% IMPORTANT: The following is UTF-8 encoded.  This means that in the presence
% of non-ASCII characters, it will not work with BibTeX 0.99 or older.
% Instead, you should use an up-to-date BibTeX implementation like “bibtex8” or
% “biber”.

@ARTICLE{Dimou:304600,
      author       = {K. Dimou and Y. Roussakis and C. Zamboglou$^*$ and T.
                      Stylianopoulos},
      title        = {{T}he impact of tumor microenvironment and treatment
                      schedule on the effectiveness of radiation therapy.},
      journal      = {PLOS ONE},
      volume       = {20},
      number       = {9},
      issn         = {1932-6203},
      address      = {San Francisco, California, US},
      publisher    = {PLOS},
      reportid     = {DKFZ-2025-01919},
      pages        = {e0331509},
      year         = {2025},
      abstract     = {External Beam Radiation Therapy (EBRT) is predominantly
                      administered using Conventionally Fractionated Radiotherapy
                      (CFRT), that is 2 Gy per fraction. However, Moderately
                      Hypofractionated Radiotherapy (MHRT) (approx. 2.5-3 Gy per
                      fraction) and Stereotactic Body Radiotherapy (SBRT) (approx.
                      6-24 Gy per fraction) regimen are currently clinically
                      investigated or even recently included in standard clinical
                      practice. In addition, hyperfractionated radiotherapy
                      (<1.8-2 Gy per fraction) is also clinically investigated or
                      already used in standard clinical practices. The therapeutic
                      effects of each of these radiotherapy schedules might depend
                      on the degree of radioresistance of the tumor but also on
                      properties of the tumor microenvironment, such as tumor
                      perfusion and oxygenation. Here, building on previous work,
                      we developed a mathematical model to investigate optimal
                      radiotherapy treatment protocols in solid tumors. The model
                      incorporates direct effects of radiation on cancer cells and
                      accounts for the impact of tumor perfusion and oxygenation
                      on the efficacy of radiation therapy. The model was able to
                      accurately reproduce both preclinical and clinical data from
                      different radiotherapy treatment schedules. It confirmed
                      that greater tumor perfusion and thus, oxygenation improves
                      treatment effectiveness by increasing the number of cancer
                      cells killed during the treatment period. It further
                      predicted that this effect is more pronounced for
                      radioresistant tumors, meaning that changes in tumor
                      perfusion of more radioresistant tumors have a greater
                      impact on the percentage of surviving cells at the end of
                      the treatment. The mathematical model provides mechanistic
                      insights into the effectiveness of various radiotherapy
                      schedules and guidelines for how modifying the tumor
                      microenvironment to restore perfusion can affect radiation
                      therapy.},
      keywords     = {Tumor Microenvironment: radiation effects / Humans /
                      Neoplasms: radiotherapy / Neoplasms: pathology / Neoplasms:
                      blood supply / Dose Fractionation, Radiation / Treatment
                      Outcome / Models, Biological / Models, Theoretical},
      cin          = {FR01},
      ddc          = {610},
      cid          = {I:(DE-He78)FR01-20160331},
      pnm          = {899 - ohne Topic (POF4-899)},
      pid          = {G:(DE-HGF)POF4-899},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:40961159},
      doi          = {10.1371/journal.pone.0331509},
      url          = {https://inrepo02.dkfz.de/record/304600},
}