Immune phenotype and histopathological growth pattern in patients with colorectal liver metastases

Stefan Stremitzer,Mark Kockx,Thomas Gruenberger,Peter Vermeulen,Wu Zhang,Friedrich Wrba,Heinz-Josef Lenz,Shannon Graver,Judith Stift,Stefan J Scherer,Dongyun Yang,Luc Dirix

doi:10.1038/s41416-020-0812-z

Abstract

BackgroundPatients with desmoplastic (angiogenic) histopathological growth pattern (HGP) colorectal liver metastases (CLM) might derive more benefit from bevacizumab-based chemotherapy than those with replacement (non-angiogenic) HGP. This study investigated the association of HGP with the immune phenotype (IP) and clinical outcome after liver resection.MethodsCLM of patients treated with perioperative bevacizumab-based chemotherapy and liver resection were investigated. Association of HGP and IP with response, recurrence-free survival (RFS) and overall survival (OS) was investigated.ResultsOne hundred and eighteen patients (M/F 66/52, median age 62.3 (31.0–80.4) years, median follow-up 32.2 (5.0–92.7) months) were enrolled. The inflamed IP was associated with the desmoplastic HGP. The desmoplastic HGP was associated with better radiological and histological response compared to the replacement HGP, respectively. The replacement HGP was associated with shorter RFS (8.7 versus 16.3 months, HR 2.60, P = 0.001) and OS (36.6 months versus not reached, HR 2.32, P = 0.027), respectively. The non-inflamed IP was associated with shorter RFS (10.8 versus 16.5 months, HR 1.85, P = 0.029). The HGP but not the IP remained significant in multivariable analysis for RFS.ConclusionsThe desmoplastic HGP is associated with the inflamed IP and HGP may be a potential biomarker for adjuvant treatment that includes targeting the immune contexture.

Highlights

Patients with desmoplastic histopathological growth pattern (HGP) colorectal liver metastases (CLM) might derive more benefit from bevacizumab-based chemotherapy than those with replacement histopathological growth patterns (HGPs)
In a previous landmark study, Frentzas et al showed that the replacement HGP is associated with vessel co-option rather than angiogenesis
The authors demonstrated that this HGP is associated with poorer histological and morphological response and survival in patients who underwent liver resection after preoperative therapy with bevacizumab.[9]

Summary

Introduction

Patients with desmoplastic (angiogenic) histopathological growth pattern (HGP) colorectal liver metastases (CLM) might derive more benefit from bevacizumab-based chemotherapy than those with replacement (non-angiogenic) HGP. Liver resection is the gold standard for the treatment of resectable colorectal liver metastases (CLM) and associated with long-term survival.[1] In combination with perioperative chemotherapy, liver resection offers the chance of cure in approximately 25% of the patients.[2] The addition of the anti-vascular endothelial growth factor (anti-VEGF) antibody bevacizumab to combination chemotherapy targeting the angiogenesis pathway is associated with high radiological response and improved histological response rates.[3,4,5] Biomarkers to predict the efficacy of bevacizumab-based chemotherapy in this setting are urgently needed.

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Conclusion