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

Sean P. Pitroda, Nikolai N. Khodarev, Lei Huang, Abhineet Uppal, Sean C. Wightman, Sabha Ganai, Nora Joseph, Jason Pitt, Miguel Brown, Martin Forde, Kathy Mangold, Lai Xue, Christopher Weber, Jeremy P. Segal, Sabah Kadri, Melinda E. Stack, Sajid Khan, Philip Paty, Karen Kaul, Jorge Andrade, Kevin P. White, Mark Talamonti, Mitchell C. Posner, Samuel Hellman and Ralph R. Weichselbaum ()
Additional contact information
Sean P. Pitroda: The University of Chicago
Nikolai N. Khodarev: The University of Chicago
Lei Huang: The University of Chicago
Abhineet Uppal: The University of Chicago
Sean C. Wightman: The University of Chicago
Sabha Ganai: Southern Illinois University
Nora Joseph: NorthShore University Hospital
Jason Pitt: The University of Chicago
Miguel Brown: The University of Chicago
Martin Forde: The University of Chicago
Kathy Mangold: NorthShore University Hospital
Lai Xue: The University of Chicago
Christopher Weber: The University of Chicago
Jeremy P. Segal: The University of Chicago
Sabah Kadri: The University of Chicago
Melinda E. Stack: The University of Chicago
Sajid Khan: Yale School of Medicine
Philip Paty: Memorial Sloan-Kettering Cancer Center
Karen Kaul: NorthShore University Hospital
Jorge Andrade: The University of Chicago
Kevin P. White: The University of Chicago
Mark Talamonti: NorthShore University Hospital
Mitchell C. Posner: The University of Chicago
Samuel Hellman: The University of Chicago
Ralph R. Weichselbaum: The University of Chicago

Nature Communications, 2018, vol. 9, issue 1, 1-8

Abstract: 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.

Date: 2018
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-04278-6

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DOI: 10.1038/s41467-018-04278-6

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