Scientific Background

Recent Technological Advancements in Radiofrequency- and Microwave-Mediated Hyperthermia for Enhancing Drug Delivery

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M.M. Paulides, H. Dobsicek Trefna, S. Curto, D.B. Rodrigues; 2020
Hyperthermia therapy is a potent enhancer of chemotherapy and radiotherapy. In particular, microwave and radiofrequency hyperthermia devices provide a variety of heating approaches that can treat most cancers regardless the size. This review introduces the physics of MW/RF hyperthermia. The main challenge of hyperthermia is the distribution of state-of-the-art heating systems. These new technologies hold great promise not only for (image-guided) perfusion modulation and sensitization for cytotoxic drugs, but also for local delivery of various compounds using thermosensitive liposomes.

Hyperthermia and radiotherapy in the management of head and neck cancers: A systematic review and meta-analysis

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N. R.. Datta, S. Rogers, S. Gómez Ordóñez, E. Puric, S. Bodis; 2016
A systematic review and meta-analysis was conducted to evaluate the outcome of controlled clinical trials in head and neck cancers (HNCs) using hyperthermia and radiotherapy versus radiotherapy alone. Hyperthermia along with radiotherapy enhances the likelihood of CR in HNCs by around 25% compared to radiotherapy alone with no significant additional acute and late morbidities. This level I evidence should justify the integration of hyperthermia into the multimodality therapy of HNCs.

Status quo and directions in deep head and neck hyperthermia

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M Paulides, G. Verduijn, N. van Holthe; 2016
Also for head and neck cancer, the impact of hyperthermia has been clinically demonstrated by a number of clinical trials. Over the last decade, we developed the technology for deep and controlled hyperthermia that allows treatment of the entire head and neck region. In this paper, we review the phase III clinical evidence for hyperthermia in head and neck tumors, as well as clinical implementation and validation of 3D guided deep hyperthermia with the HYPERcollar3D. Lastly, we discuss early clinical results and provide an outlook for this technology.

Local hyperthermia combined with radiotherapy and-/or chemotherapy: Recent advances and promises for the future

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N.R. Datta, S. Gómez Ordóñeza, U.S. Gaipl, M.M. Paulides, H. Crezee, J. Gellermann, D. Mardera, E. Purica, S. Bodis; 2015
Hyperthermia is a potent radio- and chemosensitizer, it could be potentiating radiation induced immunomodulation. Hyperthermia with radiotherapy and-/or chemotherapy improves clinical outcome. Technical developments allow more effective and safer delivery of hyperthermia. Hyperthermia is a potent addendum to the existing cancer treatment modalities.

Hallmarks of hyperthermia in driving the future of clinical hyperthermia as targeted therapy: translation into clinical application.

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R. Issels, E. Kampmann, R. Kanaar, L. Lindner; 2016
Regional hyperthermia is described as a targeted therapy and the definitions of six hallmarks of hyperthermia are proposed, representing the pleiotropic effect of this therapeutic modality to counteract tumour growth and progression. We recommend the considerations of these hallmarks in the design of clinical trials involving regional hyperthermia as targeted therapy. Randomised clinical studies using loco-regional hyperthermia as an adjuvant to radiotherapy or to chemotherapy for locally advanced tumours demonstrate the benefit of the combination compared to either of the standard treatments alone for tumour response, disease control, and patient survival outcome.

Effects of hyperthermia on DNA repair pathways: one treatment to inhibit them all

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A. Oei, L. Vriend, J. Crezee, N. Franken, P. Krawczyk; 2015
Efficient DNA repair mechanisms protect both healthy and cancer cells against the effects of treatment and contribute to the development of drug resistance. Therefore, anti-cancer treatments based on inflicting DNA damage can benefit from inhibition of DNA repair. Hyperthermia considerably affects DNA repair, among other cellular processes, and can thus sensitize (cancer) cells to DNA damaging agents. In this review we attempt to summarize the known effects of hyperthermia on DNA repair pathways relevant in clinical treatment of cancer. Furthermore, we outline the relationships between the effects of heat on DNA repair and sensitization of cells to various DNA damaging agents.

Improving efficacy of hyperthermia in oncology by exploiting biological mechanisms

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N. van den Tempel, M. Horsman, R. Kanaar; 2016
We are now at a juncture where the parameters that will influence the efficacy of hyperthermia in cancer treatment can be optimised in a more systematic and rational manner. In addition, the novel insights in hyperthermia’s many biological effects on tumour cells will ultimately result in new treatment regimes. For example, the molecular effects of hyperthermia on the essential cellular process of DNA repair suggest novel combination therapies, with DNA damage response targeting drugs that should now be clinically explored. We indicate the significance of these effects on current treatments and suggest how they will help design novel future treatments.

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