Synergistic effect of interstitial laser coagulation and doxorubicin in a murine tumor recurrence model of solitary colorectal liver metastasis.
BACKGROUND
Interstitial laser coagulation (ILC) is gaining acceptance for treatment of unresectable colorectal liver metastases. However, local recurrence rates are still high. To overcome this problem, we investigated the potential of additional systemic therapy after ILC in a murine model.


METHODS
Single C26 colon carcinoma nodules (approximately 1 mm3) expressing firefly luciferase were implanted in the left liver lobe of 32 BALB/c mice. Seven days after implantation, tumors were treated with either ILC alone (neodymium-yttrium aluminum garnet; 6 W/cm; 800 J/cm) or ILC followed by 1 mg/kg of doxorubicin intravenously. Controls received either doxorubicin alone or sham treatment. Tumor load was measured by in vivo bioluminescent imaging.


RESULTS
Solitary colorectal liver metastases developed over 7 days after tumor implantation in the liver. Extrahepatic disease was not observed. The ILC dose was set to ablate the liver metastases with recurrent tumor growth in 9 of 16 mice after 7 days. After ILC plus doxorubicin, complete tumor destruction occurred without recurrence (0 of 14). Sham treatment or treatment with doxorubicin alone showed an exponential increase in tumor load.


CONCLUSIONS
A murine tumor recurrence model after local ablative treatment of solitary liver metastasis was developed. The combination of ILC and doxorubicin had a strong synergistic effect that led to complete tumor remission in all animals treated.
Veenendaal
Liesbeth M
LM
Department of Surgery, University Medical Center Utrecht, P. O. Box 85500, 3508 GA Utrecht, The Netherlands.
van Hillegersberg
Richard
R
Smakman
Niels
N
van der Bilt
Jarmila D W
JD
van Diest
Paul J
PJ
Kranenburg
Onno
O
Borel Rinkes
Inne H M
IH
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D017024:Chemotherapy, Adjuvant; D015179:Colorectal Neoplasms / Q000473:pathology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000008:administration & dosage*; D007150:Immunohistochemistry; D017075:Laser Coagulation; D008113:Liver Neoplasms / Q000401:mortality / Q000473:pathology / Q000556:secondary* / Q000628:therapy*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009364:Neoplasm Recurrence, Local; D011897:Random Allocation; D016019:Survival Analysis
D000970:Antineoplastic Agents; D004317:Doxorubicin