RaCHy PROJECT

Radiotherapy coupled with Hyperthermia

The main goal of radiotherapy is to destroy or damage all cancer cells to stop any proliferation mechanism.
Unfortunately, normal tissue toxicity can limit dose and late effects can affect quality of life after radiotherapy, thus, it is extremely important to further optimize the therapeutic ratio. A promising approach is the combination of radiotherapy with hyperthermia, a treatment to locally increase tissue temperature, which enhances radiosensitivity by order of magnitude. The goal is to develop a metrological framework for optimization of the therapeutic ratio of new techniques for radiotherapy coupled to hyperthermia. in vitro and in vivo experiments will establish the best combination in terms of equivalent dose and biological effect.

The aim of the JRP is to provide a reliable metrology framework for the evaluation of a class of radiation-based therapies coupled with hyperthermia induced by

  • Therapeutic Ultrasound (TUS)

  • Conventional Electromagnetic Radiation (EMR)

  • Magnetic nano particles (MNPs)

Tumor cell lines have a large capacity to recover from potentially lethal radiation damage.

Since hyperthermia causes radiosensitization and inhibition of recovery from radiation damage, its combination with radiotherapy creates a potent combination for treating human tumors.

Scientific and technological objectives

The overall objective of the project is to develop a metrological framework and measurement techniques that underpin the integration of clinical radiotherapy with hyperthermia treatments. The specific objectives of the project are:

  • To develop heat delivery systems for hyperthermia treatments (TUS, EMR and MNPs) – WP1

  • To extend and better quantify temperature exposure evaluation – WP2

  • To determine by in vitro and in vivo testing, using a metrological approach, the efficiency of combined therapies – WP3

  • To develop innovative analytical tools for biological assessment – WP4

  • To facilitate the review of Biological Equivalent Dose (BED) concept related to the radiotherapy combined with hyperthermia – WP5

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PROGRESS

Progress beyond the state of the art and expected results

The project will improve the state of the art in a number of different disciplines, for example: TUS, EMR, MNP based hyperthermia, radiation therapy, RT, biological assessment and in silico modelling.

Heat delivery systems for hyperthermia treatments (TUS, EMR and MNPs)
New experimental and modelling methodologies will be developed in the medical ultrasound field to enable the prediction of power deposition and temperature profiles within biological media during TUS hyperthermia.
The temperature profile will be measured during exposure, to ensure a safe and effective treatment. The goal is therefore to improve the efficacy, safety and range of applicability of clinical TUS treatments by providing validated methods for ultrasonic field characterisation.

Temperature exposure evaluation
Advanced Electromagnetic Field, EMF, modelling will be performed to assist the design of novel RF applicators for in vivo characterisation, with the aim of generating uniform power deposition and temperature increase patterns, with limited off-target energy delivery. Although its safety and efficacy have been proved in several clinical trials, it still suffers from poor reproducibility and temperature distribution control, thus making the improvement of heating uniformity and target specificity is a significant metrological issue.

in vitro and in vivo testing using a metrological approach
A promising approach to improve selectivity and thermal homogeneity is represented by magnetically mediated hyperthermia, where MNPs are employed as local heating sources after their injection into the tissue and exposure to external magnetic fields with frequencies from 50 kHz to 1.2 MHz. Novel heat nanomediators, such as NiFe and FePd nanodisks, whose heating contribution comes from hysteresis losses, and which allow a strong enhancement of specific loss power (SLP), will be developed.

Innovative analytical tools for biological assessment
The integration of radiotherapy with hyperthermia requires experimental studies to accurately assess the biological mechanisms involved at a cellular level (e.g. the inhibition of DNA repair mechanisms caused by heat exposure). The increased understanding of the involved biological mechanisms will allow clinicians to prescribe the required thermal and radiation doses, according to the individual patient’s needs.

Review of the Biological Equivalent Dose (BED) concept
The growing interest in multimodality therapies that combine hyperthermia and ionising radiation is expected to extend the equivalent dose concept by including the synergistic effect of heat on the radiation-induced biological effect. The parameter is expected to be a complex function of a number of factors, including the local temperature, the way heating is generated and delivered with respect to ionising radiation, the heating duration, the temperature distribution within a tumour or the considered organ, the physical and biological characteristics of the tissue, the radiation dose, dose rate and fractionation.