Tumor therapy fields

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Tumor therapy fields ( TTFields ) are a recognized form of treatment for one form of malignant brain tumor ( glioblastoma ) and for small-cell lung cancer . Weak electromagnetic alternating fields in the long wave range are directed onto the diseased area of ​​the body via external electrodes. The aim is to inhibit the growth of cancerous tumors.

principle

Tumor therapy fields are alternating electrical fields with an intermediate frequency in the kilohertz range (50–200 kHz) and low intensity (1–3 V / cm). They are administered using electrically isolated transducer arrays (so-called ceramic gel pads). To do this, the head is shaved. The cap-like applicator and a battery pack are worn continuously. There is no direct current flow through the tissue, but rather the oscillation of electrically charged molecules inside the body. With this frequency and intensity, TTFields cannot stimulate nerves or muscles, nor do they lead to significant heating of the tumor or the surrounding tissue.

The mechanism of action should be based on a disruption of cell division. The tumor therapy fields are intended to interrupt the structure of the microtubules of the spindle apparatus during metaphase (polymerisation) and lead to a dielectrophoretic dislocation of intracellular macromolecules and organelles during cytokinesis . These processes should lead to the physical disruption of the cell membrane and programmed cell death (apoptosis).

These mechanisms of action are currently still being researched in animal models. In several papers, the interruption of cancer cell division up to a complete process stop and also the complete destruction of the dividing cancer cells was postulated.

Use in glioblastoma

So far, larger randomized studies have only been carried out on humans for glioblastoma (EF-11 with n = 237 and EF-14 with n = 695). EF-14 showed a 4.9 months longer survival for the additional first-line therapy with TTFields, but not for the relapse therapy. However, the study was not blinded. A committee of experts at the ASCO Congress 2015 then recommended the introduction. The cost is around $ 20,000 / month. A system marketed by the Israeli company Novocure has meanwhile been approved for initial and relapse treatment in several countries, including the USA, EU, Switzerland, Israel and Japan.

Meta-analyzes of the primary studies published to date are not yet available.

Other types of tumors

After TTFields was approved by the FDA for the treatment of recurrent glioblastoma, further studies with other tumor forms are ongoing. Mention should be made here of a phase III study on lung cancer, phase II studies on mesothelioma, ovarian cancer, pancreatic cancer and a phase II and phase III study on brain metastases.

Risks

So far only local irritation of the scalp has been reported as side effect. Tumor therapy fields are currently still contraindicated in pregnant patients or in some patients with concomitant diseases.

The patient's acceptance of the treatment method is comparatively low. The reasons given are long-term hair removal and the necessity to carry the device with you.

Coverage in Germany

On March 20, 2020, the Federal Joint Committee (G-BA) completed the method assessment of tumor therapy fields (TTFields) for patients with a newly diagnosed glioblastoma in an accelerated process. With the decision of the G-BA, TTFields is included as a recognized examination and treatment method in the guideline "Methods of Contract Medical Care" (MVV-RL) and can be prescribed at the expense of the statutory health insurance companies when the guideline comes into force. Private insurance companies generally pay for such innovations in accordance with the respective contractual conditions (see conventional medicine clause ).

literature

  • Martin JB Taphoorn, Linda Dirven, Andrew A. Kanner u. a .: Influence of Treatment With Tumor-Treating Fields on Health-Related Quality of Life of Patients With Newly Diagnosed Glioblastoma. In: JAMA Oncol. , 4 (4), 2018, pp. 495-504, doi: 10.1001 / jamaoncol.2017.5082

Web links

Individual evidence

  1. ↑ AM Davies, U. Weinberg, Y. Palti: Tumor treating fields: a new frontier in cancer therapy. In: Ann NY Acad Sci. 1291, Jul 2013, pp. 86-95. doi: 10.1111 / nyas.12112 .
  2. ^ M. Pless, U. Weinberg: Tumor treating fields: concept, evidence and future. In: Expert Opin Investig Drugs. 20 (8), Aug 2011, pp. 1099-1106. doi: 10.1517 / 13543784.2011.583236 .
  3. ↑ ED Kirson, Z. Gurvich et al. a .: Disruption of cancer cell replication by alternating electric fields. In: Cancer Res. 64 (9), 2004, pp. 3288-3295.
  4. ↑ ED Kirson, Y. Dbaly: Alternating electric fields arrest cell proliferation in animal tumor models and human brain tumors. In: Proc Natl Acad Sci. 104 (24), 2007, pp. 10152-10157.
  5. ↑ Roger Stupp, Eric T. Wong et al. a .: NovoTTF-100A versus physician's choice chemotherapy in recurrent glioblastoma: A randomized phase III trial of a novel treatment modality. In: European Journal of Cancer. 48, 2012, p. 2192, doi: 10.1016 / j.ejca.2012.04.011 .
  6. ↑ Roger Stupp, Sophie Taillibert, Andrew Kanner, William Read, David M. Steinberg: Effect of Tumor-Treating Fields Plus Maintenance Temozolomide vs Maintenance Temozolomide Alone on Survival in Patients With Glioblastoma: A Randomized Clinical Trial . In: JAMA . tape 318 , no. 23 , December 19, 2017, ISSN  0098-7484 , p. 2306-2316 , doi : 10.1001 / jama.2017.18718 ( jamanetwork.com [accessed March 24, 2020]).
  7. ↑ a b A. F. Hottinger, P. Pacheco, R. Stupp: Tumor treating fields: a novel treatment modality and its use in brain tumors. In: Neuro-oncology. Volume 18, number 10, 10 2016, pp. 1338–1349, doi: 10.1093 / neuonc / now182 . PMID 27664860 , PMC 5035531 (free full text) (review).
  8. ^ M. Mehta, P. Wen, R. Nishikawa, D. Reardon, K. Peters: Critical review of the addition of tumor treating fields (TTFields) to the existing standard of care for newly diagnosed glioblastoma patients. In: Critical Reviews in Oncology / Hematology. 111, 2017, p. 60, doi: 10.1016 / j.critrevonc.2017.01.005 .
  9. ↑ Medical Devices: NovoTTF-100A System - P100034. US Food and Drug Administration, update September 6, 2013.
  10. ^ Cancer Trial with Electric Fields. accessed on September 8, 2015.
  11. ↑ R. Stupp, A. Kanner u. a .: A prospective, randomized, open-label, phase III clinical trial of NovoTTF-100A versus best standard of care chemotherapy in patients with recurrent glioblastoma. In: Journal of Clinical Oncology. 2010 ASCO Annual Congress (post-congress edition). Vol 28, No 18_suppl (6/20 Suppl) 2010.
  12. ↑ Robert Bublak, Wolfgang Wick : Tumor therapy fields associated with longer survival in glioblastoma patients . In: In Focus Oncology. 19, 2016, p. 26, doi: 10.1007 / s15015-016-2612-0 .
  13. ↑ Federal Joint Committee: Amendment of the Guideline Methods for Contractual Medical Care (MVV-RL): tumor therapy fields in glioblastoma. Federal Joint Committee, March 20, 2020, accessed on March 24, 2020 (German).