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      Dosimetric impact of tumor treating field (TTField) transducer arrays onto treatment plans for glioblastomas – a planning study

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          Abstract

          Background

          Tumor-Treating Fields (TTFields) are a novel treatment strategy for glioblastoma (GBM) that is approved for the use concomitantly to adjuvant chemotherapy. Preclinical data suggest a synergistic interaction of TTFields and radiotherapy (RT). However, the dosimetric uncertainties caused by the highly dense arrays have led to caution of applying the TTF setup during RT.

          Methods

          In a RW3 slab phantom we compared the MV- and kV-CT based planned dose with the measured dose. VMAT-plans were optimized on MV-CTs of an Alderson head phantom without TTF arrays and then re-calculated on the same phantom equipped with TTF arrays. Dose at organs at risk (OAR) and target volumes (PTVs) were compared.

          Results

          Measurements at a depth of 2, 3 and 4 cm of a RW 3 slab phantom show an attenuation due to TTField arrays of 3.4, 3.7 and 2.7% respectively. This was in-line with calculated attenuations based on MV-CT (1.2, 2.5 and 2.5%) but not with the attenuation expected from kV-CT based calculations (7.1, 8.2 and 8.6%). Consecutive MV-CT based VMAT planning and re-calculation reveals, that the conformity and homogeneity are not affected by the presence of TTField arrays. The dose at organs at risk (OAR) can show increases or decreases by < 0.5 Gy, which should be considered especially in cases next to the scull base.

          Conclusion

          MV-CT based dose calculation results in reliable dose distributions also in the presence of TTField arrays. There is a small but clinically not relevant interaction between the TTField arrays and VMAT dose application. Thus, daily replacement of TTField arrays is not necessary in regard to deeply located OARs. RT is feasible, when a VMAT treatment plan is optimized to an array free planning CT. As the biologic effect of a concomitant treatment especially on OARs is currently unknown, a concomitant treatment should be performed only within clinical trials.

          Electronic supplementary material

          The online version of this article (10.1186/s13014-018-0976-3) contains supplementary material, which is available to authorized users.

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          Radiation plus Procarbazine, CCNU, and Vincristine in Low-Grade Glioma.

          Jan C. Buckner, Edward G. Shaw, Stephanie L. Pugh … (2016)
          Grade 2 gliomas occur most commonly in young adults and cause progressive neurologic deterioration and premature death. Early results of this trial showed that treatment with procarbazine, lomustine (also called CCNU), and vincristine after radiation therapy at the time of initial diagnosis resulted in longer progression-free survival, but not overall survival, than radiation therapy alone. We now report the long-term results.
          Article 0 comments Cited 300 times – based on 0 reviews     Review now
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            NovoTTF-100A versus physician's choice chemotherapy in recurrent glioblastoma: a randomised phase III trial of a novel treatment modality.

            Roger Stupp, Eric T. Wong, Andrew Kanner … (2012)
            NovoTTF-100A is a portable device delivering low-intensity, intermediate frequency electric fields via non-invasive, transducer arrays. Tumour Treatment Fields (TTF), a completely new therapeutic modality in cancer treatment, physically interfere with cell division. Phase III trial of chemotherapy-free treatment of NovoTTF (20-24h/day) versus active chemotherapy in the treatment of patients with recurrent glioblastoma. Primary end-point was improvement of overall survival. Patients (median age 54 years (range 23-80), Karnofsky performance status 80% (range 50-100) were randomised to TTF alone (n=120) or active chemotherapy control (n=117). Number of prior treatments was two (range 1-6). Median survival was 6.6 versus 6.0 months (hazard ratio 0.86 [95% CI 0.66-1.12]; p=0.27), 1-year survival rate was 20% and 20%, progression-free survival rate at 6 months was 21.4% and 15.1% (p=0.13), respectively in TTF and active control patients. Responses were more common in the TTF arm (14% versus 9.6%, p=0.19). The TTF-related adverse events were mild (14%) to moderate (2%) skin rash beneath the transducer arrays. Severe adverse events occurred in 6% and 16% (p=0.022) of patients treated with TTF and chemotherapy, respectively. Quality of life analyses favoured TTF therapy in most domains. This is the first controlled trial evaluating an entirely novel cancer treatment modality delivering electric fields rather than chemotherapy. No improvement in overall survival was demonstrated, however efficacy and activity with this chemotherapy-free treatment device appears comparable to chemotherapy regimens that are commonly used for recurrent glioblastoma. Toxicity and quality of life clearly favoured TTF. Copyright © 2012 Elsevier Ltd. All rights reserved.
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              Disruption of cancer cell replication by alternating electric fields.

              Eilon Kirson, Zoya Gurvich, Rosa Sara Schneiderman … (2004)
              Low-intensity, intermediate-frequency (100-300 kHz), alternating electric fields, delivered by means of insulated electrodes, were found to have a profound inhibitory effect on the growth rate of a variety of human and rodent tumor cell lines (Patricia C, U-118, U-87, H-1299, MDA231, PC3, B16F1, F-98, C-6, RG2, and CT-26) and malignant tumors in animals. This effect, shown to be nonthermal, selectively affects dividing cells while quiescent cells are left intact. These fields act in two modes: arrest of cell proliferation and destruction of cells while undergoing division. Both effects are demonstrated when such fields are applied for 24 h to cells undergoing mitosis that is oriented roughly along the field direction. The first mode of action is manifested by interference with the proper formation of the mitotic spindle, whereas the second results in rapid disintegration of the dividing cells. Both effects, which are frequency dependent, are consistent with the computed directional forces exerted by these specific fields on charges and dipoles within the dividing cells. In vivo treatment of tumors in C57BL/6 and BALB/c mice (B16F1 and CT-26 syngeneic tumor models, respectively), resulted in significant slowing of tumor growth and extensive destruction of tumor cells within 3-6 days. These findings demonstrate the potential applicability of the described electric fields as a novel therapeutic modality for malignant tumors.
              Article 0 comments Cited 238 times – based on 0 reviews     Review now
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                Author and article information

                Contributors
                Christoph Straube:
                ORCID: http://orcid.org/0000-0002-7175-0859
                +49-89-4140-4501 , Christoph.Straube@tum.de
                Markus Oechsner: markus.oechsner@mri.tum.de
                Severin Kampfer: severin.kampfer@mri.tum.de
                Sophia Scharl: sophiascharl@yahoo.de
                Friederike Schmidt-Graf: f.schmidt-graf@tum.de
                Jan J. Wilkens: wilkens@tum.de
                Stephanie E. Combs: stephanie.combs@tum.de
                Journal
                Journal ID (nlm-ta): Radiat Oncol
                Journal ID (iso-abbrev): Radiat Oncol
                Title: Radiation Oncology (London, England)
                Publisher: BioMed Central (London )
                ISSN (Electronic): 1748-717X
                Publication date (Electronic): 23 February 2018
                Publication date PMC-release: 23 February 2018
                Publication date Collection: 2018
                Volume: 13
                Electronic Location Identifier: 31
                Affiliations
                [1 ]ISNI 0000000123222966, GRID grid.6936.a, Department of Radiation Oncology, Klinikum rechts der Isar, , Technical University of Munich (TUM), ; 81675 Munich, Germany
                [2 ]Deutsches Konsortium für Translationale Krebsforschung (DKTK), Partner Site Munich, Munich, Germany
                [3 ]ISNI 0000000123222966, GRID grid.6936.a, Department of Neurology, Klinikum rechts der Isar, , Technical University of Munich (TUM), ; Munich, Germany
                [4 ]ISNI 0000 0004 0483 2525, GRID grid.4567.0, Department of Radiation Sciences (DRS), , Institute for Innovative Radiotherapy (iRT), Helmholtz Zentrum München, ; Munich, Germany
                Author information
                http://orcid.org/0000-0002-7175-0859
                Article
                Publisher ID: 976
                DOI: 10.1186/s13014-018-0976-3
                PMC ID: 5824562
                PubMed ID: 29471879
                SO-VID: 8a3a5311-c69f-4fb1-b56d-f546b273257c
                Copyright © © The Author(s). 2018
                License:

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                Date received : 19 November 2017
                Date accepted : 15 February 2018
                Categories
                Subject: Research
                Custom metadata
                issue-copyright-statement © The Author(s) 2018

                ScienceOpen disciplines: Oncology & Radiotherapy
                Data availability:
                ScienceOpen disciplines: Oncology & Radiotherapy

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