title: Range modulation in proton therapy planning: a simple method for mitigating effects of increased relative biological effectiveness at the end-of-range of clinical proton beams.
abstract: BACKGROUND
  The increase in relative biological effectiveness (RBE) of proton beams at the distal edge of the spread out Bragg peak (SOBP) is a well-known phenomenon that is difficult to quantify accurately in vivo. For purposes of treatment planning, disallowing the distal SOBP to fall within vulnerable tissues hampers sparing to the extent possible with proton beam therapy (PBT). We propose the distal RBE uncertainty may be straightforwardly mitigated with a technique we call "range modulation". With range modulation, the distal falloff is smeared, reducing both the dose and average RBE over the terminal few millimeters of the SOBP.
  
  
  METHODS
  One patient plan was selected to serve as an example for direct comparison of image-guided radiotherapy plans using non-range modulation PBT (NRMPBT), and range-modulation PBT (RMPBT). An additional plan using RMPBT was created to represent a re-treatment scenario (RMPBTrt) using a vertex beam. Planning statistics regarding dose, volume of the planning targets, and color images of the plans are shown.
  
  
  RESULTS
  The three plans generated for this patient reveal that in all cases dosimetric and device manufacturing advantages are able to be achieved using RMPBT. Organ at risk (OAR) doses to critical structures such as the cochleae, optic apparatus, hypothalamus, and temporal lobes can be selectively spared using this method. Concerns about the location of the RBE that did significantly impact beam selection and treatment planning no longer have the same impact on the process, allowing these structures to be spared dose and subsequent associated issues.
  
  
  CONCLUSIONS
  This present study has illustrated that RMPBT can improve OAR sparing while giving equivalent coverage to target volumes relative to traditional PBT methods while avoiding the increased RBE at the end of the beam. It has proven easy to design and implement and robust in our planning process. The method underscores the need to optimize treatment plans in PBT for both traditional energy dose in gray (Gy) and biologic dose (RBE).
authors.affiliation: Department of Radiation Oncology, Indiana University School of Medicine, Indianapolis, IN, USA. jbuchsba@iuhealth.org.
authors.forename: Jeffrey C
authors.initials: JC
authors.lastname: Buchsbaum
authors.forename: Mark W
authors.initials: MW
authors.lastname: McDonald
authors.forename: Peter A S
authors.initials: PA
authors.lastname: Johnstone
authors.forename: Ted
authors.initials: T
authors.lastname: Hoene
authors.forename: Marc
authors.initials: M
authors.lastname: Mendonca
authors.forename: Chee-Wei
authors.initials: CW
authors.lastname: Cheng
authors.forename: Indra J
authors.initials: IJ
authors.lastname: Das
authors.forename: Kevin P
authors.initials: KP
authors.lastname: McMullen
authors.forename: Mark R
authors.initials: MR
authors.lastname: Wolanski
mesh_terms: D001921:Brain / Q000528:radiation effects; D001932:Brain Neoplasms / Q000532:radiotherapy; D016371:Cranial Irradiation / Q000009:adverse effects / Q000592:standards; D004307:Dose-Response Relationship, Radiation; D005910:Glioma / Q000532:radiotherapy; D006801:Humans; D061214:Patient Safety; D061766:Proton Therapy / Q000009:adverse effects; D011874:Radiometry / Q000379:methods* / Q000592:standards; D011880:Radiotherapy Planning, Computer-Assisted / Q000379:methods* / Q000592:standards; D061089:Radiotherapy, Image-Guided / Q000379:methods* / Q000592:standards; D012062:Relative Biological Effectiveness; D011522:Protons
chemical_list: D011522:Protons