Blood-brain barrier permeability following conventional photon radiotherapy – A systematic review and meta-analysis of clinical and preclinical studies. / Hart, Elvin't; Odé, Zelda; Derieppe, Marc P. P. et al.
In: Clinical and Translational Radiation Oncology, Vol. 35, 01.07.2022, p. 44-55.Research output: Contribution to journal › Review article › Academic › peer-review
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TY - JOUR
T1 - Blood-brain barrier permeability following conventional photon radiotherapy – A systematic review and meta-analysis of clinical and preclinical studies
AU - Hart, Elvin't
AU - Odé, Zelda
AU - Derieppe, Marc P. P.
AU - Groenink, Lucianne
AU - Heymans, Martijn W.
AU - Otten, René
AU - Lequin, Maarten H.
AU - Janssens, Geert O. R.
AU - Hoving, Eelco W.
AU - van Vuurden, Dannis G.
N1 - Funding Information: The review has been supported by the KWF Young Investigator Award (KWF 10911, Dr. D.G. van Vuurden. Publisher Copyright: © 2022 The Authors
PY - 2022/7/1
Y1 - 2022/7/1
N2 - Radiotherapy (RT) is a cornerstone treatment strategy for brain tumours. Besides cytotoxicity, RT can cause disruption of the blood–brain barrier (BBB), resulting in an increased permeability into the surrounding brain parenchyma. Although this effect is generally acknowledged, it remains unclear how and to what extent different radiation schemes affect BBB integrity. The aim of this systematic review and meta-analysis is to investigate the effect of photon RT regimens on BBB permeability, including its reversibility, in clinical and preclinical studies. We systematically reviewed relevant clinical and preclinical literature in PubMed, Embase, and Cochrane search engines. A total of 69 included studies (20 clinical, 49 preclinical) were qualitatively and quantitatively analysed by meta-analysis and evaluated on key determinants of RT-induced BBB permeability in different disease types and RT protocols. Qualitative data synthesis showed that 35% of the included clinical studies reported BBB disruption following RT, whereas 30% were inconclusive. Interestingly, no compelling differences were observed between studies with different calculated biological effective doses based on the fractionation schemes and cumulative doses; however, increased BBB disruption was noted during patient follow-up after treatment. Qualitative analysis of preclinical studies showed RT BBB disruption in 78% of the included studies, which was significantly confirmed by meta-analysis (p < 0.01). Of note, a high risk of bias, publication bias and a high heterogeneity across the studies was observed. This systematic review and meta-analysis sheds light on the impact of RT protocols on BBB integrity and opens the discussion for integrating this factor in the decision-making process of future RT, with better study of its occurrence and influence on concomitant or adjuvant therapies.
AB - Radiotherapy (RT) is a cornerstone treatment strategy for brain tumours. Besides cytotoxicity, RT can cause disruption of the blood–brain barrier (BBB), resulting in an increased permeability into the surrounding brain parenchyma. Although this effect is generally acknowledged, it remains unclear how and to what extent different radiation schemes affect BBB integrity. The aim of this systematic review and meta-analysis is to investigate the effect of photon RT regimens on BBB permeability, including its reversibility, in clinical and preclinical studies. We systematically reviewed relevant clinical and preclinical literature in PubMed, Embase, and Cochrane search engines. A total of 69 included studies (20 clinical, 49 preclinical) were qualitatively and quantitatively analysed by meta-analysis and evaluated on key determinants of RT-induced BBB permeability in different disease types and RT protocols. Qualitative data synthesis showed that 35% of the included clinical studies reported BBB disruption following RT, whereas 30% were inconclusive. Interestingly, no compelling differences were observed between studies with different calculated biological effective doses based on the fractionation schemes and cumulative doses; however, increased BBB disruption was noted during patient follow-up after treatment. Qualitative analysis of preclinical studies showed RT BBB disruption in 78% of the included studies, which was significantly confirmed by meta-analysis (p < 0.01). Of note, a high risk of bias, publication bias and a high heterogeneity across the studies was observed. This systematic review and meta-analysis sheds light on the impact of RT protocols on BBB integrity and opens the discussion for integrating this factor in the decision-making process of future RT, with better study of its occurrence and influence on concomitant or adjuvant therapies.
KW - Blood-brain barrier
KW - Dose Fractionation
KW - Permeability
KW - Radiotherapy
KW - Radiotherapy Dosage
UR - http://www.scopus.com/inward/record.url?scp=85130131338&partnerID=8YFLogxK
U2 - 10.1016/j.ctro.2022.04.013
DO - 10.1016/j.ctro.2022.04.013
M3 - Review article
C2 - 35601799
VL - 35
SP - 44
EP - 55
JO - Clinical and Translational Radiation Oncology
JF - Clinical and Translational Radiation Oncology
SN - 2405-6308
ER -
ID: 25216968