title: Dose-volume histogram analysis for risk factors of radiation-induced rib fracture after hypofractionated proton beam therapy for hepatocellular carcinoma.
abstract: BACKGROUND
  Radiation-induced rib fracture has been reported as a late complication after external radiotherapy to the chest. The purpose of this study was to clarify the characteristics and risk factors of rib fracture after hypofractionated proton beam therapy (PBT).
  
  
  METHODS
  The retrospective study comprised 67 patients with hepatocellular carcinoma who were treated using PBT of 66 Cobalt-Gray-equivalents [Gy (RBE)] in 10 fractions. We analyzed the patients' characteristics and determined dose-volume histograms (DVHs) for the irradiated ribs, and then estimated relationships between risk of fracture and several dose-volume parameters. An irradiated rib was defined to be any rib included in the area irradiated by PBT as determined by treatment-planning computed tomography.
  
  
  RESULTS
  Among the 67 patients, a total of 310 ribs were identified as irradiated ribs. Twenty-seven (8.7%) of the irradiated ribs developed fractures in 11 patients (16.4%). No significant relationships were seen between incidence of fracture and characteristics of patients, including sex, age, tumor size, tumor site, and follow-up period (p ≥ 0.05). The results of receiver operating characteristic curve analysis using DVH parameters demonstrated that the largest area under the curve (AUC) was observed for the volume of rib receiving a biologically effective dose of more than 60 Gy(3 )(RBE) (V60) [The equivalent dose in 2 Gy fractions (EQD2); 36 Gy(3)] and the AUCs of V30 to V120 (EQD2; 18-72 Gy(3)) and Dmax to D(10 cm)(3) were similar to that of V60. No significant relationships were seen for DVH parameters and intervals from PBT to incidence of fracture.
  
  
  CONCLUSIONS
  DVH parameters are useful in predicting late adverse events of rib irradiation. This study identified that V60 was a most statistically significant parameter, and V30 to V120 and Dmax to D(10 cm)(3) were also significant and clinically useful for estimating the risk of rib fracture after hypofractionated PBT.
authors.affiliation: Proton Medical Research Center and Department of Radiation Oncology, University of Tsukuba, Tsukuba, Ibaraki, Japan. ayaek@pmrc.tsukuba.ac.jp
authors.forename: Ayae
authors.initials: A
authors.lastname: Kanemoto
authors.forename: Masashi
authors.initials: M
authors.lastname: Mizumoto
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Okumura
authors.forename: Hideto
authors.initials: H
authors.lastname: Takahashi
authors.forename: Takayuki
authors.initials: T
authors.lastname: Hashimoto
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Oshiro
authors.forename: Nobuyoshi
authors.initials: N
authors.lastname: Fukumitsu
authors.forename: Takashi
authors.initials: T
authors.lastname: Moritake
authors.forename: Koji
authors.initials: K
authors.lastname: Tsuboi
authors.forename: Takeji
authors.initials: T
authors.lastname: Sakae
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Sakurai
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D006528:Carcinoma, Hepatocellular / Q000473:pathology / Q000532:radiotherapy*; D019583:Dose Fractionation, Radiation; D004307:Dose-Response Relationship, Radiation; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000473:pathology / Q000532:radiotherapy*; D008297:Male; D008875:Middle Aged; D061766:Proton Therapy / Q000009:adverse effects* / Q000379:methods; D011832:Radiation Injuries / Q000453:epidemiology / Q000209:etiology*; D012189:Retrospective Studies; D012253:Rib Fractures / Q000453:epidemiology / Q000209:etiology*; D012307:Risk Factors; D047368:Tumor Burden / Q000528:radiation effects