Colorectal liver metastases that survive radioembolization display features of aggressive tumor behavior

Background: Radiation lobectomy is a therapeutic approach that involves targeted radiation delivery to induce future liver remnant hypertrophy and tumor control. In patients with colorectal liver metastases, only 30-40% have complete tumor regression. The importance of tumor biology in treatment response remains elusive.Methods: Patients with colorectal liver metastases who received radiation lobectomy were selected from surgical pathology files. Using a machine learning scoring protocol, pathological response was correlated to tumor absorbed dose and expression of markers of radioresistance Ki-67 (proliferation), CAIX (hypoxia), Olfm4 (cancer stem cells) and CD45 (leukocytes).Results: No linear association was found between tumor dose and response (r < 0.1, P = 0.73 (Y-90), P = 0.92 (Ho-166)). Response did correlate with proliferation (r = 0.56, P = 0.012), and non-responsive lesions had large pools (>15%) of Olfm4 positive cancer stem cells (Fisher's exact test, P = 0.0037). Responding lesions (regression grade <= 2) were highly hypoxic compared to moderate and non -responding lesions (P = 0.011). Non-responsive lesions had more tumor-infiltrating leukocytes (3240 cells/mm(2) versus 650 cells/mm(2)), although this difference was not significant (P = 0.08).Conclusion: The aggressive phenotype of a subset of surviving cancer cells emphasizes the importance of prompt resection after radiation lobectomy.

Automated summary

This study found that the treatment response in patients with colorectal liver metastases who received radiation lobectomy was correlated with tumor proliferation, hypoxia, and cancer stem cell expression. Non-responsive lesions had a high presence of cancer stem cells, while responding lesions were more hypoxic. These findings emphasize the importance of prompt resection after radiation lobectomy.