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In contrast to the enormous therapeutic efforts, the results of conventional treatments for highly malignant brain tumors (gliomas) are rather unsatisfactory. The prognosis for this tumor type is poor, its median overall survival (6-14 months) is less than one year (1,2,5,6,8). Most of the cases are inoperable, or only partial removal is possible, and the response to various chemotherapies and / or radiotherapy is unsatisfactory.

H. Sahinbas und Dietrich H. W. Grönemeyer

Introduction: In contrast to the enormous therapeutic efforts, the results of conventional treatments for highly malignant brain tumors (gliomas) are rather unsatisfactory. The prognosis for this tumor type is poor, its median overall survival (6-14 months) is less than one year (1,2,5,6,8). Most of the cases are inoperable, or only partial removal is possible, and the response to various chemotherapies and / or radiotherapy is unsatisfactory. Chemotherapies that are successful for other tumor sites often fail because of the effective blood-brain barrier (9). Electromagnetic field modification of the blood-brain barrier in combination with the direct heat generated by the electromagnetic field (12) is believed to be the most important factor in the success of electrohyperthermia (EHY, regional radio-wave deep hyperthermia).

Goal: The primary objective of this study was to demonstrate the therapeutic tolerability of electrohyperthermia for patients with advanced brain tumors, with a primary goal being to demonstrate that the overall median survival is prolonged.

Patients and Methods: Our retrospective study was performed between February 2000 and April 2007 for patients with inoperable, partially resected or recurrent glioma (WHO grade III and IV) in progression after radiotherapy and / or chemotherapy.

The evaluation included 220 patients , including children: 30% anaplastic astrocytoma (WHO III), 60% glioblastoma multiforme (WHO IV), ~ 10% metastases, median age: 39.7 years. All patients had been extensively pretreated. Electro-hyperthermia was administered as monotherapy or combined therapy (chemotherapy, radiotherapy, and supportive medications, e.g., frankincense, vit., Selenium) for three to three weeks per week for 1 hour (5, 6, 7, 10, 11)..

Results : The historical reference of overall survival from diagnosis is 11.42 months for WHO grade III and IV astrocytomas and gliomas at our institute. This agrees well with the relevant literature (1,2,5,6,8).

Overall survival (12.13) in our institute with electrohyperthermia increases by 38% in diffuse astrocytomas; by146% in anaplastic astrocytoma, by 57% in glioblastoma.

Hyperthermia survival gain:

Diffus = 38 %

Anaplastisch = 146 %

Glioblastom = 57 %


Especially noteworthy:

13 out of 92 patients with glioblastoma still live after 3 years Normally, almost nobody experiences this

Summary and conclusions : Electro-hyperthermia is a suitable adjunct to treatment in advanced inoperable brain tumors or metastases in combination or in exceptional cases as monotherapy (14).

In some cases a complete / partial response and / or a significant delay in tumor growth could be demonstrated. This combination therapy shows an improvement in quality of life and prolonged median overall survival (14). The applied hyperthermia treatment was well tolerated by patients in advanced tumor stages and in pediatric cases.

Literatur:

  1. De Vita et al. 2002; 6th Edition, 2120 table 43.2-15
  2. Walker MD, Alexander E Jr, Hunt WE, et al: Evaluation of BCNU and/or radiotherapy in the treatment of anaplastic gliomas: A cooperativeclinical trial. J Neurosurg 49: 333-343, 1978
  3. Green SB, Byar DP, Walker MD, Pistenmaa DA, et.al. Comparisons of carmustine, procarbazine, and high-dose methylprednisolone asadditions to surgery and radiotherapy for the treatment of malignant glioma. Cancer Treat Rep. 1983 Feb,67(2):121-32.
  4. Eikesdal HP, Bjorkhaug ST, Dahl O. Hyperthermia exhibits anti-vascular activity in the s.c. BT4An rat glioma: lack of interaction with theangiogenesis inhibitor batimastat. Int. J. Hyperthermia. 2002 Mar-Apr, 18(2):141-52.
  5. E.D. Hager et al: The treatment of patients with high-grade glioma with deep RF-Hyperthermia, presented in ASCO 2003, Chicago, USA.Pp.470
  6. E.D. Hager et al: Response and survival of patients with gliomas grade III/IV treated with RF capacitive-coupled hyperthermia, ICHOCongress, St. Louis USA 2004
  7. E.D. Hager et al: Clinical Response and Overall Survival of Patients with Recurrent Gliomas Grade III/IV Treated with RF Deep Hyperthermia– An Update, ICHS Conference, Shenzhen, China, 2004
  8. Ries LAG, Eisner MP, Kosary CL, et al (eds): SEER Cancer Statistics, 1973-1998. Bethesda, MD, National Cancer Institute, 2001.
  9. Friedlander DR, Zagzag D, Shiff B et all. Migration of brain tumor cells on extracellular matrix proteins in vitro correlates with tumor typeand grade and involves alphaV and beta1 integrins. Cancer Res. 1996 Apr 15;56(8):1939-47.
  10. Ebert PS, Salcman M. Differentiation therapy is potentiated by chemotherapy and hyperthermia in human and canine brain tumor cells in vitro.Neurosurgery. 1994 Apr;34(4):657-64.
  11. Pagani E, Falcinelli R, Repponi R et al. Combined effects of temozolamide- hyperthermia on cell growth and O6-Alkylguanine-DNAalkyltransferase (OGAT) activity of human melanoma cell lines. Antican. Resrch 1998, 18 (237):4807-5006.
  12. Dani A. et.al: Presented in Hyperthermia Seminar, October 26-27, 2003, Cologne, Germany
  13. A.Szasz, H.Sahinbas, A.Dani: Electro-hyperthermia for anaplastic astrocytoma and glioblastoma multiforme ICACT 2004, Paris, 9-12.February, 2004
  14. A phase II clinical study on relapsed malignant gliomas treated with electro-hyperthermia. Fiorentini G et alPMID: 17203754

Dr. med. H. Sahinbas

Kontakt: sahinbas@microtherapy.de