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Annals of Oncology Advance Access originally published online on October 23, 2006
Annals of Oncology 2007 18(2):299-304; doi:10.1093/annonc/mdl386
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© 2006 European Society for Medical Oncology

gastrointestinal tumors

Importance of histological tumor response assessment in predicting the outcome in patients with colorectal liver metastases treated with neo-adjuvant chemotherapy followed by liver surgery

L Rubbia-Brandt1, E Giostra2, C Brezault3, AD Roth4, A Andres2, V Audard5, P Sartoretti6, B Dousset7, PE Majno2, O Soubrane7, S Chaussade3, G Mentha2 and B Terris5,*

1 Unit of Gastrointestinal and Liver Pathology
2 Division of Visceral and Transplantation Surgery, University Hospital, Geneva, Switzerland
3 Division of Gastroenterology, Hôpital Cochin, Paris, France
4 Unit of Oncosurgery, University Hospital, Geneva, Switzerland
5 Division of Pathology, Hôpital Cochin, Université Paris V, Paris, France
6 Division of Clinical Pathology, University Hospital, Geneva, Switzerland
7 Division of Surgery, Hôpital Cochin, Paris, France

* Correspondence to: Prof B. Terris, Division of pathology, Hôpital Cochin, 27 rue du Faubourg Saint-Jacques, 75679 Paris Cedex 14, France. Tel: +33-158-41-14-79; Fax: +33-158-41-14-80; E-mail: benoit.terris{at}cch.ap-hop-paris.fr

Background: The purpose of the study was to characterize histological response to chemotherapy of hepatic colorectal metastases (HCRM), evaluate efficacy of different chemotherapies on histological response, and determine whether tumor regression grading (TRG) of HCRM predicts clinical outcome.

Patients and methods: TRG was evaluated on 525 HCRM surgically resected from 181 patients, 112 pretreated with chemotherapy. Disease-free survival (DFS) and overall survival (OS) were correlated to TRG.

Results: Tumor regression was characterized by fibrosis overgrowing on tumor cells, decreased necrosis, and tumor glands (if present) at the periphery of HCRM. With irinotecan/5-fluorouracil (5-FU), major (MjHR), partial (PHR), and no (NHR) histological tumor regression were observed in 17%, 13%, and 70% of patients, respectively. With oxaliplatin/5-FU, MjHR, PHR, and NHR were observed in 37%, 45%, and 18% of patients, respectively. Five patients, treated with oxaliplatin, had complete response in all their metastases. MjHR was associated with an improved 3-year DFS compared with PHR or NHR. MjHR and PHR were associated with an improved 5-year OS compared with NHR.

Conclusion: Histological tumor regression of HCRM to chemotherapy corresponds to fibrosis overgrowth and not to increase of necrosis. TRG should be considered when evaluating efficacy of chemotherapy for HCRM. Histological tumor regression was most common among oxaliplatin-treated patients and associated with better clinical outcome.

Key words: colorectal cancer, irinotecan, oxaliplatin, pathological response to chemotherapy, sinusoidal obstruction syndrome, tumor regression grade

Received for publication July 4, 2006. Revision received September 1, 2006. Accepted for publication September 11, 2006.


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