In a study reported in JAMA Oncology, Katipally et al found that an integrated clinical-molecular classification of colorectal cancer metastases to the liver distinguished risk groups for survival outcomes.
Study Details
The investigators had previously defined three biologically distinct molecular subtypes of colorectal liver metastases: canonical, immune, and stromal. The current analysis was aimed at validating a clinical-molecular classification including these subtypes in discovery (n = 93) and validation cohorts (n = 147) from the phase III New EPOC trial.
Resected metastases underwent RNA sequencing and microRNA (miRNA) profiling in the discovery cohort and messenger RNA and miRNA profiling with microarray in the validation cohort. A 31-feature (24 messenger RNAs and 7 miRNAs) neural network classifier was trained to predict molecular subtypes in the discovery cohort and applied to the validation cohort. Integrated clinical-molecular risk groups were derived on the basis of molecular subtypes and clinical risk score.
Key Findings
In the validation cohort, 73 (50%), 28 (19%), and 46 (31%) patients were classified with canonical, immune, and stromal metastases, respectively. Compared with the canonical subtype, which was associated with the worst prognosis, the immune subtype, which was associated with the best prognosis, was also associated with significantly better 5-year progression-free survival (43% vs 14%, hazard ratio [HR] = 0.37, 95% confidence interval [CI] = 0.20–0.68) and overall survival (63% vs 43%, HR = 0.38, 95% CI = 0.17–0.86).
The addition of molecular subtype to clinical risk score improved prediction of progression-free survival (from K index of 0.55 to 0.62) and overall survival (from K index of 0.59 to 0.63). Compared with the integrated high-risk group, the low-risk group had significantly better 5-year progression-free survival (44% vs 16%, HR = 0.38, 95% CI = 0.19–0.76) and overall survival (78% vs 43%, HR = 0.26, 95% CI = 0.08–0.84).
The investigators concluded, “In this prognostic study, biologically derived colorectal liver metastasis molecular subtypes and integrated clinical-molecular risk groups were highly prognostic. This novel molecular classification warrants further study as a possible predictive biomarker for personalized systemic treatment for colorectal liver metastases.”
Sean P. Pitroda, MD, and Rohan R. Katipally, MD, of the Department of Radiation and Cellular Oncology, The University of Chicago, are the corresponding authors for the JAMA Oncology article.
Disclosure: The study was supported by the UK Medical Research Council Stratified Medicine Consortium program, Cancer Research UK, Ludwig Cancer Research Foundation, and U.S. National Institutes of Health. For full disclosures of the study authors, visit jamanetwork.com.
