title: Personalized precision radiotherapy by integration of multi-parametric functional and biological imaging in prostate cancer: A feasibility study.
abstract: BACKGROUND
  To increase tumour control probability (TCP) in prostate cancer a method was developed integrating multi-parametric functional and biological information into a dose painting treatment plan aiming focal dose-escalation to tumour sub-volumes. A dose-escalation map was derived considering individual, multi-parametric estimated tumour aggressiveness.
  
  
  METHODS
  Multi-parametric functional imaging (MRI, Choline-/PSMA-/FMISO-PET/CT) was acquired for a high risk prostate cancer patient with a high level of tumour load (cT3b cN0 cM0) indicated by subtotal involvement of prostate including the right seminal vesicle and by PSA-level >100. Probability of tumour presence was determined by a combination of multi-parametric functional image information resulting in a voxel-based map of tumour aggressiveness. This probability map was directly integrated into dose optimization in order to plan for inhomogeneous, biological imaging based dose painting. Histograms of the multi-parametric prescription function were generated in addition to a differential histogram of the planned inhomogeneous doses. Comparison of prescribed doses with planned doses on a voxel level was realized using an effective DVH, containing the ratio of prescribed vs. planned dose for each tumour voxel.
  
  
  RESULTS
  Multi-parametric imaging data of PSMA, Choline and FMISO PET/CT as well as ADC maps derived from diffusion weighted MRI were combined to an individual probability map of tumour presence. Voxel-based prescription doses ranged from 75.3Gy up to 93.4Gy (median: 79.6Gy), whereas the planned dose painting doses varied only between 72.5 and 80.0Gy with a median dose of 75.7Gy. However, inhomogeneous voxel-based dose prescriptions can only be implemented into a treatment plan until a certain level.
  
  
  CONCLUSIONS
  Multi-parametric probability based dose painting in prostate cancer is technically and clinically feasible. However, detailed calibration functions to define the necessary probability functions need to be assessed in future clinical trials.
authors.affiliation: Section for Biomedical Physics, Department of Radiation Oncology, Eberhard Karls University Tübingen, Hoppe-Seyler-Strasse 3, Tübingen, Germany. Electronic address: daniela.thorwarth@med.uni-tuebingen.de.
authors.forename: Daniela
authors.initials: D
authors.lastname: Thorwarth
authors.affiliation: Department of Diagnostic and Interventional Radiology, Eberhard Karls University Tübingen, Hoppe-Seyler-Strasse 3, Tübingen, Germany.
authors.forename: Mike
authors.initials: M
authors.lastname: Notohamiprodjo
authors.affiliation: Department of Radiation Oncology, Eberhard Karls University Tübingen, Hoppe-Seyler-Strasse 3, Tübingen, Germany.
authors.forename: Daniel
authors.initials: D
authors.lastname: Zips
authors.affiliation: Department of Radiation Oncology, Eberhard Karls University Tübingen, Hoppe-Seyler-Strasse 3, Tübingen, Germany.
authors.forename: Arndt-Christan
authors.initials: AC
authors.lastname: Müller
mesh_terms: D005240:Feasibility Studies; D006801:Humans; D008297:Male; D000072078:Positron Emission Tomography Computed Tomography; D057285:Precision Medicine / Q000379:methods*; D011471:Prostatic Neoplasms / Q000000981:diagnostic imaging* / Q000532:radiotherapy*; D011879:Radiotherapy Dosage; D011880:Radiotherapy Planning, Computer-Assisted
keywords: Dose Painting; Multi-parametric imaging; Multi-parametrische Bildgebung; PET/MR; Prostatakarzinom; dose painting; functional imaging; funktionelle Bildgebung; prostate cancer