Cited by 619Cancer, Hypoxia, and MetabolismRadiation Therapy and DosimetryAdvanced Radiotherapy Techniques

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Hypoxic Radiosensitization: Adored and Ignored

Overgaard, Jens·2007·Journal of Clinical Oncology

DOI 10.1200/jco.2007.12.7878

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Abstract

Since observations from the beginning of the last century, it has become well established that solid tumors may contain oxygen-deficient hypoxic areas and that cells in such areas may cause tumors to become radioresistant. Identifying hypoxic cells in human tumors has improved by the help of new imaging and physiologic techniques, and a substantial amount of data indicates the presence of hypoxia in many types of human tumors, although with a considerable heterogeneity among individual tumors. Controlled clinical trials during the last 40 years have indicated that this source of radiation resistance can be eliminated or modified by normobaric or hyperbaric oxygen or by the use of nitroimidazoles as hypoxic radiation sensitizers. More recently, attention has been given to hypoxic cytotoxins, a group of drugs that selectively or preferably destroys cells in a hypoxic environment. An updated systematic review identified 10,108 patients in 86 randomized trials designed to modify tumor hypoxia in patients treated with curative attempted primary radiation therapy alone. Overall modification of tumor hypoxia significantly improved the effect of radiotherapy, with an odds ratio of 0.77 (95% CI, 0.71 to 0.86) for the outcome of locoregional control and with an associated significant overall survival benefit (odds ratio = 0.87; 95% CI, 0.80 to 0.95). No significant influence was found on the incidence of distant metastases or on the risk of radiation-related complications. Ample data exist to support a high level of evidence for the benefit of hypoxic modification. However, hypoxic modification still has no impact on general clinical practice.

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1 retracted

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Self-citation

Authors: Overgaard, J.
Affiliations: Aarhus University Hospital (DK)
Corresponding author: Overgaard, Jens
ORCID: Overgaard, Jens
Venue: Journal of Clinical Oncology
Publisher: American Society of Clinical Oncology (ASCO)
Published: 2007-09-10
Volume: 25
Issue: 26
Pages: 4066-4074
ISSN: 0732-183X (ISSN-L)
1527-7755
DOI: 10.1200/jco.2007.12.7878
OpenAlex: W2123838717
Cited by: 619
References: 73
Citations by year: 2026: 16 · 2025: 12 · 2024: 25 · 2023: 35 · 2022: 34 · 2021: 41 · 2020: 26 · 2019: 39 · 2018: 38 · 2017: 31 · 2016: 40 · 2015: 37 · 2014: 47 · 2013: 42 · 2012: 40
FWCI: 2.08
Type: journal article
Language: en
Open access: closed
Locations: Journal of Clinical Oncology (publishedVersion)
PubMed (publishedVersion)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
Physical Sciences › Physics and Astronomy › Radiation › Radiation Therapy and Dosimetry
Physical Sciences › Physics and Astronomy › Radiation › Advanced Radiotherapy Techniques
Keywords: tumor hypoxia, radiosensitization, radioresistance (biology), hyperbaric oxygen therapy, normobaric oxygen, nitroimidazoles, radiotherapy, locoregional control, overall survival, metastasis
MeSH terms: Combined Modality Therapy, Humans, Neoplasms, Radiation-Sensitizing Agents, Cell Hypoxia

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Hypoxic Radiosensitization: Adored and Ignored

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