AffiliationDivision of Surgical Oncology and General Surgery, Princess Margaret Hospital and University Health Network, University of Toronto, Toronto, ON, Canada
MetadataShow full item record
AbstractBackground: Constitutional loss of function (LOF) single nucleotide polymorphisms (SNPs) in pattern recognition receptors FPR1, TLR3, and TLR4 have previously been reported to predict oxaliplatin benefit in colorectal cancer. Confirmation of this association could substantially improve patient stratification. Methods: We performed a retrospective biomarker analysis of the Short Course in Oncology Therapy (SCOT) and COIN/COIN-B trials. Participant status for LOF variants in FPR1 (rs867228), TLR3 (rs3775291), and TLR4 (rs4986790/rs4986791) was determined by genotyping array or genotype imputation. Associations between LOF variants and disease-free survival (DFS) and overall survival (OS) were analyzed by Cox regression, adjusted for confounders, using additive, dominant, and recessive genetic models. All statistical tests were two-sided. Results: Our validation study populations included 2929 and 1948 patients in the SCOT and COIN/COIN-B cohorts, respectively, of whom 2728 and 1672 patients had functional status of all three SNPs determined. We found no evidence of an association between any SNP and DFS in the SCOT cohort, or with OS in either cohort, irrespective of the type of model used. This included models for which an association was previously reported for rs867228 (recessive model, multivariable-adjusted hazard ratio [HR] for DFS in SCOT?=?1.19, 95% confidence interval [CI]?=?0.99 to 1.45, P?=?.07; HR for OS in COIN/COIN-B?=?0.92, 95% CI?=?0.63 to 1.34, P?=?.66), and rs4986790 (dominant model, multivariable-adjusted HR for DFS in SCOT?=?0.86, 95% CI?=?0.65 to 1.13, P?=?.27; HR for OS in COIN/COIN-B?=?1.08, 95% CI?=?0.90 to 1.31, P?=?.40). Conclusion: In this prespecified analysis of two large clinical trials, we found no evidence that constitutional LOF SNPs in FPR1, TLR3, or TLR4 are associated with differential benefit from oxaliplatin. Our results suggest these SNPs are unlikely to be clinically useful biomarkers.
CitationChadi SA, Beets GL, Perez RO, Renehan AG. Watch-and-wait strategy in rectal cancer - authors' reply. Lancet Gastroenterol Hepatol. 2019 Feb;4(2):97.
JournalThe Lancet Gastroenterology and Hepatology
- Watch-and-wait strategy in rectal cancer.
- Authors: Bujko K, Michalski W
- Issue date: 2019 Feb
- ["Watch and wait" strategy after neoadjuvant therapy for rectal cancer: status survey of perceptions, attitudes and treatment selection in Chinese surgeons].
- Authors: Sun TT, Wang L, Yao YF, Peng YF, Zhao J, Zhan TC, Leng JH, Wang HY, Chen N, Chen PJ, Li YJ, Zhang X, Liu XZ, Zhang Y, Wu AW
- Issue date: 2019 Jun 25
- Watch-and-wait approach versus surgical resection after chemoradiotherapy for patients with rectal cancer (the OnCoRe project): a propensity-score matched cohort analysis.
- Authors: Renehan AG, Malcomson L, Emsley R, Gollins S, Maw A, Myint AS, Rooney PS, Susnerwala S, Blower A, Saunders MP, Wilson MS, Scott N, O'Dwyer ST
- Issue date: 2016 Feb
- [Diagnosis and treatment strategy for clinical complete responders after chemoradiotherapy for rectal cancer: is watch-and-wait policy safe?]
- Authors: Yao HW, Liu YH
- Issue date: 2017 Jul 1