title: Dose to the developing dentition during therapeutic irradiation: organ at risk determination and clinical implications.
abstract: OBJECTIVE
  Irradiation of pediatric facial structures can cause severe impairment of permanent teeth later in life. We therefore focused on primary and permanent teeth as organs at risk, investigating the ability to identify individual teeth in children and infants and to correlate dose distributions with subsequent dental toxicity.
  
  
  METHODS
  We retrospectively reviewed 14 pediatric patients who received a maximum dose >20 Gy(relative biological effectiveness, RBE) to 1 or more primary or permanent teeth between 2003 and 2009. The patients (aged 1-16 years) received spot-scanning proton therapy with 46 to 66 Gy(RBE) in 23 to 33 daily fractions for a variety of tumors, including rhabdomyosarcoma (n=10), sarcoma (n=2), teratoma (n=1), and carcinoma (n=1). Individual teeth were contoured on axial slices from planning computed tomography (CT) scans. Dose-volume histogram data were retrospectively obtained from total calculated delivered treatments. Dental follow-up information was obtained from external care providers.
  
  
  RESULTS
  All primary teeth and permanent incisors, canines, premolars, and first and second molars were identifiable on CT scans in all patients as early as 1 year of age. Dose-volume histogram analysis showed wide dose variability, with a median 37 Gy(RBE) per tooth dose range across all individuals, and a median 50 Gy(RBE) intraindividual dose range across all teeth. Dental follow-up revealed absence of significant toxicity in 7 of 10 patients but severe localized toxicity in teeth receiving >20 Gy(RBE) among 3 patients who were all treated at <4 years of age.
  
  
  CONCLUSIONS
  CT-based assessment of dose distribution to individual teeth is feasible, although delayed calcification may complicate tooth identification in the youngest patients. Patterns of dental dose exposure vary markedly within and among patients, corresponding to rapid dose falloff with protons. Severe localized dental toxicity was observed in a few patients receiving the largest doses of radiation at the youngest ages; however, multiple factors including concurrent chemotherapy confounded the dose-effect relationship. Further studies with larger cohorts and appropriate controls will be required.
authors: Center for Proton Therapy, Paul Scherrer Institute, Villigen, Switzerland. Reid.Thompson@uphs.upenn.edu
authors: Reid F
authors: RF
authors: Thompson
authors: Ralf A
authors: RA
authors: Schneider
authors: Francesca
authors: F
authors: Albertini
authors: Antony J
authors: AJ
authors: Lomax
authors: Carmen
authors: C
authors: Ares
authors: Gudrun
authors: G
authors: Goitein
authors: Eugen B
authors: EB
authors: Hug
mesh_terms: D000293:Adolescent; D000970:Antineoplastic Agents / Q000009:adverse effects; D002277:Carcinoma / Q000532:radiotherapy; D002648:Child; D002675:Child, Preschool; D019229:Dentition, Permanent; D005240:Feasibility Studies; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D021621:Imaging, Three-Dimensional / Q000379:methods; D007223:Infant; D008297:Male; D009369:Neoplasms / Q000188:drug therapy / Q000532:radiotherapy*; D058958:Organs at Risk / Q000000981:diagnostic imaging / Q000528:radiation effects*; D061766:Proton Therapy / Q000009:adverse effects / Q000379:methods; D011832:Radiation Injuries / Q000150:complications*; D011879:Radiotherapy Dosage; D012062:Relative Biological Effectiveness; D012189:Retrospective Studies; D012208:Rhabdomyosarcoma / Q000532:radiotherapy; D012509:Sarcoma / Q000532:radiotherapy; D013724:Teratoma / Q000532:radiotherapy; D014057:Tomography, X-Ray Computed; D014070:Tooth / Q000000981:diagnostic imaging / Q000528:radiation effects*; D014083:Tooth Germ / Q000528:radiation effects; D014094:Tooth, Deciduous
chemical_list: D000970:Antineoplastic Agents