Advancing hyperthermia treatment through treatment planning and small animal research

Hyperthermia, the heating of tumours to 40–43 °C for one hour, is an established sensitiser to radiotherapy and chemotherapy, effective in several cancers such as melanoma, sarcoma, bladder, recurrent breast, cervix, and rectum. New applications include pancreatic cancer and combinations with immunotherapy. Wider adoption, especially for deep-seated tumours, requires consistent clinical protocols, yet current progress is hindered by variability across institutes and insufficient translational models.
This thesis addresses hyperthermia treatment consistency through two main aims: improving the accuracy of hyperthermia treatment planning (HTP) for deep-seated tumours, and enabling clinically representative small-animal studies. In Chapter 2, uncertainty in tissue properties and perfusion was systematically evaluated using a Polynomial Chaos Expansion (PCE) methodology. Results showed that electrical conductivity and perfusion strongly affect predicted temperatures, with variations of up to 9 °C in pancreatic cases. In Chapter 3, robust stochastic optimisation strategies were developed to mitigate these uncertainties, reducing hotspots while maintaining effective tumour heating, thus improving treatment reliability and reducing operator adjustments.
Chapters 4, 5, and 6 focus on translational research with the ALBA micro8, a novel miniature phased-array system for mice. Simulations and phantom experiments demonstrated its ability to achieve precise and robust heating of deep-seated tumours under realistic conditions, with high spatial accuracy and tolerance to physiological variations. Dedicated bioheat models for mice further enhanced preclinical HTP accuracy. This system provides a reliable platform for studying hyperthermia’s biological and immunological effects in tumour models.
Overall, the research strengthens the foundation for standardised, reproducible hyperthermia delivery, facilitating multi-centre trials and broader clinical implementation. Standardisation and improved consistency will support wider adoption and reimbursement, ultimately advancing oncological care.