Synapse - Association of genomic profiles and survival in early onset and screening-age colorectal cancer patients with liver metastases resected over 15 years

Association of genomic profiles and survival in early onset and screening-age colorectal cancer patients with liver metastases resected over 15 years Journal Article

Authors:	Narayan, R. R.; Aveson, V. G.; Chou, J. F.; Walch, H. S.; Sanchez-Vega, F.; Dos Santos Fernandes, G.; Balachandran, V. P.; D'Angelica, M. I.; Drebin, J. A.; Jarnagin, W. R.; Wei, A. C.; Cercek, A.; Gönen, M.; Schultz, N.; Kingham, T. P.
Article Title:	Association of genomic profiles and survival in early onset and screening-age colorectal cancer patients with liver metastases resected over 15 years
Abstract:	Background This study explores whether genomic profiles of colorectal liver metastasis (CRLM) patients with early onset (EO, < 50 years old) and screening age (SA) primary diagnosis are associated with overall survival (OS). Methods All patients undergoing hepatectomy between 2002 and 2017 were identified and tumor specimens with next-generation sequencing data were cataloged. Gene and signaling-level alterations were checked for association with OS from primary diagnosis accommodating for left-truncated survival. Results Of 1822 patients, 333 were sequenced-127 (38%) EO-CRLM and 206 (62%) SA-CRLM patients. More aggressive features presented in EO-CRLM patients-synchronous metastatic presentation (83% vs. 75%, p < 0.001) and primary node-positive disease (71% vs. 61%, p < 0.001). The median OS from primary diagnosis was 11.8 years (95% confidence interval = 7.94-NA). Five-year OS did not differ by age (p = 0.702). On multivariable analysis, altered APC (EO-CRLM: [hazard ratio [HR] = 0.37, p = 0.018] vs. SA-CRLM:[HR = 0.61, p = 0.260]), BRAF (EO-CRLM:[HR = 4.38, p = 0.007] vs. SA-CRLM:[HR = 4.78, p = 0.032]), and RAS-TP53 (EO-CRLM:[HR = 2.82, p = 0.011] vs. SA-CRLM:[HR = 2.35, p = 0.003]) associated with OS. Conclusions Despite bearing more aggressive features, EO-CRLM patients had similar genomic profiles and survival as SA-CRLM patients. Better performance status in younger patients leading to increased treatment tolerance may partly explain this. As screening and treatment strategies from older patients are applied to younger patients, genomic predictors of biology identified historically in older cohorts could apply to EO patients.
Keywords:	mutation; chemotherapy; colorectal neoplasms; hepatectomy; cancer biomarker; impact; defines; distinct; prognosis; precision medicine; cancer genes
Journal Title:	Journal of Surgical Oncology
Volume:	125
Issue:	5
ISSN:	0022-4790
Publisher:	Wiley Blackwell
Date Published:	2022-04-01
Start Page:	880
End Page:	888
Language:	English
ACCESSION:	WOS:000745623700001
DOI:	10.1002/jso.26797
PROVIDER:	wos
PMCID:	PMC8917995
PUBMED:	35066881
Notes:	Article -- MSK author Michael D'Angelica is associated with the wrong ORCiD on the original publication. -- Source: Wos