Top

Published in:

Open Access 01-10-2009 | Original Research

Alternating electric fields (TTFields) inhibit metastatic spread of solid tumors to the lungs

Authors: Eilon D. Kirson, Moshe Giladi, Zoya Gurvich, Aviran Itzhaki, Daniel Mordechovich, Rosa S. Schneiderman, Yoram Wasserman, Bernhard Ryffel, Dorit Goldsher, Yoram Palti

Published in: Clinical & Experimental Metastasis | Issue 7/2009

Abstract

Tumor treating fields (TTFields) are low intensity, intermediate frequency, alternating electric fields used to treat cancerous tumors. This novel treatment modality effectively inhibits the growth of solid tumors in vivo and has shown promise in pilot clinical trials in patients with advanced stage solid tumors. TTFields were tested for their potential to inhibit metastatic spread of solid tumors to the lungs in two animal models: (1) Mice injected with malignant melanoma cells (B16F10) into the tail vein, (2) New Zealand White rabbits implanted with VX-2 tumors within the kidney capsule. Mice and rabbits were treated using two-directional TTFields at 100–200 kHz. Animals were either monitored for survival, or sacrificed for pathological and histological analysis of the lungs. The total number of lung surface metastases and the absolute weight of the lungs were both significantly lower in TTFields treated mice then in sham control mice. TTFields treated rabbits survived longer than sham control animals. This extension in survival was found to be due to an inhibition of metastatic spread, seeding or growth in the lungs of TTFields treated rabbits compared to controls. Histologically, extensive peri- and intra-tumoral immune cell infiltration was seen in TTFields treated rabbits only. These results raise the possibility that in addition to their proven inhibitory effect on the growth of solid tumors, TTFields may also have clinical benefit in the prevention of metastatic spread from primary tumors.

Friedel G (2007) Pulmonary metastasectomy: specific surgical considerations and prognostic factors. In: Schil P (ed) Lung metastases and isolated lung perfusion. Nova Science Publishers Inc., New York, pp 45–60

Sternberg DI, Sonett JR (2007) Surgical therapy of lung metastases. Semin Oncol 34(3):186–196. doi:10.1053/j.seminoncol.2007.03.004 CrossRefPubMed

Billingsley KG, Burt ME, Jara E et al (1999) Pulmonary metastases from soft tissue sarcoma: analysis of patterns of diseases and postmetastasis survival. Ann Surg 229(5):602–610. doi:10.1097/00000658-199905000-00002 discussion 10-2CrossRefPubMed

Friedel G, Pastorino U, Buyse M et al (1999) Resection of lung metastases: long-term results and prognostic analysis based on 5,206 cases—the International registry of lung metastases. Zentralbl Chir 124(2):96–103PubMed

Khan JH, McElhinney DB, Rahman SB et al (1998) Pulmonary metastases of endocrine origin: the role of surgery. Chest 114(2):526–534. doi:10.1378/chest.114.2.526 CrossRefPubMed

Zhang S, Zeng Z, Tang Z et al (2008) Prognostic analysis of pulmonary metastases from hepatocellular carcinoma. Hepatol Intl 2(2):237–243CrossRef

Pastorino U, Buyse M, Friedel J et al (1997) Long-term results of lung metastasectomy: prognostic analyses based on 5,206 cases. The International registry of lung metastases. J Thorac Cardiovasc Surg 113(1):37–49. doi:10.1016/S0022-5223(97)70397-0 CrossRef

Sardari N, Colpaert C (2007) Lung metastases: epidemiology, clinical presentation and imaging. In: Schil P (ed) Lung metastases and isolated lung perfusion. Nova Science Publishers Inc., New York, pp 3–25

Rose SC, Thistlethwaite PA, Sewell PE et al (2006) Lung cancer and radiofrequency ablation. J Vasc Interv Radiol 17(6):927–951 quiz 51PubMedCrossRef

10.

Lavrenkov K, Man S, Geffen DB et al (2002) Experience of hormonal therapy with anastrozole for previously treated metastatic breast cancer. Isr Med Assoc J 4(3):176–177PubMed

11.

Suh R, Reckamp K, Zeidler M et al (2005) Radiofrequency ablation in lung cancer: promising results in safety and efficacy. Oncology 19(11, Suppl 4):12–21 Williston ParkPubMed

12.

VanSonnenberg E, Shankar S, Morrison PR et al (2005) Radiofrequency ablation of thoracic lesions: part 2, initial clinical experience—technical and multidisciplinary considerations in 30 patients. AJR Am J Roentgenol 184(2):381–390PubMed

13.

Atzpodien J, Kirchner H, Illiger HJ et al (2001) IL-2 in combination with IFN- alpha and 5-FU versus tamoxifen in metastatic renal cell carcinoma: long-term results of a controlled randomized clinical trial. Br J Cancer 85(8):1130–1136. doi:10.1054/bjoc.2001.2076 CrossRefPubMed

14.

Zitvogel L, Apetoh L, Ghiringhelli F et al (2008) The anticancer immune response: indispensable for therapeutic success? J Clin Invest 118(6):1991–2001. doi:10.1172/JCI35180 CrossRefPubMed

15.

Whiteside TL (2008) The tumor microenvironment and its role in promoting tumor growth. Oncogene 27(45):5904–5912. doi:10.1038/onc.2008.271 CrossRefPubMed

16.

McMillan TJ, Hart IR (1987) Can cancer chemotherapy enhance the malignant behaviour of tumours? Cancer Metastasis Rev 6(4):503–519. doi:10.1007/BF00047465 CrossRefPubMed

17.

Walton B (1979) Effects of anaesthesia and surgery on immune status. Br J Anaesth 51(1):37–43. doi:10.1093/bja/51.1.37 CrossRefPubMed

18.

Kirson ED, Dbaly V, Tovarys F et al (2007) Alternating electric fields arrest cell proliferation in animal tumor models and human brain tumors. Proc Natl Acad Sci USA 104(24):10152–10157. doi:10.1073/pnas.0702916104 CrossRefPubMed

19.

Kirson ED, Gurvich Z, Schneiderman R et al (2004) Disruption of cancer cell replication by alternating electric fields. Cancer Res 64(9):3288–3295. doi:10.1158/0008-5472.CAN-04-0083 CrossRefPubMed

20.

Kirson ED, Schneiderman RS, Dbaly V et al (2009) Chemotherapeutic treatment efficacy and sensitivity are increased by adjuvant alternating electric fields (TTFields). BMC Med Phys 9(1):1. doi:10.1186/1756-6649-9-1 CrossRefPubMed

21.

Nakada SY, Jerde TJ, Warner T et al (2004) Comparison of cryotherapy and nephrectomy in treating implanted VX-2 carcinoma in rabbit kidneys. BJU Int 94(4):632–636. doi:10.1111/j.1464-410X.2004.05015.x CrossRefPubMed

22.

Suresh S (2007) Biomechanics and biophysics of cancer cells. Acta Biomater 3(4):413–438. doi:10.1016/j.actbio.2007.04.002 CrossRefPubMed

23.

Dunn GP, Bruce AT, Ikeda H et al (2002) Cancer immunoediting: from immunosurveillance to tumor escape. Nat Immunol 3(11):991–998. doi:10.1038/ni1102-991 CrossRefPubMed

24.

Hayes AL, Smith C, Foxwell BM et al (1999) CD45-induced tumor necrosis factor alpha production in monocytes is phosphatidylinositol 3-kinase-dependent and nuclear factor-kappaB-independent. J Biol Chem 274(47):33455–33461. doi:10.1074/jbc.274.47.33455 CrossRefPubMed

Title: Alternating electric fields (TTFields) inhibit metastatic spread of solid tumors to the lungs
Authors: Eilon D. Kirson
Moshe Giladi
Zoya Gurvich
Aviran Itzhaki
Daniel Mordechovich
Rosa S. Schneiderman
Yoram Wasserman
Bernhard Ryffel
Dorit Goldsher
Yoram Palti
Publication date: 01-10-2009
Publisher: Springer Netherlands
Published in: Clinical & Experimental Metastasis / Issue 7/2009
Print ISSN: 0262-0898
Electronic ISSN: 1573-7276
DOI: https://doi.org/10.1007/s10585-009-9262-y

Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras

Prof. Fabrice Barlesi

Developed by: Springer Medicine

At a glance: The STEP trials

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 7/2009

Characterization and functional analysis of a slow cycling stem cell-like subpopulation in pancreas adenocarcinoma

Expression and functional analysis of the WAP four disulfide core domain 1 gene in human melanoma

Cancer cell lines release glutamate into the extracellular environment

Activated platelets enhance ovarian cancer cell invasion in a cellular model of metastasis

Expression of GRP and its receptor is associated with improved survival in patients with colon cancer

High expression of Snail mRNA in blood from hepatocellular carcinoma patients with extra-hepatic metastasis

Keynote webinar | Spotlight on antibody–drug conjugates in cancer