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

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.

Download Full-text

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

Download Full-text

Microsatellite instability as a prognostic factor in stadium II colon cancer patients. A meta-analysis of published literature.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.e15075 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. e15075-e15075

Author(s):

Jan Novotny ◽

Ioannis Gkekas ◽

Ladislav Pecen ◽

Karin Strigard ◽

Richard Palmquist ◽

...

Keyword(s):

Colon Cancer ◽

Microsatellite Instability ◽

Cancer Patients ◽

Meta Analysis ◽

Stage Ii ◽

Survival Outcomes ◽

Prognostic Role ◽

Hazard Ratios ◽

Stage Ii Colon Cancer

e15075 Background: The prognostic role of microsatellite instability (MSI) in stage II colon cancer patients remains controversial despite it has been investigated in a number of studies. Hazard ratios differ considerably among these studies. We performed a meta-analysis to define the significance of MSI in this group of patients. Methods: Studies indexed in PubMed presenting separate data on MSI status and survival outcomes for stage II colon cancer patients have been analyzed using fixed-effect meta-analysis of hazard ratio according to the method of Peto. Results: Analysis was performed on 19 studies including 5998 patients. 47.2% patients received postoperative chemotherapy, 52.8% were males and 47.2% females. Eight studies included also rectal cancer patients. MSI was detected in 20.8 % of the patients. Hazard ration (HR) for overall survival (OS): MSI vs MSS for the entire population: 0.73 (95% confidence interval (CI): 0.33-1.65); HR for disease free survival (DFS): 0.60 (95% CI: 0.27-1.32). No statistical significant difference was found when comparing studies analyzing MSI with genotyping (MG) and immunohistochemistry (IHC) (MG vs IHC: HR OS 0.45, 95% CI 0.10-2.05 vs. 0.95, 95% CI 0.57–1.58; HR DFS 0.51, 95% CI: 0.14-1.85 vs. 0.67, 95% CI 0.26-1.70). However, numerically MSI determination with genotyping shows remarkably lower hazard ratios (further from HR equal to one) for both OS and DFS. Separate analysis of studies investigating colon cancer patients only showed HR OS 0.72 (95% CI: 0.31-1.71); HR DFS 0.60 (95% CI: 0.27-1.31). Conclusions: This is the first meta-analysis that evaluates the prognostic role of MSI in the well defined population of colon cancer patients with stage II disease. No significant relation was found between MSI status and various survival outcomes. Routine determination of MSI status to guide postoperative management of stage II colon cancer patients cannot be recommended based on the presently included studies. This study was supported from the unrestricted grant of Cancerforskningsfonden i Norrland/Lions Cancerforskningsfond LP 14-2065 and Akademisk Miljö NLL-576531.

Download Full-text

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.

Download Full-text

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

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.15_suppl.3626 ◽

2012 ◽

Vol 30 (15_suppl) ◽

pp. 3626-3626

Author(s):

Thomas H. Cartwright ◽

Calvin Chao ◽

Margarita Lopatin ◽

Tanya G. Bentley ◽

Michael S. Broder ◽

...

Keyword(s):

Colon Cancer ◽

Cancer Patients ◽

Adjuvant Treatment ◽

Treatment Recommendations ◽

Oncotype Dx ◽

Stage Ii ◽

Treatment Intensity ◽

Medical Oncologists ◽

Stage Ii Colon Cancer ◽

The Impact

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.

Download Full-text

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.

Download Full-text