This report has been coordinated by S. Curto, M. Paulides & M. Cavagnaro and it reflects discussions between MyWAVE members during an online meeting held on the 11th January, 2021. Over 90 members participated in the meeting and the needs for standaridsation related to EM hyperthermia, microwave (MW) thermal ablation and the use of nanoparticles for MW thermal therapies were discussed.
The main outcomes are summarised below.
- The Grand challenge devoted to standardization of numerical studies in Hyperthermia by Kemal Sumser.
Hyperthermia treatment adjuvant to radiotherapy and chemotherapy have been in clinical use for almost past 40 years. Hyperthermia treatment planning (HTP) has been an integral part of the hyperthermia field, used not only as a treatment optimization tool but also as a research tool. This led to development of different modelling tools, different numerical models or representative models which led itself into an impossible position in the field to objectively compare the different approaches. A standardization is needed to flourish the developments in the field of numerical studies in hyperthermia. This need can be achieved by,
- Standardized patient models;
- Standardized tissue properties for EM, thermal and ultrasound tissue property modelling;
- Simulation configuration for validation purposes.
ESHO Grand Challenge on HTP aims to solve this issue and streamline the progress in hyperthermia research by providing six open-source anatomical patient models, prescribed tissue properties, simulation configurations, treatment goals and evaluation benchmarks.
Conclusions with respect to the need for Standardisation in Hypthermia
- The need of clarifying the terminology is still an important requirement.
- Standardization is meant to provide guidelines for comparison benchmarking but should not be considered as a golden standard for numerical modelling. There is a fundamental need to add uncertainties in the reported studies.
- There are ongoing efforts on standardization on hyperthermia by ASME thermal medicine committee and the European Society of Hyperthermic Oncology (ESHO) technical committee. These will be discussed futher in a virtual meeting planned for June 2021.
2. Reporting criteria and standardization of numerical and experimental studies in MW thermal ablation by Nevio Tosoratti.
The clinical goal of this technique is to achieve ablation of the entire tumour plus the safety margin. The question whether the goal should be achieved by way of treatment planning or using real time monitoring was discussed and in order to explain the question in more detail, the influence of several factors on the outcome of the procedure are evidenced. In particular, factors are classified in target related factors and source related factors. The target related factors include,
- localization of the tumour (organ, boundary conditions),
- heat sink (vessels, air ways),
- morphology (size and shape),
- biology (histology, other diseases),
- background (dielectric and thermal properties),
- anamnesis (prior treatment change the environment and the properties).
Among the source factors, there are,
- frequency,
- antenna design and construction (cooling),
- cable losses,
- number of antennas and their location,
- overall duration of the procedure, duty factor if pulsed,
- power delivered,
- reflectivity (i.e. antenna matching),
- number of relocations of the antennas, eventual overlapping of successive ablations.
All these factors, and possibly others which have not been identified yet, influence the outcome of the procedure. Indeed, even the “same” treatment over the “same” tumour in the “same” organ gives different results, as evidenced in the clinical literature. This calls for standardization of reporting criteria prior to try developing treatment planning software.
Conclusions with respect to the need for Standardisation in MW thermal ablation
- There is a need for accurate phantom tumour models that truly model tumours in patients. Reference was given to differences between the well-established procedures to validate RF ablation devices against newly developed MW devices. There is a need for new validation paradigms specifically developed for MW apparatuses.
- Predictive models vs monitoring tools. It has been established that the most urgent tools needed in MW thermal ablation are those related to the treatment monitoring. Such systems help controlling the development of the thermally ablated area during the procedure.
- Improving knowledge about the different factors that influence variability of outcomes.
- It was agreed that given the resolution of actual imaging modalities, i.e. CT, a variability of about 10%-15% in the outcome of “identical” procedure would be acceptable.
- There is a need for identification of parameters influencing the outcomes.
- Post-procedure verification of the achievement of the treatment. It has been established that there is sufficient evidence that the thermally ablated area changes its dimensions over the time after the procedure, and, correspondingly, that its appearance in the CT image changes. However, no standard exists on how and when to perform the check about the actual achievement of MW thermal ablation procedures.
3. Nanoparticles in MW thermal therapies by Daniel Ortega
The localized heating of magnetic nanoparticles (MNPs) via the application of time-varying magnetic fields – a process known as magnetic field hyperthermia (MFH) – can greatly enhance existing options for cancer treatment; but for broad clinical uptake its optimization, reproducibility and safety must be comprehensively proven. As part of this effort, the quantification of MNP heating – characterized by the specific loss power (SLP), measured in W/g, or by the intrinsic loss power (ILP), in Hm2/kg – is frequently reported. However, in SLP/ILP measurements to date, the apparatus, the analysis techniques and the field conditions used by different researchers have varied greatly, leading to questions as to the reproducibility of the measurements.
There is a current lack of harmonization in MFH characterization of MNPs as well as growing need for standardized, quantitative characterization techniques for this emerging medical technology. A recently published European interlaboratory study shows that although there is very good intralaboratory repeatability in reported SLP/ILP data, the overall interlaboratory measurement accuracy is poor. There is a strong systematic component to the uncertainties, and a clear rank correlation between the measuring laboratory and the ILP. Both of these are indications of a current lack of normalization in this field. A number of possible sources of systematic uncertainties are identified, and means determined to alleviate or minimize them. However, no single dominant factor was identified, and significant work remains to ascertain and remove the remaining uncertainty sources.
Conclusions with respect to the need for Standardisation in the use of nanoparticles
- An overview of the preclinical assessment of nanoparticles for hyperthermic techniques was given. This included a discussion on whether it would be worth trying to push other nanoparticle compositions to provide better features than those already offered by the approved ones (mainly iron oxides). The balance between approval time/cost and improved features was considered, but it turned out that no other nanoparticle-based formulations are in the position of beating the balance and enter the preclinical approval.
- Alternative exploitation of physical properties of nanoparticles. Focusing on different physical properties of nanoparticles to improve the prospects for applications in hyperthermia was suggested, for example magnetic permeability. Also, exploring a different frequency range different from the typical kHz one in magnetic fluid hyperthermia was also proposed.
- Broader use of nanoparticles. Participants pointed out different possibilities to extend the current field of use of nanoparticles (rather than only in magnetic fluid hyperthermia), primarily to enhance the performance in other hyperthermic modalities using higher frequencies or based on different physical phenomena (MW, ultrasounds, etc.). Perhaps it will be useful to put together (collaboratively) a catalogue of applications/indications, along with improvement prospects by including nanoparticles.
- There was a discussion about different ways to deliver the particles to the tumor region and if it is possible to prevent regions of higher particle concentration, which leads to unwanted hot spots during therapy
- There was a discussion for which purpose the MNP in the tissue can be used additionally, e.g. measuring the tumor/tissue temperature by analysation of the temperature dependent alteration of the magnetic properties of the MNP or the imaging of the particle distribution by means of MPI.
