The impact of heart irradiation on dose-volume effects in the rat lung.
OBJECTIVE
To test the hypothesis that heart irradiation increases the risk of a symptomatic radiation-induced loss of lung function (SRILF) and that this can be well-described as a modulation of the functional reserve of the lung.


METHODS
Rats were irradiated with 150-MeV protons. Dose-response curves were obtained for a significant increase in breathing frequency after irradiation of 100%, 75%, 50%, or 25% of the total lung volume, either including or excluding the heart from the irradiation field. A significant increase in the mean respiratory rate after 6-12 weeks compared with 0-4 weeks was defined as SRILF, based on biweekly measurements of the respiratory rate. The critical volume (CV) model was used to describe the risk of SRILF. Fits were done using a maximum likelihood method. Consistency between model and data was tested using a previously developed goodness-of-fit test.


RESULTS
The CV model could be fitted consistently to the data for lung irradiation only. However, this fitted model failed to predict the data that also included heart irradiation. Even refitting the model to all data resulted in a significant difference between model and data. These results imply that, although the CV model describes the risk of SRILF when the heart is spared, the model needs to be modified to account for the impact of dose to the heart on the risk of SRILF. Finally, a modified CV model is described that is consistent to all data.


CONCLUSIONS
The detrimental effect of dose to the heart on the incidence of SRILF can be described by a dose dependent decrease in functional reserve of the lung.
van Luijk
Peter
P
Department of Radiation Oncology, University Medical Center, Groningen, The Netherlands. p.van.luijk@rt.umcg.nl
Faber
Hette
H
Meertens
Harm
H
Schippers
Jacobus M
JM
Langendijk
Johannes A
JA
Brandenburg
Sytze
S
Kampinga
Harm H
HH
Coppes
Robert P
RP
D000818:Animals; D004307:Dose-Response Relationship, Radiation; D006321:Heart / Q000528:radiation effects*; D008168:Lung / Q000503:physiopathology / Q000528:radiation effects*; D008954:Models, Biological; D011833:Radiation Injuries, Experimental / Q000503:physiopathology; D051381:Rats; D017208:Rats, Wistar; D012119:Respiration / Q000528:radiation effects*