Retrospective clinical study of adjuvant electro-hyperthermia treatment for advanced brain-gliomas

Summary

Malignant gliomas represent about 70 % of all brain tumors. Despite advances in standard therapy consisting of surgery, radiation therapy and chemotherapy, gliomas remain an essentially fatal disease, with a median survival time of 10 to 12 months and a 2-year survival rate of 8 % to 12 %. Electro-hyperthermia applied either alone or in combination with chemo- and/or radio-therapy is an advanced hyperthermia technique that has been used as adjuvant treatment for patients with malignant glioma. We present the results of a retrospective study of 140 patients with different stages of malignant glioma, which were treated/followed from January 2000 to February 2005. The endpoint was the overall survival and the survival from the 1st electro-hyperthermia treatment. The overall median survival time for patients with mostly advanced malignant glioma who received adjuvant electro-hyperthermia in this study was 20.4 months. The median survival time from the first electro-hyperthermia treatment was 6.6 months. Electro-hyperthermia was safe and well tolerated. The presented results show the feasibility of the treatment and suggest a benefit of the electro-hyperthermia treatment for patients with advanced malignant glioma.

Malignant glioma - hyperthermia - chemotherapy - radiotherapy - survival rates

References

• 01 Begley D J. ABC transporters and the blood-brain barrier. Current pharmaceutical design.  2004;  10 1295-1312
• 02 Borok T L, Winter A, Laing J. et al . Microwave hyperthermia radiosensitized iridium-192 for recurrent brain malignancy.  Med Dosim. 1988;  13 29-36
• 03 Davis D L, Ahlbom A, Hoel D, Percy C. Is brain cancer mortality increasing in industrial countries?.  American Journal of Industrial Medicine. 1991;  19 421-431
• 04 Eikesdal H P, Bjorkhaug S T, Dahl O. Hyperthermia exhibits anti-vascular activity in the s.c. BT4An rat glioma: lack of interaction with the angiogenesis inhibitor batimastat.  Int J Hyperthermia. 2002;  18 141-152
• 05 Fan M, Ascher P W, Schrottner O. et al . Interstitial 1.06 Nd:YAG laser thermotherapy for brain tumors under real-time monitoring of MRI: experimental study and phase I clinical trial.  Journal of Clinical Laser Medicine & Surgery.. 1992;  10 355-361
• 06 Fisher P G, Buffler P A. Malignant gliomas in 2005: where to GO from here?.  JAMA. 2005;  293 615-617
• 07 Friedlander D R, Zagzag D, Shiff B. et al . Migration of brain tumor cells on extracellular matrix proteins in vitro correlates with tumor type and grade and involves alphaV and beta1 integrins.  Cancer Research. 1996;  56 1939-1947
• 08 Greig N H, Ries L G, Yancik R, SRapoport S I. Increasing annual incidence of primary malignant brain tumors in the elderly.  Journal of the National Cancer Institute.. 1990;  82 1621-1624
• 09 Guthkelch A N, Carter L P, Cassady J R. et al . Treatment of malignant brain tumors with focused ultrasound hyperthermia and radiation: results of a phase I trial.  Journal of Neuro-oncology. 1991;  10 271-284
• 10 Hager D, Dziambor H, App E M. et al . The treatment of patients with high-grade malignant gliomas with RF-hyperthermia.  Proc Am Soc Clin Oncol. 22 2003
• 11 Hermisson M, Weller M. Hyperthermia enhanced chemosensitivity of human malignant glioma cells.  Anticancer Research. 2000;  20 1819-1823
• 12 Jendrossek V, Belka C, Bamberg M. Novel chemotherapeutic agents for the treatment of glioblastoma multiforme.  Expert Opinion on Investigational Drugs. 2003;  12 1899-1924
• 13 Kahn T, Harth T, Bettag M. et al . Preliminary experience with the application of gadolinium-DTPA before MR imaging-guided laser-induced interstitial thermotherapy of brain tumors.  J Magn Reson Imaging. 1997;  7 226-229
• 14 Kuratsu J, Ushio Y. Epidemiological study of primary intracranial tumours in elderly people.  Journal of Neurology, Neurosurgery, and Psychiatry. 1997;  63 116-118
• 15 Kurzen H, Schmitt S, Naher H, Mohler T. Inhibition of angiogenesis by non-toxic doses of temozolomide.  Anti-cancer Drugs. 2003;  14 515-522
• 16 Ley-Valle A. [Non invasive intracranial hyperthermia with Electric Capacitive Transference -ECT- Intratumoral and cerebral thermometry results].  Neurocirugia. 2003;  14 41-45
• 17 Moran C J, Marchosky J A, Wippold 2nd F J, DeFord J A, Fearnot N E. Conductive interstitial hyperthermia in the treatment of intracranial metastatic disease.  Journal of Neuro-oncology. 1995;  26 53-63
• 18 Ohgaki H, Kleihues P. Epidemiology and etiology of gliomas.  Acta neuropathologica. 2005;  109 93-108
• 19 Pagani E, Falcinelli S, Pepponi R. et al . Combined effect of temozolomide and hyperthermia on human melanoma cell growth and O6-methylguanine-DNA methyltransferase activity.  International Journal of Oncology. 2007;  30 443-451
• 20 Pontiggia P, Duppone Curto F, Rotella G. et al . Hyperthermia in the treatment of brain metastases from lung cancer. Experience on 17 cases.  Anticancer Research. 1995;  15 597-601
• 21 Sahinbas H, Groenemeyer D H W, Boecher E. et al .Hyperthermia treatment of advanced relapsed glioma and astrocytoma (abstract). 9th ICHO 85 2004
• 22 Sakaguchi Y, Stephens L C, Makino M. et al . Apoptosis in tumors and normal tissues induced by whole body hyperthermia in rats.  Cancer Research. 1995;  55 5459-5464
• 23 Selker R G, Eddy M S, Deutsch M, Arena V C, Burger P. On the development of an interstitial radiation protocol for a multicenter consortium. Experience with permanent low-dose rate and temporary high-dose rate 125I implants in failed and newly diagnosed glioblastoma patients: quality assurance methodology and a possible future adjuvant for therapeutic enhancement.  Journal of Neuro-oncology. 1995;  26 141-155
• 24 Sharma H S. Hyperthermia induced brain oedema: current status and future perspectives.  The Indian Journal of Medical Research. 2006;  123 629-652
• 25 Sneed P K, Stauffer P R, McDermott M W. et al . Survival benefit of hyperthermia in a prospective randomized trial of brachytherapy boost +/- hyperthermia for glioblastoma multiforme.  International Journal of Radiation Oncology, Biology, Physics. 1998;  40 287-295
• 26 Stupp R, Mason W P, Bent M J van den. et al . Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma.  The New England Journal of Medicine. 2005;  352 987-996
• 27 Sumiyoshi K, Strebel F R, Rowe R W, Bull J M. The effect of whole-body hyperthermia combined with ‚metronomic’ chemotherapy on rat mammary adenocarcinoma metastases.  Int J Hyperthermia. 2003;  19 103-118
• 28 Surveillance, Epidemiology, and End Results (SEER). National Cancer Institute April/2000 http://www.seer.cancer.gov
• 29 Tanaka R, Kim C H, Yamada N, Saito Y. Radiofrequency hyperthermia for malignant brain tumors: preliminary results of clinical trials.  Neurosurgery. 1987;  21 478-483

Correspondence to