Biologic Determinants of Tumor Recurrence in Stage II Colon Cancer: Validation Study of the 12-Gene Recurrence Score in Cancer and Leukemia Group B (CALGB) 9581

Venook, Alan P.; Niedzwiecki, Donna; Lopatin, Margarita; Xing, Ya; Lee, Mark; Friedman, Paula N.; Frankel, Wendy L.; Clark-Langone, Kim; Millward, Carl; Shak, Steven; Goldberg, Richard M.; Mahmoud, Najjia N.; Warren, Robert S.; Schilsky, Richard L.; Bertagnolli, Monica M.

doi:10.1200/jco.2012.45.1096

Cited by 156 publications

(107 citation statements)

References 40 publications

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“…AORs for the intermediate (18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30) and high (>30) scores were 4 and 19, respectively. The adoption of the test is associated with a trend for decrease in chemotherapy recommendations by clinicians.…”

Section: Discussionmentioning

confidence: 97%

“…The RS assay results were classified into low (<18), intermediate (18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30), and high risk (≥31). 4 In order to further evaluate the effect of cutoff point of 25 proposed by the RxPONDER trial on chemotherapy decision, the intermediate scores of 18 to 30 were further classified into categories of 18 to 25 and 26 to 30.…”

Section: Data Source and Study Populationmentioning

confidence: 99%

“…5 It became commercially available in 2004 and uses a continuous scale (from 0 to 100) to predict the 10-year cancer recurrence risk and benefit of adjuvant chemotherapy in patients with early-stage, ER-positive, lymph node-negative disease. 5,6 The RS assay results are traditionally categorized into low (RS <18), intermediate (RS [18][19][20][21][22][23][24][25][26][27][28][29][30], and high risk (RS ≥31). The cutoff points were chosen based on the retrospective analysis of NSABP trial B-20.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

The 21-Gene Recurrence Score Assay for Node-Positive, Early-Stage Breast Cancer and Impact of RxPONDER Trial on Chemotherapy Decision-Making: Have Clinicians Already Decided?

Jasem¹,

Fisher²,

Amini³

et al. 2017

J Natl Compr Canc Netw

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Background: The 21-gene recurrence score (RS) assay is retrospectively validated for assessing prognosis and benefit from chemotherapy in hormone receptor-positive, early-stage breast cancer (EBC) with low RS. We hypothesized that oncologists have already incorporated the RS assay for decision-making in higher-risk, node-positive disease, despite the lack of prospective data and contrary to NCCN Guideline recommendations. This study provides the first analysis of trends and differences in RS use and therapeutic implications in a population-based data set of patients with node-positive EBC. It also assesses the impact of the RxPONDER trial on clinicians' chemotherapy recommendations. Methods: Node-positive EBC cases diagnosed during 2010 through 2012 and included in the National Cancer Data Base were used. Multivariate logistic regression was used to estimate test use and impact on chemotherapy recommendations. Results: The RS assay was ordered for 16.5% of the 80,405 identified patients. Of all variables, the RS assay had the strongest association with chemotherapy recommendation, with adjusted odds ratios (AORs) of 19 for scores >30. Odds of chemotherapy recommendation were significantly lower for the group who received the test (AOR, 0.21; 95% CI, 0.20-0.22). When divided based on the cutoff point of 25 adopted by the RxPONDER trial, those with an RS of 18 to 25 had significantly lower odds of chemotherapy recommendation compared with those with an RS of 26 to 30 (AOR, 0.32; 95% CI, 0.26-0.40). Test use was lower for blacks, community centers, uninsured/governmentally insured patients, higher tumor grade, larger tumor size, and more nodes involved. Chemotherapy recommendation was higher for patients of younger age, with private insurance, and with higher tumor grade, size, and number of nodes involved. Black patients had significantly higher RS (AOR, 1.37; 95% CI, 1.25-1.79). Conclusions: The RS assay influences clinicians' chemotherapy recommendation in node-positive EBC. Clinicians are using the inclusion criteria of the RxPONDER trial before its final release. Black patients have higher RS, likely representing worse biology. Significant differences exist in test use and clinical implications based on race, insurance, and facility.

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Section: Discussionmentioning

confidence: 97%

Section: Data Source and Study Populationmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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The 21-Gene Recurrence Score Assay for Node-Positive, Early-Stage Breast Cancer and Impact of RxPONDER Trial on Chemotherapy Decision-Making: Have Clinicians Already Decided?

Jasem¹,

Fisher²,

Amini³

et al. 2017

J Natl Compr Canc Netw

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“…Although using slightly different Recurrence Score (RS) cut points than initially defined in QUASAR, the Venook and colleagues validation study of the 12-gene RS in CALGB 9581 confirmed the risk discrimination of Oncotype Dx in stage II patients (risk ranged 9%-26%; ref. 30). On the basis of a different prognostic assay, Kennedy and colleagues (29) reported that the 634-probes signature used in the ColDx test (Almac Diagnostics) also had the ability to discriminate risk of recurrence in patients with stage II colon cancer (HR ¼ 2.53; P ¼ 0.003).…”

Section: Discussionmentioning

confidence: 99%

“…During the last few years, gene signatures have been developed from FFPE tumor samples to identify patients with stage II colon cancer who are at higher risk of disease recurrence (28)(29)(30)(31)(32). The study by Gray and colleagues (28) was designed as a validation study based on prospectively specified retrospective analyses of the QUASAR (QUick And Simple And Reliable) trial.…”

Section: Discussionmentioning

confidence: 99%

Molecular Testing for Lymph Node Metastases as a Determinant of Colon Cancer Recurrence: Results from a Retrospective Multicenter Study

Sargent¹,

Gill

Louvet³

et al. 2014

Clinical Cancer Research

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Purpose: Recurrence risk assessment to make treatment decisions for early-stage colon cancer patients is a major unmet medical need. The aim of this retrospective multicenter study was to evaluate the clinical utility of guanylyl cyclase C (GCC) mRNA levels in lymph nodes on colon cancer recurrence.Methods: The proportion of lymph nodes with GCC-positive mRNA (LNR) was evaluated in 463 untreated T3N0 patients, blinded to clinical outcomes. One site's (n ¼ 97) tissue grossing method precluded appropriate lymph node assessment resulting in post hoc exclusion. Cox regression models tested the relationship between GCC and the primary endpoint of time to recurrence. Assay methods, primary analyses, and cut points were all prespecified.Results: Final dataset contained 366 patients, 38 (10%) of whom had recurrence. Presence of four or more GCC-positive lymph nodes was significantly associated with risk of recurrence [hazard ratio (HR) ¼ 2.46, 95% confidence interval (CI), 1.07-5.69, P ¼ 0.035], whereas binary GCC LNR risk class (HR ¼ 1.87, 95% CI, 0.99-3.54, P ¼ 0.054) and mismatch repair (MMR) status (HR ¼ 0.77, 95% CI, 0.36-1.62, P ¼ 0.49) were not. In a secondary analysis using a 3-level GCC LNR risk group classification of high (LNR > 0.20), intermediate (0.10 < LNR 0.20), and low (LNR 0.10), high-risk patients had a 2.5 times higher recurrence risk compared with low-risk patients (HR ¼ 2.53, 95% CI, 1.24-5.17, P ¼ 0.011).Conclusions: GCC status is a promising prognostic factor independent of traditional histopathology risk factors in a contemporary population of patients with stage IIa colon cancer not treated with adjuvant therapy, but GCC determination must be performed with methodology adapted to the tissue procurement and fixation technique.

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Identification and Construction of Combinatory Cancer Hallmark–Based Gene Signature Sets to Predict Recurrence and Chemotherapy Benefit in Stage II Colorectal Cancer

et al. 2016

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Biologic Determinants of Tumor Recurrence in Stage II Colon Cancer: Validation Study of the 12-Gene Recurrence Score in Cancer and Leukemia Group B (CALGB) 9581

Cited by 156 publications

References 40 publications

The 21-Gene Recurrence Score Assay for Node-Positive, Early-Stage Breast Cancer and Impact of RxPONDER Trial on Chemotherapy Decision-Making: Have Clinicians Already Decided?

The 21-Gene Recurrence Score Assay for Node-Positive, Early-Stage Breast Cancer and Impact of RxPONDER Trial on Chemotherapy Decision-Making: Have Clinicians Already Decided?

Molecular Testing for Lymph Node Metastases as a Determinant of Colon Cancer Recurrence: Results from a Retrospective Multicenter Study

Identification and Construction of Combinatory Cancer Hallmark–Based Gene Signature Sets to Predict Recurrence and Chemotherapy Benefit in Stage II Colorectal Cancer

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