Relative biological effectiveness of carbon ions for tumor control, acute skin damage and late radiation-induced fibrosis in a mouse model.
BACKGROUND
The aim of the present study was to compare the biological effectiveness of carbon ions relative to x-rays between tumor control, acute skin reaction and late RIF of CDF1 mice.


METHODS
CDF1 mice with a C3H mouse mammary carcinoma implanted subcutaneously on the foot of the right hind limb were irradiated with single fractions of either photons, or (12)C ions using a 30-mm spread-out Bragg peak. The endpoint of the study was local control (no tumor recurrence within 90 days). For the acute skin reaction, non-tumor bearing CDF1 mice were irradiated with a comparable radiation scheme, and monitored for acute skin damage between Day 7 and 40. Late RIF was assessed in the irradiated mice.


RESULTS
The TCD50 (dose producing tumor control in 50% of mice) values with 95% confidence interval were 29.7 (25.4-34.8) Gy for C ions and 43.9 (39.2-49.2) Gy for photons, with a corresponding Relative biological effectiveness (RBE) value of 1.48 (1.28-1.72). For acute skin damage the MDD50 (dose to produce moist desquamation in 50% of mice) values with 95% confidence interval were 26.3 (23.0-30.1) Gy for C ions and 35.8 (32.9-39.0) Gy for photons, resulting in a RBE of 1.36 (1.20-1.54). For late radiation-induced fibrosis the FD50 (dose to produce severe fibrosis in 50% of mice) values with 95% confidence interval were 26.5 (23.1-30.3) Gy for carbon ions and 39.8 (37.8-41.8) Gy for photons, with a RBE of 1.50 (1.33-1.69).


CONCLUSIONS
The observed RBE values were very similar for tumor response, acute skin damage and late RIF when irradiated with large doses of high- linear energy transfer (LET) carbon ions. This study adds information to the variation in biological effectiveness in different tumor and normal tissue models.
a Department of Experimental Clinical Oncology , Aarhus University Hospital , Aarhus , Denmark.
Brita S
BS
Sørensen
a Department of Experimental Clinical Oncology , Aarhus University Hospital , Aarhus , Denmark.
Michael R
MR
Horsman
a Department of Experimental Clinical Oncology , Aarhus University Hospital , Aarhus , Denmark.
Jan
J
Alsner
a Department of Experimental Clinical Oncology , Aarhus University Hospital , Aarhus , Denmark.
Jens
J
Overgaard
b GSI Helmholtzzentrum für Schwerionenforschung (GSI), Department of Biophysics , Darmstadt , Germany.
Marco
M
Durante
b GSI Helmholtzzentrum für Schwerionenforschung (GSI), Department of Biophysics , Darmstadt , Germany.
Michael
M
Scholz
b GSI Helmholtzzentrum für Schwerionenforschung (GSI), Department of Biophysics , Darmstadt , Germany.
Thomas
T
Friedrich
c Department of Physics , Aarhus University , Aarhus , Denmark.
Niels
N
Bassler
D000818:Animals; D002244:Carbon / Q000009:adverse effects / Q000627:therapeutic use*; D002277:Carcinoma / Q000532:radiotherapy*; D005260:Female; D005355:Fibrosis; D063193:Heavy Ion Radiotherapy; D020450:Heavy Ions / Q000009:adverse effects; D006614:Hindlimb; D008325:Mammary Neoplasms, Experimental / Q000532:radiotherapy*; D051379:Mice; D009368:Neoplasm Transplantation; D011833:Radiation Injuries, Experimental / Q000209:etiology*; D011879:Radiotherapy Dosage; D012062:Relative Biological Effectiveness; D012867:Skin / Q000528:radiation effects*; D040521:Subcutaneous Tissue / Q000473:pathology* / Q000528:radiation effects; D014964:X-Ray Therapy / Q000009:adverse effects; D014965:X-Rays / Q000009:adverse effects
D002244:Carbon