Effect of the 12-gene colon cancer assay results on treatment recommendations in patients with stage II colon cancer.

3626 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 clinical 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=346) 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: We analyzed survey results from 116 eligible physicians. Physicians were more often in community (86%) 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, 32–85). Most patients (81%) had T3 disease. Patients had ≤8, 9-11 and ≥12 nodes examined 3%, 13% and 84% of the time and 38% had comorbidities. Of the 76 patients tested for MMR/MSI, 13 (17%) were MMR-D or MSI-H and 46 (61%) were MMR-P or MSI-L; 17 (22%) unknown. Median RS was 20 (range, 1-77). Before obtaining the RS, chemotherapy was planned in 52 (45%) patients, observation in 40 (34%), and there was no recommendation in 24 (21%). For the 92 patients with pre-assay recommendations, recommended treatment changed after obtaining the RS for 27 patients (29%). Treatment intensity decreased for 18 (67%) and increased for 9 (33%) of 27 changed recommendations. A significant trend of decreasing treatment intensity with lower RS values was observed (p=.0035). Conclusions: These findings indicate that for stage II colon cancer patients, treatment recommendations were changed by RS results in 29% of patients. Use of the Oncotype DX assay may lead to reductions in treatment intensity, contributing to the assay’s cost effectiveness.

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

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.4_suppl.398 ◽

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.

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Prospective Multicenter Study of the Impact of Oncotype DX Colon Cancer Assay Results on Treatment Recommendations in Stage II Colon Cancer Patients

The Oncologist ◽

10.1634/theoncologist.2013-0401 ◽

2014 ◽

Vol 19 (5) ◽

pp. 492-497 ◽

Cited By ~ 34

Author(s):

Geetika Srivastava ◽

Lindsay A. Renfro ◽

Robert J. Behrens ◽

Margarita Lopatin ◽

Calvin Chao ◽

...

Keyword(s):

Colon Cancer ◽

Cancer Patients ◽

Multicenter Study ◽

Treatment Recommendations ◽

Oncotype Dx ◽

Stage Ii ◽

Prospective Multicenter Study ◽

Stage Ii Colon Cancer ◽

The Impact

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Mismatch repair status predicts survival after adjuvant treatment in stage II colon cancer patients

Journal of Surgical Oncology ◽

10.1002/jso.25798 ◽

2019 ◽

Vol 121 (2) ◽

pp. 392-401 ◽

Cited By ~ 2

Author(s):

I. Gkekas ◽

J. Novotny ◽

P. Fabian ◽

R. Nemecek ◽

R. Palmqvist ◽

...

Keyword(s):

Colon Cancer ◽

Cancer Patients ◽

Mismatch Repair ◽

Adjuvant Treatment ◽

Stage Ii ◽

Mismatch Repair Status ◽

Stage Ii Colon Cancer

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The Impact of Delayed Chemotherapy on Its Completion and Survival Outcomes in Stage II Colon Cancer Patients

PLoS ONE ◽

10.1371/journal.pone.0107993 ◽

2014 ◽

Vol 9 (9) ◽

pp. e107993 ◽

Cited By ~ 6

Author(s):

Fang Xu ◽

Alfred A. Rimm ◽

Pingfu Fu ◽

Smitha S. Krishnamurthi ◽

Gregory S. Cooper

Keyword(s):

Colon Cancer ◽

Cancer Patients ◽

Stage Ii ◽

Survival Outcomes ◽

Stage Ii Colon Cancer ◽

The Impact

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Effect of the 12-gene colon cancer assay results on adjuvant treatment recommendations in patients with stage II colon cancer

Current Medical Research and Opinion ◽

10.1185/03007995.2013.855183 ◽

2013 ◽

Vol 30 (2) ◽

pp. 321-328 ◽

Cited By ~ 10

Author(s):

T. Cartwright ◽

C. Chao ◽

M. Lee ◽

M. Lopatin ◽

T. Bentley ◽

...

Keyword(s):

Colon Cancer ◽

Adjuvant Treatment ◽

Treatment Recommendations ◽

Stage Ii ◽

Stage Ii Colon Cancer

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Polymorphisms of genes encoding for regulatory proteins in the coagulation cascade to predict outcome for stage II and III colon cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.4_suppl.227 ◽

2020 ◽

Vol 38 (4_suppl) ◽

pp. 227-227

Author(s):

Martin D. Berger ◽

Inti Zlobec ◽

Shu Cao ◽

Yuji Miyamoto ◽

Mitsukuni Suenaga ◽

...

Keyword(s):

Colon Cancer ◽

Cancer Patients ◽

Recurrence Rate ◽

Multivariate Analyses ◽

Stage Ii ◽

Regulatory Proteins ◽

Coagulation Cascade ◽

Genes Encoding ◽

Stage Ii Colon Cancer ◽

The Impact

227 Background: In cancer patients, an activated coagulation cascade might promote tumor cell dissemination. There are preliminary data suggesting that fibrinogen in combination with platelets can build a meshwork that entraps cancer cells enabling them to escape from immunosurveillance. We therefore hypothesize that variations in genes encoding for regulatory proteins within the coagulation pathway may predict outcome in patients with stage II and III colon cancer. Methods: The impact of three functional single nucleotide polymorphisms (SNPs) within the FGB, SERPINC1 and ITGA2B genes on time to recurrence and overall survival was evaluated in 209 patients with stage II and III colon cancer. Genomic DNA was isolated from formalin-fixed paraffin embedded tissue and the SNPs were analyzed by PCR-based direct sequencing. Results: Baseline characteristics were as follows: median age = 70y (19-91); female/male ratio = 42.8% / 57.2%; 111 patients had stage II, and 98 stage III colon cancer. The FGB rs4220 SNP showed significant association with recurrence rate in the overall population. Patients harboring any A allele had a higher 3-years recurrence rate compared to those with a G/G genotype (28% vs 17%) in both univariate (HR 1.83, 95% confidence interval (CI) 0.99-3.36, p = 0.048) and multivariate analyses (HR 1.94, 95% CI 1.05-3.57, p = 0.034). This trend was most evident among pts with stage II and especially the subgroup of high-risk stage II colon cancer. Again, A allele carriers had a higher 3-years recurrence rate compared to those having a G/G genotype (24% vs 10% and 44% vs 15% respectively) in both univariate (HR 3.32, 95% CI 1.26-8.74, p = 0.010 and HR 5.34, 95% CI 1.38-20.68, p = 0.006) and multivariate analyses (HR 3.34, 95% CI 1.27-8.78, p = 0.015 and HR 5.44, 95% CI 1.40-21.15, p = 0.015). Conclusions: Here, we demonstrate that the FGB polymorphism rs4220 might serve as a prognostic biomarker in stage II colon cancer. Assessment of FGB rs4220 might help us to identify those stage II colon cancer patients who will derive the most benefit from adjuvant chemotherapy.

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Prognostic impact of MSI in stage II colon cancers: An additional translational study of the SACURA trial.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.e15155 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. e15155-e15155 ◽

Cited By ~ 1

Author(s):

Toshiaki Ishikawa ◽

Megumi Ishiguro ◽

Eiji Nakatani ◽

Hiroyuki Uetake ◽

Hideki Ueno ◽

...

Keyword(s):

Colon Cancer ◽

Cancer Patients ◽

Adjuvant Treatment ◽

Stage Ii ◽

Phase Iii ◽

Prognostic Impact ◽

Translational Study ◽

Colon Cancers ◽

Stage Ii Colon Cancer ◽

Better Than

e15155 Background: The SACURA trial is a phase III study to evaluate the superiority of 1-year adjuvant treatment with oral tegafur-uracil (UFT) to surgery alone for stage II colon cancer. Superiority of adjuvant treatment with UFT to surgery alone was not demonstrated (ASCO2016 abst#3617). In an additional translational study, we assessed microsatellite instability (MSI) status of cancer tissues and prospectively examined the association of MSI with prognosis in stage II colon cancer patients. Methods: Formalin-fixed, paraffin-embedded samples were prospectively collected from 1026 patients enrolled in the SACURA trial. MSI was evaluated using 5 markers; BAT25, BAT26, D2S123, D5S346, and D17S250. MSI-high (MSI-H) was defined as the presence of instability in more than 20% of the markers. Median follow-up time was 69.6 months. Results: MSI-H, MSI-low (MSI-L) and microsatellite-stable (MSS) was observed in 74 (7.2%), 24 (2.3%), and 928 (90.5%) samples, respectively. Patients with MSI-H was significantly frequent in female, right-sided colon cancers, > 5cm tumors, poor histological type, and elevated CEA. Relapse rate for MSI-H patients (4.1%) was significantly lower than that for MSI-L/MSS cancer (13.4%, p = 0.02). Relapse free survival (RFS) in MSI-H patients was significantly better than in MSI-L/MSS patients (hazard ratio: 0.40, 95%CI: 0.17-0.98, p = 0.045), as well as adjusted results by prognostic factors. The 5-year RFS rates in MSI-H and MSI-L/MSS patients were 92.9% and 84.1%, respectively. Although there was no statistical significance, the 5-year RFS rate in MSI-H patients was tended to be better than that in MSI-L/MSS patients in the surgery alone group (94.3% vs. 83.1%, p = 0.086) as well as in the UFT group (91.7% vs. 85.1%, p = 0.233). Conclusions: MSI was an independent prognostic factor in stage II colon cancers. By considering their favorable RFS, adjuvant chemotherapy for stage II colon cancer patients with MSI-H may be unnecessary. Clinical trial information: NCT00392899.

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Immunoscore as a parameter predicting time to recurrence and disease-free survival in T4N0 stage II colon cancer patients.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.4105 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. 4105-4105

Author(s):

Jerome Galon ◽

Fabienne Hermitte ◽

Bernhard Mlecnik ◽

Alessandro Lugli ◽

Carlo Bruno Bifulco ◽

...

Keyword(s):

Colon Cancer ◽

Multivariate Analysis ◽

Survival Time ◽

Cancer Patients ◽

Adjuvant Treatment ◽

Stage Ii ◽

Mean Survival Time ◽

Relative Contribution ◽

Restricted Mean Survival Time ◽

Stage Ii Colon Cancer

4105 Background: Risk assessment is particularly important to decide when to propose an adjuvant treatment for Stage II Colon Cancer (CC) patients. However, the current tumor risk features are imperfect and additional risk factors are needed to guide treatment decisions. The consensus Immunoscore is an alternative and powerful approach that could be used in the T4N0 Stage II colon cancer population. Immunoscore is an in vitro diagnostic test that predicts the risk of relapse in patients with CC by measuring the host immune response at the tumor site. Methods: From the international Immunoscore consortium study (n = 2681) (Pagès et al. The Lancet 2018), a subgroup analysis was performed on T4N0 Stage II colon cancer patients (n = 208). Results: In stage II T4N0, Int+Hi Immunoscore represented 65.4% of the population and low-Immunoscore only 34.6%. T4N0 patients with Int+Hi Immunoscore presented a significantly prolonged survival for TTR compared to low Immunoscore patients (5 years recurrence rate Int+Hi: 84.6% (78.3-91.5), Lo: 46.3% (35.1-61); unadjusted HR [Int+Hi vs Lo] = 0.21; (95% CI 0.11-0.4); P< 0.0001), representing a restricted mean survival time (RMST) difference of 80.9 months (95% CI 51.1-110.6) ( P< 0.0001). The DFS was significantly different between Int+Hi and Low Immunoscore (5 years recurrence rate Int+Hi: 70.5% (95% CI 62.7-79.1), Lo: 38.5% (95% CI 28.2-52.5); unadjusted HR [Int+Hi vs Lo] = 0.31; (95% CI 0.19-0.49); P< 0.0001). Using restricted mean survival time (RMST) a significant ( P< 0.0001) difference of 60.4 months (95% CI 32.6-88.1) was observed between the 2 groups Importantly, Cox multivariate analysis in Stage II T4N0 colon cancer patients, revealed that Immunoscore was the only remaining significant parameter (HR [Int+Hi vs Lo] = 0.15; (95% CI 0.05-0.46); P= 0.0009). In contrast, all other parameters, gender, sidedness, mucinous, grade, T-stage, VELIPI, MSI were not significant in multivariate analysis. Finally, Immunoscore showed the highest relative contribution to predict relapse (76.2% chi2 relative contribution), stronger than all the other parameters, MSI (16.1%), Grade (5%), sidedness (2%), gender (2%), VELIPI (1%). Conclusions: Immunoscore is the most powerful parameter to predict the risk in T4N0 population, and could be a good tool for adjuvant treatment decision in Stage II patients.

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Association of chemotherapy with survival in stage II colon cancer patients who received radical surgery: a retrospective cohort study

BMC Cancer ◽

10.1186/s12885-021-08057-3 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Zhihao Lv ◽

Yuqi Liang ◽

Huaxi Liu ◽

Delong Mo

Keyword(s):

Colon Cancer ◽

Overall Survival ◽

Cancer Patients ◽

Prediction Models ◽

Radical Surgery ◽

Survival Rates ◽

Stage Ii ◽

Survival Prediction ◽

Stage Ii Colon Cancer ◽

Overall Survival Rates

Abstract Background It remains controversial whether patients with Stage II colon cancer would benefit from chemotherapy after radical surgery. This study aims to assess the real effectiveness of chemotherapy in patients with stage II colon cancer undergoing radical surgery and to construct survival prediction models to predict the survival benefits of chemotherapy. Methods Data for stage II colon cancer patients with radical surgery were retrieved from the Surveillance, Epidemiology, and End Results (SEER) database. Propensity score matching (1:1) was performed according to receive or not receive chemotherapy. Competitive risk regression models were used to assess colon cancer cause-specific death (CSD) and non-colon cancer cause-specific death (NCSD). Survival prediction nomograms were constructed to predict overall survival (OS) and colon cancer cause-specific survival (CSS). The predictive abilities of the constructed models were evaluated by the concordance indexes (C-indexes) and calibration curves. Results A total of 25,110 patients were identified, 21.7% received chemotherapy, and 78.3% were without chemotherapy. A total of 10,916 patients were extracted after propensity score matching. The estimated 3-year overall survival rates of chemotherapy were 0.7% higher than non- chemotherapy. The estimated 5-year and 10-year overall survival rates of non-chemotherapy were 1.3 and 2.1% higher than chemotherapy, respectively. Survival prediction models showed good discrimination (the C-indexes between 0.582 and 0.757) and excellent calibration. Conclusions Chemotherapy improves the short-term (43 months) survival benefit of stage II colon cancer patients who received radical surgery. Survival prediction models can be used to predict OS and CSS of patients receiving chemotherapy as well as OS and CSS of patients not receiving chemotherapy and to make individualized treatment recommendations for stage II colon cancer patients who received radical surgery.

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