Thermoradiotherapy planning: Integration in routine clinical practice

Abstract

Planning of combined radiotherapy and hyperthermia treatments should be performed taking the synergistic action between the two modalities into account. This work evaluates the available experimental data on cytotoxicity of combined radiotherapy and hyperthermia treatment and the requirements for integration of hyperthermia and radiotherapy treatment planning into a single planning platform. The underlying synergistic mechanisms of hyperthermia include inhibiting DNA repair, selective killing of radioresistant hypoxic tumour tissue and increased radiosensitivity by enhanced tissue perfusion. Each of these mechanisms displays different dose-effect relations, different optimal time intervals and different optimal sequences between radiotherapy and hyperthermia. Radiosensitisation can be modelled using the linear-quadratic (LQ) model to account for DNA repair inhibition by hyperthermia. In a recent study, an LQ model-based thermoradiotherapy planning (TRTP) system was used to demonstrate that dose escalation by hyperthermia is equivalent to $10 Gy for prostate cancer patients treated with radiotherapy. The first step for more reliable TRTP is further expansion of the data set of LQ parameters for normally oxygenated normal and tumour tissue valid over the temperature range used clinically and for the relevant time intervals between radiotherapy and hyperthermia. The next step is to model the effect of hyperthermia in hypoxic tumour cells including the physiological response to hyperthermia and the resulting reoxygenation. Thermoradiotherapy planning is feasible and a necessity for an optimal clinical application of hyperthermia combined with radiotherapy in individual patients.

A short time interval between radiotherapy and hyperthermia reduces in-field recurrence and mortality in women with advanced cervical cancer

“…These pre-clinical experiments were performed at higher temperatures (42.5–43 °C) than what is generally achieved in the clinic, and the contribution of the various mechanisms of hyperthermia (e.g. DNA repair inhibition, reoxygenation and direct cytotoxicity) may be different at lower temperatures [26]. Nonetheless, these data corroborate the difference in local control observed in this study.…”

“…Multiple mechanisms have been suggested for the radiosensitizing effect of hyperthermia [26]. In our institute, hyperthermia is delivered after radiation, and the ability of heat to interfere with DNA damage repair is an important mechanism for radiosensitization for this treatment sequence [6, 7].…”

Integrating Hyperthermia into Modern Radiation Oncology: What Evidence Is Necessary?

“…HT may as well be further improved by better planning techniques. Mathematical modeling of the earlier mentioned HT effects on cell biology has paved the way to actual thermoradiotherapy planning (4). By integrating the biological HT effect into the LQ-model, a more exact RTHT treatment planning becomes possible.…”

“…The interval of administration of HT relative to RT has great influence on its effectiveness. The actual effect is quantified with the thermal enhancement ratio (TER) defined as the ratio of the respective radiation doses of RT alone divided by the RT + HT dose necessary to receive equal survival curves (4). However, biological aspects of HT react differently to the extent of heating sequence of HT.…”

Planning, optimisation and evaluation of hyperthermia treatments

“…Ongoing research focuses on integration of radiotherapy and hyperthermia treatment planning to realise thermoradiotherapy treatment planning [97]. In the future, this framework could be extended to model also more complex multi-modality treatments including other combinations with radiotherapy and hyperthermia, such as chemotherapy, halogenated pyrimidines or poly(ADP-ribose) polymerase-1 (PARP1) inhibitors [98,99].…”