Treatment strategies with electrochemotherapy for limb in-transit melanoma: Real-world outcomes from a European, retrospective, cohort study

Luca G Campana; Francesca Tauceri; Joana Bártolo; Sarah Calabrese; Joy Odili; Giulia Carrara; Victor Farricha; Dario Piazzalunga; Kriszta Bottyán; Kamal Bisarya; Matteo Mascherini; James A Clover; Serena Sestini; Maša Bošnjak; Erika Kis; Fabrizio Fantini; Piero Covarelli; Matteo Brizio; Leela Sayed; Carlo Cabula; Rosanna Careri; Tommaso Fabrizio; Klaus Eisendle; Alastair MacKenzie Ross; Hadrian Schepler; Lorenzo Borgognoni; Gregor Sersa; Sara Valpione

doi:10.1016/j.ejso.2024.108740

Treatment strategies with electrochemotherapy for limb in-transit melanoma: Real-world outcomes from a European, retrospective, cohort study

Eur J Surg Oncol. 2024 Oct 5:108740. doi: 10.1016/j.ejso.2024.108740. Online ahead of print.

Authors

Luca G Campana¹, Francesca Tauceri², Joana Bártolo³, Sarah Calabrese⁴, Joy Odili⁵, Giulia Carrara⁶, Victor Farricha³, Dario Piazzalunga⁶, Kriszta Bottyán⁷, Kamal Bisarya⁸, Matteo Mascherini⁹, James A Clover¹⁰, Serena Sestini¹¹, Maša Bošnjak¹², Erika Kis⁷, Fabrizio Fantini¹³, Piero Covarelli¹⁴, Matteo Brizio¹⁵, Leela Sayed¹⁶, Carlo Cabula¹⁷, Rosanna Careri¹⁸, Tommaso Fabrizio¹⁹, Klaus Eisendle²⁰, Alastair MacKenzie Ross²¹, Hadrian Schepler²², Lorenzo Borgognoni¹¹, Gregor Sersa²³, Sara Valpione²⁴

Affiliations

¹ Department of Surgery, Manchester University NHS Foundation Trust, Manchester, UK; Department of Surgery, Oncology and Gastroenterology, University of Padova, Italy. Electronic address: [email protected].
² General and Oncological Surgery Unit, Morgagni-Pierantoni Hospital, Forli, Italy.
³ Instituto Portugues de Oncologia de Lisboa Francisco Gentil, Lisboa, Portugal.
⁴ Department of Plastic Surgery, ASST Spedali Civili di Brescia, Brescia, Italy.
⁵ Department of Plastic and Reconstructive Surgery, St Georges University Hospitals NHS Foundation Trust, London, UK.
⁶ General and Emergency Surgery Department, ASST Papa Giovanni XXIII, Bergamo, Italy.
⁷ Department of Dermatology and Allergology, University of Szeged, H-6720, Szeged, Hungary.
⁸ Department of Plastic Surgery, Hull Royal Infirmary, Hull, UK.
⁹ Department of Surgery, IRCCS Ospedale Policlinico San Martino, Genoa, Italy.
¹⁰ Department of Plastic Surgery, Cork University Hospital, Cork, Ireland.
¹¹ Plastic and Reconstructive Surgery, Melanoma & Skin Cancer Unit, Santa Maria Annunziata Hospital, Florence, Italy.
¹² Institute of Oncology Ljubljana, Department of Experimental Oncology, Ljubljana, Slovenia.
¹³ Dermatology Unit, ASST Lecco, Alessandro Manzoni Hospital, Lecco, Italy.
¹⁴ Surgical Oncology Section, Department of Medicine and Surgery, University of Perugia, Perugia, Italy.
¹⁵ Dermatologic Clinic, Department of Medical Sciences, University of Turin, Italy.
¹⁶ Plastic Surgery Unit, Salisbury District Hospital, Salisbury, UK.
¹⁷ Chirurgia Senologica Azienda Ospedaliera Brotzu, Cagliari, Italy.
¹⁸ Department of Dermatology and Plastic Surgery, University La Sapienza, Rome, Italy.
¹⁹ Plastic Surgery Unit, Centro di Riferimento Oncologico della Basilicata (IRCCS-CROB), Rionero in Vulture, Italy.
²⁰ Department of Dermatology and Venerology, Central Teaching Hospital Bolzano, Bolzano, Italy.
²¹ Department of Plastic and Reconstructive Surgery, St Thomas' Hospital, London, UK.
²² Department of Dermatology, University Clinic Mainz, Mainz, Germany.
²³ Department of Experimental Oncology, Institute of Oncology Ljubljana, Ljubljana, Slovenia; Faculty of Health Sciences, University of Ljubljana, Ljubljana, Slovenia.
²⁴ Department of Medical Oncology, The Christie NHS Foundation Trust, Manchester, UK; Division of Oncological Sciences, The University of Manchester, Manchester, UK; Cancer Research UK National Biomarker Centre, The University of Manchester, Manchester, UK.

PMID: 39448361
DOI: 10.1016/j.ejso.2024.108740

Abstract

Background: This study analysed treatment strategies with electrochemotherapy (ECT) in melanoma with limb in-transit metastases (ITM).

Methods: We audited AJCC v.8 stage IIIB-IIID patients treated across 22 centres (2006-2020) within the International Network for Sharing Practices of ECT (InspECT).

Results: 452 patients were included, 58 % pre-treated (93 % had lower limb ITM, 44 % had ≤10 metastases [median size 1.5 cm]. Treatment strategies included first-line ECT (n = 145, 32 %), ECT with concurrent locoregional/systemic treatment (n = 163, 36 %), and salvage ECT (n = 144, 32 %). The objective response rate was 63 % (complete response [CR], 24 %), increasing to 74 % (CR, 39 %) following retreatment (median two ECT, range 1-8). CR rate in treatment-naïve and pre-treated patients was 50 % vs 32 % (p < 0.001). Bleomycin de-escalation was associated with lower CR (p = 0.004). Small tumour number and size, hexagonal electrode, retreatment, and post-ECT skin ulceration predicted response in multivariable analysis. At a median follow-up of 61 months, local and locoregional recurrence occurred in 55 % and 81 % of patients. Median local progression-free, new lesions-free, and regional recurrence-free survival were 32.9, 6.9, and 7.7 months. Grade-3 toxicity was 15 %. Concurrent treatment and CR correlated with improved regional control and survival. Concomitant checkpoint inhibition did not impact toxicity or survival outcomes. The median overall survival was 5.7 years.

Conclusions: Among patients with low-burden limb-only ITM, standard-dose bleomycin ECT results in durable local response. Treatment naivety, low tumour volume, hexagonal electrode application, retreatment, and post-ECT ulceration predict response. CR and concurrent treatment correlate with improved regional control and survival outcomes. Combination with checkpoint inhibitors is safe but lacks conclusive support.

Keywords: Checkpoint inhibitors; Electrochemotherapy; In-transit metastases; Locoregional therapies; Melanoma.