Histopathologic Changes After Yttrium-90 Radioembolization of Colorectal Liver Metastases: A Pilot Feasibility Study.

PURPOSE: To evaluate the histopathologic changes and potential correlations of tissue radiation absorbed dose (TAD) after 90 Y transarterial radioembolization (TARE) for colorectal liver metastases (CLM).

MATERIALS AND METHODS: This prospective pilot study assessed 12 patients with 13 (CLM) through PET/CT--guided biopsies before, immediately (T0) and 3 weeks (T3) after TARE. Subsequent sampling from the same location was enabled by fiducial placement. Biopsy samples were evaluated with hematoxylin-eosin (H&E), TUNEL, Ki67, OxPhos, caspase-3 (CC3), and pH2AX antibodies. Proliferation changes (Ki67) and double-strand DNA breaks (DSBs) were evaluated quantitatively. TAD was calculated on post-TARE PET/CT scan of the biopsy needle location at T0 and T3.

RESULTS: Median TAD at 3 weeks post-TARE was 162 (IQ R:92-211) Gy. DSBs decreased significantly from T0 (median 77%; IQR:75-100%) to T3 (median 14%; IQR:0-54%, p=0.03). A decrease in Ki67 was also documented (median: 73%, IQR:70-80% at T0 vs 41%, IQR:0-66% at T3, p=0.05). There was a strong negative correlation between TAD and DSBs at T0 (r(9)=0.68) and a strong negative correlation at T3 (r(10)=-0.855), (p=0.042 and p=0.002, respectively). There was a strong negative correlation between TAD and Ki67 at both T0 (r(9)=-0.733; p=0.025) and T3 (r(10)=-0.681; p=0.03). Tumors that exhibited caspase-3 activation (8/13, 62%) at either T0 or T3 time point were more likely to develop progression (7/8, 88% vs 1/5, 20%, p=0.015).

CONCLUSION: Post-TARE biopsy can be used to assess TAD and histopathologic changes. Significant decreases in double-strand DNA breaks and proliferation index were noted post TARE. Post-TARE CC3 activation deserves further exploration.