The results from experimental studies indicate that hyperthermia is both an effective complementary treatment to, and a strong sensitiser of, radiotherapy and many cytotoxic drugs. Since the first international hyperthermia conference in 1975, Washington DC, techniques to increase tumour temperature have been developed and tested clinically. Hyperthermia can be applied by several methods: local hyperthermia by external or internal energy sources, perfusion hyperthermia of organs, limbs, or body cavities, and whole body hyperthermia. The clinical value of hyperthermia in combination with other treatment modalities has been shown by randomised trials. Significant improvement in clinical outcome has been demonstrated for tumours of the head and neck, breast, brain, bladder, cervix, rectum, lung, oesophagus, for melanoma and sarcoma. The addition of hyperthermia resulted in remarkably higher (complete) response rates, accompanied by improved local tumour control rates, better palliative effects, and/or better overall survival rates. Toxicity from hyperthermia cannot always be avoided, but is usually of limited clinical relevance. In spite of these good clinical results, hyperthermia has received little attention. Problems with acceptance concern the limited availability of equipment, the lack of awareness concerning clinical results, and the lack of financial resources. In this paper the most relevant literature describing the clinical effects of hyperthermia is reviewed and discussed, and means to overcome the lack of awareness and use of this modality is described.

For superficial hyperthermia a custom-built multi-applicator multi-amplifier superficial hyperthermia system operating at 433 MHz is utilised. Up to 6 Lucite Cone applicators can be used simultaneously to treat an area of 600 cm². Temperatures are measured continuously with fibre optic multi-sensor probes. For patients with non-standard clinical problems, hyperthermia treatment planning is used to support decision making with regard to treatment strategy. In 74% of our patients with recurrent breast cancer treated with a reirradiation scheme of 8 fractions of 4 Gy in 4 weeks, combined with 4 or 8 hyperthermia treatments, a complete response is achieved, approximately twice as high as the CR rate following the same reirradation alone. The CR rate in tumours smaller than 30 mm is 80–90%, for larger tumours it is 65%. Hyperthermia appears beneficial for patients with microscopic residual tumour as well. To achieve high CR rates it is important to heat the whole radiotherapy field, and to use an adequate heating technique.

Background: For many years, the standard treatment of advanced cervical cancer has been radiotherapy (RT), including brachytherapy. The achievement of locoregional tumour control is essential for cure. Results of RT in early stages are reasonably satisfactory, but locoregional failure rates for stage IIIb and IVa are high. In several randomized trials, the addition of hyperthermia (HT) to RT has been investigated. Randomized trials: The Dutch Deep Hyperthermia Trial was completed in 1996. In this trial a beneficial effect of additional hyperthermia was clearly demonstrated. Three-year locoregional control and overall survival rates were significantly higher in the RT + HT group than in the RT alone group, while radiation toxicity was not affected. Cost-per-life-year-gained was less than 4000 Euros. The results of this trial have led to the acceptance of RT plus HT as standard treatment for advanced cervical cancer in the Netherlands. Five trials conducted in Asia have been published, of which three showed significant better complete response, locoregional tumour control and/or disease-free survival rates. One trial showed a trend of better locoregional tumour control and one did not show any benefit. Conclusion: Hyperthermia added to standard radiotherapy of locally advanced cervical tumours results in considerable therapeutic gain and is cost-effective. For a beneficial effect, the use of an adequate heating technique is an important requirement.

BACKGROUND: The objective of this study was to evaluate the palliative effect of reirradiation and hyperthermia in patients with unresectable, recurrent colorectal carcinoma.METHODS: The medical records of 54 patients with unresectable, recurrent colorectal carcinoma that caused pain and who were treated with reirradiation and hyperthermia, were evaluated retrospectively. Previous radiotherapy was given up to a total dose ranging from 25–70 grays (Gy). The median interval between prior radiotherapy and reirradiation was 22 months (range, 4–97 months). The total reirradiation dose varied from 24 Gy to 32 Gy given in fractions of 4 Gy twice weekly. Three or four hyperthermia treatments were given once weekly. Toxicity was registered. The influence of World Health Organization (WHO) performance status, maximum tumor dimension, and time between first radiotherapy and reirradiation on therapeutic outcome was evaluated. The results of this study were compared with published results on patients who received radiotherapy with or without hyperthermia.RESULTS: Forty‐seven patients (87%) completed the planned treatment schedule. The maximum toxicity was Grade 2. All patients were evaluated for palliative effect. The median follow‐up was 10 months. A good or complete palliative effect was achieved in 72% of patients for a median duration of 6 months. Patients who had a better WHO performance status, smaller tumors, and a longer interval between first radiotherapy and reirradiation had slightly better outcomes, although none of those parameters reached statistical significance.CONCLUSIONS: The described combined treatment was feasible and well tolerated. Comparison of results from radiotherapy plus hyperthermia with results after radiotherapy alone suggested that additional hyperthermia prolonged the duration of palliation. Firm proof of the contribution of hyperthermia will require performing a Phase III study. Cancer 2003. © 2003 American Cancer Society.DOI 10.1002/cncr.11719

Based on the good results of re-irradiation plus hyperthermia in breast cancer recurrences on the chest wall, it was decided to offer similar treatment to a patient with recurrent metastatic breast cancer in the orbital region. A female patient was diagnosed in 1997 with breast cancer stage T4N0M0. She was treated with six neo-adjuvant chemotherapy courses and mastectomy, followed by hormonal treatment. In December 1998, she was diagnosed with metastatic disease in the medial upper quadrant of the left orbit. This was excised, followed by 40 Gy radiotherapy. Nine months later, the tumour had recurred in the left orbit at the margin of the radiotherapy field. This again was treated with surgery, followed by 30 Gy radiotherapy. Two months thereafter, the eyelid tumour progressed and hormonal therapy was changed, without an effect on the eyelid tumour. Screening gave no evidence of tumour activity elsewhere. The patient preferred treatment with re-irradiation plus hyperthermia to a surgical approach. Eight fractions of 4 Gy were given in 4 weeks, combined with once weekly hyperthermia. One week after treatment, the tumour had regressed completely. The patient died 22 months following treatment. Until last follow-up, a few weeks before death, the patient mentioned a dry left eye for which she used eyedrops, an unchanged vision and no further difficulties. On examination, there was epilation of the eyelids, a slight conjunctival oedema, no subcutaneous fibrosis and no evidence of tumour regrowth. For this patient, a surgical approach would have resulted in loss of the left eye. Toxicity of re-irradiation plus hyperthermia might lead to either a loss of vision or a delayed loss of her left eye due to treatment-induced toxicity. The chosen local treatment resulted in a very good palliative effect, which lasted for the patient's remaining lifetime of 22 months.

Background: After observing rather severe acute neurotoxicity in a few patients following deep hyperthermia treatment for a pelvic tumour, we evaluated the incidence of neurotoxicity in all patients treated with deep hyperthermia of the pelvis between June 1990 and April 2004. Materials and methods: Hyperthermia treatment registrations and hospital charts of all 736 patients were reviewed. Differences between the incidence of neurotoxicity in subgroups of patients were evaluated by 2 × 2 exact tests. Results: Grade 2 or 3 acute neurotoxicity occurred in 2.3% of patients, grade 3 in 0.7%. The duration of symptoms was longer than 3 months in 6 patients (0.8%). Neurological examination in 5 patients showed that the most commonly involved structures are the sacral and lower lumbar nerve roots and the sacral plexus. Acute neurotoxicity occurred only after November 1999 and only in patients treated for primary cervical cancer. Comparison of applied powers and achieved temperatures in patients developing neurotoxicity did not show differences between treatment sessions which resulted in neurotoxicity and sessions not resulting in neurotoxicity. Conclusion: Acute neurotoxicity following hyperthermia for pelvic tumours is a rare complication, but can result in symptoms affecting the activities of daily life. We found no patient, tumour or treatment characteristics predictive for a risk of neurotoxicity.