title: Is there a causal relationship between genetic changes and radiomics-based image features? An in vivo preclinical experiment with doxycycline inducible GADD34 tumor cells.
abstract: OBJECTIVE
  The central hypothesis of "radiomics" is that imaging features reflect tumor phenotype and genotype. Until now only correlative studies have been performed. The main objective of our study is to determine whether a causal relationship exists between genetic changes and image features. The secondary objective is to assess whether the combination with radiotherapy (RT) influences these image features.
  
  
  METHODS
  HCT116 doxycycline (dox) inducible GADD34 cells were grown as xenografts in the flanks of NMRI-nu mice. GADD34 overexpression decreases hypoxic fraction. Radiomics analyses were performed on computed tomography images obtained at 40kVp and again at 80kVp for validation, before radiotherapy at a volume of 200mm(3), 4days post RT (10Gy) and 500mm(3). To select reproducible features test-retest experiments were performed at baseline.
  
  
  RESULTS
  Gene induction and/or irradiation translated into significant changes in radiomics features. Post irradiation, 17 features for 40kVp and 9 features for 80kVp differed significantly between dox+ and dox- combined with RT. 8 and 4 of these features remained consistent for 40 and 80kVp, respectively.
  
  
  CONCLUSIONS
  Radiomics is able to identify early effects of changed gene expression combined with radiation treatment in tumors with similar volumes which are not visible to human eye.
authors.affiliation: Department of Radiation Oncology (MAASTRO), GROW, MUMC, Maastricht, The Netherlands. Electronic address: kranthi.panth@maastrichtuniversity.nl.
authors.forename: Kranthi Marella
authors.initials: KM
authors.lastname: Panth
authors.affiliation: Department of Radiation Oncology (MAASTRO), GROW, MUMC, Maastricht, The Netherlands.
authors.forename: Ralph T H
authors.initials: RT
authors.lastname: Leijenaar
authors.affiliation: Department of Radiation Oncology (MAASTRO), GROW, MUMC, Maastricht, The Netherlands.
authors.forename: Sara
authors.initials: S
authors.lastname: Carvalho
authors.affiliation: Department of Radiation Oncology (MAASTRO), GROW, MUMC, Maastricht, The Netherlands.
authors.forename: Natasja G
authors.initials: NG
authors.lastname: Lieuwes
authors.affiliation: Department of Radiation Oncology (MAASTRO), GROW, MUMC, Maastricht, The Netherlands.
authors.forename: Ala
authors.initials: A
authors.lastname: Yaromina
authors.affiliation: Department of Radiation Oncology (MAASTRO), GROW, MUMC, Maastricht, The Netherlands.
authors.forename: Ludwig
authors.initials: L
authors.lastname: Dubois
authors.affiliation: Department of Radiation Oncology (MAASTRO), GROW, MUMC, Maastricht, The Netherlands.
authors.forename: Philippe
authors.initials: P
authors.lastname: Lambin
mesh_terms: D000818:Animals; D015179:Colorectal Neoplasms / Q000000981:diagnostic imaging / Q000235:genetics* / Q000532:radiotherapy; D004318:Doxycycline / Q000494:pharmacology; D023281:Genomics / Q000379:methods; D005838:Genotype; D045325:HCT116 Cells; D064593:Heterografts; D006801:Humans; D051379:Mice; D008815:Mice, Inbred Strains; D009368:Neoplasm Transplantation; D015588:Observer Variation; D010641:Phenotype; D054645:Protein Phosphatase 1 / Q000235:genetics* / Q000378:metabolism; D014057:Tomography, X-Ray Computed / Q000379:methods; D014183:Transplantation, Heterologous; D047368:Tumor Burden
chemical_list: C513256:Ppp1r15a protein, mouse; D054645:Protein Phosphatase 1; D004318:Doxycycline
keywords: CT imaging; Preclinical; Radiogenomics; Radiotherapy