title: Dose uncertainties in IMPT for oropharyngeal cancer in the presence of anatomical, range, and setup errors.
abstract: OBJECTIVE
  Setup, range, and anatomical uncertainties influence the dose delivered with intensity modulated proton therapy (IMPT), but clinical quantification of these errors for oropharyngeal cancer is lacking. We quantified these factors and investigated treatment fidelity, that is, robustness, as influenced by adaptive planning and by applying more beam directions.
  
  
  METHODS
  We used an in-house treatment planning system with multicriteria optimization of pencil beam energies, directions, and weights to create treatment plans for 3-, 5-, and 7-beam directions for 10 oropharyngeal cancer patients. The dose prescription was a simultaneously integrated boost scheme, prescribing 66 Gy to primary tumor and positive neck levels (clinical target volume-66 Gy; CTV-66 Gy) and 54 Gy to elective neck levels (CTV-54 Gy). Doses were recalculated in 3700 simulations of setup, range, and anatomical uncertainties. Repeat computed tomography (CT) scans were used to evaluate an adaptive planning strategy using nonrigid registration for dose accumulation.
  
  
  RESULTS
  For the recalculated 3-beam plans including all treatment uncertainty sources, only 69% (CTV-66 Gy) and 88% (CTV-54 Gy) of the simulations had a dose received by 98% of the target volume (D98%) >95% of the prescription dose. Doses to organs at risk (OARs) showed considerable spread around planned values. Causes for major deviations were mixed. Adaptive planning based on repeat imaging positively affected dose delivery accuracy: in the presence of the other errors, percentages of treatments with D98% >95% increased to 96% (CTV-66 Gy) and 100% (CTV-54 Gy). Plans with more beam directions were not more robust.
  
  
  CONCLUSIONS
  For oropharyngeal cancer patients, treatment uncertainties can result in significant differences between planned and delivered IMPT doses. Given the mixed causes for major deviations, we advise repeat diagnostic CT scans during treatment, recalculation of the dose, and if required, adaptive planning to improve adequate IMPT dose delivery.
authors.affiliation: Erasmus MC Daniel den Hoed Cancer Center, Rotterdam, The Netherlands. Electronic address: aafke.kraan@pi.infn.it.
authors.forename: Aafke C
authors.initials: AC
authors.lastname: Kraan
authors.affiliation: Erasmus MC Daniel den Hoed Cancer Center, Rotterdam, The Netherlands.
authors.forename: Steven
authors.initials: S
authors.lastname: van de Water
authors.affiliation: Erasmus MC Daniel den Hoed Cancer Center, Rotterdam, The Netherlands.
authors.forename: David N
authors.initials: DN
authors.lastname: Teguh
authors.affiliation: Erasmus MC Daniel den Hoed Cancer Center, Rotterdam, The Netherlands.
authors.forename: Abrahim
authors.initials: A
authors.lastname: Al-Mamgani
authors.affiliation: Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.
authors.forename: Tom
authors.initials: T
authors.lastname: Madden
authors.affiliation: Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.
authors.forename: Hanne M
authors.initials: HM
authors.lastname: Kooy
authors.affiliation: Erasmus MC Daniel den Hoed Cancer Center, Rotterdam, The Netherlands.
authors.forename: Ben J M
authors.initials: BJ
authors.lastname: Heijmen
authors.affiliation: Erasmus MC Daniel den Hoed Cancer Center, Rotterdam, The Netherlands.
authors.forename: Mischa S
authors.initials: MS
authors.lastname: Hoogeman
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D006801:Humans; D008875:Middle Aged; D058958:Organs at Risk / Q000033:anatomy & histology / Q000000981:diagnostic imaging / Q000528:radiation effects*; D009959:Oropharyngeal Neoplasms / Q000000981:diagnostic imaging / Q000473:pathology / Q000532:radiotherapy*; D010157:Palatal Neoplasms / Q000000981:diagnostic imaging / Q000473:pathology / Q000532:radiotherapy; D010160:Palate, Soft; D061766:Proton Therapy / Q000379:methods*; D058996:Quality Improvement; D011859:Radiography; D011880:Radiotherapy Planning, Computer-Assisted / Q000379:methods*; D061106:Radiotherapy Setup Errors / Q000009:adverse effects*; D050397:Radiotherapy, Intensity-Modulated / Q000379:methods*; D014062:Tongue Neoplasms / Q000000981:diagnostic imaging / Q000473:pathology / Q000532:radiotherapy; D014067:Tonsillar Neoplasms / Q000000981:diagnostic imaging / Q000473:pathology / Q000532:radiotherapy; D035501:Uncertainty