Hyperthermia: The Optimal Treatment to Overcome Radiation Resistant Hypoxia

Regions of low oxygenation (hypoxia) are a characteristic feature of solid tumors, and cells existing in these regions are a major factor influencing radiation resistance as well as playing a significant role in malignant progression. Consequently, numerous pre-clinical and clinical attempts have be...

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Published in:Cancers Vol. 11; no. 1; p. 60
Main Authors: Elming, Pernille, Sørensen, Brita, Oei, Arlene, Franken, Nicolaas, Crezee, Johannes, Overgaard, Jens, Horsman, Michael
Format: Journal Article
Language:English
Published: Switzerland MDPI AG 09.01.2019
MDPI
Subjects:
Blood flow
Clinical trials
DNA repair
Fever
Heat
Heat treatments
Hyperthermia
Hypoxia
Oxygen
Oxygenation
Radiation therapy
Review
Solid tumors
Tumors
hypoxia
hyperthermia
radiation therapy
ISSN:2072-6694, 2072-6694
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Abstract Regions of low oxygenation (hypoxia) are a characteristic feature of solid tumors, and cells existing in these regions are a major factor influencing radiation resistance as well as playing a significant role in malignant progression. Consequently, numerous pre-clinical and clinical attempts have been made to try and overcome this hypoxia. These approaches involve improving oxygen availability, radio-sensitizing or killing the hypoxic cells, or utilizing high LET (linear energy transfer) radiation leading to a lower OER (oxygen enhancement ratio). Interestingly, hyperthermia (heat treatments of 39–45 °C) induces many of these effects. Specifically, it increases blood flow thereby improving tissue oxygenation, radio-sensitizes via DNA repair inhibition, and can kill cells either directly or indirectly by causing vascular damage. Combining hyperthermia with low LET radiation can even result in anti-tumor effects equivalent to those seen with high LET. The various mechanisms depend on the time and sequence between radiation and hyperthermia, the heating temperature, and the time of heating. We will discuss the role these factors play in influencing the interaction between hyperthermia and radiation, and summarize the randomized clinical trials showing a benefit of such a combination as well as suggest the potential future clinical application of this combination.
AbstractList Regions of low oxygenation (hypoxia) are a characteristic feature of solid tumors, and cells existing in these regions are a major factor influencing radiation resistance as well as playing a significant role in malignant progression. Consequently, numerous pre-clinical and clinical attempts have been made to try and overcome this hypoxia. These approaches involve improving oxygen availability, radio-sensitizing or killing the hypoxic cells, or utilizing high LET (linear energy transfer) radiation leading to a lower OER (oxygen enhancement ratio). Interestingly, hyperthermia (heat treatments of 39–45 °C) induces many of these effects. Specifically, it increases blood flow thereby improving tissue oxygenation, radio-sensitizes via DNA repair inhibition, and can kill cells either directly or indirectly by causing vascular damage. Combining hyperthermia with low LET radiation can even result in anti-tumor effects equivalent to those seen with high LET. The various mechanisms depend on the time and sequence between radiation and hyperthermia, the heating temperature, and the time of heating. We will discuss the role these factors play in influencing the interaction between hyperthermia and radiation, and summarize the randomized clinical trials showing a benefit of such a combination as well as suggest the potential future clinical application of this combination.
Regions of low oxygenation (hypoxia) are a characteristic feature of solid tumors, and cells existing in these regions are a major factor influencing radiation resistance as well as playing a significant role in malignant progression. Consequently, numerous pre-clinical and clinical attempts have been made to try and overcome this hypoxia. These approaches involve improving oxygen availability, radio-sensitizing or killing the hypoxic cells, or utilizing high LET (linear energy transfer) radiation leading to a lower OER (oxygen enhancement ratio). Interestingly, hyperthermia (heat treatments of 39⁻45 °C) induces many of these effects. Specifically, it increases blood flow thereby improving tissue oxygenation, radio-sensitizes via DNA repair inhibition, and can kill cells either directly or indirectly by causing vascular damage. Combining hyperthermia with low LET radiation can even result in anti-tumor effects equivalent to those seen with high LET. The various mechanisms depend on the time and sequence between radiation and hyperthermia, the heating temperature, and the time of heating. We will discuss the role these factors play in influencing the interaction between hyperthermia and radiation, and summarize the randomized clinical trials showing a benefit of such a combination as well as suggest the potential future clinical application of this combination.
Regions of low oxygenation (hypoxia) are a characteristic feature of solid tumors, and cells existing in these regions are a major factor influencing radiation resistance as well as playing a significant role in malignant progression. Consequently, numerous pre-clinical and clinical attempts have been made to try and overcome this hypoxia. These approaches involve improving oxygen availability, radio-sensitizing or killing the hypoxic cells, or utilizing high LET (linear energy transfer) radiation leading to a lower OER (oxygen enhancement ratio). Interestingly, hyperthermia (heat treatments of 39⁻45 °C) induces many of these effects. Specifically, it increases blood flow thereby improving tissue oxygenation, radio-sensitizes via DNA repair inhibition, and can kill cells either directly or indirectly by causing vascular damage. Combining hyperthermia with low LET radiation can even result in anti-tumor effects equivalent to those seen with high LET. The various mechanisms depend on the time and sequence between radiation and hyperthermia, the heating temperature, and the time of heating. We will discuss the role these factors play in influencing the interaction between hyperthermia and radiation, and summarize the randomized clinical trials showing a benefit of such a combination as well as suggest the potential future clinical application of this combination.Regions of low oxygenation (hypoxia) are a characteristic feature of solid tumors, and cells existing in these regions are a major factor influencing radiation resistance as well as playing a significant role in malignant progression. Consequently, numerous pre-clinical and clinical attempts have been made to try and overcome this hypoxia. These approaches involve improving oxygen availability, radio-sensitizing or killing the hypoxic cells, or utilizing high LET (linear energy transfer) radiation leading to a lower OER (oxygen enhancement ratio). Interestingly, hyperthermia (heat treatments of 39⁻45 °C) induces many of these effects. Specifically, it increases blood flow thereby improving tissue oxygenation, radio-sensitizes via DNA repair inhibition, and can kill cells either directly or indirectly by causing vascular damage. Combining hyperthermia with low LET radiation can even result in anti-tumor effects equivalent to those seen with high LET. The various mechanisms depend on the time and sequence between radiation and hyperthermia, the heating temperature, and the time of heating. We will discuss the role these factors play in influencing the interaction between hyperthermia and radiation, and summarize the randomized clinical trials showing a benefit of such a combination as well as suggest the potential future clinical application of this combination.
Author Elming, Pernille
Oei, Arlene
Franken, Nicolaas
Sørensen, Brita
Crezee, Johannes
Overgaard, Jens
Horsman, Michael
AuthorAffiliation 1 Department of Experimental Clinical Oncology, Aarhus University Hospital, DK-8000 Aarhus C, Denmark; pernille.elming@oncology.au.dk (P.B.E.); bsin@oncology.au.dk (B.S.S.); jens@oncology.au.dk (J.O.)
2 Department of Radiation Oncology, Amsterdam University Medical Centers, University of Amsterdam, 1105AZ Amsterdam, The Netherlands; a.l.oei@amc.uva.nl (A.L.O.); n.a.franken@amc.uva.nl (N.A.P.F.); h.crezee@amc.uva.nl (J.C.)
AuthorAffiliation_xml – name: 2 Department of Radiation Oncology, Amsterdam University Medical Centers, University of Amsterdam, 1105AZ Amsterdam, The Netherlands; a.l.oei@amc.uva.nl (A.L.O.); n.a.franken@amc.uva.nl (N.A.P.F.); h.crezee@amc.uva.nl (J.C.)
– name: 1 Department of Experimental Clinical Oncology, Aarhus University Hospital, DK-8000 Aarhus C, Denmark; pernille.elming@oncology.au.dk (P.B.E.); bsin@oncology.au.dk (B.S.S.); jens@oncology.au.dk (J.O.)
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  givenname: Pernille
  surname: Elming
  fullname: Elming, Pernille
– sequence: 2
  givenname: Brita
  orcidid: 0000-0002-3955-4735
  surname: Sørensen
  fullname: Sørensen, Brita
– sequence: 3
  givenname: Arlene
  surname: Oei
  fullname: Oei, Arlene
– sequence: 4
  givenname: Nicolaas
  orcidid: 0000-0002-5522-9406
  surname: Franken
  fullname: Franken, Nicolaas
– sequence: 5
  givenname: Johannes
  orcidid: 0000-0002-7474-0533
  surname: Crezee
  fullname: Crezee, Johannes
– sequence: 6
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  orcidid: 0000-0002-0814-8179
  surname: Overgaard
  fullname: Overgaard, Jens
– sequence: 7
  givenname: Michael
  surname: Horsman
  fullname: Horsman, Michael
BackLink https://www.ncbi.nlm.nih.gov/pubmed/30634444$$D View this record in MEDLINE/PubMed
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2019 by the authors. 2019
Copyright_xml – notice: 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.
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Issue 1
Keywords hypoxia
hyperthermia
radiation therapy
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Snippet Regions of low oxygenation (hypoxia) are a characteristic feature of solid tumors, and cells existing in these regions are a major factor influencing radiation...
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StartPage 60
SubjectTerms Blood flow
Clinical trials
DNA repair
Fever
Heat
Heat treatments
Hyperthermia
Hypoxia
Oxygen
Oxygenation
Radiation therapy
Review
Solid tumors
Tumors
Title Hyperthermia: The Optimal Treatment to Overcome Radiation Resistant Hypoxia
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