In vivo assessment of the tolerance dose of small liver volumes after single-fraction HDR irradiation.
OBJECTIVE
To prospectively assess a dose-response relationship for small volumes of liver parenchyma after single-fraction irradiation.


METHODS
Twenty-five liver metastases were treated by computed tomography (CT)-guided interstitial brachytherapy. Magnetic resonance imaging was performed 1 day before and 3 days and 6, 12, and 24 weeks after therapy. MR sequences included T1-w gradient echo (GRE) enhanced by hepatocyte-targeted gadobenate dimeglumine. All MRI data sets were merged with 3D dosimetry data and evaluated by two radiologists. The reviewers indicated the border of hyperintensity on T2-w images (edema) or hypointensity on T1-w images (loss of hepatocyte function). Based on the total 3D data, a dose-volume histogram was calculated. We estimated the threshold dose for either edema or function loss as the D(90), i.e., the dose achieved in at least 90% of the pseudolesion volume.


RESULTS
Between 3 days and 6 weeks, the extension of the edema increased significantly from the 12.9 Gy isosurface to 9.9 Gy (standard deviation [SD], 3.3 and 2.6). No significant change was detected between 6 and 12 weeks. After 24 weeks, the edematous tissue had shrunk significantly to 14.7 Gy (SD, 4.2). Three days postbrachytherapy, the D(90) for hepatocyte function loss reached the 14.9 Gy isosurface (SD, 3.9). At 6 weeks, the respective zone had increased significantly to 9.9 Gy (SD, 2.3). After 12 and 24 weeks, the dysfunction volume had decreased significantly to the 11.9 Gy and 15.2 Gy isosurface, respectively (SD, 3 and 4.1).


CONCLUSIONS
The 95% interval from 7.6 to 12.2 Gy found as the minimal hepatocyte tolerance after 6 weeks accounts for the radiobiologic variations found in CT-guided brachytherapy, including heterogeneous dose rates by variable catheter arrays.
Ricke
Jens
J
Klinik für Strahlenheilkunde, Charité, Campus Virchow-Klinikum, Humboldt-University Medical School, Berlin, Germany. jens.ricke@charite.de
Seidensticker
Max
M
Lüdemann
Lutz
L
Pech
Maciej
M
Wieners
Gero
G
Hengst
Susanne
S
Mohnike
Konrad
K
Cho
Chie Hee
CH
Lopez Hänninen
Enrique
E
Al-Abadi
Hussain
H
Felix
Roland
R
Wust
Peter
P
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001918:Brachytherapy / Q000379:methods*; D003287:Contrast Media; D004307:Dose-Response Relationship, Radiation; D004487:Edema / Q000473:pathology; D005260:Female; D022781:Hepatocytes / Q000502:physiology / Q000528:radiation effects*; D006801:Humans; D008099:Liver / Q000503:physiopathology / Q000528:radiation effects*; D008107:Liver Diseases / Q000473:pathology; D008113:Liver Neoplasms / Q000532:radiotherapy* / Q000556:secondary; D008279:Magnetic Resonance Imaging; D008297:Male; D008536:Meglumine / Q000031:analogs & derivatives*; D008875:Middle Aged; D009942:Organometallic Compounds; D011446:Prospective Studies; D011836:Radiation Tolerance
D003287:Contrast Media; D009942:Organometallic Compounds; C064572:gadobenic acid; D008536:Meglumine