Quality Assurance and Regulatory Frameworks for Hyperthermia Therapy
Doctoral thesis, 2025
Hyperthermia (HT) has shown to be a powerful enhancer of chemotherapy and radiotherapy in numerous clinical trials. Its therapeutic effectiveness depends on the thermal dose delivered, which is determined by the quality and consistency of the applied heating. Quality Assurance (QA) guidelines ensure that HT devices deliver heat in a controlled, safe, and reproducible manner.
However, translation of QA guidelines into routine clinical practice has been limited by the lack of suitable tools and the lack of practical implementation guidance. This thesis addresses these gaps by (i) developing new phantoms for HT QA and (ii) demonstrating the application of the latest QA guidelines for both superficial (SHT) and deep HT (DHT).
For SHT applications, a novel fat-mimicking phantom was developed using an ethylcellulose-stabilized glycerol-in-oil emulsion. This material exhibited dielectric and thermal properties representative of fat tissue, with acceptable variability across the frequency range relevant for HT. Subsequently, it was applied in the QA evaluation of the DHT Lucite Cone Applicator (LCA), following the quality metrics defined in current HT guidelines. This experience provided practical insight into the implementation of guidelines in the clinical environment.
For DHT, the phantom design was optimised, supported by computational studies, to represent different anatomical areas. These phantoms were then used in a multi-institutional QA comparative study involving six European HT centress, in which the heating and focusing ability of clinically used DHT devices was evaluated. The study also revealed several practical challenges in QA implementation, including experimental setup, probe calibration, procedure duration, and the definition of suitable quality metrics. These findings directly contributed to the development of the latest QA guidelines for deep HT and support their integration into routine clinical practice.
Finally, the relationship between QA guidelines and the EU Medical Devices Regulation (MDR) regulatory framework was clarified using an in-house developed phased-array radiative applicator as a case study, outlining key steps from preliminary investigation to system verification and validation.
However, translation of QA guidelines into routine clinical practice has been limited by the lack of suitable tools and the lack of practical implementation guidance. This thesis addresses these gaps by (i) developing new phantoms for HT QA and (ii) demonstrating the application of the latest QA guidelines for both superficial (SHT) and deep HT (DHT).
For SHT applications, a novel fat-mimicking phantom was developed using an ethylcellulose-stabilized glycerol-in-oil emulsion. This material exhibited dielectric and thermal properties representative of fat tissue, with acceptable variability across the frequency range relevant for HT. Subsequently, it was applied in the QA evaluation of the DHT Lucite Cone Applicator (LCA), following the quality metrics defined in current HT guidelines. This experience provided practical insight into the implementation of guidelines in the clinical environment.
For DHT, the phantom design was optimised, supported by computational studies, to represent different anatomical areas. These phantoms were then used in a multi-institutional QA comparative study involving six European HT centress, in which the heating and focusing ability of clinically used DHT devices was evaluated. The study also revealed several practical challenges in QA implementation, including experimental setup, probe calibration, procedure duration, and the definition of suitable quality metrics. These findings directly contributed to the development of the latest QA guidelines for deep HT and support their integration into routine clinical practice.
Finally, the relationship between QA guidelines and the EU Medical Devices Regulation (MDR) regulatory framework was clarified using an in-house developed phased-array radiative applicator as a case study, outlining key steps from preliminary investigation to system verification and validation.
MDR
Quality Assurance
Hyperthermia
Phantoms
Thermal Dosimetry
EB, Hörsalsvägen 11
Opponent: Professor Kavitha Arunachalam, Indian Institute of Technology Madras
Author
Mattia de Lazzari
Chalmers, Electrical Engineering, Signal Processing and Biomedical Engineering
Ethylcellulose-stabilized fat-tissue phantom for quality assurance in clinical hyperthermia
International Journal of Hyperthermia,;Vol. 40(2023)
Journal article
Application of the ESHO-QA guidelines for determining the performance of the LCA superficial hyperthermia heating system
International Journal of Hyperthermia,;Vol. 40(2023)
Journal article
Toward enhanced quality assurance guidelines for deep hyperthermia devices: a multi-institution study
International Journal of Hyperthermia,;Vol. 41(2024)
Journal article
Mattia De Lazzari, Hana Dobšíček Trefná, Carolina C. Seabra, Sergio Curto, Dario B. Rodrigues; Quality Assurance Phantoms for Deep Hyperthermia Devices: Design Principles Informed by Computational Modeling
Mattia De Lazzari, Anton Rink, Patrick V. Granton, Dario B. Rodrigues, Hana Dobšíček Trefná; Navigating EU MDR 2017/745 for in-house deep hyperthermia systems: A practical workflow and case study
Treating cancer with heat? That’s the idea behind hyperthermia, a technique in which a tumor is gently warmed to about 40-44 °C for roughly an hour. Why heat? Because elevated temperatures make cancer cells more sensitive to standard treatments like radiotherapy and chemotherapy. In practice, this means these therapies can work more effectively, or achieve the same results with lower doses.
To deliver this heat, the patient lies inside (or beneath) a device called applicator that functions, in simple terms, a bit like a patient-sized microwave oven. But unlike the one in your kitchen, these medical systems focus their energy precisely on the tumor, leaving surrounding healthy tissues largely unaffected. This naturally raises an important question: how do we know such systems are safe, accurate, and ready for patient care?
This thesis addresses that challenge. It focuses on developing and implementing Quality Assurance (QA) procedures, routine checks that ensure the device performs exactly as intended. This required designing dedicated test tools, called phantoms, which stand in for patients and allow the system to be evaluated safely and repeatedly. Using these tools, the proposed QA procedures were tested, refined, and made more practical for clinical use. In parallel, the work explores how these QA activities relate to the European Medical Device Regulation (MDR), the legal framework that defines the safety and performance requirements for all medical devices. Understanding this connection is essential for bringing new hyperthermia technologies from the lab to the clinic.
Together, these contributions help bridge the gap between regulation and everyday clinical practice, ultimately supporting safer treatments and the development of future hyperthermia technology.
To deliver this heat, the patient lies inside (or beneath) a device called applicator that functions, in simple terms, a bit like a patient-sized microwave oven. But unlike the one in your kitchen, these medical systems focus their energy precisely on the tumor, leaving surrounding healthy tissues largely unaffected. This naturally raises an important question: how do we know such systems are safe, accurate, and ready for patient care?
This thesis addresses that challenge. It focuses on developing and implementing Quality Assurance (QA) procedures, routine checks that ensure the device performs exactly as intended. This required designing dedicated test tools, called phantoms, which stand in for patients and allow the system to be evaluated safely and repeatedly. Using these tools, the proposed QA procedures were tested, refined, and made more practical for clinical use. In parallel, the work explores how these QA activities relate to the European Medical Device Regulation (MDR), the legal framework that defines the safety and performance requirements for all medical devices. Understanding this connection is essential for bringing new hyperthermia technologies from the lab to the clinic.
Together, these contributions help bridge the gap between regulation and everyday clinical practice, ultimately supporting safer treatments and the development of future hyperthermia technology.
Subject Categories (SSIF 2025)
Medical Engineering
Health Sciences
Electrical Engineering, Electronic Engineering, Information Engineering
Areas of Advance
Health Engineering
DOI
10.63959/chalmers.dt/5794
ISBN
978-91-8103-337-3
Doktorsavhandlingar vid Chalmers tekniska högskola. Ny serie: 5794
Publisher
Chalmers
EB, Hörsalsvägen 11
Opponent: Professor Kavitha Arunachalam, Indian Institute of Technology Madras