title: Treatment efficacy with electrochemotherapy: A multi-institutional prospective observational study on 376 patients with superficial tumors.
abstract: BACKGROUND
  Cutaneous metastases represent a therapeutic challenge. An increasing body of experience suggests that electrochemotherapy (ECT) provides effective tumor control, although its evidence basis should be strengthened.
  
  
  METHODS
  This prospective, multicenter, observational study enrolled patients with superficial metastases, who underwent ECT at 10 centers between 2008 and 2013. Outcomes included adherence to European Standard Operating Procedures of ECT (ESOPE), tumor response, local progression-free survival (LPFS), toxicity and patient-reported outcomes (PROs, EORTC QLQ-C30 plus an 8-item questionnaire).
  
  
  RESULTS
  We enrolled 376 eligible patients. Tumor histotype distribution was as follows: melanoma, 56%; squamous cell carcinoma, 11%; Kaposi sarcoma, 11%; breast carcinoma, 8%; basal cell carcinoma, 6%; soft tissue sarcomas, 3%; others, 5%. We registered 1304 target tumors (median size 1 cm). Treatment adhered to ESOPE in 88% of patients as to the route of drug administration, and in 70% as to electrode application. The procedure was mainly performed under sedation (64.6%) and by using intravenous chemotherapy (93.4%). Tumor response rate at 60 days was 88% (complete, 50%). Small tumor size predicted complete response achievement (OR 2.24, p = 0.003), higher LPFS (HR 0.68, p = 0.004) and improved PROs (Global Health Status, p < 0.001; wound bleeding, p < 0.001; healing, p = 0.002; and aesthetics, p < 0.001). Skin toxicity (grade ≥3, 7.8%) was lower in patients with tumors <2 cm (p≤0.001). One-year LPFS was 73.7% (95%CI 68.4-78.3).
  
  
  CONCLUSIONS
  ECT represents a valuable skin-directed therapy across a range of malignancies. The most frequently applied treatment modality is intravenous chemotherapy under sedation. Small tumor size predicts durable tumor control, fewer side-effects and better PROs.
authors.affiliation: Surgical Oncology Unit, Veneto Institute of Oncology IOV-IRCCS, Padova, Italy; Department of Surgery, Oncology and Gastroenterology, University of Padova, Italy. Electronic address: luca.campana@ioveneto.it.
authors.forename: L G
authors.initials: LG
authors.lastname: Campana
authors.affiliation: European Institute of Oncology (IEO), Milano, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Testori
authors.affiliation: Department of Dermatology and Plastic Surgery, University of Rome ''La Sapienza'', Roma, Italy.
authors.forename: P
authors.initials: P
authors.lastname: Curatolo
authors.affiliation: Department of Biomedical Sciences and Human Oncology, University of Torino, Torino, Italy.
authors.forename: P
authors.initials: P
authors.lastname: Quaglino
authors.affiliation: Surgical Oncology Unit, Veneto Institute of Oncology IOV-IRCCS, Padova, Italy; Department of Surgery, Oncology and Gastroenterology, University of Padova, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Mocellin
authors.affiliation: Department of Surgery and Advanced Cancer Therapies, Morgagni-Pierantoni Hospital, Forlì, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Framarini
authors.affiliation: Plastic Surgery Unit, Tuscan Tumor Institute (ITT), Santa Maria Annunziata Hospital, Firenze, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Borgognoni
authors.affiliation: National Cancer Institute, Fondazione Pascale, Naples, Italy.
authors.forename: P A
authors.initials: PA
authors.lastname: Ascierto
authors.affiliation: National Cancer Institute, Fondazione Pascale, Naples, Italy.
authors.forename: N
authors.initials: N
authors.lastname: Mozzillo
authors.affiliation: Medical Oncology Unit, Giovanni Paolo II Cancer Institute, Bari, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Guida
authors.affiliation: Plastic Surgery Unit, San Gallicano Dermatology Institute, Roma, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Bucher
authors.affiliation: Department of Dermatology and Plastic Surgery, University of Rome ''La Sapienza'', Roma, Italy.
authors.forename: R
authors.initials: R
authors.lastname: Rotunno
authors.affiliation: Department of Biomedical Sciences and Human Oncology, University of Torino, Torino, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Marenco
authors.affiliation: Clinical Trials and Biostatistics Unit, Veneto Institute of Oncology IOV-IRCCS, Padova, Italy.
authors.forename: G L
authors.initials: GL
authors.lastname: De Salvo
authors.affiliation: Clinical Trials and Biostatistics Unit, Veneto Institute of Oncology IOV-IRCCS, Padova, Italy.
authors.forename: A
authors.initials: A
authors.lastname: De Paoli
authors.affiliation: Surgical Oncology Unit, Veneto Institute of Oncology IOV-IRCCS, Padova, Italy; Department of Surgery, Oncology and Gastroenterology, University of Padova, Italy.
authors.forename: C R
authors.initials: CR
authors.lastname: Rossi
authors.affiliation: Plastic Surgery Unit, San Gallicano Dermatology Institute, Roma, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Bonadies
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001761:Bleomycin / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000473:pathology; D002277:Carcinoma / Q000556:secondary / Q000628:therapy*; D002280:Basal Cell Carcinoma / Q000556:secondary / Q000628:therapy; D002294:Carcinoma, Squamous Cell / Q000556:secondary / Q000628:therapy; D002945:Cisplatin / Q000627:therapeutic use; D053672:Electrochemotherapy / Q000379:methods*; D005260:Female; D006801:Humans; D015552:Injections, Intralesional; D053208:Kaplan-Meier Estimate; D008297:Male; D008545:Melanoma / Q000556:secondary / Q000628:therapy*; D008875:Middle Aged; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012509:Sarcoma / Q000556:secondary / Q000628:therapy*; D012514:Sarcoma, Kaposi / Q000556:secondary / Q000628:therapy*; D012878:Skin Neoplasms / Q000473:pathology / Q000556:secondary / Q000628:therapy*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D001761:Bleomycin; D002945:Cisplatin
keywords: Basal cell carcinoma; Breast cancer; Cutaneous metastases; Electrochemotherapy; Melanoma; Squamous cell carcinoma