title: Variations in linear energy transfer within clinical proton therapy fields and the potential for biological treatment planning.
abstract: OBJECTIVE
  To calculate the linear energy transfer (LET) distributions in patients undergoing proton therapy. These distributions can be used to identify areas of elevated or diminished biological effect. The location of such areas might be influenced in intensity-modulated proton therapy (IMPT) optimization.
  
  
  METHODS
  Because Monte Carlo studies to investigate the LET distribution in patients have not been undertaken so far, the code is first validated with simulations in water. The code was used in five patients, for each of them three planning and delivery techniques were simulated: passive scattering, three-dimensional modulation IMPT (3D-IMPT), and distal edge tracking IMPT (DET-IMPT).
  
  
  RESULTS
  The inclusion of secondary particles led to significant differences compared with analytical techniques. In addition, passive scattering and 3D-IMPT led to largely comparable LET distributions, whereas the DET-IMPT plans resulted in considerably increased LET values in normal tissues and critical structures. In the brainstem, dose-averaged LET values exceeding 5 keV/μm were observed in areas with significant dose (>70% of prescribed dose). In noncritical normal tissues, even values >8 keV/μm occurred.
  
  
  CONCLUSIONS
  This work demonstrates that active scanning offers the possibility of influencing the distribution of dose-averaged LET (i.e., the biological effect) without significantly altering the distribution of physical dose. On the basis of this finding, we propose a method to alter deliberately the LET distribution of a treatment plan in such a manner that the LET is maximized within certain target areas and minimized in normal tissues, while maintaining the prescribed target dose and dose constraints for organs at risk.
authors.affiliation: Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA. cgrassberger@partners.org
authors.forename: Clemens
authors.initials: C
authors.lastname: Grassberger
authors.forename: Alexei
authors.initials: A
authors.lastname: Trofimov
authors.forename: Anthony
authors.initials: A
authors.lastname: Lomax
authors.forename: Harald
authors.initials: H
authors.lastname: Paganetti
mesh_terms: D001932:Brain Neoplasms / Q000000981:diagnostic imaging / Q000532:radiotherapy; D002648:Child; D002817:Chordoma / Q000000981:diagnostic imaging / Q000532:radiotherapy; D006801:Humans; D018499:Linear Energy Transfer; D008297:Male; D009010:Monte Carlo Method; D009369:Neoplasms / Q000000981:diagnostic imaging / Q000532:radiotherapy*; D058958:Organs at Risk / Q000000981:diagnostic imaging / Q000528:radiation effects; D019047:Phantoms, Imaging; D011471:Prostatic Neoplasms / Q000000981:diagnostic imaging / Q000532:radiotherapy; D061766:Proton Therapy; D011859:Radiography; D011880:Radiotherapy Planning, Computer-Assisted / Q000379:methods*; D050397:Radiotherapy, Intensity-Modulated / Q000379:methods*; D012062:Relative Biological Effectiveness; D012542:Scattering, Radiation; D011522:Protons
chemical_list: D011522:Protons