Combination radiofrequency hyperthermia and chemotherapy (BCNU) for brain malignancy

Abstract

Patients with high-grade primary and metastatic brain malignancies have a median survival time of 3-8 months, regardless of therapy. Because MagnetrodeTM hyperthermia provides safe, deep internal heating without normal-tissue injury, we studied its effects first on the brain and surrounding tissues of rabbits. The normal rabbit brain (n = 26) could be heated to potentially tumoricidal temperatures (42-43 degrees C) without apparent histopathologic or clinical damage to the brain, skull, external eye, subcutaneous tissue or skin. Intracranial pressure did not rise significantly. Using transplanted VX-2 carcinoma, we showed both the safety and potential efficacy of thermochemotherapy (IV BCNU: 14 mg/kg) in the presence of a solid brain tumor. The average maximum brain temperature achieved was 43.06 degrees C. Mean survival from the time of tumor implantation in the treated group (n = 16) was 18.56 days, compared to 9.3 days for untreated controls (n = 30) (p less than .0001). Two patients have been treated with localized brain hyperthermia combined with intravenous BCNU (80 mg/m2) for a total of eight treatments. Maximum normal brain temperature achieved was 40.0 degrees C in Patient #1 and 41.5 degrees C in Patient #2. A tumor temperature of 42.9 degrees C was achieved in Patient #2. Intracranial pressure remained within the upper limits of normal. Swan-Ganz monitoring in Patient #1 revealed a stable cardiac index and mean pulmonary artery pressure with mild fluctuations in the CVP, PAD, and PCW. No increase in chemotherapy toxicity was observed and no normal tissue injury occurred in either patient. We conclude that non-invasive localized radiofrequency hyperthermia to the brain is feasible and can be performed safely in the presence of a solid brain tumor.

Interstitial hyperthermia of malignant brain tumors by implant heating system: Clinical experience

“…In 1983, Britt et al [19] suggested the feasibility of ultrasonic hyperthermia for treating of malignant brain tumors. Tanaka et al [7] and Silberman et al [5] nearly at the same time, developed a method for local heating of brain tumor using radiofrequency waves of 13.56 MHz. However, the temperatures achieved in the tumor and brain were unpredictable, and bilateral bone flaps must be removed for the wave to penetrate into brain tissue.…”

“…Two methods are currently used to induce hyperthermia of brain tumor: 1) Capacitive heating using RF wave with a frequency of 13.57MHz [5,7]. Because of the attenuation of energy by bone, portions of skull must be removed bilaterally.…”

“…Over the past 15 years there have been many clinical reports on hyperthermia used for treating brain tumors and inducing necrosis [1][2][3][4][5][6][7]. However, no satisfactory method for heating and thus destroying the tumor has been developed.…”

PET in clinical oncology

“…10 was also entered in a radiofrequency hyperthermia treatment program [99,100]. Using implanted probes, it is possible to reach tumoricidal temperatures of 42 ° C to 43 ° C in tumors without damage to adjacent struc- Fig.…”

Effects of Moderate Hyperthermia on the Rabbit Sarcoma Model.

“…Moderate hyperthermia is a potential adjuvant treatment for conventional chemoradiation therapy. Various methods of moderate hyperthermia have been described, including dielectric warming with microwaves 4,15) or radiowaves 11,16) and magnetic induction implant heating. 10) The theory is based on inhibition of ribonucleic acid and/or deoxyribonucleic acid synthesis in proliferating cells in the S and early G 2 phases.…”