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Growth pattern of colorectal liver metastasis as a marker of recurrence risk

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Abstract

Despite improved therapy of advanced colorectal cancer, the median overall survival (OS) is still low. A surgical removal has significantly improved survival, if lesions are entirely removed. The purpose of this retrospective explorative study was to evaluate the prognostic value of histological growth patterns (GP) in chemonaive and patients receiving neo-adjuvant therapy. Two-hundred-fifty-four patients who underwent liver resection of colorectal liver metastases between 2007 and 2011 were included in the study. Clinicopathological data and information on neo-adjuvant treatment were retrieved from patient and pathology records. Histological GP were evaluated and related to recurrence free and OS. Kaplan–Meier curves, log-rank test and Cox regression analysis were used. The 5-year OS was 41.8 % (95 % CI 33.8–49.8 %). Growth pattern evaluation of the largest liver metastasis was possible in 224 cases, with the following distribution: desmoplastic 63 patients (28.1 %); pushing 77 patients (34.4 %); replacement 28 patients (12.5 %); mixed 56 patients (25.0 %). The Kaplan–Meier analyses demonstrated that patients resected for liver metastases with desmoplastic growth pattern had a longer recurrence free survival (RFS) than patients resected for non-desmoplastic liver metastases (p = 0.05). When patients were stratified according to neo-adjuvant treatment in the multivariate Cox regression model, hazard ratios for RFS compared to desmoplastic were: pushing (HR = 1.37, 95 % CI 0.93–2.02, p = 0.116), replacement (HR = 2.16, 95 % CI 1.29–3.62, p = 0.003) and mixed (HR = 1.70, 95 % CI 1.12–2.59, p = 0.013). This was true for chemonaive patients as well as for patients who received neo-adjuvant treatment.

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Abbreviations

bev:

Bevacizumab

BRAF :

v-Raf murine sarcoma viral oncogene homolog B

CEA:

Carcinoembryonic antigen

CI:

Confidence interval

CLM:

Colorectal liver metastasis

CRC:

Colorectal cancer

CT:

Computed tomography

CTx:

Chemotherapy

EGFR:

Epidermal growth factor receptor

5FU:

5-Fluorouracil

GP:

Growth pattern

H&E:

Haematoxylin and eosin

HR:

Hazard ratio

KRAS :

Kirsten rat sarcoma viral oncogene homolog

mCRC:

Metastatic colorectal cancer

OS:

Overall survival

oxa:

Oxaliplatin

pts:

Patients

RFS:

Recurrence free survival

RTx:

Radiotherapy

uPAR:

Urokinase-type plasminogen activator receptor

VEGF:

Vascular endothelial growth factor

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Acknowledgments

The authors wish to thank the medical staff at Department of Oncology at the hospitals in Aalborg, Herlev, Hillerød, Nuuk, Næstved, Roskilde and Rigshospitalet for their assistance when retrieving patient records and charts. We also thank John Post for the great work on illustrations and laboratory technicians Lotte Frederiksen and Lene Kjaer Callesen for skilful assistance. This study was supported by the Capital Region of Denmark Foundation for Health Research (GHH), The Oncological Research Foundation of Rigshospitalet, Danish Cancer Research Foundation, Danish Cancer Society, unrestricted grant from Roche, politician J. Christensen og K. Christensen Foundation for support of research in cancer and AIDS, Hede Nielsen's Family Foundation, The Erichsens Family Foundation, Kristian Kjær born la Cour-Holmens Foundation, King Christian the 10th Foundation, Mimi og Victor Larsen's Foundation, Sigvald og Edith Rasmussen's Foundation and the Villum Foundation (MI).

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Authors and Affiliations

  1. The Finsen Laboratory, Rigshospitalet, Ole Maaleoes Vej 5, Building 3, 3rd Floor, 2200, Copenhagen, Denmark

    R. L. Eefsen, I. J. Christensen, O. D. Laerum, H. C. Rolff, G. Høyer-Hansen & M. Illemann

  2. Biotech Research and Innovation Centre (BRIC), University of Copenhagen, 2200, Copenhagen, Denmark

    R. L. Eefsen, I. J. Christensen, O. D. Laerum, H. C. Rolff, G. Høyer-Hansen & M. Illemann

  3. Department of Oncology, Rigshospitalet, Blegdamsvej 9, 5073, 2100, Copenhagen, Denmark

    R. L. Eefsen, M. B. Mogensen & K. Osterlind

  4. Translational Cancer Research Unit, GZA Hospitals St. Augustinus, Osterveldlaan 24, 2610, Wilrijk, Antwerp, Belgium

    P. B. Vermeulen & G. G. Van den Eynden

  5. Department of Surgery, Rigshospitalet, Blegdamsvej 9, 2100, Copenhagen, Denmark

    H. C. Rolff

  6. Department of Pathology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark

    B. Vainer

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  1. R. L. Eefsen
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  2. P. B. Vermeulen
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  3. I. J. Christensen
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  4. O. D. Laerum
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  5. M. B. Mogensen
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  7. G. G. Van den Eynden
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  8. G. Høyer-Hansen
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  10. B. Vainer
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  11. M. Illemann
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Correspondence to R. L. Eefsen.

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Eefsen, R.L., Vermeulen, P.B., Christensen, I.J. et al. Growth pattern of colorectal liver metastasis as a marker of recurrence risk. Clin Exp Metastasis 32, 369–381 (2015). https://doi.org/10.1007/s10585-015-9715-4

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