Liver Regeneration in Patients With Intrahepatic Malignancies Treated with Focal Liver Radiation Therapy

Article Outline

• Purpose/Objective(s)
• Materials/Methods
• Results
• Conclusions
• Copyright

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Purpose/Objective(s) 

Hepatocytes display regenerative capabilities following partial tissue loss, such as after surgical resection. We have noted anecdotally that within 6 months of treatment, the liver undergoes fibrosis in the high dose region and regenerates in the low dose region. The aim of this study was to quantify liver segment volume changes following radiotherapy (RT) and determine any relationship to radiation dose.

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Materials/Methods 

Serial CT scans (pre-RT and 1–6 months post-RT) of patients with intrahepatic malignancies treated with focal liver 3D-conformal RT and intrahepatic arterial chemotherapy were used for this retrospective study. Stable, anatomical landmarks were used to delineate the left lateral and medial segments, right anterior and posterior segments, and caudate lobe. Volume changes and mean radiation doses delivered to liver segments are reported. The change in volume (% ΔV) between pre-RT and 1–6 months post-RT as a function of mean dose to a segment was modeled using a repeated measures ANOVA.

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Results 

54 patients were studied, including 12 hepatocellular carcinomas (HCC), 16 cholangiocarcinomas (CC), and 26 metastatic colorectal carcinomas (CRC). In 31 patients, both liver atrophy and hypertrophy were observed in different segments, with a radiation dose dependency. Eighty-seven percent (27/31) had hypertrophy in the segment receiving the lowest radiation dose. Seventy-four percent (23/31) had the most atrophy in the segment receiving the highest radiation dose. At 60 days post-RT, the atrophying segments had a mean volume change (range) of −145.8 cm³ (−79.3, −212.3) and a mean dose of 43.7 Gy (39.9, 47.5). The hypertrophying segments showed a mean increase of 115.7 cm³ (88.7, 142.7), with a mean dose of 17.8 Gy (14.7, 20.9). These changes persisted when measured >100 days post-RT. A mixed linear model for liver %ΔV between pre-RT and 1–6 months post-RT versus dose revealed a slope of −1.1%/Gy (−1.3%/Gy, −1.0%/Gy) with an intercept of 26.8% (21.6%, 31.9%), p < 0.0001. This model was most significant regardless of liver segment or histology. On average, liver regeneration may be inhibited for mean liver segment doses >23.9 Gy.

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Conclusions 

Initial results suggest that liver regeneration can occur in the minimally irradiated liver segments following high-dose focal RT. A model based on these data may predict volume changes in specific liver segments as a function of radiation dose. This model can help guide future IMRT treatment planning in patients with limited liver function.