Integrated molecular subtyping defines a curable oligometastatic state in colorectal liver metastasis Journal Article


Authors: Pitroda, S. P.; Khodarev, N. N.; Huang, L.; Uppal, A.; Wightman, S. C.; Ganai, S.; Joseph, N.; Pitt, J.; Brown, M.; Forde, M.; Mangold, K.; Xue, L.; Weber, C.; Segal, J. P.; Kadri, S.; Stack, M. E.; Khan, S.; Paty, P.; Kaul, K.; Andrade, J.; White, K. P.; Talamonti, M.; Posner, M. C.; Hellman, S.; Weichselbaum, R. R.
Article Title: Integrated molecular subtyping defines a curable oligometastatic state in colorectal liver metastasis
Abstract: The oligometastasis hypothesis suggests a spectrum of metastatic virulence where some metastases are limited in extent and curable with focal therapies. A subset of patients with metastatic colorectal cancer achieves prolonged survival after resection of liver metastases consistent with oligometastasis. Here we define three robust subtypes of de novo colorectal liver metastasis through integrative molecular analysis. Patients with metastases exhibiting MSI-independent immune activation experience the most favorable survival. Subtypes with adverse outcomes demonstrate VEGFA amplification in concert with (i) stromal, mesenchymal, and angiogenic signatures, or (ii) exclusive NOTCH1 and PIK3C2B mutations with E2F/MYC activation. Molecular subtypes complement clinical risk stratification to distinguish low-risk, intermediate-risk, and high-risk patients with 10-year overall survivals of 94%, 45%, and 19%, respectively. Our findings provide a framework for integrated classification and treatment of metastasis and support the biological basis of curable oligometastatic colorectal cancer. These concepts may be applicable to many patients with metastatic cancer. © 2018 The Author(s).
Keywords: survival; immune system; public health; molecular analysis; health risk; stratification; virulence; cancer; integrated approach
Journal Title: Nature Communications
Volume: 9
ISSN: 2041-1723
Publisher: Nature Publishing Group  
Date Published: 2018-05-04
Start Page: 1793
Language: English
DOI: 10.1038/s41467-018-04278-6
PROVIDER: scopus
PMCID: PMC5935683
PUBMED: 29728604
DOI/URL:
Notes: Erratum issued, see DOI: 10.1038/s41467-018-07303-w -- Article -- Export Date: 1 June 2018 -- Source: Scopus
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  1. Philip B Paty
    367 Paty