title: Lifetime increased cancer risk in mice following exposure to clinical proton beam-generated neutrons.
abstract: OBJECTIVE
  To evaluate the life span and risk of cancer following whole-body exposure of mice to neutrons generated by a passively scattered clinical spread-out Bragg peak (SOBP) proton beam.
  
  
  METHODS
  Three hundred young adult female FVB/N mice, 152 test and 148 control, were entered into the experiment. Mice were placed in an annular cassette around a cylindrical phantom, which was positioned lateral to the mid-SOBP of a 165-MeV, clinical proton beam. The average distance from the edge of the mid-SOBP to the conscious active mice was 21.5 cm. The phantom was irradiated with once-daily fractions of 25 Gy, 4 days per week, for 6 weeks. The age at death and cause of death (ie, cancer and type vs noncancer causes) were assessed over the life span of the mice.
  
  
  RESULTS
  Exposure of mice to a dose of 600 Gy of proton beam-generated neutrons, reduced the median life span of the mice by 4.2% (Kaplan-Meier cumulative survival, P=.053). The relative risk of death from cancer in neutron exposed versus control mice was 1.40 for cancer of all types (P=.0006) and 1.22 for solid cancers (P=.09). For a typical 60 Gy dose of clinical protons, the observed 22% increased risk of solid cancer would be expected to decrease by a factor of 10.
  
  
  CONCLUSIONS
  Exposure of mice to neutrons generated by a proton dose that exceeds a typical course of radiation therapy by a factor of 10, resulted in a statistically significant increase in the background incidence of leukemia and a marginally significant increase in solid cancer. The results indicate that the risk of out-of-field second solid cancers from SOBP proton-generated neutrons and typical treatment schedules, is 6 to 10 times less than is suggested by current neutron risk estimates.
authors.affiliation: Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts. Electronic address: lgerweck@mgh.harvard.edu.
authors.forename: Leo E
authors.initials: LE
authors.lastname: Gerweck
authors.affiliation: Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts.
authors.forename: Peigen
authors.initials: P
authors.lastname: Huang
authors.affiliation: Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts.
authors.forename: Hsiao-Ming
authors.initials: HM
authors.lastname: Lu
authors.affiliation: Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts.
authors.forename: Harald
authors.initials: H
authors.lastname: Paganetti
authors.affiliation: Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts.
authors.forename: Yenong
authors.initials: Y
authors.lastname: Zhou
mesh_terms: D000367:Age Factors; D000818:Animals; D002423:Cause of Death; D019583:Dose Fractionation, Radiation; D005260:Female; D008136:Longevity / Q000528:radiation effects*; D051379:Mice; D009010:Monte Carlo Method; D009374:Neoplasms, Experimental / Q000209:etiology* / Q000401:mortality; D009381:Neoplasms, Radiation-Induced / Q000209:etiology* / Q000401:mortality; D009502:Neutrons / Q000009:adverse effects*; D061766:Proton Therapy / Q000009:adverse effects*; D012542:Scattering, Radiation; D014916:Whole-Body Irradiation / Q000009:adverse effects* / Q000379:methods / Q000401:mortality
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