TY - JOUR
T1 - 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
AU - Yothers, Greg
AU - Venook, Alan P.
AU - Oki, Eiji
AU - Niedzwiecki, Donna
AU - Lin, Yan
AU - Crager, Michael R.
AU - Chao, Calvin
AU - Baehner, Frederick L.
AU - Wolmark, Norman
AU - Yoshino, Takayuki
N1 - Funding Information:
Reporting Checklist: The authors have completed the PRISMA reporting checklist. Available at https://jgo. amegroups.com/article/view/10.21037/jgo-21-620/rc 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.
Funding Information:
This analysis was presented as a poster at the 2021 ASCO Annual Meeting. Funding: Funding in support of manuscript preparation was provided by the National Cancer Institute grants #U10CA180868 and U10CA180822.
Publisher Copyright:
© 2022 AME Publishing Company. All rights reserved.
PY - 2022/2
Y1 - 2022/2
N2 - 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.
AB - 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.
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U2 - 10.21037/jgo-21-620
DO - 10.21037/jgo-21-620
M3 - Article
AN - SCOPUS:85125598454
SN - 2078-6891
VL - 13
SP - 126
EP - 136
JO - Journal of Gastrointestinal Oncology
JF - Journal of Gastrointestinal Oncology
IS - 1
ER -
