Biological modeling in thermoradiotherapy: present status and ongoing developments toward routine clinical use

Abstract

Biological modeling for anti-cancer treatments using mathematical models can be very supportive in gaining more insight into dynamic processes responsible for cellular response to treatment, and predicting, evaluating and optimizing therapeutic effects of treatment. This review presents an overview of the current status of biological modeling for hyperthermia in combination with radiotherapy (thermoradiotherapy). Various distinct models have been proposed in the literature, with varying complexity; initially aiming to model the effect of hyperthermia alone, and later on to predict the effect of the combined thermoradiotherapy treatment. Most commonly used models are based on an extension of the linear-quadratic (LQ)-model enabling an easy translation to radiotherapy where the LQ model is widely used. Basic predictions of cell survival have further progressed toward 3 D equivalent dose predictions, i.e., the radiation dose that would be needed without hyperthermia to achieve the same biological effect as the combined thermoradiotherapy treatment. This approach, with the use of temperature-dependent model parameters, allows theoretical evaluation of the effectiveness of different treatment strategies in individual patients, as well as in patient cohorts. This review discusses the significant progress that has been made in biological modeling for hyperthermia combined with radiotherapy. In the future, when adequate temperature-dependent LQ-parameters will be available for a large number of tumor sites and normal tissues, biological modeling can be expected to be of great clinical importance to further optimize combined treatments, optimize clinical protocols and guide further clinical studies.

Development of Cationic Lipid LAH4-L1 siRNA Complexes for Focused Ultrasound Enhanced Tumor Uptake

“…34 For decades, it has been observed that hyperthermia has a synergistic effect with neoadjuvant chemotherapeutics and radiotherapy in the clinic, improving the treatments. 35,36 Tumor vascular permeability presents one of the important challenges which needs to be overcome to improve drug delivery. Local hyperthermia increases the pore size in tumor vasculature, reduce hydrodynamic burdens, like those stimulated by the intratumoral interstitial fluid flow and pressure which could lead to nanoparticle (∼100 to 150 nm in diameter) extravasation.…”

Biological treatment evaluation in thermoradiotherapy: application in cervical cancer patients

“…The biological treatment evaluation provides insight into the effect of time interval, which is not accounted for in standard thermal dose evaluation and allows qualitative evaluation of dose heterogeneity and different treatment scenarios with varying time intervals. Future research aims at more advanced models also including other relevant hyperthermia mechanisms [ 19 ]. This challenging task requires carefully designed preclinical experiments to obtain essential modelling parameters as a function of temperature and time interval.…”

“…Biological modelling could be very helpful to model dynamic processes responsible for cellular response to treatment, thereby providing more insight into clinical implications of the complex synergy between radiotherapy and hyperthermia [ 19 ]. In radiotherapy, biological modelling is quite common to compare fractionation schemes, or to predict tumor control and normal tissue toxicity [ 20 , 21 ].…”

Application of an artificial intelligence segmentation for deep hyperthermia treatment planning in the pelvic region

“…However, the EVPR models consist of a limited amount of tissues, such as fat, muscle, bone, internal air and tumour. The implemented AI segmentation allows to conduct simulation studies including temperature and thermoradiotherapy modelling with realistic patient 3D models [28][29][30]. These 3D models can be obtained from widely available public repositories, enabling non-clinical groups to also work in this area of research.…”