Integrating Loco-Regional Hyperthermia in Clinical Oncology

A special issue of Cancers (ISSN 2072-6694).

Deadline for manuscript submissions: closed (30 November 2022) | Viewed by 10551

Special Issue Editors


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Guest Editor
Department of Biotechnics, The Hungarian University of Agriculture and Life Sciences, Godollo, Hungary
Interests: hyperthermia; hyperthermal biophysics; cancer biophysics; hyperthermia technics; bioelectromagnetism; fractal physiology

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Co-Guest Editor
Department of Radiotherapy, Mahatma Gandhi Institute of Medical Sciences, Sevagram, India
Interests: radiotherapy; hyperthermia; radiotherapy infrastructure; LMICs; brachytherapy; meta-analysis; telemedicine

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Co-Guest Editor
1. ITIS Foundation Zurich, Zurich, Switzerland
2. Department of Radiation Oncology, University Hospital Zurich, Zurich, Switzerland
Interests: evidence-based thermotherapy/hyperthermia in oncology; clinical thermoradiotherapy; hardware–software innovations in thermotherapy/hyperthermia; multidisciplinary clinical oncology; radiation oncology infrastructure in LMI countries
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Special Issue Information

Dear Colleagues,

Oncologic HT is a well-known, but only partially established, therapeutic modality that is combined with systemic therapy and/or local radiotherapy in the global oncology community. Its acceptance has been slow over the last 20 years, primarily due to a lack of evidence-based preclinical and clinical research data. However, in recent years, due to advances in biology, physics, technology, and clinical oncology, its acceptance in the oncology community has grown. The reimbursement policies for oncologic hyperthermia in an increasing number of national health care systems support the recognition processes. 
The emerging complementary applications synergize different methods, increase their capabilities, and open new perspectives in the field of oncotherapies. Hyperthermia at 39°– 45°C sensitizes tumors to conventional therapies even in refractory cases, while typical other treatments promote cell distortion in addition to thermal degradation. Hyperthermia produces higher chemical reaction rates and better membrane permeability and impacts the cell cycle of the proliferating malignancy. Furthermore, hyperthermia reduces the adverse effects of conventional treatments, and its suppressed toxicity increases the patient's quality of life. 
Two main categories of local-regional hyperthermia offer heating possibilities: 
•    The homogeneous heating of the tumor mass with isothermal intent; 
•    The selective energy absorption of various inserted artificial particles (mostly nanoparticles) or selecting natural compounds in the heterogenic target. 
Intensive research covers the preclinical and clinical applications of bimodal and multimodal therapies, confirming high-level expectations. The previously observed abscopal effect of conventional treatments became a curative goal with immune activation in complementary therapy combinations, thereby opening a new perspective for advanced metastatic diseases. In this way, oncological hyperthermia provides a novel vision in immuno-oncology, extending radiotherapy from local to systemic and improving the systemic processes of various drugs. 
This Special Issue summarises results and explores the achievements and trends of research on local oncologic hyperthermia, including various heating methods. The articles explore and discuss numerous challenges and solutions, including the promising effects complementing both conventional and new oncotherapies. 

Prof. Dr. András Szász
Prof. Dr. Niloy R. Datta
Prof. Dr. Stephan Bodis
Guest Editors

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Keywords

  • thermoradiotherapy
  • thermochemotherapy
  • multimodal therapies
  • resensitizing
  • abscopal effect
  • toxicity
  • quality of life
  • immune activity
  • impact on metastases

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Published Papers (3 papers)

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24 pages, 2870 KiB  
Article
Individualized Multimodal Immunotherapy for Adults with IDH1 Wild-Type GBM: A Single Institute Experience
by Stefaan W. Van Gool, Jennifer Makalowski, Peter Van de Vliet, Stefanie Van Gool, Tobias Sprenger, Volker Schirrmacher and Wilfried Stuecker
Cancers 2023, 15(4), 1194; https://doi.org/10.3390/cancers15041194 - 13 Feb 2023
Cited by 5 | Viewed by 3191
Abstract
Synergistic activity between maintenance temozolomide (TMZm) and individualized multimodal immunotherapy (IMI) during/after first-line treatment has been suggested to improve the overall survival (OS) of adults with IDH1 wild-type MGMT promoter-unmethylated (unmeth) GBM. We expand the data and include the OS of MGMT promoter-methylated [...] Read more.
Synergistic activity between maintenance temozolomide (TMZm) and individualized multimodal immunotherapy (IMI) during/after first-line treatment has been suggested to improve the overall survival (OS) of adults with IDH1 wild-type MGMT promoter-unmethylated (unmeth) GBM. We expand the data and include the OS of MGMT promoter-methylated (meth) adults with GBM. Unmeth (10 f, 18 m) and meth (12 f, 10 m) patients treated between 27 May 2015 and 1 January 2022 were analyzed retrospectively. There were no differences in age (median: 48 y) or Karnofsky performance index (median: 80). The IMI consisted of 5-day immunogenic cell death (ICD) therapies during TMZm: Newcastle disease virus (NDV) bolus injections and sessions of modulated electrohyperthermia (mEHT); subsequent active specific immunotherapy: dendritic cell (DC) vaccines plus modulatory immunotherapy; and maintenance ICD therapy. There were no differences in the number of vaccines (median: 2), total number of DCs (median: 25.6 × 106), number of NDV injections (median: 31), and number of mEHT sessions (median: 28) between both groups. The median OS of 28 unmeth patients was 22 m (2y-OS: 39%), confirming previous results. OS of 22 meth patients was significantly better (p = 0.0414) with 38 m (2y-OS: 81%). There were no major treatment-related adverse reactions. The addition of IMI during/after standard of care should be prospectively explored. Full article
(This article belongs to the Special Issue Integrating Loco-Regional Hyperthermia in Clinical Oncology)
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20 pages, 3368 KiB  
Article
Radiofrequency Electromagnetic Fields Cause Non-Temperature-Induced Physical and Biological Effects in Cancer Cells
by Peter Wust, Paraskevi D. Veltsista, Eva Oberacker, Prabhusrinivas Yavvari, Wolfgang Walther, Olof Bengtsson, Anja Sterner-Kock, Marie Weinhart, Florian Heyd, Patricia Grabowski, Sebastian Stintzing, Wolfgang Heinrich, Ulrike Stein and Pirus Ghadjar
Cancers 2022, 14(21), 5349; https://doi.org/10.3390/cancers14215349 - 30 Oct 2022
Cited by 11 | Viewed by 2765
Abstract
Non-temperature-induced effects of radiofrequency electromagnetic fields (RF) have been controversial for decades. Here, we established measurement techniques to prove their existence by investigating energy deposition in tumor cells under RF exposure and upon adding amplitude modulation (AM) (AMRF). Using a preclinical device LabEHY-200 [...] Read more.
Non-temperature-induced effects of radiofrequency electromagnetic fields (RF) have been controversial for decades. Here, we established measurement techniques to prove their existence by investigating energy deposition in tumor cells under RF exposure and upon adding amplitude modulation (AM) (AMRF). Using a preclinical device LabEHY-200 with a novel in vitro applicator, we analyzed the power deposition and system parameters for five human colorectal cancer cell lines and measured the apoptosis rates in vitro and tumor growth inhibition in vivo in comparison to water bath heating. We showed enhanced anticancer effects of RF and AMRF in vitro and in vivo and verified the non-temperature-induced origin of the effects. Furthermore, apoptotic enhancement by AM was correlated with cell membrane stiffness. Our findings not only provide a strategy to significantly enhance non-temperature-induced anticancer cell effects in vitro and in vivo but also provide a perspective for a potentially more effective tumor therapy. Full article
(This article belongs to the Special Issue Integrating Loco-Regional Hyperthermia in Clinical Oncology)
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18 pages, 3330 KiB  
Systematic Review
Meta-Analysis of Modulated Electro-Hyperthermia and Tumor Treating Fields in the Treatment of Glioblastomas
by Attila Marcell Szasz, Elisabeth Estefanía Arrojo Alvarez, Giammaria Fiorentini, Magdolna Herold, Zoltan Herold, Donatella Sarti and Magdolna Dank
Cancers 2023, 15(3), 880; https://doi.org/10.3390/cancers15030880 - 31 Jan 2023
Cited by 3 | Viewed by 3438
Abstract
Background: Glioblastoma is one of the most difficult to treat and most aggressive brain tumors, having a poor survival rate. The use of non-invasive modulated electro-hyperthermia (mEHT) and Tumor Treating Fields (TTF) devices has been introduced in the last few decades, both of [...] Read more.
Background: Glioblastoma is one of the most difficult to treat and most aggressive brain tumors, having a poor survival rate. The use of non-invasive modulated electro-hyperthermia (mEHT) and Tumor Treating Fields (TTF) devices has been introduced in the last few decades, both of which having proven anti-tumor effects. Methods: A meta-analysis of randomized and observational studies about mEHT and TTF was conducted. Results: A total of seven and fourteen studies about mEHT and TTF were included, with a total number of 450 and 1309 cases, respectively. A 42% [95% confidence interval (95% CI): 25–59%] 1-year survival rate was found for mEHT, which was raised to 61% (95% CI: 32–89%) if only the studies conducted after 2008 were investigated. In the case of TTF, 1-year survival was 67% (95% CI: 53–81%). Subgroup analyses revealed that newly diagnosed patients might get extra benefits from the early introduction of the devices (mEHT all studies: 73% vs. 37%, p = 0.0021; mEHT studies after 2008: 73% vs. 54%, p = 0.4214; TTF studies: 83% vs. 52%, p = 0.0083), compared with recurrent glioblastoma. Conclusions: Our meta-analysis showed that both mEHT and TTF can improve glioblastoma survival, and the most benefit may be achieved in newly diagnosed cases. Full article
(This article belongs to the Special Issue Integrating Loco-Regional Hyperthermia in Clinical Oncology)
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