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.

Details

Title
Integrated molecular subtyping defines a curable oligometastatic state in colorectal liver metastasis
Author
Pitroda, Sean P 1 ; Khodarev, Nikolai N 1 ; Huang, Lei 2 ; Uppal, Abhineet 3 ; Wightman, Sean C 3 ; Ganai, Sabha 4 ; Joseph, Nora 5 ; Pitt, Jason 6 ; Brown, Miguel 6 ; Forde, Martin 6 ; Mangold, Kathy 5   VIAFID ORCID Logo  ; Lai, Xue 3 ; Weber, Christopher 7 ; Segal, Jeremy P 7 ; Kadri, Sabah 7 ; Stack, Melinda E 3 ; Khan, Sajid 8 ; Paty, Philip 9 ; Kaul, Karen 5 ; Andrade, Jorge 2 ; White, Kevin P 10 ; Talamonti, Mark 11 ; Posner, Mitchell C 3 ; Hellman, Samuel 1 ; Weichselbaum, Ralph R 1 

1  Department of Radiation and Cellular Oncology, The University of Chicago, Chicago, IL, USA; Ludwig Center for Metastasis Research, The University of Chicago, Chicago, IL, USA 
2  Center for Research Informatics, The University of Chicago, Chicago, IL, USA 
3  Department of Surgery, The University of Chicago, Chicago, IL, USA 
4  Department of Surgery, Southern Illinois University, Springfield, IL, USA 
5  Department of Pathology, NorthShore University Hospital, Evanston, IL, USA 
6  Institute for Genomics and Systems Biology, The University of Chicago, Chicago, IL, USA 
7  Department of Pathology, The University of Chicago, Chicago, IL, USA 
8  Department of Surgery, Yale School of Medicine, New Haven, CT, USA 
9  Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY, USA 
10  Institute for Genomics and Systems Biology, The University of Chicago, Chicago, IL, USA; Tempus Labs, Chicago, IL, USA 
11  Department of Surgery, NorthShore University Hospital, Evanston, IL, USA 
Pages
1-8
Publication year
2018
Publication date
May 2018
Publisher
Nature Publishing Group
e-ISSN
20411723
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s41467-018-04278-6
ProQuest document ID
2034682809
Copyright
© 2018. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.