期刊论文详细信息
World Journal of Surgical Oncology
The effect of field strength on glioblastoma multiforme response in patients treated with the NovoTTF™-100A system
Steven A Toms1  Michel Lacroix2  Hueizhi Wu1  Thomas Gergel1  Scott G Turner1 
[1] Geisinger Medical Center, 17822 Danville, PA, USA;Geisinger Wyoming Valley, 18702 Wilkes-Barre, PA, USA
关键词: NovoTTF-100A System;    NovoTTF therapy;    cytotoxic;    tumor treating fields;    glioblastoma;   
Others  :  811377
DOI  :  10.1186/1477-7819-12-162
 received in 2014-02-28, accepted in 2014-05-11,  发布年份 2014
PDF
【 摘 要 】

The NovoTTF™-100A system is a portable device that delivers intermediate frequency alternating electric fields (TTFields, tumor treating fields) through transducer arrays arranged on the scalp. An ongoing trial is assessing its efficacy for newly diagnosed glioblastoma multiforme (GBM) and it has been FDA-approved for recurrent GBM.

The fields are believed to interfere with formation of the mitotic spindle as well as to affect polar molecules at telophase, thus preventing cell division. The position of the four arrays is unique to each patient and optimized based on the patient’s imaging. We present three patients with GBM in whom the fields were adjusted at recurrence and the effects of each adjustment. We believe there may be a higher risk of treatment failure on the edges of the field where the field strength may be lower.

The first patient underwent subtotal resection, radiotherapy with temozolomide (TMZ), and then began NovoTTF Therapy with metronomic TMZ. She had good control for nine months; however, new bifrontal lesions developed, and her fields were adjusted with a subsequent radiographic response. Over the next five months, her tumor burden increased and death was preceded by a right insular recurrence.

A second patient underwent two resections followed by radiotherapy/TMZ and NovoTTF Therapy/TMZ. Six months later, two new distal lesions were noted, and he underwent further resection with adjustment of his fields. He remained stable over the subsequent year on NovoTTF Therapy and bevacizumab.

A third patient on NovoTTF Therapy/TMZ remained stable for two years but developed a small, slow growing enhancing lesion, which was resected, and his fields were adjusted accordingly. Interestingly, the pathology showed giant cell GBM with multiple syncitial-type cells.

Based on these observations, we believe that field strength may play a role in ‘out of field’ recurrences and that either the presence of a certain field strength may select for cells that are of a different size or that tumor cells may change size to avoid the effects of the TTFields.

【 授权许可】

   
2014 Turner et al.; licensee BioMed Central Ltd.

【 预 览 】
附件列表
Files Size Format View
20140709063519919.pdf 1386KB PDF download
Figure 4. 130KB Image download
Figure 3. 111KB Image download
Figure 2. 116KB Image download
Figure 1. 66KB Image download
【 图 表 】

Figure 1.

Figure 2.

Figure 3.

Figure 4.

【 参考文献 】
  • [1]Dolecek TA, Propp JM, Stroup NE, Kruchko C: CBTRUS statistical report: primary brain and central nervous system tumors diagnosed in the United States in 2005–2009. Neuro-Oncol 2012, 14(Suppl 5):v1-v49.
  • [2]Stupp R, Mason WP, van den Bent MJ, Weller M, Fisher B, Taphoorn MJB, Belanger K, Brandes AA, Marosi C, Bogdahn U, Curschmann J, Janzer RC, Ludwin SK, Gorlia T, Allgeier A, Lacombe D, Cairncross JG, Eisenhauer E, Mirimanoff RO: Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med 2005, 352:987-996.
  • [3]Cohen MH, Shen YL, Keegan P, Pazdur R: FDA drug approval summary: bevacizumab (Avastin) as treatment of recurrent glioblastoma multiforme. Oncologist 2009, 14:1131-1138.
  • [4]Stupp R, Wong ET, Kanner AA, Steinberg D, Engelhard H, Heidecke V, Kirson ED, Taillibert S, Liebermann F, Dbalý V, Ram Z, Villano JL, Rainov N, Weinberg U, Schiff D, Kunschner L, Raizer J, Honnorat J, Sloan A, Malkin M, Landolfi JC, Payer F, Mehdorn M, Weil RJ, Pannullo SC, Westphal M, Smrcka M, Chin L, Kostron H, Hofer S, et al.: NovoTTF-100A versus physician’s choice chemotherapy in recurrent glioblastoma: a randomised phase III trial of a novel treatment modality. Eur J Cancer 2012, 48:2192-2202.
  • [5]Chou CK: Radiofrequency hyperthermia in Cancer Therapy. In The Biomedical Engineering Handbook. Edited by Bronzino JD. Boca Raton, FL: CRC Press, Inc; 1995:1425-1430.
  • [6]Zimmermann U, Vienken J, Pilwat G: Rotation of cells in an alternating electric field: the occurrence of a resonance frequency. Z Naturforsch C 1981, 36:173-177.
  • [7]Takashima S, Schwan HP: Alignment of microscopic particles in electric fields and its biological implications. Biophys J 1985, 47:513-518.
  • [8]Kirson ED, Gurvich Z, Schneiderman R, Dekel E, Itzhaki A, Wasserman Y, Schatzberger R, Palti Y: Disruption of cancer cell replication by alternating electric fields. Cancer Res 2004, 64:3288-3295.
  • [9]Kirson ED, Dbalý V, Tovarys F, Vymazal J, Soustiel JF, Itzhaki A, Mordechovich D, Steinberg-Shapira S, Gurvich Z, Schneiderman R, Wasserman Y, Salzberg M, Ryffel B, Goldsher D, Dekel E, Palti Y: Alternating electric fields arrest cell proliferation in animal tumor models and human brain tumors. Proc Natl Acad Sci U S A 2007, 104:10152-10157.
  • [10]Kumar R, Reddy SJ, Wani AA, Pal L: Primary spinal primitive neuroectodermal tumor: case series and review of the literature. Pediatr Neurosurg 2007, 43:1-6.
  • [11]Kirson ED, Schneiderman RS, Dbalý V, Tovarys F, Vymazal J, Itzhaki A, Mordechovich D, Gurvich Z, Shmueli E, Goldsher D, Wasserman Y, Palti Y: Chemotherapeutic treatment efficacy and sensitivity are increased by adjuvant alternating electric fields (TTFields). BMC Med Phys 2009, 9:1.
  • [12]Brandes AA, Tosoni A, Franceschi E, Sotti G, Frezza G, Amistà P, Morandi L, Spagnolli F, Ermani M: Recurrence pattern after temozolomide concomitant with and adjuvant to radiotherapy in newly diagnosed patients with glioblastoma: correlation With MGMT promoter methylation status. J Clin Oncol 2009, 27:1275-1279.
  • [13]Lucio-Eterovic AK, Piao Y, de Groot JF: Mediators of glioblastoma resistance and invasion during antivascular endothelial growth factor therapy. Clin Cancer Res 2009, 15:4589-4599.
  • [14]Narayana A, Kunnakkat SD, Medabalmi P, Golfinos J, Parker E, Knopp E, Zagzag D, Eagan P, Gruber D, Gruber ML: Change in pattern of relapse after antiangiogenic therapy in high-grade glioma. Int J Radiat Oncol Biol Phys 2012, 82:77-82.
  • [15]Zuniga RM, Torcuator R, Jain R, Anderson J, Doyle T, Ellika S, Schultz L, Mikkelsen T: Efficacy, safety and patterns of response and recurrence in patients with recurrent high-grade gliomas treated with bevacizumab plus irinotecan. J Neurooncol 2009, 91:329-336.
  • [16]Kaur B, Khwaja FW, Severson EA, Matheny SL, Brat DJ, Van Meir EG: Hypoxia and the hypoxia-inducible-factor pathway in glioma growth and angiogenesis. Neuro Oncol 2005, 7:134-153.
  文献评价指标  
  下载次数:12次 浏览次数:6次