Simultaneous superficial hyperthermia and external radiotherapy: report of thermal dosimetry and tolerance to treatment

Abstract

Background : In vitro and animal studies indicate that a moderate temperature of 41°C maintained for ∼ 1h will provide radiosensitization if radiation (RT) and hyperthermia (HT) are delivered simultaneously, but not with sequential treatment. A minimum tumour temperature of 41°C is a more feasible goal than the goal of >42°C needed for sequential treatment. Methods and materials: Forty-four patients with 47 recurrent superficial cancers received simultaneous external beam radiotherapy and superficial hyperthermia on successive IRB approved phase I/II studies. All lesions had failed previous therapy, 35 were previously irradiated (mean dose 52.7Gy). Hyperthermia was delivered with 915MHz microwave or 1-3.5MHz ultrasound using commercially available applicators. The average dimensions of 19 lesions treated with microwave were 4.7 3.6 1.7cm and the average dimensions of 28 lesions treated with ultrasound were 8.0 6.1 2.9cm. The most common sites were chest wall (15 cases) and head and neck (21 cases). Temperatures were monitored at an average of six intratumoral locations using multisensor probes. The median number of hyperthermia treatments was three and the median radiation dose 30Gy. Radiation dose per fraction was 4Gy with hyperthermia and 2Gy or 4Gy (depending on protocol) on non-hyperthermia days. Results: Six different measures of minimum monitored temperature and duration were found to be highly correlated with each other. There was nearly a one-to-one correspondence between minimum tumour time at or above 41°C (Min t41) and minimum tumour Sapareto Dewey equivalent time at 42°C (Min teq42). After four sessions 63% of cases had a per session average Sapareto Dewey equivalent time at 41°C which exceeded 60min in all monitored tumour locations. The complete and partial response rate in evaluable lesions were respectively 21/41 (51% ) and 7/41 (17% ) and were best correlated with site (chest wall showing best response). Toxicity consisted of 10/47 (21% ) slow healing soft tissue ulcers which healed in all cases but required a median of 7 months. The most important predictors for chronic ulceration were cumulative radiation dose >80Gy and complete response to treatment. Conclusions: Minimum tumour temperatures maintained for durations compatible in vitro with thermal radiosensitization (if RT and HT are delivered simultaneously) are clinically feasible and tolerable for broad but superficial lesions amenable to externally applied ultrasound or microwave hyperthermia. The current in-house protocol is evaluating the impact of more than four hyperthermia sessions on the overall thermal dose distribution and toxicity.

• Superficial Simultaneous Hyperthermia;Ionizing Radiation;Thermal;Dosimetry;Ultrasound Hyperthermia;Microwave Hyperthermia