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

Abstract

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 (ρ < 0.1, P = 0.73 (90Y), P = 0.92 (166Ho)). Response did correlate with proliferation (ρ = 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/mm2 versus 650 cells/mm2), 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.