title: Incidence of CNS Injury for a Cohort of 111 Patients Treated With Proton Therapy for Medulloblastoma: LET and RBE Associations for Areas of Injury.
abstract: BACKGROUND
  Central nervous system (CNS) injury is a rare complication of radiation therapy for pediatric brain tumors, but its incidence with proton radiation therapy (PRT) is less well defined. Increased linear energy transfer (LET) and relative biological effectiveness (RBE) at the distal end of proton beams may influence this risk. We report the incidence of CNS injury in medulloblastoma patients treated with PRT and investigate correlations with LET and RBE values.
  
  
  METHODS
  We reviewed 111 consecutive patients treated with PRT for medulloblastoma between 2002 and 2011 and selected patients with clinical symptoms of CNS injury. Magnetic resonance imaging (MRI) findings for all patients were contoured on original planning scans (treatment change areas [TCA]). Dose and LET distributions were calculated for the treated plans using Monte Carlo system. RBE values were estimated based on LET-based published models.
  
  
  RESULTS
  At a median follow-up of 4.2 years, the 5-year cumulative incidence of CNS injury was 3.6% for any grade and 2.7% for grade 3+. Three of 4 symptomatic patients were treated with a whole posterior fossa boost. Eight of 10 defined TCAs had higher LET values than the target but statistically nonsignificant differences in RBE values (P=.12).
  
  
  CONCLUSIONS
  Central nervous system and brainstem injury incidence for PRT in this series is similar to that reported for photon radiation therapy. The risk of CNS injury was higher for whole posterior fossa boost than for involved field. Although no clear correlation with RBE values was found, numbers were small and additional investigation is warranted to better determine the relationship between injury and LET.
authors.affiliation: Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts.
authors.forename: Drosoula
authors.initials: D
authors.lastname: Giantsoudi
authors.affiliation: Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts.
authors.forename: Roshan V
authors.initials: RV
authors.lastname: Sethi
authors.affiliation: Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts.
authors.forename: Beow Y
authors.initials: BY
authors.lastname: Yeap
authors.affiliation: Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts.
authors.forename: Bree R
authors.initials: BR
authors.lastname: Eaton
authors.affiliation: Department of Pediatrics, Massachusetts General Hospital, Boston, Massachusetts.
authors.forename: David H
authors.initials: DH
authors.lastname: Ebb
authors.affiliation: Department of Radiology (O.R.) at the Massachusetts General Hospital, Boston, Massachusetts.
authors.forename: Paul A
authors.initials: PA
authors.lastname: Caruso
authors.affiliation: Department of Radiology (O.R.) at the Massachusetts General Hospital, Boston, Massachusetts.
authors.forename: Otto
authors.initials: O
authors.lastname: Rapalino
authors.affiliation: Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts.
authors.forename: Yen-Lin E
authors.initials: YE
authors.lastname: Chen
authors.affiliation: Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts.
authors.forename: Judith A
authors.initials: JA
authors.lastname: Adams
authors.affiliation: Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts.
authors.forename: Torunn I
authors.initials: TI
authors.lastname: Yock
authors.affiliation: Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts.
authors.forename: Nancy J
authors.initials: NJ
authors.lastname: Tarbell
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. Electronic address: smacdonald@mgh.harvard.edu.
authors.forename: Shannon M
authors.initials: SM
authors.lastname: MacDonald
mesh_terms: D000293:Adolescent; D001933:Brain Stem / Q000000981:diagnostic imaging / Q000528:radiation effects*; D002528:Cerebellar Neoplasms / Q000188:drug therapy / Q000532:radiotherapy*; D002531:Cerebellum / Q000528:radiation effects; D002574:Cervical Vertebrae; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D016371:Cranial Irradiation / Q000009:adverse effects* / Q000379:methods; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015994:Incidence; D018499:Linear Energy Transfer; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008527:Medulloblastoma / Q000188:drug therapy / Q000532:radiotherapy*; D009010:Monte Carlo Method; D059351:Organ Sparing Treatments / Q000009:adverse effects / Q000379:methods; D061766:Proton Therapy / Q000009:adverse effects* / Q000379:methods; D011832:Radiation Injuries / Q000175:diagnosis / Q000000981:diagnostic imaging / Q000453:epidemiology*; D011859:Radiography; D011879:Radiotherapy Dosage; D012062:Relative Biological Effectiveness; D013116:Spinal Cord / Q000528:radiation effects*; D013997:Time Factors; D055815:Young Adult