Better thermal-based EM therapeutics
This group works on three focus areas:
- optimising the technology for existing thermal-based EM applications and developing ideas for novel clinical applications,
- improving Treatment Planning protocols,
- improving Quality Assurance (QA) of existing thermal-based EM technologies.
You can download the latest progress report here.
Establishing the needs for Standardisation in EM hyperthermic technologies.
Clinical needs to be addressed with EM Therapeutics (Deliverable 2.1)
First issued: September 2019
Coordinated by: Gennaro Bellizzi – g.bellizzi[at]erasmusmc.nl, Marta Cavagnaro – marta.cavagnaro[at]uniroma1.it and Maarten Paulides – m.m.paulides[at]tue.nl
Background and motivation
Electromagnetic (EM) hyperthermic technologies hold great potential in the treatment of diseases, especially for cancers that are resistant to standard regimens. These technologies modify tissue temperature: hyperthermia heats the diseased tissue to make it susceptible to treatments, and ablation heats the tissue until it is destroyed. Overall, these techniques have shown significant potential and there is substantial opportunity to solidify their use clinically and to apply them to a wider range of medical conditions.
However, the increase in the market share of these techniques doesn’t reflect their potentialities nor the great number of researchers working in these areas. Contributing to the stagnant market of EM hyperthermic medical devices is the fact that researchers working on the development of medical technologies are often not fully aware of the clinical challenges related to these medical devices. Hence, workgroup (WG) 2 the MyWAVE Action takes a holistic approach, by bringing together key players in the field of fundamental and translational research and medical professionals, to create a comprehensive overview of the clinical needs to be addressed with EM Therapeutics. In this way, we aim to stimulate and guide efforts into design and development of novel EM hyperthermic technologies, so that they can reach patients faster and improve treatment outcomes.
This deliverable is strictly related to the first milestone of the action,
Establish clinical needs that thermal-based interventions may be used to address.
Following the discussion in the network, the identified clinical needs to be addressed with EM therapeutics were divided in four different categories, defined as:
1. Devices and Device QA
2. Treatment planning
3. Real time dosimetry
4. Quality assurance
Here below, the clinical needs are reported and discussed.
1 – Devices and Device QA
- Affordable systems
In view of ever-growing costs of healthcare, it is of utmost importance to have affordable and competitive thermal therapy (hyperthermia and ablation) systems. Here not only the costs of the system but also the total costs of ownership (acquisition, operation and maintenance) are important. These combined costs should balance well against the benefits, which is often expressed in the costs per quality adjusted life year (costs per QALY). The threshold for introduction is country dependent but for e.g. the Netherlands in the range of 20.000 € or 80.000 € per QALY for low or high-tech medical systems, respectively.
- System QA compliance
Reproducibility of system’s performance over its life time has a pivotal role in encouraging thermal therapies clinical acceptance. This item states the need of developing appropriate standard procedures to verify system QA compliance before entering the market (see section 4). Additionally, standard procedures are needed to verify systems performances during their lifetime, to look for possible degradation due to the use. These procedures should be easy and quick to perform but they should be repeated over a regular basis and appropriately reported. Finally, procedures to verify system performances during the delivery of the treatment are needed; they should foresee suitable measurements to be performed, possibly without interfering with the treatment.
- Actual magnetic contrast dose administration
This item is related to magnetic field hyperthermia, wherein the heating is mediated by the targeting of a magnetic fluid (e.g. contrast agent). The related needs are the definition of the dose of the magnetic fluid to be injected in the tissue, and the development of prediction tools for the magnetic nanoparticle (MNP) distribution and the related distribution of the temperature increase within the target tissue
2 – Treatment planning
- TP validation
Definition of case-studies to be used to validate the software used for treatment planning should be defined. Moreover, methods to verify veracity of the achieved results and their applicability in the clinical settings should be defined.
- Knowledge on dielectric and thermal tissue properties [this item connects to the work in MyWave WG1]
Dielectric and thermal properties of human body tissues are crucial in the accuracy of 3D electromagnetic and thermal simulations. These simulations are becoming inevitable for optimizing treatment settings before or during treatment, as well as for optimized device designs. Important in this respect are also the temperature and time (thermoregulation) dependence of the (EM&T) tissue properties. In addition, these values are very different among different patients, different biological tissues, and among benign, malign and normal tissue.
- Predictive treatment quality surrogate parameters
Therapy outcome critically depends on the optimization of the correct performance parameter. In thermal therapies, several parameters, based on Specific Absorption Rate (SAR), temperature, and/or thermal dose exist, but their validation against clinical outcome is sparse.
- Uncertainty/variability management
Tissue properties are not known with the required accuracy; accordingly, comprehensive methods to deal with these uncertainties are required to design the best devices and provide the clinicians insight in modelling uncertainties.
- User interaction
Treatment planning tools should be operator friendly and the combination of tool and procedures should make the treatment operator independent.
3 – Realtime dosimetry
- Standardized treatment monitoring procedures for invasive thermometry
Invasive thermometry is long being used for documentation of the treatment but, although guidelines exists, these are not standardly applied due to their complexity. A revision of the guidelines is required.
- Standardized treatment monitoring tools for non-invasive thermometry
A number of tools are under development (MRI-, simulation- and drug-delivery based) for non-invasive real-time dose assessment but clinical validation and standardisation are still highly required.
The definition of Key Performances Indicators to test and compare the different tools is highly recommended.
- Assessment of the relation between temperature and tissue damage
The biological mechanisms of action, different between hyperthermia and thermal ablation, should be investigated to allow defining the relation between the “thermal dose” and tissue damage, as well as to translate in-vitro/ex-vivo findings and evaluation methods to in-vivo. This investigation should tackle the diverse characteristics of normal and cancerous tissues, that have different time-temperature dependent tolerance against heat.
In addition, in hyperthermia treatments, repeated application of heat might lead to thermotolerance.
A deep investigation of applicability of CEM43 in the different tissues is needed
5 – Quality assurance
- Quality assurance protocols
Quality assurance protocols, accepted by the authorised organisations (e.g. ESHO, STM, etc.) should be defined. They should form the basis for deriving protocols per device, treatment planning and treatment quality monitoring technology.
- Repository
Creation of repository of all performed treatments would help exchange of information and experiences and development of meta-analysis to prove efficacy of the treatments and related parameters to maintain under control.
- Lexicon
A common lexicon should be developed to help correct exchange of information among the different disciplines involved in EM-based therapeutics, e.g., clinicians, engineers, physicians, biologists, etc
6 – Conclusions and future perspectives
The above-listed clinical needs delineate several research lines to be followed by the community to help improving clinical application of electromagnetics therapies. They will be the object of the work undertaken by the MyWave network. In particular, following the roadmap of the action, future efforts will be devoted to the discussion of standardized simulations for treatment planning, aiming at investigating the deficiencies and challenges in existing treatment protocols, and new approaches in treatment planning and standardization.
Procedure towards the final draft of D2.1:
- v0.1 – expanded inventory from the Malta meeting
- v0.2 (June 2019) – version after updates based on comments and suggestions from the WG2 members. This version was presented at the Sibiu meeting (July 2019)
- v1.0 (October 2019) – updated version after the Sibiu meeting. This is released as deliverable D2.1, but we intend the document as a “live” document to be updated during the action if new contributions come from the network
- v2.0 (2022) – final version at the end of MyWave
