Hyperthermia treatment planning [
25] is a standard clinical procedure at the AMC and is based on a CT-scan in hyperthermia treatment position, i.e. in supine position on a water bolus and mattresses. Treatment planning was performed using a non-commercial software package developed at the AMC. Hounsfield Unit based segmentation was applied to segment the CT scan into muscle, fat, bone and air [
32], to which literature-based dielectric and thermal tissue properties were assigned (Table
1). The tumor was delineated manually by a radiation oncologist. Hyperthermia treatment was simulated for the AMC-4 locoregional heating device. Electric field distributions in the patient were calculated at a resolution of 2.5x2.5x2.5 mm
3 by solving Maxwell’s equations with the Finite Difference Time Domain method [
33]. Antenna settings yielding an optimal steady-state tumor temperature distribution were determined using temperature-based optimization [
34]. Heat-transfer computations for perfused tissues were based on the Pennes bio heat model [
35]. In clinical hyperthermia tumor temperatures are usually reported as
T10,
T50 and
T90, i.e. the temperature at least achieved in 10, 50 and 90 % of the target volume, respectively [
36,
37]. A tumor temperature of 43 °C was the objective for optimization, normal tissue temperatures were constrained to 45 °C.
Table 1
Dielectric and thermal tissue properties used in hyperthermia treatment planning
Air | 0 | 1 | 1.29 | 0 | 0.024 | 10,000a
|
Bone | 0.05 | 10 | 1595 | 0.12 | 0.65 | 1420 |
Muscle | 0.75 | 75 | 1050 | 3.6 | 0.56 | 3639 |
Fat | 0.06 | 10 | 888 | 1.1 | 0.217 | 2387 |
Cervical tumor | 0.74 | 65 | 1050 | 1.8 | 0.56 | 3639 |
Subsequently five weekly treatment sessions were given during the period external beam irradiation was given, one hour after a radiotherapy session. Hyperthermia was performed with the AMC-4 system consisting of four 70 MHz waveguides around the pelvis of the patient, with water bags cooled to 13 °C between waveguide and skin provide coupling of energy and skin cooling [
38]. Thermometry consisted of thermocouple thermometry probes in the bladder, rectum and in a vaginal pelotte for temperature measurements during hyperthermia, yielding measurement points bordering the GTV. Phase settings during treatment are the pre-planned settings, modified after performing phase sweeps at the start of treatment [
36], followed by a final phase optimization using three delta T pulses to achieve preferential heating of the cervix compared to bladder and rectum [
39]. The simulated tumor temperatures for these phase and amplitude settings were used for biological modelling and were also compared with temperatures measured during the first hyperthermia session. The first session was chosen since the patient anatomy during this session best matches the anatomy as determined during CT and are thus expected to yield more reliable planning results than for later sessions.