title: In vivo measurement of dose distribution in patients' lymphocytes: helical tomotherapy versus step-and-shoot IMRT in prostate cancer.
abstract: In radiotherapy, in vivo measurement of dose distribution within patients' lymphocytes can be performed by detecting gamma-H2AX foci in lymphocyte nuclei. This method can help in determining the whole-body dose. Options for risk estimations for toxicities in normal tissue and for the incidence of secondary malignancy are still under debate. In this investigation, helical tomotherapy (TOMO) is compared with step-and-shoot IMRT (SSIMRT) of the prostate gland by measuring the dose distribution within patients' lymphocytes. In this prospective study, blood was taken from 20 patients before and 10 min after their first irradiation fraction for each technique. The isolated leukocytes were fixed 2 h after radiation. DNA double-stranded breaks in lymphocyte nuclei were stained immunocytochemically using anti-gamma-H2AX antibodies. Gamma-H2AX foci distribution in lymphocytes was determined for each patient. Using a calibration line, dose distributions in patients' lymphocytes were determined by studying the gamma-H2AX foci distribution, and these data were used to generate a cumulative dose-lymphocyte histogram (DLH). Measured in vivo (DLH), significantly fewer lymphocytes indicated low-dose exposure (<40% of the applied dose) during TOMO compared with SSIMRT. The dose exposure range, between 45 and 100%, was equal with both radiation techniques. The mean number of gamma-H2AX foci per lymphocyte was significantly lower in the TOMO group compared with the SSIMRT group. In radiotherapy of the prostate gland, TOMO generates a smaller fraction of patients' lymphocytes with low-dose exposure relative to the whole body compared with SSIMRT. Differences in the constructional buildup of the different linear accelerator systems, e.g. the flattening filter, may be the cause thereof. The influence of these methods on the incidence of secondary malignancy should be investigated in further studies.
authors.affiliation: Department of Radiation Oncology, University of Heidelberg, Im Neuenheimer Feld 400, 69120 Heidelberg, Germany Clinical Cooperation Unit Radiation Oncology, German Cancer Research Center (DKFZ), Heidelberg, Germany f.zwicker@dkfz.de.
authors.forename: Felix
authors.initials: F
authors.lastname: Zwicker
authors.affiliation: Department of Radiation Oncology, University of Heidelberg, Im Neuenheimer Feld 400, 69120 Heidelberg, Germany.
authors.forename: Benedict
authors.initials: B
authors.lastname: Swartman
authors.affiliation: Department of Radiation Oncology, University of Heidelberg, Im Neuenheimer Feld 400, 69120 Heidelberg, Germany Clinical Cooperation Unit Radiation Oncology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Falk
authors.initials: F
authors.lastname: Roeder
authors.affiliation: Department of Radiation Oncology, University of Heidelberg, Im Neuenheimer Feld 400, 69120 Heidelberg, Germany Clinical Cooperation Unit Radiation Oncology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Florian
authors.initials: F
authors.lastname: Sterzing
authors.affiliation: Department of Radiation Oncology, University of Heidelberg, Im Neuenheimer Feld 400, 69120 Heidelberg, Germany.
authors.forename: Henrik
authors.initials: H
authors.lastname: Hauswald
authors.affiliation: Department of Radiation Oncology, University of Heidelberg, Im Neuenheimer Feld 400, 69120 Heidelberg, Germany Clinical Cooperation Unit Radiation Oncology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Thieke
authors.affiliation: Department of Radiation Oncology, University of Heidelberg, Im Neuenheimer Feld 400, 69120 Heidelberg, Germany.
authors.forename: Klaus-Josef
authors.initials: KJ
authors.lastname: Weber
authors.affiliation: Department of Radiation Oncology, University of Heidelberg, Im Neuenheimer Feld 400, 69120 Heidelberg, Germany Clinical Cooperation Unit Radiation Oncology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Peter E
authors.initials: PE
authors.lastname: Huber
authors.affiliation: Department of Radiation Oncology, University of Heidelberg, Im Neuenheimer Feld 400, 69120 Heidelberg, Germany.
authors.forename: Kai
authors.initials: K
authors.lastname: Schubert
authors.affiliation: Department of Radiation Oncology, University of Heidelberg, Im Neuenheimer Feld 400, 69120 Heidelberg, Germany Clinical Cooperation Unit Radiation Oncology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Debus
authors.affiliation: Department of Radiation Oncology, University of Heidelberg, Im Neuenheimer Feld 400, 69120 Heidelberg, Germany.
authors.forename: Klaus
authors.initials: K
authors.lastname: Herfarth
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001822:Body Burden; D002478:Cells, Cultured; D004307:Dose-Response Relationship, Radiation; D006801:Humans; D008214:Lymphocytes / Q000528:radiation effects*; D008297:Male; D008875:Middle Aged; D011471:Prostatic Neoplasms / Q000473:pathology / Q000532:radiotherapy*; D011874:Radiometry / Q000379:methods*; D011879:Radiotherapy Dosage; D020266:Radiotherapy, Conformal / Q000379:methods*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D014915:Whole-Body Counting / Q000379:methods*
keywords: dose distribution; gamma-H2AX; helical IMRT; in vivo dosimetry; lymphocytes; prostate cancer; step-and-shoot IMRT; tomotherapy