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.
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.
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.
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%
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
- 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.