Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2022 Feb;13(1):126-136.
doi: 10.21037/jgo-21-620.

Patient-specific meta-analysis of 12-gene colon cancer recurrence score validation studies for recurrence risk assessment after surgery with or without 5FU and oxaliplatin

Greg Yothers  1 , Alan P Venook  2 , Eiji Oki  3 , Donna Niedzwiecki  4 , Yan Lin  1 , Michael R Crager  5 , Calvin Chao  6 , Frederick L Baehner  2   7 , Norman Wolmark  1 , Takayuki Yoshino  8
Affiliations

Patient-specific meta-analysis of 12-gene colon cancer recurrence score validation studies for recurrence risk assessment after surgery with or without 5FU and oxaliplatin

Greg Yothers et al. J Gastrointest Oncol. 2022 Feb.

Abstract

Background: Individualized estimates of the risk of recurrence in colon cancer patients are needed that reflect current medical practice and available treatment options.

Methods: Three validation studies of the 12-gene colon recurrence score assay were used with pre-specified patient-specific meta-analysis (PSMA) methods to integrate the 12-gene Oncotype DX Colon Recurrence Score result (RS) with the clinical and pathology risk factors stage, T-stage, mis-match repair (MMR) status, and number of nodes examined to calculate individualized recurrence risk estimates. Baseline risk estimation used the most recent studies, so the risk estimates reflect current medical practice. The effect of fluorouracil (5FU) was estimated with a meta-analysis of two studies. The effect of oxaliplatin was estimated using one of the RS assay validation studies, in which patients were randomized to 5FU with or without oxaliplatin.

Results: The RS result and each of the clinical-pathologic factors provided independent prognostic information for recurrence. Among stage II, T3, MMR-proficient patients with ≥12 nodes examined (the most common scenario), patients with RS ≤30 (approximately 48%) have estimated 5-year recurrence risk ≤10% with surgery alone. Among stage IIIA/B, T3, MMR-deficient patients with ≥12 nodes examined, patients with RS ≤19 (approximately 14%) have an estimated 5-year recurrence risk ≤10% with surgery alone. Among stage IIIA/B, T3, MMR-proficient patients with ≥12 nodes examined, those with RS ≤14 (approximately 6%) have estimated 5-year recurrence risk ≤10% with 5FU alone.

Discussion: The PSMA integrates the 12-gene colon RS result with clinical and pathology factors to provide individualized recurrence risk estimates that reflect current medical practice. The risk estimates are in a range that may help inform treatment decisions for a substantial number of stage II and stage III patients.

Keywords: 12-gene assay; Colon cancer; meta-analysis; recurrence risk.

PubMed Disclaimer

Conflict of interest statement

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jgo.amegroups.com/article/view/10.21037/jgo-21-620/coif). MRC, FLB and CC are or were employees of and received remuneration and stock from Genomic Health, Inc., a wholly owned subsidiary of Exact Sciences Corporation, which provides test results based on the 12-gene assay. EO received lecture fees from Bayer Japan, Chugai Pharmaceutical Co., Ltd., Taiho Pharmaceutical Co., Ltd., Eli Lilly, Ono Pharmaceutical Co., Ltd., and Takeda Pharmaceutical Co., Ltd. NW reports support for the present manuscript via NCI grant #U10CA180868, directly to his institution only. TY reports grants from Taiho Pharmaceutical Co., Ltd., Sumitomo Dainippon Pharma Co., Ltd., Ono Pharmaceutical Co., Ltd., Chugai Pharmaceutical Co., Ltd., Amgen K.K., Parexel International Inc., MSD K.K., Daiichi Sankyo Co., Ltd., and Sanofi K.K., outside the submitted work. The other authors have no conflicts of interest to declare.

Figures

Figure 1
Figure 1
Meta-analysis estimate of 5FU treatment effect HR by stage. Meta-analysis test for interaction of stage with treatment P=0.075. 5FU, fluorouracil; HR, hazard ratio.
Figure 2
Figure 2
Meta-analysis estimate (with SE) of proportional contributions of each of the common covariates to the risk score variance, controlling for stage and treatment effects. RS, 12-gene Oncotype DX Colon Recurrence Score result; MMR, mis-match repair; SE, standard error.
Figure 3
Figure 3
Example PSMA 5-year recurrence risk estimates and 95% CI. 5FU, fluorouracil; MMR, mis-match repair; PSMA, patient-specific meta-analysis; CI, confidence intervals.
Figure 4
Figure 4
Comparison of recurrence risk estimates (95% CI) from the PSMA and the existing Oncotype DX Colon Recurrence Score patient report (Genomic Health, Inc., a wholly owned subsidiary of Exact Sciences Corporation). MMR, mis-match repair; PSMA, patient-specific meta-analysis; 5FU, fluorouracil; CI, confidence intervals.
See this image and copyright information in PMC

References

    1. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2020. CA Cancer J Clin 2020;70:7-30. 10.3322/caac.21590 - DOI - PubMed
    1. Gray RG, Quirke P, Handley K, et al. Validation study of a quantitative multigene reverse transcriptase-polymerase chain reaction assay for assessment of recurrence risk in patients with stage II colon cancer. J Clin Oncol 2011;29:4611-9. 10.1200/JCO.2010.32.8732 - DOI - PubMed
    1. Niedzwiecki D, Bertagnolli MM, Warren RS, et al. Documenting the natural history of patients with resected stage II adenocarcinoma of the colon after random assignment to adjuvant treatment with edrecolomab or observation: results from CALGB 9581. J Clin Oncol 2011;29:3146-52. 10.1200/JCO.2010.32.5357 - DOI - PMC - PubMed
    1. Kuebler JP, Wieand HS, O'Connell MJ, et al. Oxaliplatin combined with weekly bolus fluorouracil and leucovorin as surgical adjuvant chemotherapy for stage II and III colon cancer: results from NSABP C-07. J Clin Oncol 2007;25:2198-204. 10.1200/JCO.2006.08.2974 - DOI - PubMed
    1. Yamanaka T, Oki E, Yamazaki K, et al. 12-Gene Recurrence Score Assay Stratifies the Recurrence Risk in Stage II/III Colon Cancer With Surgery Alone: The SUNRISE Study. J Clin Oncol 2016;34:2906-13. 10.1200/JCO.2016.67.0414 - DOI - PubMed