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Electrochemotherapy Treatment of Locally Advanced and Metastatic Soft Tissue Sarcomas: Results of a Non-Comparative Phase II Study

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Abstract

Aims

Our aim was to evaluate the activity, toxicity, and feasibility of electrochemotherapy (ECT) in patients with soft-tissue sarcomas (STS).

Methods

A two-stage phase II trial was conducted between October 2006 and March 2012. Patients (N = 34) with locally advanced or metastatic STS, unsuitable for standard oncological treatments and with maximum 3-cm deep tumors, received an intravenous bolus of bleomycin (15,000 IU/m2), followed by tumor electroporation according to the European Standard Operating Procedures of ECT. Outcome measures included local response according to response evaluation criteria in solid tumors (RECIST), toxicity and tumor control. Feasibility measures included the accuracy of electrode placement and the intensity of electric current flowing in tumor tissue.

Results

Median tumor size was 4.0 cm (range 2–12). Objective response, assessed on 71 target lesions, was 92.2 % (complete 32.3, 95 % CI 28–64). A total of 15 patients received up to four cycles due to incomplete response, but re-treatment did not significantly improve outcome (p = 0.205). After a median follow-up of 19.3 months, 2-year local control rate was 72.5 %. Median time to local failure (N = 11 patients) was 5.1 months. Tumor response (p = 0.041) and control (p = 0.047) correlated with histological grading. Relevant toxicity consisted of G3 skin ulceration and soft tissue necrosis (35 and 23 % of patients, respectively), although this was manageable on an outpatient basis. The accuracy of electrode placement was 47.1 %, and the adequacy of electroporative current 85.3 %.

Conclusions

ECT may represent an active and safe treatment to achieve local control in advanced STS patients with symptomatic disease. Future research challenges include the improvement of electrode placement and voltage delivery together with the containment of soft tissue toxicity.

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Acknowledgments

Participating investigators: Angelo Ciccarese, Sandra Cappellato, Connie Celentano, Anaesthesiology Section, Sara Galuppo, Luigi Corti, Radiotherapy Section, Antonella Vecchiato, Sarcoma and Melanoma Unit, cared for patients at the Veneto Oncology Institute; Maria Di Fiore, Stefano Bonarelli, Anaesthesiology Section, Stefano Ferrari, Medical Oncology, Andrea Galuppi, Radiotherapy Section (Sant’Orsola Malpighi Hospital of Bologna), cared for patients at the Orthopaedic Oncology Rizzoli Institute. Paolo Del Fiore retrieved demographic data. Romina Spina administered the quality-of-life questionnaire and managed the study-dedicated database. Francesca Deterlizzi analyzed EQ-5D data. The authors gratefully thank Professor Damian Miklavčič and his research group from Ljubljana University, Slovenia, for the fruitful discussions on mechanism of action of electrochemotherapy and currently investigated technical advancements.

Conflict of interest

Luca G. Campana, Giuseppe Bianchi and Carlo R. Rossi were sponsored by IGEA Company for travel and accommodation at the “Electrochemotherapy 2nd International Users’ Meeting”, Bologna, Italy, March 1–2, 2013. No financial benefit was obtained. The other authors declare no conflict of interest.

Author information

Authors and Affiliations

  1. Sarcoma and Melanoma Unit, Veneto Institute of Oncology (IOV-IRCCS), Via Gattamelata-64, 35128, Padua, Italy

    Luca G. Campana & Carlo R. Rossi

  2. Oncologic, Orthopaedic and Trauma Surgery, Rizzoli Orthopaedic Institute, Bologna, Italy

    Giuseppe Bianchi, Laura Campanacci & Davide Donati

  3. Surgery Branch, Department of Surgery Oncology and Gastroenterology, University of Padova, Padua, Italy

    Simone Mocellin

  4. Medical Oncology School, University of Padova, Padua, Italy

    Sara Valpione

  5. Medical Oncology-I, Veneto Institute of Oncology (IOV-IRCCS), Padua, Italy

    Antonella Brunello

  6. Department of Industrial Engineering, University of Padova, Padua, Italy

    Elisabetta Sieni

Authors
  1. Luca G. Campana
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  2. Giuseppe Bianchi
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  3. Simone Mocellin
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  4. Sara Valpione
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  5. Laura Campanacci
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  6. Antonella Brunello
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  7. Davide Donati
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  8. Elisabetta Sieni
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  9. Carlo R. Rossi
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Corresponding author

Correspondence to Luca G. Campana.

Additional information

Communication of preliminary results

“Electrochemotherapy: 2nd International Users’ Meeting”, Bologna, Italy, 1–2 March 2013 and 7th Conference of Experimental and Translational Oncology, 20–24 April 2013, Portoroz, Slovenia (www.ceto.si).

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268_2013_2321_MOESM3_ESM.tif

eFig. 1 Patient reported health status according to the EuroQoL Group (EQ-5D) after electrochemotherapy. a Percentage of patients with problems in one or more of the five dimensions explored by the EQ-5D descriptive system; b Visual analog scale (EQ-VAS) scores (* p = 0.003) (TIFF 82 kb)

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Campana, L.G., Bianchi, G., Mocellin, S. et al. Electrochemotherapy Treatment of Locally Advanced and Metastatic Soft Tissue Sarcomas: Results of a Non-Comparative Phase II Study. World J Surg 38, 813–822 (2014). https://doi.org/10.1007/s00268-013-2321-1

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