Modeling volume effects of experimental brachytherapy in the rat rectum: uncovering the limitations of a radiobiologic concept.
OBJECTIVE
To analyze the significance of volume effects in experimental brachytherapy, based on modeling normal tissue complication probability.


METHODS
Experimental brachytherapy in the rat rectum was based on an eight-step 2.5-mm step size source configuration for 192Ir, afterloaded into an unshielded polystyrene applicator. Volume effects were studied using a half-circumferential lead-shielded applicator and a shorter (two-step) source configuration. The main end point was rectal stenosis.


RESULTS
Rectal stenosis was always caused by a radiation ulcer. With the shielded configuration, single-dose ED50 (50% incidence of rectal stenosis) increased from 23 Gy to 36.5 Gy. Single-dose ED50 for the short configuration was 77.9 Gy. The data showed a reasonable fit to a three-parameter version of the biophysical model described by Jackson et al. (1995). This model assumes that organs consist of a large number of radiobiologically independent subunits and that radiation causes a complication if the fraction of the organ damaged is greater than its functional reserve. The fraction of the organ damaged is calculated summing over fractions of the organ damaged at each dose level. The calculated mean functional reserve (nu50) of the rat rectum, assuming a cumulative functional reserve distribution in the group of experimental rats, was 0.53.


CONCLUSIONS
The volume effect observed within small brachytherapy volumes agreed well with clinical experience of large tolerance doses in contact X-ray therapy. However, the nu50 value was comparable to the high functional reserve value reported for liver. Experimental volume effects probably reflect repair processes originating in the areas adjacent to small radiation fields of brachytherapy more than the radiobiologic characteristics of the cells in the irradiated volume.
Johannessen
Hans-Olaf
HO
Department of Surgical Oncology, The Norwegian Radium Hospital, University of Oslo, Oslo, Norway. hansjoha@online.no
Dale
Einar
E
Hellebust
Taran P
TP
Olsen
Dag R
DR
Nesland
Jahn M
JM
Giercksky
Karl-Erik
KE
D000818:Animals; D055592:Biophysical Phenomena; D001703:Biophysics; D001835:Body Weight / Q000528:radiation effects; D001918:Brachytherapy / Q000379:methods*; D004307:Dose-Response Relationship, Radiation; D007496:Iridium Radioisotopes / Q000627:therapeutic use; D008099:Liver / Q000473:pathology; D008297:Male; D008962:Models, Theoretical; D011874:Radiometry; D051381:Rats; D011916:Rats, Inbred F344; D012004:Rectal Neoplasms / Q000532:radiotherapy*; D012007:Rectum / Q000528:radiation effects*; D014965:X-Rays
D007496:Iridium Radioisotopes