Biological modelling of the radiation dose escalation effect of regional hyperthermia in cervical cancer

Abstract

Background: Locoregional hyperthermia combined with radiotherapy significantly improves locoregional control and overall survival for cervical tumors compared to radiotherapy alone. In this study biological modelling is applied to quantify the effect of radiosensitization for three cervical cancer patients to evaluate the improvement in equivalent dose for the combination treatment with radiotherapy and hyperthermia.

Methods: The Linear-Quadratic (LQ) model extended with temperature-dependent LQ-parameters α and β was used to model radiosensitization by hyperthermia and to calculate the conventional radiation dose that is equivalent in biological effect to the combined radiotherapy and hyperthermia treatment. External beam radiotherapy planning was performed based on a prescription dose of 46Gy in 23 fractions of 2Gy. Hyperthermia treatment using the AMC-4 system was simulated based on the actual optimized system settings used during treatment.

Results: The simulated hyperthermia treatments for the 3 patients yielded a T50 of 40.1 °C, 40.5 °C, 41.1 °C and a T90 of 39.2 °C, 39.7 °C, 40.4 °C, respectively. The combined radiotherapy and hyperthermia treatment resulted in a D95 of 52.5Gy, 55.5Gy, 56.9Gy in the GTV, a dose escalation of 7.3-11.9Gy compared to radiotherapy alone (D95 = 45.0-45.5Gy).

Conclusions: This study applied biological modelling to evaluate radiosensitization by hyperthermia as a radiation-dose escalation for cervical cancer patients. This model is very useful to compare the effectiveness of different treatment schedules for combined radiotherapy and hyperthermia treatments and to guide the design of clinical studies on dose escalation using hyperthermia in a multi-modality setting.

Fig. 1

Workflow. The workflow used consists of first computation of the hyperthermia and radiotherapy dose distributions, followed by matching the radiotherapy dose distribution onto the geometry of the hyperthermia CT scan and finally computation of the equivalent dose distribution

Fig. 2

Image registration/matching. Radiotherapy and hyperthermia CT scans are rigidly matched by visual assessment of the bony anatomy, followed by deformable registration using intensity-based deformable image registration software of Velocity Medical Solutions (Varian Medical systems, Palo Alto). Left: overlay showing the excellent match of the RT-CT onto the HT-CT in the Region of Interest (ROI) indicated with the dotted rectangle. Right: Outlines of rectum, cervix, bladder and part of the bony anatomy are shown in the RT-CT and the HT-CT

Fig. 3

Temperature Volume Histogram. Temperature Volume Histogram (TVH) representing the simulated temperature distribution within the GTV for patient 1, 2 and 3

Fig. 4

Dose Volume Histogram. Dose Volume Histogram reflecting the radiotherapy dose distribution within the GTV for patient 1, 2 and 3 comparing 3 different cases: Radiotherapy alone (RT only), radiotherapy and hyperthermia using a linear interpolation (RT + HT lin) or a piecewise linear interpolation (RT + HT pw lin) to the α and β values from Franken et al. [29]. EBRT only, brachytherapy boost not taken into account

Fig. 5

Radiotherapy and hyperthermia dose distributions. Radiotherapy isodose curves (top left), equivalent radiotherapy isodose curves for radiotherapy + hyperthermia (top right), idem with the hyperthermia temperature distribution overlaid as a color wash (bottom right) for patient #1 with cervical cancer. Radiotherapy isodose curves overlaid on the CT scan of the patient made in hyperthermia position lying on a hyperthermia water bolus. Gross tumour volume (GTV) is indicated by the bold red contour. The contribution of hyperthermia to equivalent radiotherapy isodose is visible within the GTV and increases with increasing temperature in ventral direction. Vaginal pelotte for temperature measurements during hyperthermia is visible adjacent to GTV