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Mathematical modelling of the synergistic combination of radiotherapy and indoleamine-2,3-dioxygenase (IDO) inhibitory immunotherapy against glioblastoma

Chakwizira, Arthur ; Ahlstedt, Jonatan LU ; Redebrandt, Henrietta Nittby LU and Ceberg, Crister LU (2018) In British Journal of Radiology 91(1087).
Abstract

Objective: Recent research has shown that combining radiotherapy and immunotherapy can counteract the ability of cancer to evade and suppress the native immune system. To optimise the synergy of the combined therapies, factors such as radiation dose and fractionation must be considered, alongside numerous parameters resulting from the complexity of cancer-immune system interactions. It is instructive to use mathematical models to tackle this problem. Methods: In this work, we adapted a model primarily to describe the synergistic effect between single-fraction radiotherapy and immunotherapy (1-methyl tryptophan) observed in previous experiments with glioblastoma-carrying rats. We also showed how the model can be used to generate... (More)

Objective: Recent research has shown that combining radiotherapy and immunotherapy can counteract the ability of cancer to evade and suppress the native immune system. To optimise the synergy of the combined therapies, factors such as radiation dose and fractionation must be considered, alongside numerous parameters resulting from the complexity of cancer-immune system interactions. It is instructive to use mathematical models to tackle this problem. Methods: In this work, we adapted a model primarily to describe the synergistic effect between single-fraction radiotherapy and immunotherapy (1-methyl tryptophan) observed in previous experiments with glioblastoma-carrying rats. We also showed how the model can be used to generate hypotheses on the outcome of other treatment fractionation schemes. Results: The model successfully reproduced the results of the experiments. Moreover, it provided support for the hypothesis that, for a given biologically effective dose, the efficacy of the combination therapy and the synergy between the two therapies are favoured by the administration of radiotherapy in a hypofractionated regime. Furthermore, for a double-fraction irradiation regimen, the synergy is favoured by a short time interval between the treatment fractions. Conclusion: It was concluded that the model could be fitted to reproduce the experimental data well within its uncertainties. It was also demonstrated that the fitted model can be used to form hypotheses to be validated by further pre-clinical experiments. Advances in knowledge: The results of this work support the hypothesis that the synergetic action of combined radiotherapy and immunotherapy is favoured by using a hypofractionated radiation treatment regimen, given over a short time interval.

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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
British Journal of Radiology
volume
91
issue
1087
article number
20170857
publisher
British Inst Radiology
external identifiers
  • scopus:85049206032
  • pmid:29688039
ISSN
0007-1285
DOI
10.1259/bjr.20170857
language
English
LU publication?
yes
id
68bc0915-c6db-4ee1-9a37-28f016b66c9c
date added to LUP
2018-07-17 12:26:05
date last changed
2020-02-19 05:02:15
@article{68bc0915-c6db-4ee1-9a37-28f016b66c9c,
  abstract     = {<p>Objective: Recent research has shown that combining radiotherapy and immunotherapy can counteract the ability of cancer to evade and suppress the native immune system. To optimise the synergy of the combined therapies, factors such as radiation dose and fractionation must be considered, alongside numerous parameters resulting from the complexity of cancer-immune system interactions. It is instructive to use mathematical models to tackle this problem. Methods: In this work, we adapted a model primarily to describe the synergistic effect between single-fraction radiotherapy and immunotherapy (1-methyl tryptophan) observed in previous experiments with glioblastoma-carrying rats. We also showed how the model can be used to generate hypotheses on the outcome of other treatment fractionation schemes. Results: The model successfully reproduced the results of the experiments. Moreover, it provided support for the hypothesis that, for a given biologically effective dose, the efficacy of the combination therapy and the synergy between the two therapies are favoured by the administration of radiotherapy in a hypofractionated regime. Furthermore, for a double-fraction irradiation regimen, the synergy is favoured by a short time interval between the treatment fractions. Conclusion: It was concluded that the model could be fitted to reproduce the experimental data well within its uncertainties. It was also demonstrated that the fitted model can be used to form hypotheses to be validated by further pre-clinical experiments. Advances in knowledge: The results of this work support the hypothesis that the synergetic action of combined radiotherapy and immunotherapy is favoured by using a hypofractionated radiation treatment regimen, given over a short time interval.</p>},
  author       = {Chakwizira, Arthur and Ahlstedt, Jonatan and Redebrandt, Henrietta Nittby and Ceberg, Crister},
  issn         = {0007-1285},
  language     = {eng},
  month        = {01},
  number       = {1087},
  publisher    = {British Inst Radiology},
  series       = {British Journal of Radiology},
  title        = {Mathematical modelling of the synergistic combination of radiotherapy and indoleamine-2,3-dioxygenase (IDO) inhibitory immunotherapy against glioblastoma},
  url          = {http://dx.doi.org/10.1259/bjr.20170857},
  doi          = {10.1259/bjr.20170857},
  volume       = {91},
  year         = {2018},
}