- Email: [email protected]
Evaluation of PTGS2 Expression, PIK3CA Mutation, Aspirin use and Colon Cancer Survival in a Population-Based Cohort Study
Aspirin use and colorectal cancer-specific survival stratified by PIK3CA mutation status and PTGS2 immunohistochemical expression.
AGA Abstracts
The association between LN yield and recurrence was analyzed using Cox proportional hazard regression analysis with 10 LNs as cut-off, as this is the lowest recommended minimum for stage II CRC in current guidelines. A propensity score analysis using inverse probability weighting was performed to adjust for confounding. Results Among 1017 patients with a median follow-up of 49.0 months (IQR 19.6 - 81.5), 41 patients (4.0%) developed recurrence. In 405 patients (39.8%) a LN yield ≥10 was achieved. LN yield ≥10 was inversely associated with recurrence (6.0% versus 1.0%; adjusted HR 0.20; 95%CI 0.06 - 0.67; p= 0.009). LN metastases were detected in 84 patients (8.3%). LN yield ≥10 was independently associated with an increased detection rate of LNM (11.6% versus 6.0%; adjusted OR 2.27; 95%CI 1.39 - 3.69; p=0.001). Post-operative complications were observed in 250 patients (24.6%). LN yield ≥10 was not associated with an increased risk for complications (23.2% versus 26.2%; adjusted OR: 1.01; 95%CI 0.99 - 1.04; p=0.23). Conclusion Our results underline the importance to perform an appropriate oncologic resection and diligent LN search when patients with T1 CRC at high-risk for LNM are referred for surgical resection. Association between LN yield and recurrence, lymph node metastases and surgery-related complications in T1 colorectal cancer
Abbreviations: HR - hazard ratio; CI - confidence interval. †Multivariable model adjusted for age, gender, year of diagnosis, grade, MSI status, ECOG performance status, family history of colorectal cancer, adjuvant chemotherapy use and stage. Aspirin use and overall survival stratified by PIK3CA mutation status and PTGS2 immunohistochemical expression.
* Age, gender, tumor location, tumor size, tumor morphology and presence of lymph node metastasis (the latter only in the total cohort for the endpoint recurrence) ** Age, gender, tumor location, tumor size, tumor morphology, invasion depth, presence of lymphovascular invasion , differentiation grade, and presence of lymph node metastasis (the latter only in the total cohort for the endpoint recurrence) *** Age, gender, tumor location, body mass index, ASA score, and previous abdominal surgery
Tu1978 EVALUATION OF PTGS2 EXPRESSION, PIK3CA MUTATION, ASPIRIN USE AND COLON CANCER SURVIVAL IN A POPULATION-BASED COHORT STUDY Ronan T. Gray, Marie M. Cantwell, Helen G. Coleman, Maurice B. Loughrey, Peter Bankhead, Stephen McQuaid, Roisin O'Neill, Kenneth Arthur, Victoria Bingham, Claire McGready, Anna T. Gavin, Chris Cardwell, Brian Johnston, Jacqueline A. James, Peter Hamilton, Manuel Salto-Tellez, Liam J. Murray Background The association between aspirin use and improved survival after colorectal cancer diagnosis may be more pronounced in tumors that have PIK3CA mutations or high PTGS2 expression. However, the evidence of a difference in association by biomarker status lacks consistency. In this population-based colon cancer cohort study the interaction between these biomarkers, low-dose aspirin use, and survival was assessed. Methods The cohort consisted of 740 stage II and III colon cancer patients diagnosed between 2004-2008. Aspirin use was determined through clinical note review. Tissue blocks were retrieved to determine immunohistochemical assessment of PTGS2 expression in tissue microarrays and the presence of PIK3CA mutations in extracted DNA. Cox proportional hazards models were used to calculate hazard ratios (HR) and 95% confidence intervals (CI) for colorectal cancer-specific and overall survival. Results In this cohort low-dose aspirin use was associated with a 31% improvement in cancer-specific survival compared to non-use (adjusted HR=0.69, 95% CI 0.47-0.98). This effect was more pronounced in tumors with high PTGS2 expression (PTGS2high adjusted HR=0.55, 95% CI 0.32-0.96) compared to those with low PTGS2 expression (PTGS2-low adjusted HR=1.19, 95% CI 0.68-2.07, P for interaction=0.09). The aspirin by PTGS2 interaction was significant for overall survival (PTGS2-high adjusted HR=0.64, 95% CI 0.42-0.98 versus PTGS2-low adjusted HR=1.28, 95% CI 0.80-2.03, P for interaction= 0.04). However, no interaction was observed between aspirin use and PIK3CA mutation status for colorectal cancer-specific or overall survival. Conclusion Low-dose aspirin use was associated with improved survival outcomes in this population-based cohort of colon cancer patients. This association differed according to PTGS2 expression but not PIK3CA mutation status.
Abbreviations: HR - hazard ratio; CI - confidence interval. ‡Multivariable model adjusted for age, gender, year of diagnosis, grade, MSI status, ECOG performance status, family history of colorectal cancer, adjuvant chemotherapy use, stage and also adjusted for Charlson comorbidity score.
Tu1979 STATIN USE, CANDIDATE MEVALONATE PATHWAY BIOMARKERS, AND COLON CANCER SURVIVAL IN A POPULATION-BASED COHORT STUDY Ronan T. Gray, Maurice B. Loughrey, Peter Bankhead, Chris Cardwell, Stephen McQuaid, Roisin O'Neill, Kenneth Arthur, Victoria Bingham, Claire McGready, Anna T. Gavin, Jacqueline A. James, Peter Hamilton, Manuel Salto-Tellez, Liam J. Murray, Helen G. Coleman Background Statin use after colorectal cancer diagnosis may improve survival but evidence from observational studies is conflicting. The anti-cancer effect of statins may be restricted to certain molecular subgroups. In this population-based cohort study the interaction between p53 and HMGCR expression, KRAS mutations, and the association between statin use and colon cancer survival was assessed. Methods The cohort consisted of 740 stage II and III colon cancer patients diagnosed between 2004-2008. Statin use was determined through clinical note review. Tissue blocks were retrieved to determine immunohistochemical expression of p53 and HMGCR in tissue microarrays and the presence of KRAS mutations in extracted DNA. Cox proportional hazards models were used to calculate hazard ratios (HR) and 95% confidence intervals (CI) for colorectal cancer-specific and overall survival. Results Statin use was not associated with improved cancer-specific survival in this cohort (HR= 0.82, 95% CI 0.59-1.15). However, there was some evidence of a difference in the association between statins and survival by HMGCR status (HMGCR-high HR=0.65, 95% CI 0.38-1.10 versus HMGCR-low HR=1.03, 95% CI 0.63-1.68, P for interaction=0.07) and by KRAS status (KRAS-wild-type HR=0.63, 95% CI 0.39-1.02 versus KRAS-mutant HR=1.22, 95%
S-1023
AGA Abstracts
AGA Abstracts
The association between LN yield and recurrence was analyzed using Cox proportional hazard regression analysis with 10 LNs as cut-off, as this is the lowest recommended minimum for stage II CRC in current guidelines. A propensity score analysis using inverse probability weighting was performed to adjust for confounding. Results Among 1017 patients with a median follow-up of 49.0 months (IQR 19.6 - 81.5), 41 patients (4.0%) developed recurrence. In 405 patients (39.8%) a LN yield ≥10 was achieved. LN yield ≥10 was inversely associated with recurrence (6.0% versus 1.0%; adjusted HR 0.20; 95%CI 0.06 - 0.67; p= 0.009). LN metastases were detected in 84 patients (8.3%). LN yield ≥10 was independently associated with an increased detection rate of LNM (11.6% versus 6.0%; adjusted OR 2.27; 95%CI 1.39 - 3.69; p=0.001). Post-operative complications were observed in 250 patients (24.6%). LN yield ≥10 was not associated with an increased risk for complications (23.2% versus 26.2%; adjusted OR: 1.01; 95%CI 0.99 - 1.04; p=0.23). Conclusion Our results underline the importance to perform an appropriate oncologic resection and diligent LN search when patients with T1 CRC at high-risk for LNM are referred for surgical resection. Association between LN yield and recurrence, lymph node metastases and surgery-related complications in T1 colorectal cancer
Abbreviations: HR - hazard ratio; CI - confidence interval. †Multivariable model adjusted for age, gender, year of diagnosis, grade, MSI status, ECOG performance status, family history of colorectal cancer, adjuvant chemotherapy use and stage. Aspirin use and overall survival stratified by PIK3CA mutation status and PTGS2 immunohistochemical expression.
* Age, gender, tumor location, tumor size, tumor morphology and presence of lymph node metastasis (the latter only in the total cohort for the endpoint recurrence) ** Age, gender, tumor location, tumor size, tumor morphology, invasion depth, presence of lymphovascular invasion , differentiation grade, and presence of lymph node metastasis (the latter only in the total cohort for the endpoint recurrence) *** Age, gender, tumor location, body mass index, ASA score, and previous abdominal surgery
Tu1978 EVALUATION OF PTGS2 EXPRESSION, PIK3CA MUTATION, ASPIRIN USE AND COLON CANCER SURVIVAL IN A POPULATION-BASED COHORT STUDY Ronan T. Gray, Marie M. Cantwell, Helen G. Coleman, Maurice B. Loughrey, Peter Bankhead, Stephen McQuaid, Roisin O'Neill, Kenneth Arthur, Victoria Bingham, Claire McGready, Anna T. Gavin, Chris Cardwell, Brian Johnston, Jacqueline A. James, Peter Hamilton, Manuel Salto-Tellez, Liam J. Murray Background The association between aspirin use and improved survival after colorectal cancer diagnosis may be more pronounced in tumors that have PIK3CA mutations or high PTGS2 expression. However, the evidence of a difference in association by biomarker status lacks consistency. In this population-based colon cancer cohort study the interaction between these biomarkers, low-dose aspirin use, and survival was assessed. Methods The cohort consisted of 740 stage II and III colon cancer patients diagnosed between 2004-2008. Aspirin use was determined through clinical note review. Tissue blocks were retrieved to determine immunohistochemical assessment of PTGS2 expression in tissue microarrays and the presence of PIK3CA mutations in extracted DNA. Cox proportional hazards models were used to calculate hazard ratios (HR) and 95% confidence intervals (CI) for colorectal cancer-specific and overall survival. Results In this cohort low-dose aspirin use was associated with a 31% improvement in cancer-specific survival compared to non-use (adjusted HR=0.69, 95% CI 0.47-0.98). This effect was more pronounced in tumors with high PTGS2 expression (PTGS2high adjusted HR=0.55, 95% CI 0.32-0.96) compared to those with low PTGS2 expression (PTGS2-low adjusted HR=1.19, 95% CI 0.68-2.07, P for interaction=0.09). The aspirin by PTGS2 interaction was significant for overall survival (PTGS2-high adjusted HR=0.64, 95% CI 0.42-0.98 versus PTGS2-low adjusted HR=1.28, 95% CI 0.80-2.03, P for interaction= 0.04). However, no interaction was observed between aspirin use and PIK3CA mutation status for colorectal cancer-specific or overall survival. Conclusion Low-dose aspirin use was associated with improved survival outcomes in this population-based cohort of colon cancer patients. This association differed according to PTGS2 expression but not PIK3CA mutation status.
Abbreviations: HR - hazard ratio; CI - confidence interval. ‡Multivariable model adjusted for age, gender, year of diagnosis, grade, MSI status, ECOG performance status, family history of colorectal cancer, adjuvant chemotherapy use, stage and also adjusted for Charlson comorbidity score.
Tu1979 STATIN USE, CANDIDATE MEVALONATE PATHWAY BIOMARKERS, AND COLON CANCER SURVIVAL IN A POPULATION-BASED COHORT STUDY Ronan T. Gray, Maurice B. Loughrey, Peter Bankhead, Chris Cardwell, Stephen McQuaid, Roisin O'Neill, Kenneth Arthur, Victoria Bingham, Claire McGready, Anna T. Gavin, Jacqueline A. James, Peter Hamilton, Manuel Salto-Tellez, Liam J. Murray, Helen G. Coleman Background Statin use after colorectal cancer diagnosis may improve survival but evidence from observational studies is conflicting. The anti-cancer effect of statins may be restricted to certain molecular subgroups. In this population-based cohort study the interaction between p53 and HMGCR expression, KRAS mutations, and the association between statin use and colon cancer survival was assessed. Methods The cohort consisted of 740 stage II and III colon cancer patients diagnosed between 2004-2008. Statin use was determined through clinical note review. Tissue blocks were retrieved to determine immunohistochemical expression of p53 and HMGCR in tissue microarrays and the presence of KRAS mutations in extracted DNA. Cox proportional hazards models were used to calculate hazard ratios (HR) and 95% confidence intervals (CI) for colorectal cancer-specific and overall survival. Results Statin use was not associated with improved cancer-specific survival in this cohort (HR= 0.82, 95% CI 0.59-1.15). However, there was some evidence of a difference in the association between statins and survival by HMGCR status (HMGCR-high HR=0.65, 95% CI 0.38-1.10 versus HMGCR-low HR=1.03, 95% CI 0.63-1.68, P for interaction=0.07) and by KRAS status (KRAS-wild-type HR=0.63, 95% CI 0.39-1.02 versus KRAS-mutant HR=1.22, 95%
S-1023
AGA Abstracts