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

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

Abstract

Background: 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. This study investigated the association of HGP with the immune phenotype (IP) and clinical outcome after liver resection.

Methods: CLM 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.

Results: One 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.

Conclusions: The desmoplastic HGP is associated with the inflamed IP and HGP may be a potential biomarker for adjuvant treatment that includes targeting the immune contexture.

Conflict of interest statement

T.G. is member of the advisory boards of Roche, Merck-Serono and Sanofi-Aventis. H.-J.L. is member of the advisory board of Genentech, Merck KG, Bayer and BMS. All remaining authors have declared no conflict of interest.

Figures

Fig. 1. HGP and association with RFS.
Fig. 1. HGP and association with RFS.
The replacement HGP is associated with shorter RFS than the desmoplastic HGP (median 8.7 versus 16.3 months, log-rank P < 0.001).
Fig. 2. HGP and association with OS.
Fig. 2. HGP and association with OS.
The replacement HGP is associated with shorter OS than the desmoplastic HGP (median 36.6. months versus not reached, log-rank P = 0.023).
Fig. 3. IP and association with RFS.
Fig. 3. IP and association with RFS.
The non-inflamed IP is associated with shorter RFS than the inflamed IP (median 10.8 versus 16.5 months, log-rank P = 0.026).
Fig. 4. IP and association with OS.
Fig. 4. IP and association with OS.
The non-inflamed IP is not associated with a statistically significant difference in OS compared to the inflamed IP (median 48.2 months versus not reached, log-rank P = 0.23).

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