scholarly journals Validation of the 12-Gene Colon Cancer Recurrence Score as a Predictor of Recurrence Risk in Stage II and III Rectal Cancer Patients

2014 ◽  
Vol 106 (11) ◽  
Author(s):  
Marlies S. Reimers ◽  
Peter J. K. Kuppen ◽  
Mark Lee ◽  
Margarita Lopatin ◽  
Haluk Tezcan ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Colon Cancer ◽  
Cancer Patients ◽  
Cancer Recurrence ◽  
Recurrence Score ◽  
Recurrence Risk ◽  
Stage Ii ◽  
Colon Cancer Recurrence

Association of the colon cancer recurrence score with treatments received in patients with stage II colon cancer: The Clalit Health Services experience.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e22111-e22111
Author(s):  
Baruch Brenner ◽  
Ravit Geva ◽  
Alexander Beny ◽  
Ygael Dror ◽  
Mariana Steiner ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Health Services ◽  
Cancer Recurrence ◽  
Recurrence Score ◽  
Treatment Decisions ◽  
Oncotype Dx ◽  
Stage Ii ◽  
Technical Failure ◽  
Stage Ii Colon Cancer ◽  
Colon Cancer Recurrence

e22111 Background: The Oncotype DX Colon Cancer Recurrence Score (RS) is a validated prognosticator in stage II colon cancer following surgery. However, the impact of the RS on daily practice is still unclear. Clalit Health Services(CHS) has reimbursed Oncotype DX colon testing since 1/2011. This prospective study examined the use of the RS and its association with treatment decisions in this setting in Israel. Methods: Eligible patients had stage II colon cancer and testing reimbursed by CHS from 1/2011 to 5/2012. Patient/tumor data and treatment information were gathered prospectively. Data were analyzed using the Chi-squared test. Results: The study included 341 patients of whom 314 had confirmed stage II, T3N0 disease, and were included in the analysis. Median age was 68 years (range: 29-89); 18.2%, 68.5%, and 9.9% had grade 1, 2, and 3 tumors, respectively; 15.3% had colonic obstruction and 5.7% had lymphovascular invasion. Thirty-nine patients (12.4%) had mismatch repair (MMR)-deficient tumors and their samples were not tested further. Of the 275 tested patients, 160 (58.2%), 87 (31.6%), and 27 (9.8%) had low (<30), intermediate (30-40), and high (>40) RS, respectively (1 patient [0.4%] had no RS due to technical failure of the assay). The grade 3 group had a higher proportion of MMR-deficient tumors than the grade 2 and grade 1 groups (35.5%, 7.9% and 10.5%, respectively, P<.0001). In the MMR-proficient tumors, the proportions of low RS tumors according to grade were 60.8%, 58.1% and 70.0% for grades 1, 2 and 3, respectively (P=0.57). Chemotherapy was administered to 86/314 (27.4%) patients, including 3/39 (7.7%) in the MMR-deficient, 27/160 (16.9%) in the low, 39/87 (44.8%) in the intermediate, and 17/27 (63.0%) in the high RS groups. The most commonly used regimen was capecitabine monotherapy (61/86 treated patients, 70.9%). The differences in the proportions of patients receiving chemotherapy between the MMR-deficient, low, intermediate, and high RS groups were significant (P<.0001). Conclusions: Our findings suggest that the RS results and MMR-deficient status are significantly associated with treatment decisions in stage II colon cancer patients in Israel.

scholarly journals Validation of the 12-Gene Colon Cancer Recurrence Score in NSABP C-07 As a Predictor of Recurrence in Patients With Stage II and III Colon Cancer Treated With Fluorouracil and Leucovorin (FU/LV) and FU/LV Plus Oxaliplatin

2013 ◽  
Vol 31 (36) ◽  
pp. 4512-4519 ◽  
Author(s):  
Greg Yothers ◽  
Michael J. O'Connell ◽  
Mark Lee ◽  
Margarita Lopatin ◽  
Kim M. Clark-Langone ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Adjuvant Therapy ◽  
Cox Regression ◽  
Cancer Recurrence ◽  
Recurrence Score ◽  
Recurrence Risk ◽  
Stage Ii ◽  
Stage Iii ◽  
Treatment Benefit ◽  
Stage Ii Colon Cancer

Purpose Accurate assessments of recurrence risk and absolute treatment benefit are needed to inform colon cancer adjuvant therapy. The 12-gene Recurrence Score assay has been validated in patients with stage II colon cancer from the Cancer and Leukemia Group B 9581 and Quick and Simple and Reliable (QUASAR) trials. We conducted an independent, prospectively designed clinical validation study of Recurrence Score, with prespecified end points and analysis plan, in archival specimens from patients with stage II and III colon cancer randomly assigned to fluorouracil (FU) or FU plus oxaliplatin in National Surgical Adjuvant Breast and Bowel Project C-07. Methods Recurrence Score was assessed in 892 fixed, paraffin-embedded tumor specimens (randomly selected 50% of patients with tissue). Data were analyzed by Cox regression adjusting for stage and treatment. Results Continuous Recurrence Score predicted recurrence (hazard ratio for a 25-unit increase in score, 1.96; 95% CI, 1.50 to 2.55; P < .001), as well as disease-free and overall survival (both P < .001). Recurrence Score predicted recurrence risk (P = .001) after adjustment for stage, mismatch repair, nodes examined, grade, and treatment. Recurrence Score did not have significant interaction with stage (P = .90) or age (P = .76). Relative benefit of oxaliplatin was similar across the range of Recurrence Score (interaction P = .48); accordingly, absolute benefit of oxaliplatin increased with higher scores, most notably in patients with stage II and IIIA/B disease. Conclusion The 12-gene Recurrence Score predicts recurrence risk in stage II and stage III colon cancer and provides additional information beyond conventional clinical and pathologic factors. Incorporating Recurrence Score into the clinical context may better inform adjuvant therapy decisions in stage III as well as stage II colon cancer.

Validation of a 12-gene colon cancer recurrence score (RS) in patients (pts) with stage II colon cancer (CC) from CALGB 9581.

2011 ◽  
Vol 29 (15_suppl) ◽  
pp. 3518-3518 ◽  
Author(s):  
A. P. Venook ◽  
D. Niedzwiecki ◽  
M. Lopatin ◽  
M. Lee ◽  
P. N. Friedman ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Cancer Recurrence ◽  
Recurrence Score ◽  
Stage Ii ◽  
Stage Ii Colon Cancer ◽  
Colon Cancer Recurrence

Effect of Oncotype DX colon cancer test results on treatment recommendations in patients with stage II colon cancer: Preliminary results.

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 398-398
Author(s):  
Thomas H. Cartwright ◽  
Calvin Chao ◽  
Margarita Lopatin ◽  
Tanya GK Bentley ◽  
Michael Samuel Broder ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Cancer Patients ◽  
Adjuvant Treatment ◽  
Recurrence Score ◽  
Treatment Recommendations ◽  
Oncotype Dx ◽  
Stage Ii ◽  
Medical Oncologists ◽  
Stage Ii Colon Cancer ◽  
The Impact

398 Background: The Oncotype DX Colon Cancer Recurrence Score (RS) has been clinically validated as an independent predictor of individual recurrence risk in stage II colon cancer patients following surgery. As a result, physicians have been ordering the Oncotype DX assay for stage II colon cancer patients since January 2010, yet no data exist on the assay’s impact on adjuvant treatment planning in practice. We performed a survey to characterize the impact of the assay on adjuvant treatment recommendations in stage II colon cancer. Methods: U.S. medical oncologists (N=277) who ordered Oncotype DX for ≥3 patients with stage II colon cancer were contacted and asked to complete a web-based survey regarding the single most recent stage II colon cancer patient for whom the assay was ordered. The survey was developed through cognitive interviews with four medical oncologists, and the protocol was institutional review board approved. Results: As a planned preliminary analysis, we analyzed surveys from 92 eligible physicians. Physicians were more often in community (85%) than academic or other practices, and had a median of 14.5 years (range, 2-40) of practice experience. The median patient age was 62 years (range, 34–81). 84% of patients had T3 disease. Patients had ≤8, 9-11 and ≥12 nodes examined 2%, 14% and 84% of the time and 36% had comorbidities. Of the 60 patients tested for MMR/MSI, 9 (15%) were MMR-D or MSI-high and 37 (62%) were MMR-P or MSI-low; 14 (23%) unknown. Median RS was 20 (range, 1-77). Before obtaining the RS, chemotherapy was planned in 38 (41%) patients, observation in 35 (38%), and there was no recommendation in 19 (21%). For the 73 patients with pre-assay recommendations, recommended treatment changed after obtaining the RS for 23 patients (32%), including changes from chemotherapy to observation and vice-versa. Conclusions: These preliminary findings indicate that for stage II colon cancer patients, treatment recommendations were changed by RS results approximately one-third of the time. Final results will be reported to include accrual through December 2011.

Specific activity of cyclin dependent kinase 1 as a novel predictor of recurrence risk in stage II colon cancer.

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 402-402
Author(s):  
M. Maak ◽  
E. Zeestraten ◽  
M. Shibayama ◽  
T. Schuster ◽  
H. Friess ◽  
...  
Keyword(s):  
Colon Cancer ◽  
High Risk ◽  
Cancer Patients ◽  
Specific Activity ◽  
Risk Group ◽  
Tumor Resection ◽  
Recurrence Risk ◽  
High Risk Group ◽  
Stage Ii ◽  
Stage Ii Colon Cancer

402 Background: Altered cell cycle dynamics and check points are typical features of solid tumors, and cyclin dependent kinases (CDKs) play pivotal roles in these processes. Previously we have demonstrated that CDK-based analysis, composed of CDK1 and CDK2, is useful in the prediction of outcomes in early breast cancer patients (Ann Oncol. 19(1):68-72, 2008, Br J Cancer. 100(3):494-500, 2009). Clinically, there is a need for risk stratification in patients with stage II colon cancer who have a recurrence risk of 20 to 30%. Therefore we investigated the use of CDK-based analysis for recurrence prediction of stage II colon cancer patients. Methods: Fresh frozen tissue samples of 254 patients with histologically confirmed adenocarcinoma of the colon, UICC stage II, who received primary tumor resection in Munich (217 cases), and Leiden (37 cases) were used. Protein expression and activity of CDK1 and CDK2 were determined by in vitro assays as previously described. Specific activity (SA) of CDKs was calculated as kinase activity in relation to its corresponding mass concentration. Results: Development of distant metastasis was observed in 27 patients (10.6%) after a median follow up of 86 months. We found that predictive performance of CDK1SA, but not CDK2SA, for the metastasis was substantial and almost constant for long-term event prediction (average area under the curve (AUC) = 0.69). Tumor recurrence risk analysis in association with CDK1SA identified a low- (41% of population) and high- risk group (59%). Cox proportional hazard model analysis retained the CDK-based patient classification as an independent prognostic factor for distant metastases-free survival (low vs. high-risk group: Hazard ratio = 6.2, 95% CI: 1.45 to 26.9, p=0.0049). Clinical parameters such as grading, T-categories, age, and sex were excluded as confounding factors for CDK1SA-risk. Conclusions: CDK1SA allows stratification of different risk subgroups of stage II colon cancer patients. CDK1SA-based analysis is useful for predicting patients with high risk of distant recurrence, who should be treated with chemotherapy. No significant financial relationships to disclose.

Prospective evaluation of a 12-gene assay on treatment recommendations in patients with stage II colon cancer.

2013 ◽  
Vol 31 (4_suppl) ◽  
pp. 453-453 ◽  
Author(s):  
Geetika Srivastava ◽  
Lindsay Anne Renfro ◽  
Robert J. Behrens ◽  
Margarita Lopatin ◽  
Calvin Chao ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Adjuvant Chemotherapy ◽  
Cancer Patients ◽  
Score Test ◽  
Recurrence Score ◽  
Recurrence Risk ◽  
Treatment Recommendation ◽  
Medical Oncologists ◽  
Gene Assay ◽  
Stage Ii Colon Cancer

453 Background: A 12-gene assay (Oncotype DX Colon Cancer) has been clinically validated as a predictor of recurrence risk in stage 2 colon cancer patients following surgery. We conducted the first prospective study to characterize the impact of Recurrence Score results on medical oncologists’ recommendations regarding adjuvant chemotherapy in T3, Mismatch Repair-proficient (MMR-P) stage 2 colon cancer patients. Methods: Consecutive patients with resected stage 2A colon cancer who were candidates for adjuvant chemotherapy were consented and enrolled by 105 medical oncologists from 17 sites in the Mayo Clinic Cancer Research Consortium. Each patient’s tumor specimen was assessed by the Recurrence Score test (quantitative RT-PCR) and MMR (IHC). Prior to and after receiving these results, physicians completed surveys indicating their planned treatments given hypothetical or known MMR results, recorded as Observation (Obs), 5FU-based chemotherapy (5FU), or 5FU + Oxaliplatin (Oxal). Change in treatment recommendation intensity from baseline to follow-up was defined as: increased if change from Obs to 5FU +/- Oxal or from 5FU to 5FU+Oxal, decreased if change from 5FU + Oxal to 5FU or Obs, or from 5FU to Obs, or no change. Results: 187 of 221 patients enrolled were evaluable including 141 who were MMR-P (avg age 63, 65% ECOG PS 0, med tumor size 5 cm, 11% high grade, 91% with 12+ nodes examined). In the primary analysis treatment recommendations changed for 63 (45%) of 141 MMR-P patients, with intensity decreasing for 47 (33%) and increasing for 16 (11%). Recommendations for chemotherapy (5-FU +/- Oxal) decreased from 73 (52%) patients pre-assay to 42 (30%) post-assay. Increased treatment intensity was more likely at higher Recurrence Score values and decreased intensity at lower Recurrence Score values (p=0.011), and any change was more likely when MMR status was unknown at baseline (p = 0.041). Conclusions: In this prospective study, quantitative recurrence risk information provided by the Recurrence Score test was associated with treatment recommendation changes for 45% of T3 MMR-P stage II colon cancer patients. Use of the 12-gene assay may lead to overall reductions in chemotherapy.

Adjuvant treatment in extreme elderly patients with colorectal cancer.

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 784-784
Author(s):  
Marta Llopis Cuquerella ◽  
Maria del Carmen Ors Castaño ◽  
María Ballester Espinosa ◽  
Alejandra Magdaleno Cremades ◽  
Vicente Boix Aracil ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Rectal Cancer ◽  
Colon Cancer ◽  
Elderly Patients ◽  
Cancer Patients ◽  
Adjuvant Treatment ◽  
Stage Ii ◽  
Stage Iii ◽  
Complementary Treatment ◽  
Colorectal Cancer Patients

784 Background: Surgical and adjuvant treatment in extreme elderly ( > 80 years) patients with localized colorectal cancer is an unresolved issue. Owing to the lack of available neither clinical practice nor investigational data in this field we present our experience in this scenario. Methods: We retrospectively reviewed data regarding surgical and complementary treatment for colorectal cancer patients aged more than 80 consecutively attended by General Surgery Department in Vega Baja Hospital between 2008 and 2013. Results: A total number of 115 colorectal cancer patients were registered. 95 patients diagnosed of localized disease were selected for analysis. Colon vs rectal cancer ratio was 4:1. Median age was 83.6 years (80-94). Male sex was predominant (60 patients, 63.2%). Emergency surgery was performed in 15 patients (15.8%). Complementary treatment to surgery was advised, according to international guidelines, in 53 patients (55.8%). 10 patients (18.9%) with an advise of adjuvant treatment finally received it. More patients with rectal cancer received recommended treatment (41.7% rectal vs 12.2% colon cancer). Patients with stage III disease were more frequently finally treated according to guidelines (22.2 % stage III vs 11.8% stage II). More patients with stage II rectal cancer were advised and received treatment (recommendation: 66.7% rectal vs 36.1% colon cancer; administration: 25% rectal vs 7.7% colon cancer). Treatment was also more frequently administered to stage III rectal cancer (50% rectal vs 14.3% rectal cancer) (Table). Conclusions: Our experience in localized colorectal cancer in extreme elderly patients ( > 80 years) showed that, although advised according to guidelines, most of them did not receive adjuvant treatment to surgery. Complementary treatment administration was more common in rectal cancer patients and with more advanced disease. [Table: see text]

Patient-specific meta-analysis of 3 validation studies of the 12-gene colon cancer recurrence score assay for recurrence risk assessment after surgery with or without 5FU and oxaliplatin.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 3599-3599
Author(s):  
Greg Yothers ◽  
Alan P. Venook ◽  
Takeharu Yamanaka ◽  
Yan Lin ◽  
Michael Crager ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Meta Analysis ◽  
Recurrence Score ◽  
Recurrence Risk ◽  
Current Medical ◽  
Stage Ii ◽  
Patient Specific ◽  
Risk Estimates ◽  
Oxaliplatin Treatment ◽  
Current Medical Practice

3599 Background: The 12-gene Oncotype DX Colon Recurrence Score assay is a clinically validated genomic assay that evaluates recurrence risks in stage II and stage III colon cancer patients independent of clinical-pathologic features. Improved colon cancer care has reduced recurrence rates since the late 1990’s. Methods: Pre-specified patient-specific meta-analysis methods were used to estimate 1-, 3- and 5-year recurrence risk combining the 12-gene colon recurrence score (RS) validation studies CALGB 9581, NSABP C-07 and SUNRISE. Cox models had effects for RS result, number of nodes examined (<12 or ≥ 12), T-stage, MMR status, and stage (II, IIIAB or IIIC). Baseline cumulative hazard estimates used the latest two studies to reflect current medical practice. Estimates for surgery, surgery+5FU and surgery+5FU+oxaliplatin treatment were provided by integrating stage-specific 5FU hazard ratios from a meta-analysis of the QUASAR study (2007) and a pooled analysis of NSABP studies (Wilkinson 2010), and oxaliplatin treatment effect estimates from NSABP C-07. Recurrence risk with 5FU alone was not estimated for MMR-deficient patients due to expected lack of 5FU efficacy in these patients (Sargent 2010). Results: In the overall population of 2,179 patients, 55%, 32% and 13% were Stage II, IIIA/B and IIIC, 63% had ≥12 nodes examined, 90% were T3, and 88% were MMR proficient. Median RS result was 31 (IQR 23–39). RS result and each clinical-pathologic factor contributed independent prognostic information (meta-analysis Wald tests, all p<.001). Risk estimates are generally lower than previous RS report risk estimates. For patients with pathological stage II, T3, MMR-proficient tumors with ≥12 nodes examined, approximately 40% are expected to have 5-year recurrence risk ≤10% with surgery alone based on the distribution of RS results. The table shows example 5-year recurrence risk estimates for specific RS results and clinical-pathologic characteristics. Conclusions: The new recurrence risk estimates provide more patient-specific information reflecting more current medical practice than previous reports using RS result, allowing better, more individualized treatment decisions.[Table: see text]

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