Radiofrequency hyperthermia in the palliative treatment of mucinous carcinomatosis of appendiceal origin: Optimizing and monitoring heat delivery in western patients

Abstract

Mucinous peritoneal carcinomatosis from a primary gastrointestinal malignancy is a lethal condition that has few treatment options with the use of surgery, chemotherapy or radiation therapy. Recent advances in hyperthermia technology and in knowledge of the natural history of this disease has suggested the possible utility of hyperthermia in the application of aggressive local-regional therapy. Radiofrequency (RF) hyperthermia to the whole abdomen, to the hemithorax, or to an isolated mucinous tumour deposit obstructing the gastrointestinal tract was used in patients with disseminated mucinous adenocarcinoma of appendiceal origin. There were 228 hyperthermia treatments in 21 patients, with a median of 10 treatments per patient. The maximum number of treatments was 26, and minimum was one. For the first six hyperthermia treatments, escalating doses of deep hyperthermia (41-45°C) was monitored with multiple sensor internal temperature probes and a single sensor subcutaneous temperature probe. After reaching a maximal hyperthermia treatment, this was maintained for all subsequent treatments. Initially, the maximal temperature allowed in tumour and subcutaneous tissue was 43°C. After 50 hyperthermia treatments, this was changed to 45°C. If disease stabilization or response was insufficient and maximal tolerable hyperthermia had been established, the frequency of treatment was increased from every 4 weeks to every 2 weeks, and escalating doses of mitomycin C at 8 mg/m2 were added to the regimen. Mitomycin C was infused during the hyperthermia treatment. For the first 165 treatments, patients were monitored just before and 10 days after hyperthermia with a complete blood count and a full battery of laboratory tests including amylase and lipase. Response was monitored by carcinoembryonic antigen assays on a monthly basis and CT scans on a 6 monthly basis. None of the 21 patients included in this study died, required intensive care, or required major surgical interventions as a result of hyperthermia treatments. One potentially life-endangering event was profound bradycardia and hypotension observed in a 76-year-old male receiving hyperthermia treatment to his right hemithorax. Two patients developed an enterocutaneous fistula (a frequent spontaneous event in this group of patients) while under treatment. No abnormal laboratory tests were observed in the first 165 hyperthermia treatments. Heat damage to normal tissue was limited to skin blisters in three patients and induration of the subcutaneous tissues in 10 patients. Skin pain on an analogue scale of 0-10 was scored by patients as a mean of 3.6 (range 0-8) before skin analgesia was routinely utilized. With anesthetic gel, the skin discomfort was greatly reduced. Prolonged abdominal pain for 4-20 days following treatment which required narcotic analgesia was seen in four patients. A complication rate of 62% was caused by the long-term indwelling temperature probe sheaths. Infection was observed in four patients, small bowel fistula in one, and dislodgement of the temperature probe sheath requiring repeat CT was necessary in seven patients. After maximal escalation of RF power in seven patients (33%), deep hyperthermia compatible with thermal destruction of tumour (≥ 43°C for 45 min) was recorded in all subsequent treatments. In eight patients (38%), heat generation compatible with chemotherapy augmentation (41.5-43°C) was consistently recorded. In six patients, non-therapeutic temperatures were recorded. There was no correlation of maximal tumour temperature, maximal subcutaneous tissue temperature and maximal RF power. With the use of skin anaesthetic there was no correlation of tumour temperature and the thickness of the subcutaneous layer of the skin. Progression was seen in 14 patients, and 11 of these patients died. No patients who showed disease stabilization have died with a minimum of 2 year follow-up. Approximately 2/3 of Western patients can safely tolerate deep hyperthermia compatible with thermal destruction or chemotherapy augmentation with the use of skin anaesthetics. Thermal monitoring remained a problem in this investigation, in that there was a high incidence of adverse events. Increased temperature measured in subcutaneous tissue and tumour did not show a correlation with each other, with RF power, or with occurrence of complications. With localized mucinous tumours of appendiceal origin, deep hyperthermia with escalations of heat to maximal levels tolerated by the patient should continue to be pursued for a remarkable prolonged survival and excellent quality of life was seen in selected patients.