Clinical Evidence by Indication

Breast cancer is the most common cancer in women worldwide according to the World Cancer Research Fund International. With nearly 2 million new cases diagnosed in 2018 (second most common cancer overall). This represents about 12% of all new cancer cases and 25% of all cancers in women.

Clinical results like the one below reveal that both Chemotherapy and Radiation treatment are more effective when combined with Hyperthermia. Hyperthermia warms the tumor to temperatures in the "fever range" which makes the cancer cells more sensitive to treatment. Normal healthy cells recover while cancer cells die.

Randomized trial of hyperthermia and radiation for superficial tumors, Jones et al.

By adding twice-weekly hyperthermia treatments to the daily radiation therapy treatments, the success rate for complete response (no cancer) was tripled.  Hyperthermia is known to increase blood flow and perfusion, prevent damaged cancer cells from repairing during treatment, and helping the body's immune system identify and destroy cancer cells.

Clinical Results:

One hundred twenty-two patients were enrolled; 109 (89%) were deemed heatable and were randomly assigned. The complete response rate was 66.1% in the HT arm and 42.3% in the no-HT arm. The odds ratio for complete response was 2.7 (95% CI, 1.2 to 5.8; P = .02). Previously irradiated patients had the greatest incremental gain in complete response: 23.5% in the no-HT arm versus 68.2% in the HT arm. No overall survival benefit was seen.

 How the BSD-500 Treat Breast Cancer

 The MA-120 applicator with a water bolus is placed in skin contact over the tumor area.  Deionized water is circulated into the bolus during treatment. The circulating water has three purposes; 1) complete surface contact to assist in directing RF energy toward the tumor; 2) manage patient comfort by cooling skin surface; 3)by adjusting bolus temperature, RF energy depth can be controlled.  1 to 2 treatments per week are generally prescribed along with radiotherapy and chemotherapy treatments.

Cervical cancer is the fourth most common cancer affecting women worldwide according to the World Health Organization. With nearly 528,000 new cases diagnosed every year. It is also the fourth most common cause of cancer death (266,000 deaths in 2012) in women worldwide.

Level 1 Clinical results like the one below reveal that both Chemotherapy and Radiation treatment are more effective when combined with Hyperthermia. Hyperthermia warms the tumor to temperatures in the "fever range" which makes the cancer cells more sensitive to treatment. Normal healthy cells recover while cancer cells die.

Clinical Evidence

Tumor Entity:

A Cochrane review was performed to investigate whether adding hyperthermia to standard radiotherapy or chemoradiation for locally advanced cervical cancer has an impact on local tumor control, survival, and treatment related morbidity. The review included six randomized trials in patients with primary cervical cancer stage IIB, IIIB and IV.

Treatment Modality:

Conventional external beam radiotherapy and brachytherapy, in one trial with chemotherapy as well. Patients were randomized for additional hyperthermia, 3-12 treatments in the period of external radiotherapy.Patients recruitment sites: AMC Amsterdam using a device similar to the earlier designed BSD-1000, Erasmus MC Rotterdam used the BSD-2000 Hyperthermia device.

Clinical Results:

The majority of patients (74%) included in the studies had FIGO stage IIIB cervical carcinoma. Overall, treatment outcome was significantly better for patients receiving the combined treatment. The pooled data analysis yielded a significantly higher complete response rate (RR 0.56; 95% CI 0.39-0.79; p<0.001), reduced local recurrence rate at 3 years (HR 0.48; 95% CI 0.37-0.63; p<0.001), and better overall survival at 3 years (HR 0.67; 95% CI 0.45-0.99; p=0.05) after combined treatment. No significant difference was observed in treatment related acute (RR 0.99; 95% CI 0.30-3.31; p=0.99) or late grade 3-4 toxicity (RR 1.01; 95% CI 0.44-2.30; p=0.96) between the two treatment arms.

From one of these randomized trials long-term results have been published, showing a significant better overall survival up to 12 years after radiotherapy plus hyperthermia.

• 12 year Overall Survival with Radiotherapy alone 20%
• 12 year Overall Survival with Radiotherapy plus Hyperthermia 40%

Endorsements:

These bodies recommend Radiotherapy and Hyperthermia as a combination therapy for cervical cancer:

• The Health Insurance Council of the Netherlands
• FDA US Food & Drug Administration: Patients with advanced disease not apt for chemotherapy; HDE Humanitarian Device Exemption
• Integrated Cancer Center of the Netherlands - Guidelines for oncological care

Hyperthermia and Radiotherapy:

When hyperthermia is combined with radiotherapy, general treatment guidelines of the ESHO European Society of Hyperthermic Oncology recommend:

• Target volume for hyperthermia: When the radiotherapy total dose is considered to be sufficient for a high probability of local control for microscopic disease, the target volume for hyperthermia is the gross tumor volume. When the radiotherapy total dose is lower, the target volume for hyperthermia is the clinical target volume.
• Sequence of treatment modalities: Hyperthermia is given after the radiotherapy fraction, once or twice weekly with a time interval between two hyperthermia treatments of minimum 72 hours. The time interval between radiotherapy and hyperthermia may vary from 30 minutes to five hours.
• Duration of hyperthermia treatment: Superficial hyperthermia total 60 minutes, deep hyperthermia total 90 minutes (including 30 minutes heating-up
  time)

References:

• L. Lutgens et al. Combined use of hyperthermia and radiation therapy for treating locally advanced cervix carcinoma. Cochrane Database Syst Rev. 2010 Mar 17;(3):CD006377.
• M. Franckena et al. Radiotherapy and hyperthermia for treatment of primary locally advanced cervix cancer: results in 378 patients. Int J Radiat Oncol Biol Phys. 2008 Jan 1;73(1):242-50.

Esophageal (Oesophageal) cancer is the eighth most common cancer worldwide according to the World Cancer Research Fund International. With nearly 456,000 new cases diagnosed in 2012. About 75% of those cases are diagnosed in Asia.

Level 1 Clinical results like the one below reveal that both Chemotherapy and Radiation treatment are more effective when combined with Hyperthermia. Hyperthermia warms the tumor to temperatures in the "fever range" which makes the cancer cells more sensitive to treatment. Normal healthy cells recover while cancer cells die.

Clinical Evidence

Tumor Entity:

Primary thoracic esophageal cancer stage III and IV

Treatment Modality:

Three randomized studies were performed in esophageal cancer, comparing radio and/or chemotherapy with or without intraluminal hyperthermia. Kitamura et al. compared preoperative radiochemotherapy with or without hyperthermia. Wang et al. compared 60 Gy alone to 40 Gy plus hyperthermia. Sugimachi et al. compared preoperative chemotherapy with or without hyperthermia. Third party hyperthermia devices used.

Clinical Results:

• Kitamura et al. found a significantly higher pCR in the plus hyperthermia treatment arm: 25% vs 6%.
• Wang et al. found a significantly better 3-y overall survival with hyperthermia: 42 vs 24%.
• Sugimachi et al. found that the local effects tended to be better in the plus hyperthermia group: improvement of dysphagia 70% vs 40%; radiographic improvement 50% vs 25%, and histopathological evidence of treatment effect 41% vs 19%.

Duration of hyperthermia treatment

Intraluminal hyperthermia total 30 minutes

References:

• Kitamura et al. Prospective Randomised Study of Hyperthermia Combined with Chemoradiotherapy for Esophageal Carcinoma. J Surgical Oncology. 1995; 60:55-58.
• Wang et al. Intracavitary microwave hyperthermia combined with external irradiation in the treatment of esophageal cancer. Chung Hua Chung Liu Tsa Chih 1996;18:51-54.
• Sugimachi et al. Chemotherapy combined with or without hyperthermia for patients with oesophageal carcinoma: a prospective trial. Int J Hyperthermia 1994;10:485-4

Head and Neck cancer is the sixth most common cancer in worldwide according to World Health Organization and the most common cancer in developing countries. With nearly 664,000 new cases annually. Two-thirds of these occurring in developing countries.

Clinical results like the one below reveal that Radiation treatment are more effective when combined with Hyperthermia. Hyperthermia warms the tumor to temperatures in the "fever range" which makes the cancer cells more sensitive to treatment. Normal healthy cells recover while cancer cells die.

Clinical Evidence

Tumor Entity:

Advanced Head and Neck Tumors with Lymph Node Metastasis

Treatment Modality:

In three trials patients with head and neck tumors were randomized to radio(chemo)therapy with or without hyperthermia. Radiotherapy was applied with 2 Gy fractions up to a total dose of 66-70 Gy. Chemotherapy was only applied in the study by Hua et al., to patients with T3-T4 tumors only. Hyperthermia was given once or twice weekly Valdagni, Trento Italy study used BSD-1000.  

Clinical Results:

All three studies showed a significant improvement in complete response rate, and higher local tumor control and overall survival rates, or a longer median survival, when radio(chemo)therapy was combined with hyperthermia.

• 41 pts, 44 nodes. Radiotherapy 64-70 GY, 5 fractions/week of 2-2.5 Gy
• Complete Remission Rate without Hyperthermia: 41 %
• Complete Remission Rate with Hyperthermia: 83 %
• 5yr nodal control RT - 24%; RT+HT - 69%
• 5yr overall survival RT - 0% RT+HT - 53%
• No enhancement of acute or late toxicity

Endorsements:

The combination of Radiotherapy and Hyperthermia is the treatment of choice for Head & Neck Cancer (Level I Evidence) recommended by

• DEGRO German Society of Radiation Oncology
• DKG Deutsche Krebsgesellschaft, Germany
• Dutch Society for Radiation Oncology, The Netherlands
• Dutch Cancer Society, The Netherlands
• ESHO European Society of Hyperhermic Oncology

Hyperthermia and Chemotherapy:

When hyperthermia is combined with chemotherapy, general treatment guidelines of the ESHO European Society of Hyperthermic Oncology recommend:

• Target volume for hyperthermia: The target volume for hyperthermia is the gross tumor volume.
• Sequence of treatment modalities: Hyperthermia is given simultaneously with chemotherapy during cytostasis.
• Duration of hyperthermia treatment: Superficial hyperthermia total 60 minutes, deep hyperthermia total 90 minutes (including 30 minutes heating-up time) ) at temperatures of 40 to 44 °C in the whole target volume

References:

• R. Valdagni et al. Radical radiation alone versus radical radiation plus microwave hyperthermia for N3 (TNMUICC) neck nodes: a prospective randomized clinical trial. Int J Radiat Oncol Biol Phys. 1988 Jul;15(1):13-24.
• R. Valdagni et al. Report of long-term follow-up in a randomized trial comparing radiation therapy and radiation therapy plus hyperthermia to metastatic lymph nodes in stage IV head and neck patients. Int J Radiat Oncol Biol Phys. 1994 Jan 1;28(1):163-9.
• Hua et al. Intracavity hyperthermia in nasopharyngeal cancer: a phase III clinical study. Int J Hyperthermia 2011;27:180-186.
• Huilgol et al. Hyperthermia with radiation in the treatment of locally advanced head and neck cancer: a report of a randomized trial. J Can Res Ther 2010;6:492-496.