A model of primary culture of colorectal cancer and liver metastasis to predict chemosensitivity.
BACKGROUND
Prediction of chemosensitivity is a major goal of modern oncology. The aim of this study was to establish a simple and effective model of primary culture of colorectal cancer fragments and to test whether it allows prediction of chemosensitivity.


METHODS
Colorectal cancer fragments (primary tumors or liver metastases) of 94 consecutive and previously untreated patients were obtained, prepared, and cultured in polyHEMA. For each fragment cultured, a proliferative index (PI) was calculated after immunostaining at d 0 and after 7 d in culture with media alone or supplemented for 24h with the topoisomerase I inhibitor metabolite SN-38. The correlation between in vitro response (decrease in PI after exposure to the drug) and in vivo response (RECIST criteria) was studied in a subset of patients who had measurable metastases and were treated with a topoisomerase I inhibitor.


RESULTS
PolyHEMA allowed three-dimensional culture of tumor fragments up to 7 d without fibroblastic invasion and with a slight but significant decrease of PI (59% at d 0 versus 51% after 7 d in culture, P < 0.001). In vitro drug efficacy was tested in 67 fragments, the mean PI after culture with SN-38 dropped to 22% (P < 0.001). In a subset of 12 patients, there was no statistically significant correlation between in vitro and in vivo response (P = 0.13).


CONCLUSIONS
Primary culture in polyHEMA was easy to perform successfully in 71% of cases. On this model, the antiproliferative effect of SN-38 could be measured and results correlated to clinical data.
Brouquet
Antoine
A
Department of Digestive Surgery, AP-HP, Hôpital Ambroise-Paré, Boulogne, France.
Taleb
Philippe
P
Lot
Anne-Sophie
AS
Beauchet
Alain
A
Julie
Catherine
C
Prevost
Gregoire
G
Nordlinger
Bernard
B
Penna
Christophe
C
D000230:Adenocarcinoma / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000556:secondary; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000494:pharmacology; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D018929:Cell Culture Techniques / Q000379:methods*; D002455:Cell Division / Q000187:drug effects; D015179:Colorectal Neoplasms / Q000473:pathology*; D016903:Drug Monitoring / Q000379:methods; D019008:Drug Resistance, Neoplasm; D019073:HT29 Cells; D006801:Humans; D000077146:Irinotecan; D019394:Ki-67 Antigen / Q000378:metabolism; D008113:Liver Neoplasms / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000556:secondary; D011102:Polyhydroxyethyl Methacrylate / Q000494:pharmacology; D011859:Radiography; D059004:Topoisomerase I Inhibitors / Q000008:administration & dosage / Q000494:pharmacology
D000972:Antineoplastic Agents, Phytogenic; D019394:Ki-67 Antigen; D059004:Topoisomerase I Inhibitors; D011102:Polyhydroxyethyl Methacrylate; D000077146:Irinotecan; D002166:Camptothecin