TY - JOUR
T1 - Colorectal liver metastases that survive radioembolization display features of aggressive tumor behavior
AU - Andel, Daan
AU - Hagendoorn, Jeroen
AU - Alsultan, Ahmed Aziz
AU - Lacle, Miangela Marie
AU - Smits, Maarten Leonard Johannes
AU - Braat, Arthur Johannes Anthonius Theodorus
AU - Kranenburg, Onno
AU - Lam, Marnix Gerard Ernest Hendrik
AU - Borel Rinkes, Inne Hilbrand Max
N1 - Funding Information:
The authors thank Domenico Castigliego and colleagues of the UMCU tissue facility for continuous support and Niek Peters, Esther Strating and Susanne van Schelven for scientific discussions and practical help.
Publisher Copyright:
© 2023 The Authors
PY - 2023/11
Y1 - 2023/11
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85164417879&partnerID=8YFLogxK
U2 - 10.1016/j.hpb.2023.06.011
DO - 10.1016/j.hpb.2023.06.011
M3 - Article
C2 - 37442645
SN - 1365-182X
VL - 25
SP - 1345
EP - 1353
JO - International Hepato-Pancreato Biliary Association.
JF - International Hepato-Pancreato Biliary Association.
IS - 11
ER -