Hyperthermia was first described in a radiation text in 1935, in a paper that was titled, “Preliminary study of the effect of artificial fever upon hopeless tumor cases.” I think “hopeless tumor cases” is the key here. There were a number of well-designed trials in the 1970s and 1980s looking at the use of heat or hyperthermia and radiation, but by the late 1980s, most hyperthermia trials were abandoned because of technical issues. 1989 was the last year of a report from a phase III trial of any size through the Radiation Therapy Oncology Group (RTOG), and it was a negative trial. Heat added nothing to radiation in a palliative setting. But in the last decade, there have been six randomized trials, including the one from Duke, looking again at this issue. These six trials together included a total of less than 400 women with breast cancer and less than 160 women with re-irradiation of a chest wall lesion. None of the trials showed any survival advantage but palliation was achieved.
Hyperthermia has a place in standard therapeutic armamentarium for breast cancer. National Comprehensive Cancer Network (NCCN) has for the first time included it in its 2007 Breast Cancer Guidelines for recurrent cancer of the chest wall (breast cancer) and other localized cancer recurrences.
This was possible because surface cancers are accessible to heat. Internal mets are much harder to treat. The Germans at St. Geirge are exploring nanotechnology heating, and others are using microwaves but this is cearly a very experimental approach at thsi time, as is combination of hyperthermia and chemotherapy for breast cancer.
At this point, there are several supporting trials in other cancers than breast. I list them as presented in a recent review ACRO 2/2007). In a clinical study conducted in Italy involving 41 patients (44 nodes) with inoperable Stage IV head and neck cancer, patients receiving hyperthermia and radiation therapy had an 83% complete response rate compared to 41% for patients who received radiation therapy alone, and the 3-year local relapse-free survival rate was 24% for patients receiving only radiation and 68% for those who received both radiation and hyperthermia therapy. (International Journal of Radiation Oncology, Biology, Physics Vol. 28, pp. 163-169.)
– In an international clinical study conducted in Denmark, the Netherlands and Norway involving 128 patients with recurrent or metastatic malignant melanoma, patients who received hyperthermia therapy along with radiation had a complete response rate for recurrent malignant melanoma lesions of 62% compared to 35% for those who received radiation treatments alone, and the local relapse-free survival rate at 5 years was 46% for those who received both hyperthermia and radiation and 28% for those who received radiation alone. (See International Journal of Hyperthermia, Vol., 12, No. 1, 3-20.)
– In a clinical study conducted at UCSF involving 112 patients with glioblastoma maltiforme (brain cancer), patients who received both hyperthermia and interstitial radiation therapy (brachytherapy) had a more than double 2-year survival rate as compared to patients who received brachytherapy alone. (See International Journal of Radiation Oncology, Biology, Physics, Vol. 40, No. 2, pp. 287-295.)
– In a clinical study conducted in the Netherlands involving 358 patients with locally advanced pelvic tumors, bladder cancer patients who received radiation alone had a complete response rate of 51% compared to 73% for those who received hyperthermia and radiation. The complete response rate for patients with advanced cervical cancer was 83% for those who received radiation plus hyperthermia and 57% for those who received radiation alone. (See The Lancet, Vol. 355, pp. 1119-1125.) In addition, a clinical study of 61 patients at Duke University using the tri-modality treatments hyperthermia, radiation and chemotherapy together for the treatment of advanced cervical cancer resulted in a complete remission in 90%. (See CANCER, August 14, 2005, Vol. 104, No. 4.)
– In a clinical study conducted in the United Kingdom, the Netherlands and Canada involving 306 patients with superficial localized breast cancer, patients who received both hyperthermia and radiation therapy had a complete response rate of 59% compared to 41% for those who received radiation treatments alone. Local relapse-free survival was 50% for those who received both therapies and 30% for those who received radiation alone. (See International Journal of Radiation Oncology, Biology, Physics, Vol. 35, No. 4, pp. 731-744.) In addition, a clinical study conducted at Duke University involving patients with previously irradiated superficial tumors, 23.5% had a complete response when treated with radiation alone compared to a response rate of 68.2% for patients treated with hyperthermia plus radiation. (See Journal of Clinical Oncology, Vol. 23, No. 13, May 1, 2005.)
National Clinical Practice Guidelines in Oncology for Soft Tissue Sarcoma (V.2.2008) issued by the National Comprehensive Cancer Network (NCCN) include reference to the preliminary results from a 341 patient phase III randomized multi-center clinical trial (EORTC-62961 and NCT00003052) involving the use of regional hyperthermia and chemotherapy with EIA (etoposide, ifosfamide and adriamycin), as compared to EIA alone.
In conclusion, hypertehrmia with radiation clearly is effective to palliate as seen in various cancers in superficial locations. There is also supporting evdidence specifically in melanoma.
Sakurai H, Mitsuhashi N, Tamaki Y, et al. Interaction between low dose-rate irradiation, mild hyperthermia and low-dose caffeine in a human lung cancer cell line. Int J Radiat Biol. 1999 Jun;75(6):739-45.
nccn.org, breast cancer
L. Kronberger, P. Wagner, M. Puchinger, H. Stranzl, P. Kohek: Radiofrequency-Hyperthermia in Combination with Chemo and Radiotherapy in Palliative Treatment of Breast Cancer: A Case Report. The Internet Journal of Surgery. 2004. Volume 5 Number 2.
Vernon C C and Hand J W (2002) Hyperthermia in the treatment of cancer in Treatment Of Cancer (4th Edition) Eds. Price P and Sikora K. London, Arnold, 81 –102.Wust P et al (2002)
Hafstrom L, Rudenstam CM, Blomquist E, et al. Regional hyperthermic perfusion with melphalan after surgery for recurrent malignant melanoma. J Clin Oncol. 1991;9(12):2091-2094.