Regional hyperthermia: Application in the palliative phase or as a co-therapy for neuropathic pain associated with tumor diseases

The majority of available hyperthermia studies were conducted in the context of curative intent. That makes sense from the perspective of the researchers because it has become evident that hyperthermia shows promising potential to impact local tumor control, progression-free survival and overall survival in combination with conventional therapies such as radiation therapy, chemotherapy and immunotherapies.

Another interesting aspect – although not as spectacularly presentable – is the potential to use moderate regional hyperthermia sessions in the palliative phase for the primary purpose of pain reduction. Users keep reporting interesting case observations, in which patients benefited from hyperthermia in advanced tumor stages. A number of such application observations from a variety of sources appear to indicate that hyperthermia can reduce the dosage of pain medications, especially opioids. The effect appears to last 4-5 days and is perceived as a significant quality of life factor by patients and their family members since the patient can develop a much better waking consciousness than would be possible under high-dose opioids. As mentioned above, the effect does not last long, but appears to justify a regional hyperthermia treatment session once a week.

Another observation concerns neuropathic pain, which primarily develops as a side effect of platinum-based chemotherapies, but also in association with alkaloid and anti-metabolite treatment. Hyperthermia can reduce such pain, in part to a significant extent.
Although these individual and subjective application observations don’t constitute a scientific standard yet, experience reports make valuable contributions and the small number of studies on the topic deserve to be shared and discussed.
One of them is a small study of ten patients, which was performed in Bangalore, India by Dr. Sridhar P.S. It involved seven female and three male patients, ranging in age from 40 to 72 years, in a stage of tumor progression that was classified as palliative (4 patients with cervical cancer, 2 with rectal cancer, 1 cholangiosarcoma, 1 pancreatic cancer, 1 esophageal cancer with supraclavicular lymph node involvement and 1 mucoepidermoid cancer of the maxilla).
All received a single high-dose radiation fraction via CyberKnife and six sessions of weekly hyperthermia with the aim to reduce the pain associated with the tumor and the tumor treatment. The author reported no toxicity resulting from the additional hyperthermia. Results: All patients reported a reduction of pain; 7 patients indicated a pain reduction of over 60% after one week; 8 patients experienced >80% less pain at the end of the observation period and no longer needed pain medication.
A more comprehensive study was conducted in Taiwan. As a large prospective and randomized phase-III study, it analyzed the difference between treating painful bone metastases with radiation therapy, either with and without local hyperthermia.

Chi MS, Yang KL, Chang YC, Ko HL, Lin YH, Huang SC, Huang YY, Liao KW, Kondo M, Chi KH: Comparing the Effectiveness of Combined External Beam Radiation and Hyperthermia Versus External Beam Radiation Alone in Treating Patients With Painful Bony Metastases: A Phase 3 Prospective, Randomized, Controlled Trial.
Int.J.Radiat Oncol Biol Phys.2018 Jan 1;100(1):78-87. doi: 10.1016/j.ijrobp.2017.09.030.Epub 27-9-2017

The starting point were patients with bone metastases and a pain score of ≥4 according to the Brief Pain Inventory (BPI). The target criterion was the length of pain reduction as well as the time interval to complete freedom from pain after radiation therapy.
All patients received a radiation dose of 30 Gy in 10 fractions; the patients in the arm with hyperthermia received this dose in a total of four fractions, involving two sessions in the first two weeks, respectively.
Results: The study was terminated prematurely after three years based on the analysis of 57 patients. The “complete response” rate in the combined group (RT + HT) after 3 months was 37.9% versus 7.1% in the RT-only group (P = .006). The accumulated “complete response” rate after 3 months was 58.6% in the RT + HT group versus 32.1% in the RT-only group (P = .045).
The median time to recurring pain progression was 55 days for patients with “complete response” (n = 9) in the RT-only group, while this endpoint was not reached in the combined group (RT + HT) during the 24-week follow-up phase (P < .01).
The authors concluded that supplementary hyperthermia treatment significantly improves pain control in the treatment of painful bone metastases compared to exclusive treatment with radiation therapy and that hyperthermia extends the period of pain reduction.

Overall, it was again noted in this application that local hyperthermia has a highly favorable ratio of efficacy to undesirable side effects.