Hyperthermia, elevating tumor temperatures to 40-43°C, is used to sensitize tumors to maximize radiotherapy and chemotherapy efficacy. The benefit of adding hyperthermia has been clinically proven in randomized trials during the past decades. This evidence led to reimbursement in the Netherlands for its application in combination with radiotherapy and/or chemotherapy for a number of tumor sites, including melanoma, rectum cancer, cervical cancer, recurrent breast cancer, non-muscle-invasive bladder cancer (HIVEC) and peritoneal metastases of different origin (HIPEC). There are also strong indications that hyperthermia treatment may be beneficial for patients with other tumor types.
The effects of hyperthermia on tumor cells are pleiotropic, and there is still much debate regarding the most relevant effects for its clinical efficacy as well as the implications for optimal clinical delivery of hyperthermia. Determining the ideal temperature, along with the timing and sequence of combining hyperthermia with radiotherapy or chemotherapy, remains a topic of active research. While treatment delivery and temperature monitoring and control work effectively for a number of tumor sites, they pose challenges for others. Clinical practitioners must be thoroughly trained to maintain strict quality assurance when administrating hyperthermia to ensure optimal clinical results.
The aims of the Hyperthermia Research Team include:
1) The development and optimization of clinical hyperthermia techniques
2) Clinical research to establish and improve the clinical benefit of hyperthermia
3) Fundamental research into the clinically relevant working mechanisms of hyperthermia
An interdisciplinary team at Amsterdam UMC—Cancer Center Amsterdam, composed of biologists, clinicians, and physicists, is collaborating to achieve these goals,
together with group leaders and principal investigators from various departments
of Amsterdam UMC (radiation oncology, CEMM, medical biology, radiology, medical
oncology, surgery, gynecology and urology). The effort also engages national
and international networks, including our initiative Hyperboost, an
interdisciplinary consortium of 11 European institutes funded by the European
Union (www.hyperboost.eu), and an international group comprised of researchers using hyperthermia equipment developed at Amsterdam UMC. At a national level, the team is involved in projects like the Dutch Cancer Society (KWF) RT-HYPE project, targeting recurrent breast cancer, and the Dutch Research Council (NWO) CARES, focusing on the innovation of novel applicator designs.
The Aims of the Hyperthermia Research Team
1) The development and optimization of clinical hyperthermia techniques
A key objective is the development of effective and user-friendly hyperthermia technology for various tumor sites, ensuring the achievement of therapeutic temperatures crucial for treatment efficacy. This is critical due to the strong dose-effect relationships we encountered in both our clinical and preclinical research. We need to enhance the control of the heat distribution, guided by real-time temperature monitoring and dedicated treatment planning systems. The technology, primarily based on electromagnetic energy deposition in various tumor targets, continues to improve due to our collaborative research efforts. Commercializing this technology is an important final step to promote its worldwide application and create an international hyperthermia community to facilitate high quality and well-controlled treatment applications. A growing number of institutes in Europe and Asia are already using the commercial version of our technology.
2) Clinical research to establish and improve the clinical benefit of hyperthermia
Establishing robust clinical evidence is crucial for the clinical acceptance and use of hyperthermia treatment. We are analyzing the clinical benefit and efficacy of combining hyperthermia with radiotherapy and chemotherapy for various cancers, including but not limited to, breast, cervix, bladder, and peritoneal metastases. Collaborating with various groups within and outside Amsterdam UMC, this work has led to the reimbursement for hyperthermia for a number of indications and elucidated dose-effect relationships, stressing the importance of advanced technology and good quality assurance to ensure optimal therapeutic outcomes. These investigations aim to reinforce hyperthermia’s role in cancer treatment.
3) Fundamental research into the working mechanisms of hyperthermia.
Our fundamental research includes in vitro and in vivo studies to study various working mechanisms and to optimize the synergistic effects of hyperthermia with radiotherapy and chemotherapy. We have also developed a small animal hyperthermia device to study hyperthermia effects in an orthotopic mouse model in collaboration with other Dutch institutes. This research has led to a better understanding of the optimal temperature dose and best sequence and timing with radiotherapy, chemotherapy and immunotherapy. This important knowledge is being utilized to improve the design of clinical equipment and to modify clinical treatment schedules to maximize therapeutic synergies and improve patient outcome.
For more information, contact Dr. Hans Crezee.
Team members:
Daphne de Vries-Huizing (technical physicist)
Pierre Agnass (PhD student)
Bella Bokan (PhD student)
Jort Groen (PhD student)
Timoteo Herrera (PhD student)
Marloes IJff (PhD student)
Artemis Kontogoula (PhD student)
Pouya Namakshenas (PhD student)
Paola Tello Valverde (PhD student)
Fan Yang (PhD student)
Enzo Scutigliani (PostDoc)
Hans Crezee (PI)
Collaborating PI’s and group leaders
Petra Kok
Arlene Oei
Jurriaan Tuynman
Oliver Gurney-Champion
Marc Besselink
Maarten Bijlsma
Przemek Krawczyk
Desirée van den Bongard
Hanneke van Laarhoven
Lukas Stalpers
Collaborating companies:
Medlogix: https://www.albahyperthermia.com/
Financial support:
Dutch Cancer Society (KWF)
Dutch Research Council (NWO)
European Union
Website: https://researchinformation.amsterdamumc.org/en/persons/johannes-crezee
Text Hans Crezee.
This article was created for Cancer Center Amsterdam.