Clinical hyperthermia: Results of a phase I trial employing hyperthermia alone or in combination with external beam or interstitial radiotherapy

Abstract

Forty-three patients with advanced, locally accessible neoplasms were treated in a Phase I clinical trial employing hyperthermia alone or hyperthermia combined with either high-dose-rate external beam or low-dose-rate interstitial radiotherapy (interstitial thermoradiotherapy). All patients had failed previous conventional therapeutic attempts, including various combinations of surgery, chemotherapy and radiation therapy. Many had received tolerance or near tolerance levels of prior radiation that restricted dose prescriptions in this trial to subcurative values. A number of tumors with different histologies were treated, including squamous cell carcinoma (14), adenocarcinoma (14), melanoma (8), malignant fibrous histiocytoma (2), and sarcoma (5). The response evaluation criteria used included no response (NR-less than 50% decrease in tumor volume), partial response (PR-50% I tumor volume reduction < 100%) and complete response (CR-complete tumor disappearance). For all tumor types, hyperthermia therapy alone resulted in a total response rate of 45% (27% PR, 18% CR). Hyperthermia combined with high-dose-rate external beam radiotherapy yielded a total response rate of 80% (53% PR, 27% CR). Seventeen patients treated with interstitial thermoradiotherapy displayed a 100% total response rate (29% PR, 71% CR). By tumor histologies for all treatment groups, total response rates have ranged from 50 to 79% for all types except melanoma, which has shown a 100% (8/8) response rate to date. Response durations have varied from one to 24 months. Twelve of the 43 patients remain alive; three have no evidence of disease (NED) while nine have either stable local disease or are NED in the treated volumes but have metastatic disease. Complications have been minimal and have included one third-degree burn and three second-degree burns from fringing R F fields, one vaginal-rectal fistula, a superficial focal soft tissue necrosis, and some minor blistering. The results of this Phase I trial demonstrate that hyperthermia alone or combined with radiation can be safely applied in the treatment of malignant disease. Most importantly, the data suggest that hyperthermia, especially when combined with interstitial thermoradiotherapy, can yield remarkable results in the eradication of local cancers. Cancer 49205-216,1982. H E RATIONALE for the use of hyperthermia in the T treatment of human malignancies is based on a spectrum of biologic and physical research, much of the evidence accumulating over the past ten years. Hyper

Cancer immunity and therapy using hyperthermia with immunotherapy, radiotherapy, chemotherapy, and surgery

“…In the early days, hyperthermia alone at 42-44 °C was performed against recurrent tumors derived from head and neck cancer and breast cancer, which appeared on the surface of the body. The objective antitumor response in this set of superficial tumors was around 40% [10][11][12] . However, most cancers, including primary sites as well as recurrent or metastatic sites, are located deep inside the body.…”

A Predictive-Adaptive, Multipoint Feedback Controller for Local Heat Therapy of Solid Tumors

“…Complementary technological means of enhancing selectivity include schemes for focusing power deposition within the tumor mass, such as multiple ultrasonic beams or interstitial microwave antennas [4]- [6]. There remains, however, the problem of achieving maximal uniformity of tumor temperatures.…”

Interstitial Hyperthermia in Combination with Radiation Brachytherapy for Treatment of Breast Tumor

“…Hyperthermia is an established form of cancer treatment therapy in which the temperature of a tumor is increased to over 42.5℃ in an artificial way [1][2][3] by delivering heat using external sources, such as microwaves, ultrasound. Several studies have shown that high temperature causes direct damage to the cancerous cells 2,[4][5][6][7][8][9][10] or sensitizes the cancerous cells to other treatment modalities 10) such as radiotherapy, chemotherapy, immunotherapy, with lesser injury to the normal tissues 11) than to the tumor tissues.…”

“…Several studies have shown that high temperature causes direct damage to the cancerous cells 2,[4][5][6][7][8][9][10] or sensitizes the cancerous cells to other treatment modalities 10) such as radiotherapy, chemotherapy, immunotherapy, with lesser injury to the normal tissues 11) than to the tumor tissues. Furthermore, over the past few decades various randomized clinical trials conducted on patients with different types of cancer have shown improved clinical response, local control and survival, due to combination of hyperthermia and radiotherapy 1,3,[11][12][13][14][15][16] . Hyperthermia increases oxygen content-a strong radio-sensitizer-inside the cells.…”