Hyperthermia for the Treatment of Brain Tumors

  • Roy C. Page
  • Gregory F. Ricca
  • F. Curtis DohanJr.
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 267)


Brain cancer therapy often produces disappointing results even though there have been great strides in the treatment of cancer in general. Of the primary brain tumors, glioblastoma multiforme is by far the most common (32) and unfortunately, the most rapidly fatal (30, 31). Following surgical resection, without any other therapy, median survival of patients with glioblastoma multiforme is approximately 20 weeks. The addition of postoperative radiation extends median survival to approximately 39 weeks, and when combining surgery, radiation therapy and chemotherapy the median survival can be extended to approximately 55 to 60 weeks (31, 32, 33, 52). When compared to the most common solid malignancies of other parts of the body, glioblastoma multiforme has the most rapidly fatal course (30, 31). Many malignant gliomas are surgically accessible and ‘gross total removal’ is not uncommonly obtained, however, since tumor cells spread along fiber tracts and can be found far from the center of the tumor, malignant cells are usually left behind and recurrences are the norm (5). Glioblastoma multiforme has a biologically heterogeneous population of cells and in order for therapy to be completely effective and achieve total cell kill it must be directed at each of the various cell types (34, 35). Radiation therapy and chemotherapy in addition to surgery are unable to obtain total cell kill though they seem to slow the growth of these aggressive tumors. In 1989, in the United States, it is estimated that there will be approximately 15,000 new cases of brain malignancies with approximately 11,000 deaths (2).


Brain Tumor Malignant Glioma Glioblastoma Multiforme Malignant Brain Tumor Canine Brain 
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  1. 1.
    Allen, I. V. Cerebral changes in experimental heatstroke. Ir. J. Med. Sc. 6: 517–527; 1964.Google Scholar
  2. 2.
    American Cancer Society, Cancer Facts and Fig ures - 1989; monograph No. 5008-LE; 1989.Google Scholar
  3. 3.
    American Cancer Society, Facts on Cancer of the Brain; monograph No. 2648LE; 1988.Google Scholar
  4. 4.
    Britt, R. H.; Lyons, B. E.; Pounds, D. W.; Prionas, S. D. Feasibility of ultrasound hyperthermia in the treatment of malignant brain tumors. Med. Instrum. 17 (2): 172–177; 1983.PubMedGoogle Scholar
  5. 5.
    Burger, P. C.: Malignant astrocytic neoplasms: Classification, pathologic anatomy, and response to treatment. Seminars in Oncology 13: 18–26, 1988.Google Scholar
  6. 6.
    Crile, G. Heat as an adjunct to the treatment of cancer. Cleve. Clin. Q. 28: 7589; 1961.Google Scholar
  7. 7.
    Da Silva, V. F.; Raaphorst, G. P.; Goyal R.; Feeley, M. Drug cytotoxicity at elevated temperature. In vitro study on the U-87MG glioma cell line. J. Neurosurg. 67:885–8; 1987.Google Scholar
  8. 8.
    Dewey, W. C.; Holahn, E. V. Hyperthermia–Basic biology. Prog. Exp. Tumor Res. 28: 198–219; 1984.PubMedGoogle Scholar
  9. 9.
    Dunlop, P. R. C.; Howard, G. C. W. Has hyperthermia a place in cancer treatment? Clin. Radiol. 40: 76–82; 1989.Google Scholar
  10. 10.
    Gelber, R. D.; Larson, M.; Borgelt, B. B.; Kramer, S..: Equivalence of Radiation schedules for the palliative treatment of brain metastases in patients with favorable prognosis. Cancer 48: 1749–1753, 1981.PubMedCrossRefGoogle Scholar
  11. 11.
    Hahn, G. M. Potential for therapy of drugs and hyperthermia. Cancer Res. 39: 2264–2268; 1979.PubMedGoogle Scholar
  12. 12.
    Hahn, G. M.; Li, G. C. Interactions of hyperthermia and durgs. Treatments and probes. NCI. Monogr. 61: 317–323; 1982.Google Scholar
  13. 13.
    Hand, J. W.; ter Haar, G. Heating techniques in hyperthermia. 1. Introduction and assessment of techniques. Br. J. Radiol. 54: 443–466; 1981.PubMedCrossRefGoogle Scholar
  14. 14.
    Harris, A. B.; Erickson, L.; Kendig, J. H.; Mingrino, S.; Goldring, S. Observations on selective brain heating in dogs. J. Neurosurg. 19: 514–521; 1962.PubMedCrossRefGoogle Scholar
  15. 15.
    Hochberg, F. H.; Pruitt, A.: Assumptions in the radiotherapy of glioblastoma. Neurology 30: 907–911; 1980.PubMedGoogle Scholar
  16. 16.
    Hornback, N. B.: Historical aspects of hyperthermia in cancer therapy. In: Steeves, R. A. ed. Hyperthermia. The Radiologic Clinics of North America 27:481–488, 1989.Google Scholar
  17. 17.
    Hornback, N. B.; Shupe, R.; Homayoon, S.; Joe, B. T.; Sayoc, E.; George, R.; Marshall, C. Radiation and Microwave therapy in the treatment of advanced cancer. Radiology 130: 459–464; 1979.PubMedGoogle Scholar
  18. 18.
    Kobayashi, T.; Kida, Y.; Tanaka, T.; et. al.: Magnetic induction hyperthermia for brain tumor using ferromagnetic implant with low Curie temperature. J. Neurooncol. 4: 175–181, 1986.PubMedCrossRefGoogle Scholar
  19. 19.
    Koga, H.; Mori, K.: Interstitial radiofrequency hyperthermia. Clinical application to brain tumor. abstr. XII International Symposium on Clinical Hyperthermia. Rome, April 27–29, 1989.Google Scholar
  20. 20.
    Lin, J. C.; Guy, A. W.; Kraft, G. H. Microwave selective brain heating. J. Microwave Power 8: 275–281; 1973.Google Scholar
  21. 21.
    Lyons, B. E.; Britt, R. H.; Strohbehn, J. W. Localized hyperthermia in the treatment of malignant brain tumors using an interstitial microwave antenna array. IEEE Trans. Biomed. Eng. BME-31(1): 53–62; 1984.Google Scholar
  22. 22.
    Lyons, B. E.; Obana, W. G.; Borcich, J. K.; Kleinman, R.; Singh, D.; Britt, R. H. Chronic histological effects of ultrasonic hyperthermia on normal feline brain tissue. Radiat. Res. 106: 234–251; 1986.PubMedCrossRefGoogle Scholar
  23. 23.
    Moidel, R. A.; Wolfron, S. K.; Selker, R. G.; Weiner, S. B.: Materials for selective tissue heating in a radiofrequency electromagnetic field for the combined chemothermal treatment of brain tumors. J. Biomed. Mater. Res. 10: 327–334, 1076.CrossRefGoogle Scholar
  24. 24.
    Overgaard, J.: Simultaneous and sequential hyperthermia and radiation treatment of an experimental tumor and its surrounding normal tissue in vivo. Int. J. Radiat. Oncol. Biol. Phys. 6: 1507–1517, 1980.PubMedGoogle Scholar
  25. 25.
    Ricca, G. F.; Drerup, M. L.; Dohan, F. C. Jr.; Page, R. C.; Clark, D. C.; Robertson, J. T.: Transcranial 434 MHz microwave hyperthermia in a canine model. Submitted for publication.Google Scholar
  26. 26.
    Roberts, D. W.; Coughlin, C. T.; Wong, T. Z.; Fratkin, J. T.; Douple, E. B.; Strohbehn, J. W. Interstitial hyperthermia and iridium brachytherapy in treatment of malignant glioma. A phase I clinical trial. J Neurosurg 64: 581–587; 1986.PubMedCrossRefGoogle Scholar
  27. 27.
    Roberts, D. W.; Strohbehn, J. W.; Coughlin, C. T.; et. al.: Iridium-192 brachytherapy in combination with interstitial microwave-induced hyperthermia for malignant glioma. Appl. Neurophysiol. 50: 287–291; 1987.PubMedGoogle Scholar
  28. 28.
    Rohdenburg, G. L.; Prime, F. The effect of combined radiation and heat on neoplasms. Arch. of Surg. 2: 116–129; 1921.CrossRefGoogle Scholar
  29. 29.
    Salcman, M.; Feasibility of microwave hyperthermia for brain tumor therapy. Prog. exp. Tumor Res. 28: 220–231; 1984.Google Scholar
  30. 30.
    Salcman, M.; Glioblastoma multirorme. Am. J. Med. Sci., 279: 84–94, 1980.CrossRefGoogle Scholar
  31. 31.
    Salcman, M.; Survival in glioblastoma: Historical perspective. Neurosurgery, 7: 435–439, 1980.PubMedCrossRefGoogle Scholar
  32. 32.
    Salcman, M. The morbidity and mortality of brain tumors. A perspective on recent advances in therapy. Neurol. Clin. 3 (2): 229–257; 1985.PubMedGoogle Scholar
  33. 33.
    Salcman, M.; Kaplan, R. S.; Ducker, T. B., et. al.: Effect of age and reoperation on survival in the combined modality treatment of malignant astrocytoma. Neurosurgery, 10: 454–463, 1982.PubMedCrossRefGoogle Scholar
  34. 34.
    Salcman, M.; Kaplan, R. S.; Samaras, G. M.; Ducker, T. B.; Broadwell, R. D. Aggressive multimodality therapy based on a multicompartmental model of glioblastoma. Surgery 92 (2): 250–259; 1982PubMedGoogle Scholar
  35. 35.
    Salcman, M.; Samaras, G. M. Hyperthermia for brain tumors: Biophysical rationale. Nuerosurgery 9: 327–335; 1981.CrossRefGoogle Scholar
  36. 36.
    Salcman, M.; Samaras, G. M.; Mena, H.; Monteiro, P.; Garcia, J. Whole body hyperthermia: potential hazards in its application to glioblastoma. In: Paoletti, P., Walker, M. D., Butti, G., Kenerich, R., eds. Multidisciplinary Aspects of Brain Tumor Therapy. Amsterdam: Elsevier; 1979: 351–356.Google Scholar
  37. 37.
    Samaras, G. M.; Salcman, M.; Cheung, A. Y,; Abdo, H. S.; Schepp, R. S. Microwave-induced hyperthermia: an experimental adjunct for brain tumor therapy. Natl. Cancer Inst. Monogr. 61: 477–482; 1982.Google Scholar
  38. 38.
    Sapareto, S. A.; Rapphorst, G.; Dewey, W. C. Cell killing and sequencing of hyperthermia and radiation. Int. J. Radiat. Oncol. Biol. Phys. 5: 343–347; 1979.PubMedCrossRefGoogle Scholar
  39. 39.
    Schold, Jr., S. C.; Cairncross, J. G.; Bullard, D. E. Chemotherapy of primary Brain Tumors. In: Wilkins, R. H.; Rengachary, S. S., eds. Neurosurgery. New York, NY: McGraw-Hill Book Co; 1985: 1143–1153.Google Scholar
  40. 40.
    Selker, R. G.; Hyperthermia in the treatment of intracranial turmos. In: Wilkins, R. H.; Rengachary, S. S., eds. Neurosurgery. New York, NY: McGraw-Hill Book Co; 1985: 1159–1163.Google Scholar
  41. 41.
    Silberman, A. W.; Morgan, D. F.; Storm, F. K.; Rand, R. W.; Benz M.; Drury, B.; Morton, D. L. Combination hyperthermia and chemotherapy (BCNU) for brain malignancy. Animal experience and two case reports. J. Neurooncol. 2: 19–28; 1984.PubMedCrossRefGoogle Scholar
  42. 42.
    Silberman, A. W.; Morgan, D. F.; Storm, F. K.; Rand, R. W.; Bubbers, J. E.; Brown, W. J.; Morton, D. L. Localized magnetic-loop induction hyperthremia of the rabbit brain. J. Sur. Oncol. 20: 174–178; 1982.CrossRefGoogle Scholar
  43. 43.
    Silberman, A. W.; Rand, R. W.; Krag, D. N.; Storm, F. K.; Benz, M.; Drury, B.; Morton, D. L. Effect of localized magenitic-induction hyperthermia on the brain. Temperature versus intracranial pressure Cancer 57: 1401–1404; 1986.Google Scholar
  44. 44.
    Silberman, A. W.; Rand, R. W.; Storm, F. K.; Drury, B.; Benz, M.; Morton, D. L. Phase 1 trial of thermochemotherapy for brain malignancy. Cancer 56: 48–56; 1985.PubMedCrossRefGoogle Scholar
  45. 45.
    Sneed, P. K.; Matsumoto, K,; Stauffer, P. R.; Fike, J. R.; Smith, V.; Gutin, P. H. Interstitial microwave hyperthermia in a canine brain model. Int. J. Radiat. Oncol. Biol. Phys. 12: 1887–1897; 1986.Google Scholar
  46. 46.
    Stehlin, J. S.; Giovanella, B. C.; de Impolyi, P. D.; et. al.: Results of hyperthermia perfusion for melenoma of the extremity. Surg. Gynecol. Obstet. 140: 338–340, 1975.Google Scholar
  47. 47.
    Stewart, J. R.; Gibbs, F. A. Hyperthermia in the treatment of cancer. Perspectives on its promise and its problems. Cancer 54: 2823–2830; 1984.PubMedCrossRefGoogle Scholar
  48. 48.
    Storm, K. F.: Clinical hyperthermia and chermotherapy. In: Steeves, R. A., ed. Hyperthermia. The Radiologic Clinics of North America 27:481–488, 1989.Google Scholar
  49. 49.
    Storm, K. F.; Harrison, W. H.; Elliott, R. S.; Morton, D. L.: Physical aspects of localized heating by magnetic-loop induction. In: Storm, K. F., ed. Hyperthermia In Cancer Therapy. Boston, Massachusetts: G. K. Hall Medical Publishers; 1983: 305–313.Google Scholar
  50. 50.
    Tanaka, R.; Kim, C. H.; Yamada, N.; Saito, Y.: Radiofrequency hyperthermia for malignant brain tumors: Preliminary results of clinical trials. Neurosurgery 21: 478–483, 1987.PubMedCrossRefGoogle Scholar
  51. 51.
    Thrall, D. E.; Page, R. L.; Dewhirst, M. W.; Meyer, R. E.; Hoopes, P. J.; Kornegay, J. N.: Temperature measurements in normal and tumor tissue of dogs undergoing whole body hyperthermia. Cancer Research 46: 6229–6235; 1986.PubMedGoogle Scholar
  52. 52.
    Walker, M. D.; Green, S. B.; Byar, D. P.; Alexander, E, Jr.; Batzdorf, U.; Brooks, W. H.; Hunt, W. E.; MacCarty, C. S.; Mahaley, M. S. Jr.; Mealey, J. Jr.; Owens, G.; Ransohoff, J.; Robertson, J. T.; Shapiro, W. R.; Smith, K. R. Jr.; Wilson, C. B.; Strike, T. A.: Randomized comparison of radiotherapy and nitorsoureas for the treatment of malignant glioma after surgery. N. Engl. J. Med. 303: 1322–1329, 1980.Google Scholar
  53. 53.
    Weinstein, J. N.; Magin, R. L.; Yatvin, M. B.; Zaharko, D. S. Liposomes and local hyperthermia: Selective delivery of methotrexate to heated tumors. Science 204: 188–191; 1979.PubMedCrossRefGoogle Scholar
  54. 54.
    Winter, A.; Laing, J.; Paglione, R.; Sterzer, F. Microwave hyperthermia for brain tumors. Neurosurgery 17: 387–399; 1985.PubMedCrossRefGoogle Scholar
  55. 55.
    Zimm, S.; Wampler, G. L.; Stablein, D.; Hazra, T.; Young, H. F.: Intracerebral metastases in solid-tumor patients: Natural history and results of treatment. Cancer 48: 384–394, 1981.PubMedCrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1990

Authors and Affiliations

  • Roy C. Page
    • 1
  • Gregory F. Ricca
    • 1
  • F. Curtis DohanJr.
    • 1
  1. 1.Baptist Memorial HospitalUniversity of TennesseeMemphisUSA

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