Tumor Vascular Microenvironment of Colorectal Hepatic Metastasis and Chemotherapy Response.

Shugo Shiba,Makoto Sudoh,Hiroshi Iino,Hirotaka Okamoto,Daisuke Ichikawa

doi:10.21873/anticanres.15261

Shugo Shiba, Makoto Sudoh + Show 3 more

Open Access

https://doi.org/10.21873/anticanres.15261

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Abstract

The tumor vascular microenvironment has an important role in tumor progression and metastasis. The objective of this study was to assess the significance of metastatic hepatic tumor vascular microenvironment in relation to the response to systemic fluorouracil-based chemotherapy [folinic acid/fluorouracil/oxaliplatin (FOLFOX) or folinic acid/fluorouracil/irinotecan (FOLFIRI)]. A total of 48 consecutive patients with colorectal cancer (CRC) with hepatic metastasis were retrospectively reviewed, and factors such as metastatic tumor vascular microenvironment, chemotherapy response and hepatic resection, were analyzed. Tumor angiogenesis was microscopically evaluated by microvessel density (MVD) in sections stained immunochemically with antibody to CD34 in patients with hepatic resection. Angiogenesis in the tumor microenvironment in association with ring enhancement (RE) on computed tomography (CT) was also examined. Microscopic examination revealed that peripheral RE on CT of the metastatic tumor was associated with tumor angiogenesis by MVD. The overall response rate after six courses of first-line chemotherapy for liver metastasis with RE on CT was 64% (23/36), whereas the response rate for those without RE was 25% (3/12), which was significantly lower, although the survival of patients with RE-positive and RE-negative tumors did not differ significantly. Peripheral RE of metastatic hepatic tumor on CT was associated with angiogenesis in the tumor microenvironment and higher chemotherapy response.

Highlights

Colorectal carcinoma (CRC) is one of the most common cancers
Microscopic examination revealed that peripheral ring enhancement (RE) on computed tomography (CT) of the metastatic tumor is associated with tumor angiogenesis by microvessel density (MVD)
The peripheral RE on CT of the metastatic hepatic tumor was associated with the angiogenesis in tumor micro-environment and higher chemotherapy response

Summary

Introduction

50% of patients develop liver metastases at some point during their disease course[1,2,3]). Patients who are candidates for surgical resection of their liver metastases can expect a prolonged survival or even cure[4,5]). Only 10 to 25% of patients are candidates for liver resection[6,7]). In patients with unresectable metastases, chemotherapy is the treatment of choice, and it is often used with palliative intent, it may be used in an attempt to render the metastases resectable[8,9]). The objective of this study was to assess the significance of metastatic hepatic tumor vascular micro-environment in relation to the response to the systemic 5-FU-based chemotherapy (FOLFOX or FOLFIRI)

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