title: Worst case optimization for interfractional motion mitigation in carbon ion therapy of pancreatic cancer.
abstract: BACKGROUND
  The efficacy of radiation therapy treatments for pancreatic cancer is compromised by abdominal motion which limits the spatial accuracy for dose delivery - especially for particles. In this work we investigate the potential of worst case optimization for interfractional offline motion mitigation in carbon ion treatments of pancreatic cancer.
  
  
  METHODS
  We implement a worst case optimization algorithm that explicitly models the relative biological effectiveness of carbon ions during inverse planning. We perform a comparative treatment planning study for seven pancreatic cancer patients. Treatment plans that have been generated using worst case optimization are compared against (1) conventional intensity-modulated carbon ion therapy, (2) single field uniform dose carbon ion therapy, and (3) an ideal yet impractical scenario relying on daily re-planning. The dosimetric quality and robustness of the resulting treatment plans is evaluated using reconstructions of the daily delivered dose distributions on fractional control CTs.
  
  
  RESULTS
  Idealized daily re-planning consistently gives the best dosimetric results with regard to both target coverage and organ at risk sparing. The absolute reduction of D95within the gross tumor volume during fractional dose reconstruction is most pronounced for conventional intensity-modulated carbon ion therapy. Single field uniform dose optimization exhibits no substantial reduction for six of seven patients and values for D95for worst case optimization fall in between. The treated volume (D>95 % prescription dose) outside of the gross tumor volume is reduced by a factor of two by worst case optimization compared to conventional optimization and single field uniform dose optimization. Single field uniform dose optimization comes at an increased radiation exposure of normal tissues, e.g. ≈2 Gy (RBE) in the mean dose in the kidneys compared to conventional and worst case optimization and ≈4 Gy (RBE) in D1in the spinal cord compared to worst case optimization.
  
  
  CONCLUSIONS
  Interfractional motion substantially deteriorates dose distributions for carbon ion treatments of pancreatic cancer patients. Single field uniform dose optimization mitigates the negative influence of motion on target coverage at an increased radiation exposure of normal tissue. Worst case optimization enables an exploration of the trade-off between robust target coverage and organ at risk sparing during inverse treatment planning beyond margin concepts.
authors.affiliation: German Cancer Reserach Center - DKFZ, Im Neuenheimer Feld 280, Heidelberg, Germany.
authors.forename: Julian
authors.initials: J
authors.lastname: Steitz
authors.affiliation: Department of Radiation Oncology, University Hospital Heidelberg, Heidelberg, Germany.
authors.forename: Patrick
authors.initials: P
authors.lastname: Naumann
authors.affiliation: German Cancer Reserach Center - DKFZ, Im Neuenheimer Feld 280, Heidelberg, Germany.
authors.forename: Silke
authors.initials: S
authors.lastname: Ulrich
authors.affiliation: Department of Radiation Oncology, University Hospital Heidelberg, Heidelberg, Germany.
authors.forename: Matthias F
authors.initials: MF
authors.lastname: Haefner
authors.affiliation: German Cancer Reserach Center - DKFZ, Im Neuenheimer Feld 280, Heidelberg, Germany.|Department of Radiation Oncology, University Hospital Heidelberg, Heidelberg, Germany.
authors.forename: Florian
authors.initials: F
authors.lastname: Sterzing
authors.affiliation: Joint Department of Physics at The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust, London, UK.
authors.forename: Uwe
authors.initials: U
authors.lastname: Oelfke
authors.affiliation: German Cancer Reserach Center - DKFZ, Im Neuenheimer Feld 280, Heidelberg, Germany. m.bangert@dkfz.de.
authors.forename: Mark
authors.initials: M
authors.lastname: Bangert
mesh_terms: D000465:Algorithms; D002244:Carbon / Q000737:chemistry*; D015331:Cohort Studies; D019583:Dose Fractionation, Radiation; D063193:Heavy Ion Radiotherapy / Q000379:methods*; D006801:Humans; D007477:Ions / Q000627:therapeutic use*; D009038:Motion; D010190:Pancreatic Neoplasms / Q000532:radiotherapy*; D011874:Radiometry / Q000379:methods*; D011879:Radiotherapy Dosage; D011880:Radiotherapy Planning, Computer-Assisted / Q000379:methods; D012062:Relative Biological Effectiveness
chemical_list: D007477:Ions; D002244:Carbon
keywords: Carbon ion therapy; Interfractional motion; Pancreatic cancer; Treatment planning; Worst case optimization