title: Early biomarkers related to secondary primary cancer risk in radiotherapy treated prostate cancer patients: IMRT versus IMAT.
abstract: OBJECTIVE
  To investigate whether rotational techniques (Volumetric Modulated Arc Therapy - VMAT) are associated with a higher risk for secondary primary malignancies compared to step-and-shoot Intensity Modulated Radiation Therapy (ss-IMRT). To this end, radiation therapy (RT) induced DNA double-strand-breaks and the resulting chromosomal damage were assessed in peripheral blood T-lymphocytes of prostate cancer (PCa) patients applying γH2AX foci and G0 micronucleus (MN) assays.
  
  
  METHODS
  The study comprised 33PCa patients. A blood sample was taken before start of therapy and after the 1st and 3rd RT fraction to determine respectively the RT-induced γH2AX foci and MN. The equivalent total body dose (D(ETB)) was calculated based on treatment planning data.
  
  
  RESULTS
  A linear dose response was obtained for γH2AX foci yields versus D(ETB) while MN showed a linear-quadratic dose response. Patients treated with large volume (LV) VMAT show a significantly higher level of induced γH2AX foci and MN compared to IMRT and small volume (SV) VMAT (p<0.01). Assuming a linear-quadratic relationship, a satisfactory correlation was found between both endpoints (R(2) 0.86).
  
  
  CONCLUSIONS
  Biomarker responses were governed by dose and irradiated volume of normal tissues. No significant differences between IMRT and rotational therapy inherent to the technique itself were observed.
authors.affiliation: Department of Basic Medical Sciences, Ghent University, Gent, Belgium.
authors.forename: Joke
authors.initials: J
authors.lastname: Werbrouck
authors.forename: Piet
authors.initials: P
authors.lastname: Ost
authors.forename: Valerie
authors.initials: V
authors.lastname: Fonteyne
authors.forename: Gert
authors.initials: G
authors.lastname: De Meerleer
authors.forename: Wilfried
authors.initials: W
authors.lastname: De Neve
authors.forename: Evelien
authors.initials: E
authors.lastname: Bogaert
authors.forename: Laurence
authors.initials: L
authors.lastname: Beels
authors.forename: Klaus
authors.initials: K
authors.lastname: Bacher
authors.forename: Anne
authors.initials: A
authors.lastname: Vral
authors.forename: Hubert
authors.initials: H
authors.lastname: Thierens
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis*; D004307:Dose-Response Relationship, Radiation; D006657:Histones / Q000032:analysis; D006801:Humans; D008297:Male; D048629:Micronuclei, Chromosome-Defective; D008875:Middle Aged; D016609:Neoplasms, Second Primary / Q000209:etiology*; D011471:Prostatic Neoplasms / Q000235:genetics / Q000532:radiotherapy*; D011879:Radiotherapy Dosage; D050397:Radiotherapy, Intensity-Modulated / Q000009:adverse effects*; D012306:Risk
chemical_list: D014408:Biomarkers, Tumor; C468783:H2AX protein, human; D006657:Histones
keywords: IMRT; Micronuclei; Rotational radiation therapy; Secondary cancer risk; γH2AX foci