gms | German Medical Science

48th Meeting of the Particle Therapy Co-Operative Group

Particle Therapy Co-Operative Group (PTCOG)

28.09. - 03.10.2009, Heidelberg

Effectiveness of protons in human prostate cell lines: the genetic background possibly determines the RBE in the Spread-out-bragg-peak compared to Plateau region

Meeting Abstract

  • A. Staab - Center for Proton Therapy, Paul Scherrer Institute, Villigen, Switzerland
  • N. Frenzel - Laboratory for Molecular Radiobiology, Department of Radiation Oncology, University Hospital, Zürich, Switzerland
  • A. Coray - Center for Proton Therapy, Paul Scherrer Institute, Villigen, Switzerland
  • A. Lomax - Center for Proton Therapy, Paul Scherrer Institute, Villigen, Switzerland
  • R. Schneider - Center for Proton Therapy, Paul Scherrer Institute, Villigen, Switzerland
  • M. Pruschy - Laboratory for Molecular Radiobiology, Department of Radiation Oncology, University Hospital, Zürich, Switzerland
  • E. Hug - Center for Proton Therapy, Paul Scherrer Institute, Villigen, Switzerland

PTCOG 48. Meeting of the Particle Therapy Co-Operative Group. Heidelberg, 28.09.-03.10.2009. Düsseldorf: German Medical Science GMS Publishing House; 2009. Doc09ptcog192

DOI: 10.3205/09ptcog192, URN: urn:nbn:de:0183-09ptcog1922

Published: September 24, 2009

© 2009 Staab et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.en). You are free: to Share – to copy, distribute and transmit the work, provided the original author and source are credited.


Outline

Text

Background: Proton therapy is an effective therapy for localized prostate cancer. Even though a constant RBE of 1.1 is used in clinical routine there still exists an uncertainty regarding the relative biological effectiveness (RBE). The tumor suppressor protein p53 is considered to have an impact on the radiosensitivity of prostate cancer cells. Here we calculated the RBE in two different prostate tumor cell lines with varying p53 status using clonogenic assays.

Methods and material: Two different human prostate cell lines, DU145 (p53mut/mut) and LnCap (p53wt/wt), were irradiated with either photons (Pantak Therapax 300kV X-ray) or 138 MeV protons at the middle of spread-out Bragg peak (SOBP) or in the plateau region: Cell survival was quantified in three independent experiments by standardized colony-forming assay. Survival curves were generated by plotting S as a function of radiation dose (D) and survival data were fitted with the linear-quadratic model: S(D) = exp [-(αD + βD2)] by optimizing α and β. The RBE at a certain dose was calculated at cell survival levels of 50%, 37% and 10% using the phenomenogical RBE model: RBE (Dpxxpp)=[(αx 2+4βxDpppDp))1/2x]/(2βxDp) [1].

Results: DU145 cells were significantly more radioresistant than LnCap cells after proton and photon irradiation at dose levels >2Gy. The calculated RBE in DU145 cells at 50%, 37% and 10% clonogenic survival levels were 1.6, 1.5 and 1.3 in the SOBP and 1.7, 1.5 and 1.3 in the plateau region, respectively. The calculated RBE2Gy in DU145 cells was 1.5 for irradiation in the SOBP as well as in the plateau region. In LnCap cells the calculated RBE was stable at a level of 1.3 in the SOBP at all survival levels (50%, 37%, 10%) and at 0.6, 0.7 and 0.9 in the plateau region (50%, 37%, 10% survival level). The calculated RBE2Gy in the SOBP region was 1.3 and 0.7 in the plateau region, respectively.

Conclusion: The increased RBE of protons in the SOBP or plateau region in DU145 cells compared to the RBE values determined in LnCap cells indicates that the genetic cellular background possibly affects the overall RBE and influences a dose-dependent aspect. RBE values <1 in LnCap cells in the plateau region indicates a more efficient repair of sublethal DNA damage and possibly suggests that protons in the plateau region induce a different form of DNA damage compared to the SOBP. Detailed analyses of DNA repair mechanisms after proton irradiation will be performed.


References

1.
Wilkens JJ, Oelfke U. A phenomenological model for the relative biological effectiveness in therapeutic proton beams. Phys Med Biol. 2004;49(13):2811-25.