title: Proton Minibeam Radiation Therapy Reduces Side Effects in an In Vivo Mouse Ear Model.
abstract: OBJECTIVE
  Proton minibeam radiation therapy is a novel approach to minimize normal tissue damage in the entrance channel by spatial fractionation while keeping tumor control through a homogeneous tumor dose using beam widening with an increasing track length. In the present study, the dose distributions for homogeneous broad beam and minibeam irradiation sessions were simulated. Also, in an animal study, acute normal tissue side effects of proton minibeam irradiation were compared with homogeneous irradiation in a tumor-free mouse ear model to account for the complex effects on the immune system and vasculature in an in vivo normal tissue model.
  
  
  METHODS
  At the ion microprobe SNAKE, 20-MeV protons were administered to the central part (7.2 × 7.2 mm(2)) of the ear of BALB/c mice, using either a homogeneous field with a dose of 60 Gy or 16 minibeams with a nominal 6000 Gy (4 × 4 minibeams, size 0.18 × 0.18 mm(2), with a distance of 1.8 mm). The same average dose was used over the irradiated area.
  
  
  RESULTS
  No ear swelling or other skin reactions were observed at any point after minibeam irradiation. In contrast, significant ear swelling (up to fourfold), erythema, and desquamation developed in homogeneously irradiated ears 3 to 4 weeks after irradiation. Hair loss and the disappearance of sebaceous glands were only detected in the homogeneously irradiated fields.
  
  
  CONCLUSIONS
  These results show that proton minibeam radiation therapy results in reduced adverse effects compared with conventional homogeneous broad-beam irradiation and, therefore, might have the potential to decrease the incidence of side effects resulting from clinical proton and/or heavy ion therapy.
authors.affiliation: Institut für Angewandte Physik und Messtechnik (LRT2), Universität der Bundeswehr München, Neubiberg, Germany. Electronic address: stefanie.girst@unibw.de.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Girst
authors.affiliation: Institut für Angewandte Physik und Messtechnik (LRT2), Universität der Bundeswehr München, Neubiberg, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Greubel
authors.affiliation: Institut für Angewandte Physik und Messtechnik (LRT2), Universität der Bundeswehr München, Neubiberg, Germany.
authors.forename: Judith
authors.initials: J
authors.lastname: Reindl
authors.affiliation: Institut für Angewandte Physik und Messtechnik (LRT2), Universität der Bundeswehr München, Neubiberg, Germany; Department of Radiation Oncology, Klinikum rechts der Isar, Technische Universität München, Munich, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Siebenwirth
authors.affiliation: Department of Radiation Oncology, Klinikum rechts der Isar, Technische Universität München, Munich, Germany.
authors.forename: Olga
authors.initials: O
authors.lastname: Zlobinskaya
authors.affiliation: Institut für Angewandte Physik und Messtechnik (LRT2), Universität der Bundeswehr München, Neubiberg, Germany; Department of Radiation Oncology, Klinikum rechts der Isar, Technische Universität München, Munich, Germany.
authors.forename: Dietrich W M
authors.initials: DWM
authors.lastname: Walsh
authors.affiliation: Department of Radiation Oncology, Klinikum rechts der Isar, Technische Universität München, Munich, Germany.
authors.forename: Katarina
authors.initials: K
authors.lastname: Ilicic
authors.affiliation: Research Unit Analytical Pathology, Helmholtz Zentrum München, German Research Center for Environmental Health, Oberschleißheim, Germany.
authors.forename: Michaela
authors.initials: M
authors.lastname: Aichler
authors.affiliation: Research Unit Analytical Pathology, Helmholtz Zentrum München, German Research Center for Environmental Health, Oberschleißheim, Germany.
authors.forename: Axel
authors.initials: A
authors.lastname: Walch
authors.affiliation: Department of Radiation Oncology, Klinikum rechts der Isar, Technische Universität München, Munich, Germany.
authors.forename: Jan J
authors.initials: JJ
authors.lastname: Wilkens
authors.affiliation: Department of Radiation Oncology, Klinikum rechts der Isar, Technische Universität München, Munich, Germany.
authors.forename: Gabriele
authors.initials: G
authors.lastname: Multhoff
authors.affiliation: Institut für Angewandte Physik und Messtechnik (LRT2), Universität der Bundeswehr München, Neubiberg, Germany.
authors.forename: Günther
authors.initials: G
authors.lastname: Dollinger
authors.affiliation: Department of Radiation Oncology, Klinikum rechts der Isar, Technische Universität München, Munich, Germany.
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Schmid
mesh_terms: D000818:Animals; D054644:Ear Auricle / Q000528:radiation effects*; D004427:Ear Diseases / Q000209:etiology / Q000473:pathology; D004890:Erythema / Q000209:etiology / Q000473:pathology; D005260:Female; D051379:Mice; D008807:Mice, Inbred BALB C; D023421:Models, Animal; D010032:Otitis Externa / Q000209:etiology / Q000473:pathology; D061766:Proton Therapy / Q000009:adverse effects* / Q000379:methods*; D011829:Radiation Dosage; D011833:Radiation Injuries, Experimental / Q000473:pathology / Q000517:prevention & control*