Cardiac sub-volume targeting demonstrates regional radiosensitivity in the mouse heart
Butterworth, K. Williams, K. van Herk, Marcel Aznar, Marianne Camille McMahon, S. Vasquez Osorio, Eliana Edgar, K. Walls, G. Gill, E Ghita, M.
Butterworth, K.
Williams, K.
van Herk, Marcel
Aznar, Marianne Camille
McMahon, S.
Vasquez Osorio, Eliana
Edgar, K.
Walls, G.
Gill, E
Ghita, M.
Citations
Altmetric:
Abstract
Purpose or Objective
Radiation induced cardiac toxicity remains one of the most
critical dose limiting constraint in radiotherapy and a
major cause of mortality amongst cancer survivors. Recent
clinical evidence has shown higher doses to the base of the
heart are associated with worse overall survival in lung
cancer patients receiving curative intent radiotherapy.
This work aimed to investigate the impact of subvolume
heart irradiation in a mouse model, and to identify critical
radiosensitive regions towards developing a mechanistic
understanding of regional radiosensitivity.
Material and Methods
C57BL/6 mice were irradiated with a single fraction of 16
Gy targeted to the base, middle and apex of the heart,
with a 3 x 9 mm field and parallel opposed geometry, using
a small animal radiotherapy research platform (SARRP,
Xstrahl Life Sciences). Cone beam CT and
echocardiography were performed at baseline and at 10
week intervals for 50 weeks after treatment. Left ventricle
(LV) wall thickness was quantified from M-mode
parasternal short-axis scans at the level of the papillary
muscles. Fractional shortening (FS) was calculated from
the LV end-diastolic and end-systolic diameters, and pulsewave
Doppler used to quantify mitral valve (MV) flow,
expressed as E/A ratio. Structural and functional
parameters were correlated with mean heart dose (MHD)
and V5.
Results
All irradiated mice showed a time dependent increase in
LV wall thickness detected as early as 10 weeks following
treatment, with the most significant and persistent
changes occurring in the base irradiated animals.
Similarly, differential effects were observed on cardiac
function with base irradiated animals showing the most
significant decreases in FS, ejection fraction and E/A ratio
compared to control animals at 40 and 50 weeks following
irradiation. The observed structural and functional changes did not correlate with MHD and V5 indicating that
whole heart dosimetry parameters do not predict
physiological changes resulting from irradiation of cardiac
subvolumes.
Conclusion
This is the first report demonstrating structural and
functional consequences of subvolume targeting in the
mouse heart. Our data are in close agreement with clinical
observations indicating the base of the heart as a
radiosensitive region and form the basis for further
mechanistic investigations.
Description
Date
2020
Publisher
Collections
Keywords
Type
Meetings and Proceedings
Citation
Butterworth K, Williams K, Van Herk M, McWilliam A, Aznar M, McMahon S, et al. OC-0196: Cardiac sub-volume targeting demonstrates regional radiosensitivity in the mouse heart. Radiotherapy and Oncology . 2020 Nov;152:S97–8.