Pietro Curatolo

Predicting patients at risk for pain associated with electrochemotherapy

Abstract Background. Electrochemotherapy describes the use of electric pulses to enhance chemotherapy uptake, and has proven highly efficient in treating cutaneous metastases. Patients referred for electrochemotherapy present with diverse clinical pictures, from multiple small lesions to large, ulcerated lesions. Post-electrochemotherapy pain has been observed in some patients. The objectives of this study were to evaluate pain scores before and after electrochemotherapy, and to investigate if patients at risk of post-procedure pain could be identified. Methods. Seven cancer centres in the International Network for Sharing Practices on Electrochemotherapy (INSPECT) consecutively and prospectively reported to a common database. Electrochemotherapy consisted of intratumoural or intravenous injection of bleomycin, followed by delivery of electric pulses in local or general anesthesia. Results. Of 121 patients 39% had metastatic melanoma, 18% squamous cell carcinoma, 16% breast cancer, 13% basal-cell carcinoma, and 14% other malignancies. Median size of the largest nodules was 2.3 cm (range 0.3–40 cm). A majority of patients presented with low pain scores, and this continued through follow-up (74%). A subset of patients had moderate (13%) or severe pain (13%) after treatment. Post-procedure pain was statistically significantly associated with: 1) moderate or severe pain before treatment (p < 0.0001); 2) size of the largest treated lesion (p < 0.01); 3) previous irradiation (p < 0.02); and 4) high treatment current value (p < 0.0001). Conclusion. The majority of patients had no or mild pain after electrochemotherapy. Patients at risk for post-procedure pain could be identified at the pre-treatment visit, and/or at the time of treatment, enabling a pain management strategy for this group.

Electrochemotherapy in the treatment of metastatic malignant melanoma: a prospective cohort study by InspECT.

(ECT) is an effective local treatment for cutaneous metastasis. Treatment involves the administration of chemotherapeutic drugs followed by delivery of electrical pulses to the tumour.

Successful Treatment of Penile Kaposi's Sarcoma with Electrochemotherapy

Electrochemotherapy is a procedure that consists of the injection of highly cytotoxic drugs (like bleomycin or cisplatin) followed up by applications of current electric pulses directly into the tumor lesions on the skin or subcutaneous tissue, so as to improve membrane permeability and increase drug cytotoxicity.At the appropriate pulse parameters, pore formation on the cell membrane allows low permanent drugs like bleomycin or cisplatin to enter the cell and thus locally increase thereby their toxicity: up to 10,000 times for bleomycin and 80 times for cisplatin.

Updated standard operating procedures for electrochemotherapy of cutaneous tumours and skin metastases

Abstract Electrochemotherapy is now in routine clinical use to treat cutaneous metastases of any histology, and is listed in national and international guidelines for cutaneous metastases and primary skin cancer. Electrochemotherapy is used by dermatologists, surgeons, and oncologists, and for different degrees and manifestations of metastases to skin and primary skin tumours not amenable to surgery. This treatment utilises electric pulses to permeabilize cell membranes in tumours, thus allowing a dramatic increase of the cytotoxicity of anti-cancer agents. Response rates, often after only one treatment, are very high across all tumour types. The most frequent indications are cutaneous metastases from malignant melanoma and breast cancer. In 2006, standard operating procedures (SOPs) were written for this novel technology, greatly facilitating introduction and dissemination of the therapy. Since then considerable experience has been obtained treating a wider range of tumour histologies and increasing size of tumours which was not originally thought possible. A pan-European expert panel drawn from a range of disciplines from dermatology, general surgery, head and neck surgery, plastic surgery, and oncology met to form a consensus opinion to update the SOPs based on the experience obtained. This paper contains these updated recommendations for indications for electrochemotherapy, pre-treatment information and evaluation, treatment choices, as well as follow-up.

Electrochemotherapy, a potential new treatment for the management of squamous cell carcinoma in patients with recessive dystrophic epidermolysis bullosa: report of three cases.

Editor Epidermolysis bullosa (EB) is a rare congenital disorder caused by mutations in structural proteins of the dermal/epidermal junction and defined by high skin fragility and impaired wound healing. Generalized Severe Recessive Dystrophic EB (RDEB-sev gen) is a severe form, and squamous cell carcinoma (SCC) is one of the most feared complication. To date, surgery is the primary treatment option. Frequent relapses and metastasis require radiotherapy and chemotherapy. Despite this multimodal approach, in some cases, excisional surgery is not a possible option, and amputation is inevitable; over two-third of RDEB patients die from SCC. Therefore, alternative approaches should be considered. Electrochemotherapy (ECT) is a local treatment that combines low-dose systemic or intralesional cytotoxic drugs (bleomycin or cisplatin) and the application of high-intensity electric pulses. The electric fields temporarily increase the cell permeability allowing the delivery of drugs into tumour cells. ECT has been successfully used to treat cutaneous and subcutaneous metastasis and non-melanoma skin cancer, including SCC. We report the cases of three patients with SCC in RDEB-sev gen treated with ECT (Table 1). They were unsuitable for standard treatments because of tumour characteristics and general status. The ethics committee of the Bambino Ges u Children’s Hospital approved an expanded access program. Written consent was obtained from the patients. Inclusion criteria and technical procedures followed the European Standard Operating Procedures for ECT (ESOPE). Before treatment, a digital mapping of all lesions was performed and the tumour areas were calculated. A history, clinical examination, biopsy of the lesions, routine blood and instrumental exams were required for all patients. The procedures were performed under general anaesthesia, using the CliniporatorTM device (IGEA, Italy) and variable length hexagonal needle electrodes. Bleomycin was injected in an i.v. bolus at a dose of 15 mg/m for two of the three patients, 5 mg/m for one of them because of renal failure. Electrical pulses started 8 minutes after the drug administration and continued for 25 min (8 square wave pulses 1000 V/cm for 100 ms at 5 kHz). A simple dressing was used to cover the treated areas. The patients were seen at 1, 2, 4 weeks and then every month after ECT; the lesions were examined and measured to determine the response. We assessed the efficacy according to the Response Evaluation Criteria in Solid Tumours (RECIST).

Local treatment with electrochemotherapy of superficial angiosarcomas: Efficacy and safety results from a multi-institutional retrospective study

Angiosarcoma is an aggressive vascular neoplasm with a high propensity for local recurrence. Electrochemotherapy is an emerging skin‐directed therapy, exerting prominent cytotoxic activity, and antivascular effects. Its efficacy in angiosarcoma has not been investigated.

Giant neglected squamous cell carcinoma of the skin

Nonmelanoma skin cancers (NMSCs) are the most common type of skin tumor, representing about one‐third of all malignancies diagnosed worldwide each year. Cutaneous squamous cell carcinoma (cSCC) is the second most common form of NMSCs and the risk of cSCC invasiveness should be assessed on the basis of tumor size, anatomical location, and histological subtype. Although most cSCCs are early diagnosed and successfully treated, in a small percentage of patients with giant cSCC (maximum diameter >5 cm), metastases may occur; treatment options are limited and not really effective. We report the case of a giant metastatic cSCC that had been neglected for more than 20 years. Radiotherapy or surgery were not feasible and polichemotherapy (cisplatin, 5‐fluorouracil and paclitaxel) was not effective. Therefore, the patient was treated with palliative electrochemotherapy (ECT) achieving a partial reduction of cutaneous metastasis and pain relief but unfortunately the patient died 3 months after the second ECT treatment.

Electrochemotherapy of unresectable cutaneous tumours with reduced dosages of intravenous bleomycin: analysis of 57 patients from the International Network for Sharing Practices of Electrochemotherapy registry

Electrochemotherapy (ECT) is currently used to treat unresectable superficial tumours of different histotypes through the combination of cytotoxic chemotherapy and local application of electric pulses. In 2006, a collaborative project defined the ESOPE (European Standard Operating Procedures of Electrochemotherapy) guidelines to standardize the procedure. The International Network for Sharing Practices of Electrochemotherapy (InspECT) aims to refine the ESOPE and improve clinical practice. Limiting patient exposure to systemic chemotherapy would be advisable to ameliorate ECT safety profile.

Electrochemotherapy for Breast Cancer—Results From the INSPECT Database

Background Cutaneous recurrence from breast cancer can pose a clinical challenge. It might be the only disease site, or could be part of disseminated disease, and often profoundly affects quality of life. Electrochemotherapy is a palliative treatment using electric pulses to locally permeabilize tumor cells and thereby significantly increase bleomycin cytotoxicity. Collaborating with the International Network for Sharing Practice on ElectroChemoTherapy (INSPECT), we consecutively and prospectively accrued data on patients treated with electrochemotherapy for cutaneous metastases from breast cancer. Patients and Methods Patients were treated with electrochemotherapy at 10 European centers. Under either local or general anaesthesia patients were treated with either local injection (1000 IU/mL intratumoral) or systemic infusion (15,000 IU/m2) of bleomycin. Results One hundred nineteen patients were included at 10 institutions in the INSPECT network. The primary location was the chest (89%), the median diameter of the cutaneous metastases was 25 mm. Ninety patients were available for response evaluation after 2 months. Complete response was observed in 45 patients (50%), partial response in 19 (21%), stable disease in 16 (18%), and progressive disease in 7 (8%). Three patients were not evaluable. Common side effects were ulceration, long‐lasting hyperpigmentation, and low‐grade pain. No serious adverse events were observed. Conclusion Electrochemotherapy showed high response rates after a single treatment. Electrochemotherapy has few side effects and can be used as an adjunct to systemic therapies or as a solo treatment. We therefore recommend considering electrochemotherapy for patients with cutaneous metastases. Micro‐Abstract Electrochemotherapy is a palliative treatment for patients with cutaneous metastases and provides symptomatic relief for these patients. Here are results for breast cancer patients included in the International Network for Sharing Practice on ElectroChemoTherapy database. It shows that electrochemotherapy is a safe and efficient treatment with few side effects. We therefore recommend considering electrochemotherapy for patients with cutaneous metastases.

Recurrent cutaneous abscesses in two Italian family members.

Environmental mycobacteria are the causative factors of an increasing number of infections worldwide. Cutaneous infections as a result of such mycobacteria are often misdiagnosed, and their treatment is difficult since they can show in vivo and in vitro multidrug resistance. Absence of pathognomonic clinical signs and variable histological findings often delay diagnosis. We report a case of localized recurrent soft tissue swelling by Mycobacterium marinum in 2 members of the same family. The cases are being reported for their uncommon clinical presentation and the associated etiological agent. Patients recovered completely following therapy with rifampicin 600 mg plus isoniazide 300 mg daily for 45 days.