Update on ElectroChemoTherapy in Bristol Antonio Orlando Department

Update on Electro-Chemo-Therapy in Bristol Antonio Orlando Department of Plastic Surgery Southmead Hospital – North Bristol Trust SWAG Skin SSG meeting, 17 th May 2016

Electroporation of the cellular membrane: The application of electric pulses induces cells to form a transient pore in the cell membrane Cell membrane before electroporation Pores formation Low dosage chemotherapeutic drug can enter the cell e. g. Bleomycin / Cisplatin (non/ poorly permeable anticancer drug possessing a high intrinsic cytotoxicity).

ELECTROCHEMOTHERAPY TUMOR RESPONSE The efficacy of bleomycin in the treatment of melanoma is increased by over 100% when associated with electroporation MEDICAL DEVICE AND CHEMOTHERAPEUTIC DRUG COMBINATION: LOCALLY ENHANCED CHEMOTHERAPY

CLINIPORATOR EPSO 2, ECT, CE Mark, Class IIa Elettric field amplitude: 1000 V/cm Electric field distribution: omogeneous Pulse number: 8 Pulse lenght: 100 s

STANDARD OPERATING PROCEDURe. S

CLINIPORATOR ELECTRODES PLATE: P-30 -8 B HEXAGONAL NEEDLE: FINGER ELECTRODE: N– 10/20/30 -HG F– 05/10 -LG LINEAR NEEDLE: N-10/20/30 -HG FINGER ELECTRODE: Handles F– 05/10 -OR

Adjustable leght exagonal electrode

Indications ECT is an effective treatment of neoplastic lesions located in the skin or subcutaneous tissue, both primary and metastatic, regardless of the histological type of the neoplasm or previous treatments. It can be used as an adjunct to normal treatment options or as an additional option for patients unresponsive or unfit for normal treatment regimes

Indications melanoma basal cell carcinoma squamous cell carcinoma kaposi sarcoma local recurrences or cutaneous metastases from breast cancer, head and neck cancers

STANDARD OPERATING PROCEDURES: DRUG ADMINISTRATION Intra-tumoral administration: BLM and CDDP Volume ab 2 /6 V < 0. 5 cm 3 BLM 1000 IU/ml 1 ml/cm 3 (> 0, 1 ml) CDDP 2 mg/ml 1 ml (2 mg)/cm 3 0. 5 cm 3 < V < 1 cm 3 V > 1 cm 3 0. 5 ml/cm 3 0, 25 ml/cm 3 0. 5 ml (1 mg)/cm 3 0, 25 ml (0. 5 mg)/cm 3 Intravenous administration: Bleomycin § Standard dose 15. 000 IU/m 2 in bolus; § Electric pulses delivered after 8 minutes of the drug administration to allow optimized diffusion; § Window timing for electric pulses: 30 -40 minutes.

ECT centres in Europe 4 7 12 28 3 5 Country Centres Italy 28 Germany 12 Austria 1 Portugal 1 Spain 3 Sweden 3 Greece 5 Great Britain 7 (6*) Hungary 1 Poland 1 The Netherlands 1 Lithuania 1 ESOPE 4 Research 12 Total 80 * A further 6 UK Trusts have applied for new CLINIPORATOR set up

ECT in North Bristol Trust Total of 70 ECT procedures on 52 patients January 2012 – May 2016 (see bar chart) Most commonly used for melanoma (pie chart), but also successfully used for breast cancer, SCC, BCC (including 2 Gorlin’s cases), Merkel cell, angiosarcoma and T-cell lymphoma

ECT – Southmead experience 52 patients: 30 females, 22 males Age range: 29 -98 yrs Mean age: 73. 7 yrs Median age: 77. 5 yrs

Diagnosis Melanoma BCC (incl. Gorlin's) SCC Breast Ca Angiosarcoma Merkel cell T-cell lymphoma

Annual Breakdown 25 20 15 10 5 0 2012 2013 2014 2015 2016

ECT Pathway - Referral to the SSMDT Consultation with plastic surgeon Lung function test/pre op assessment for GA Oncology referral Day case GA Follow up 6/weeks Re-treat not before 8 -12 weeks

ECT +Lesional Excision Lesional excision % ECT cases Yes 56% No 44%

Thank you