Tumor size and effectiveness of electrochemotherapy

Open access


Background. Electrochemotherapy (ECT) is an effective and safe method for local treatment of tumors. However, relatively large variability in effectiveness of ECT has been observed, which likely results from different treatment conditions and tumor characteristics. The aim of this study was to investigate the relationship between tumor size and effectiveness of a single-session ECT.

Materials and methods. A systematic search of various bibliographic databases was performed and nine studies eligible for this study were extracted. Different statistical methods including meta-analysis were applied to analyze the data.

Results. The results of analysis based on data from 1466 tumors of any histotype show significantly lower effectiveness of ECT on tumors with maximal diameter equal to or larger than 3 cm (complete response (CR) of 33.3%, objective response (OR) of 68.2%) in comparison to smaller tumors (CR% of 59.5%, OR% of 85.7%). The results of meta-analysis indicated that ECT performed on tumors smaller than 3 cm statistically significantly increases the probability of CR by 31.0% and OR by 24.9% on average in comparison to larger tumors. The analysis of raw data about the size and response of tumors showed statistically significant decrease in effectiveness of ECT progressively with increasing tumor diameter. The biggest drop in CR% was detected at tumor diameters as small as 2 cm.

Conclusions. The standard operating procedures for ECT should be reexamined and refined for the treatment of large tumors. We propose that future clinical trials should include accurate ECT treatment planning and/or multiple ECT cycles, besides a prolonged observation for tumor response evaluation.

1. Marty M, Sersa G, Garbay JR, Gehl J, Collins CG, Snoj M, et al. Electrochemotherapy - An easy, highly effective and safe treatment of cutaneous and subcutaneous metastases: Results of ESOPE (European Standard Operating Procedures of Electrochemotherapy) study. Eur J Cancer Suppl 2006; 4: 3-13.

2. Sersa G, Miklavcic D, Cemazar M, Rudolf Z, Pucihar G, Snoj M. Electrochemotherapy in treatment of tumours. Eur J Surg Oncol 2008; 34: 232-240.

3. Snoj M, Rudolf Z, Cemazar M, Jancar B, Sersa G. Successful sphincter-saving treatment of anorectal malignant melanoma with electrochemotherapy, local excision and adjuvant brachytherapy. Anticancer Drugs 2005; 16: 345-348.

4. Snoj M, Cemazar M, Srnovrsnik T, Paulin-Kosir SM, Sersa G. Limb sparing treatment of bleeding melanoma recurrence by electrochemotherapy. Tumori 2009; 95: 398-402.

5. Colombo GL, Di Matteo S, Mir LM. Cost-effectiveness analysis of electrochemotherapy with the CliniporatorTM vs other methods for the control and treatment of cutaneous and subcutaneous tumors. Ther Clin Risk Manag 2008; 4: 541-548.

6. Moller MG, Salwa S, Soden DM, O’Sullivan GC. Electrochemotherapy as an adjunct or alternative to other treatments for unresectable or in-transit melanoma. Expert Rev Anticancer Ther 2009; 9: 1611-1630.

7. Testori A, Faries MB, Thompson JF, Pennacchioli E, Deroose JP, van Geel AN, et al. Local and intralesional therapy of in-transit melanoma metastases. JSurg Oncol 2011; 104: 391-396.

8. Mir LM, Gehl J, Sersa G, Collins CG, Garbay JR, Billard V, et al. Standard operating procedures of the electrochemotherapy: Instructions for the use of bleomycin or cisplatin administered either systemically or locally and electric pulses delivered by the CliniporatorTM by means of invasive or noninvasive electrodes. Eur J Cancer Suppl 2006; 4: 14-25.

9. Campana LG, Mocellin S, Basso M, Puccetti O, De Salvo GL, Chiarion-Sileni V, et al. Bleomycin-based electrochemotherapy: clinical outcome from a single institution’s experience with 52 patients. Ann Surg Oncol 2009; 16: 191-199.

10. Curatolo P, Quaglino P, Marenco F, Mancini M, Nardo T, Mortera C, et al. Electrochemotherapy in the treatment of Kaposi sarcoma cutaneous lesions: a two-center prospective phase II trial. Ann Surg Oncol 2012; 19: 192-198.

11. Quaglino P, Mortera C, Osella-Abate S, Barberis M, Illengo M, Rissone M, et al. Electrochemotherapy with intravenous bleomycin in the local treatment of skin melanoma metastases. Ann Surg Oncol 2008; 15: 2215-2222.

12. Liberati A, Altman DG, Tetzlaff J, Mulrow C, Gotzsche PC, Ioannidis JPA, et al. The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate healthcare interventions: explanation and elaboration. BMJ 2009; 339: b2700.

13. Wieseler B, McGauran N. Reporting a systematic review. Chest 2010; 137: 1240-1246.

14. Higgins JPT, Green S. Cochrane handbook for systematic reviews of interventions. UK: Wiley-Blackwell; 2008.

15. World Health Organization. WHO handbook for reporting results of cancertreatment. Switzerland: World Health Organization; 1979.

16. Therasse P, Arbuck SG, Eisenhauer EA, Wanders J, Kaplan RS, Rubinstein L, et al. New guidelines to evaluate the response to treatment in solid tumors. J Natl Cancer Inst 2000; 92: 205-216.

17. Borenstein M, Hedges LV, Higgins JPT, Rothstein HR. Introduction to metaanalysis. UK: Wiley; 2009.

18. Byrne CM, Thompson JF, Johnston H, Hersey P, Quinn MJ, Hughes TM, et al. Treatment of metastatic melanoma using electroporation therapy with bleomycin (electrochemotherapy). Melanoma Res 2005; 15: 45-51.

19. Landstrom FJ, Nilsson COS, Crafoord S, Reizenstein JA, Adamsson GBM, Lofgren LA. Electroporation therapy of skin cancer in the head and neck area. Dermatol Surg 2010; 36: 1245-1250.

20. Larkin JO, Collins CG, Aarons S, Tangney M, Whelan M, O’Reily S, et al. Electrochemotherapy - Aspects of preclinical development and early clinical experience. Ann Surg 2007; 245: 469-479.

21. Matthiessen LW, Chalmers RL, Sainsbury DCG, Veeramani S, Kessell G, Humphreys AC, et al. Management of cutaneous metastases using electrochemotherapy. Acta Oncol 2011; 50: 621-629.

22. Rols MP, Bachaud JM, Giraud P, Chevreau C, Roche H, Teissie J. Electrochemotherapy of cutaneous metastases in malignant melanoma. Melanoma Res 2000; 10: 468-474.

23. Domenge C, Orlowski S, Luboinski B, DeBaere T, Schwaab G, Belehradek J, et al. Antitumor electrochemotherapy - New advances in the clinical protocol. Cancer 1996; 77: 956-963.

24. Miklavcic D, Beravs K, Semrov D, Cemazar M, Demsar F, Sersa G. The importance of electric field distribution for effective in vivo electroporation of tissues. Biophys J 1998; 74: 2152-2158.

25. Miklavcic D, Corovic S, Pucihar G, Pavselj N. Importance of tumour coverage by sufficiently high local electric field for effective electrochemotherapy. EurJ Cancer Suppl 2006; 4: 45-51.

26. Miklavcic D, Towhidi L. Numerical study of the electroporation pulse shape effect on molecular uptake of biological cells. Radiol Oncol 2010; 44: 34-41.

27. Cemazar M, Milacic R, Miklavcic D, Dolzan V, Sersa G. Intratumoral cisplatin administration in electrochemotherapy: antitumor effectiveness, sequence dependence and platinum content. Anticancer Drugs 1998; 9: 525-530.

28. Front D, Israel O, Iosilevsky G, Even-Sapir E, Ben-Haim S, Frenkel A, et al. Administered dose and tumor dose of bleomycin labeled with cobalt-57 in mice and men. J Nucl Med 1990; 31: 1784-1790.

29. Mir LM, Tounekti O, Orlowski S. Bleomycin: Revival of an old drug. GenPharmac 1996; 27: 745-748.

30. Hall SW, Strong JE, Broughton A, Frazier ML, Benjamin RS. Bleomycin clinical pharmacology by radioimmunoassay. Cancer Chemother Pharmacol 1982; 9: 22-25.

31. Alberts DS, Chen HS, Liu R, Himmelstein KJ, Mayersohn M, Perrier D, et al. Bleomycin pharmacokinetics in man. I. Intravenous administration. CancerChemother Pharmacol 1978; 1: 177-181.

32. Sersa G, Jarm T, Kotnik T, Coer A, Podkrajsek M, Sentjurc M, et al. Vascular disrupting action of electroporation and electrochemotherapy with bleomycin in murine sarcoma. Br J Cancer 2008; 98: 388-398.

33. Sersa G, Krzic M, Sentjurc M, Ivanusa T, Beravs K, Kotnik V, et al. Reduced blood flow and oxygenation in SA-1 tumours after electrochemotherapy with cisplatin. Br J Cancer 2002; 87: 1047-1054.

34. Sersa G, Cemazar M, Miklavcic D. Tumor blood flow modifying effects of electrochemotherapy: a potential vascular targeted mechanism. RadiolOncol 2003; 37: 43-48.

35. Jarm T, Cemazar M, Miklavcic D, Sersa G. Antivascular effects of electrochemotherapy: implications in treatment of bleeding metastases. ExpertRev Anticancer Ther 2010; 10: 729-746.

36. Miklavcic D, Snoj M, Zupanic A, Kos B, Cemazar M, Kropivnik M, et al. Towards treatment planning and treatment of deep-seated solid tumors by electrochemotherapy. BioMed Eng OnLine 2010; 9: 10.

37. Edhemovic I, Gadzijev EM, Brecelj E, MIklavcic M, Kos B, Zupanic A, et al. Electrochemotherapy: a new technological approach in treatment of metastases in the liver. Technol Cancer Res Treat 2011; 10: 475-485.

38. Pavliha D, Kos B, Zupanic A, Marcan M, Sersa G, Miklavcic D. Patient-specific treatment planning of electrochemotherapy: Procedure design and possible pitfalls. Bioelectrochemistry 2012; 87: 265-273.

39. Adeyanju OO, Al-Angari HM, Sahakian AV. The optimization of needle electrode number and placement for irreversible electroporation of hepatocellular carcinoma. Radiol Oncol 2012; 46: 126-135.

Radiology and Oncology

The Journal of Association of Radiology and Oncology

Journal Information

IMPACT FACTOR 2017: 1.722
5-year IMPACT FACTOR: 1.729

CiteScore 2017: 1.84

SCImago Journal Rank (SJR) 2017: 0.574
Source Normalized Impact per Paper (SNIP) 2017: 0.814

Cited By


All Time Past Year Past 30 Days
Abstract Views 0 0 0
Full Text Views 129 129 24
PDF Downloads 31 31 10