed to intravenous paclitaxel, followed by intravenous doxorubicin, and was ultimately changed to intravenous gemcitabine. The systemic chemotherapy regimen failed to control the disease and was associated with relevant toxicity, that is, grade 2 hepatotoxicity with vinblastine, recurrent urinary tract infections with paclitaxel, and grade 3 neutropenia with doxorubicin. During the course of the disease, pruritus was referred to as one of the main complaints by the patient and required treatment with antihistamine agents; several episodes of cellulitis, likely caused by over-infection of the lesions via the ulcerated skin, had to be treated with systemic antibiotics.
Given the disease progression after several lines of chemotherapy, the development of chemotherapy-related toxicity, and the increasing symptoms impacting her quality of life, the patient was referred to the surgical oncology clinic for evaluation of palliative electrochemotherapy with bleomycin. On examination, the left foot and ankle appeared oedematous and several purplish, ulcerated sarcomatous nodules were evident on the plantar, calcaneal, and lateral areas (Fig. 1). In November 2020, she underwent electrochemotherapy with bleomycin (15 g/m2) on the lesion of the left foot and ankle. The procedure was carried out under spinal anesthesia; following intravenous infusion of bleomycin, electroporation of visible lesions was carried out. The postoperative course was uneventful and the patient was discharged home on the first postoperative day. Local response was assessed weekly for the first month and monthly thereafter: the initial response was vigorous and the nodules developed necrosis within 2 weeks. Necrotic ulcers developed at the base of the lesions and were successfully treated with surgical curettage and topic hyaluronidase cream: granulation tissue quickly developed and the skin ulcers were not evident two months after surgery. Local edema and erythema disappeared and so did the chronic pruritus (Fig. 2). Sixteen months after the initial procedure, the patient showed no signs of local recurrence.
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Fig. 1: Preoperative presentation of the left lower limb. Multiple sarcomatous lesions are seen on the lateral and plantar surfaces.
Fig. 2: Postoperative presentation at routine 12-month follow-up, in keeping with complete clinical response.
Discussion
We present satisfactory results in the local control in the context of palliative treatment of Kaposi’s sarcoma using electrochemotherapy with bleomycin in frail elderly patients.
Electrochemotherapy combines the advantages of intralesional chemotherapy and electroporation therapy [4]. The antineoplastic effects of electrochemotherapy mainly depend on the increased cytoplasmatic uptake of the hydrophilic molecule chosen as intravenous chemotherapy (i.e. bleomycin or cisplatin) given by electroporation, which is itself obtained with high-voltage direct current. Moreover, some anti-vascular action, also known as the ‘vascular lock’, might be part of the antineoplastic action of electrochemotherapy, especially in neoplasms with accentuated angio-proliferative activity, such as Kaposi’s sarcoma. Damage to the endothelial cells arises from a direct action of the chemotherapy agent, especially bleomycin, and indirect effects of infiltration of host cells and changes in tumor blood flow [5].
The clinical effectiveness of electrochemotherapy has been shown in several prospective clinical trials [6–8]. Electrochemotherapy with bleomycin or cisplatin has been shown to be safe and effective for the treatment of cutaneous and subcutaneous metastases of melanoma, various carcinomas, and sarcoma [9]. Recently, Ferioli et al. published a systematic review reporting outcomes of patients treated with electrochemotherapy for Kaposi’s sarcoma [10]. In particular, the clinical response rate was reported as 65–100% and seemed to decrease with an increasing number of lesions. In the current study, the clinical response was complete and no lesions were visible at follow-up appointments. A limited number of lesions were treated and this might in part explain the complete clinical response after one electrochemotherapy; the success rate after a single cycle is reported to be as high as 73.6% by Di Monta et al. [6]. Toxicity is reported as a rare event after electrochemotherapy in the Literature (incidence of 5.5–8.7% [10]) and no adverse effects were reported in the current case.
Data on long-term survival and rate of local control after electrochemotherapy for Kaposi’s sarcoma are only reported in one prospective study [8] and this warrants further prospective investigation to obtain definitive evidence. Moreover, information regarding the quality of life indicators is missing; this is relevant, as tailoring treatment to minimize adverse outcomes and maximize the quality of life remains central when caring for patients with Kaposi’s sarcoma. In our case, the patient had a complete clinical response. She was asymptomatic at 16 months after surgical intervention: the pruritus resolved and no additional treatment for local complications of the sarcomatous lesions was needed.
Conclusion
electrochemotherapy represents a valid option for the treatment of Kaposi’s sarcoma, also in elderly and frail patients with the prolonged disease, as it can yield satisfactory local control of the disease with improvement in patient-reported symptoms and minimal toxicity.
Acknowledgements
Conflicts of interest
There are no conflicts of interest.
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