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Gene Expression Signature Associated With Rectal Cancers With Poor Response To Chemoradiation
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ASSOCIATION FOR ACADEMIC SURGERY AND SOCIETY OF UNIVERSITY SURGEONS—ABSTRACTS among primary care physicians and other non-oncologists following colorectal cancer patients may improve adherence to current guidelines. The comparative effectiveness of CT and PET/PET CT in the surveillance of colorectal cancer patients needs to be further examined. 28.9. Gene Expression Signature Associated With Rectal Cancers With Poor Response To Chemoradiation. G. A. Gantt,1 Y. Chen,2 D. Sohal,3 K. DeJulius,4 A. G. Mace,1 J. S. Barnholtz-Sloan,2 M. F. Kalady1,4; 1Department of Colorectal Surgery, Digestive Disease Institute, Cleveland Clinic, Cleveland, OH; 2University Hospital-Case Medical Center and Case Comprehensive Cancer Center, Cleveland, OH; 3 Solid Tumor Oncology, Cleveland Clinic, Cleveland, OH; 4 Cancer Biology Department, Lerner Research Institute, Cleveland Clinic, Cleveland, OH
28.8. Physician Follow-up and Guideline Adherence in PostTreatment Surveillance of Colorectal Cancer. G. M. Vargas,1 K. M. Sheffield,1 A. Parmar,1,2 Y. Han,1 K. M. Brown,1 T. S. Riall1; 1University of Texas Medical Branch, Galveston, Texas; 2University of California San Francisco East Bay, Oakland, California Introduction: Current guidelines for post-resection surveillance of colorectal cancer uniformly recommend history and physical exam, carcinoembryonic antigen (CEA) testing, and colonoscopy. No consistent guidelines exist for the use of computed tomography (CT) of the abdomen and positron emission tomography (PET/PET CT). The goal of our study was to describe current trends and the impact of oncologic follow-up in adherence to guidelines and patterns of use of non-recommended tests. Methods: We used Texas Cancer Registry-Medicare linked data (2001-2006) to identify physician visits, CEA testing, colonoscopy, abdominal CT, and PET/PET CT scans in patients 66 and older with stage I-III colorectal cancer who underwent curative resection. Adherence to guidelines was assessed with a composite measure of physician visits (>2 per year x 3 years), CEA tests (>2 per year x 2 years), and colonoscopy use (>1 in three years) from start of surveillance (90 days after surgery). Results: In patients who survived 3 years (N¼8080), the overall adherence to guidelines was 25.1%. 85.4% had physician visits, 29.5% had CEA testing, and 75.3% had colonoscopy as defined above. Adherence to guidelines was increased in younger, healthier patients and those with regional disease or poorly differentiated tumors. 57.5% of patients saw a medical oncologist in the 3 years after surgery and 38.2% saw a medical oncologist at least once a year for the 3 years. In patients seen by a medical oncologist after surgery, adherence to guidelines increased to 41.6%. It improved to 56.7% in those who saw a medical oncologist at least once a year. For those who did not see a medical oncologist, guideline adherence was only 2.9% (P<0.0001). For those with regular medical oncology visits, 48.6% met CEA recommendations, and 83.1% met colonoscopy recommendations. While guideline adherence remained fairly constant, the use of abdominal CT and PET/PET CT increased from 57.5% and 9.5%, respectively, for patients diagnosed in 2001 to 65.8% and 24.6% (P<0.0001) for patients diagnosed in 2006 Patients who saw a medical oncologist were more likely to get abdominal CT (79.1% vs. 41.0%, P<0.0001) and PET/ PET CT (30.5% vs. 3.5%, P<0.0001) than those who did not. Conclusions: Overall compliance with current minimum guidelines for post-treatment surveillance of resected colorectal cancer remains low and the use of non-recommended testing has increased over time. Adherence to guidelines and use of non-recommended tests are markedly increased in patients who have regular follow-up by a medical oncologist. Improved awareness of recommendations
Introduction: Preoperative chemoradiation is the standard of care for locally advanced rectal cancer. Patients who achieve a complete pathological response have improved oncologic outcomes, but unfortunately this only occurs in approximately 20% of cases. Identifying factors associated with poor response could help understand the underlying biology of treatment resistance. The goal of this study was to identify rectal cancer gene expression patterns relevant to therapy response. Methods: Pretreatment rectal adenocarcinoma biopsies were obtained and snap frozen within an IRB-approved protocol. Patients underwent neoadjuvant standard long course 5-FU based chemoradiation (CRT) and post-treatment responses were determined on the surgical resection specimen based on American Joint Committee on Cancer (AJCC) criteria. Total tumor mRNA was extracted from pretreatment specimens and run on an Illumina platform for microarray analysis. The study population was divided into 23 samples for discovery of the signature, and 10 samples for verification of the signature. Non-responders were compared to complete or incomplete responders by gene using non-parametric Wilcoxon t-test. Results were verified in the verification set using Prediction Analysis for Microarrays (PAM). Genes found to be differentially expressed were analyzed for functional analysis using the Ingenuity Pathway Analysis (IPA) software. In addition, unsupervised hierarchical clustering was performed using the significant gene lists from each nonparametric comparison and was visualized with heatmaps using the R package ‘‘gplots’’. Results: 33 patients were included between the years 20062009. A total 25,034 genes were analyzed. Non-responders (AJCC 3) were compared with complete or incomplete responders (AJCC 0-2) and 919 genes were differentially expressed. IPA canonical pathway analysis revealed a significant ratio of differentially expressed genes in the ‘‘DNA double strand break repair by homologous recombination’’ pathway. Key genes involved in this pathway included Rad50 and BRCA2, which were both down-regulated in the chemoradiation-resistant group. Validation of the differences between non-responders and responders using PAM, showed a sensitivity of 100% and specificity of 71.4% for predicting non-responders. Conclusions: Distinct rectal cancer gene profiles associated with poor response to chemoradiation identify alterations in the DNA double strand break repair pathway. Further work and validation is necessary, but this pathway could be a potential target to improve treatment response. 28.10. Signet Ring Cells in Pseudomyxoma Peritonei’s a Marker for Poor Survival. P. K. Shah,1 K. Lohani,1 S. Shetty,1 P. Thomas,2 G. Venkatesh,2 B. Natarajan,1 P. Sharma,3 B. Loggie1; 1Creighton University Medical Center, Omaha, NE; 2Creighton University Medical Center, Omaha, NE; 3Creighton University Medical Center, Omaha, N/A Introduction: Pseudomyxoma peritonei (PMP) is a rare but unique tumor known to arise out of an appendiceal tumor in majority of the patients. Various clinical and radiological criteria that predict a poor
ASSOCIATION FOR ACADEMIC SURGERY AND SOCIETY OF UNIVERSITY SURGEONS—ABSTRACTS among primary care physicians and other non-oncologists following colorectal cancer patients may improve adherence to current guidelines. The comparative effectiveness of CT and PET/PET CT in the surveillance of colorectal cancer patients needs to be further examined. 28.9. Gene Expression Signature Associated With Rectal Cancers With Poor Response To Chemoradiation. G. A. Gantt,1 Y. Chen,2 D. Sohal,3 K. DeJulius,4 A. G. Mace,1 J. S. Barnholtz-Sloan,2 M. F. Kalady1,4; 1Department of Colorectal Surgery, Digestive Disease Institute, Cleveland Clinic, Cleveland, OH; 2University Hospital-Case Medical Center and Case Comprehensive Cancer Center, Cleveland, OH; 3 Solid Tumor Oncology, Cleveland Clinic, Cleveland, OH; 4 Cancer Biology Department, Lerner Research Institute, Cleveland Clinic, Cleveland, OH
28.8. Physician Follow-up and Guideline Adherence in PostTreatment Surveillance of Colorectal Cancer. G. M. Vargas,1 K. M. Sheffield,1 A. Parmar,1,2 Y. Han,1 K. M. Brown,1 T. S. Riall1; 1University of Texas Medical Branch, Galveston, Texas; 2University of California San Francisco East Bay, Oakland, California Introduction: Current guidelines for post-resection surveillance of colorectal cancer uniformly recommend history and physical exam, carcinoembryonic antigen (CEA) testing, and colonoscopy. No consistent guidelines exist for the use of computed tomography (CT) of the abdomen and positron emission tomography (PET/PET CT). The goal of our study was to describe current trends and the impact of oncologic follow-up in adherence to guidelines and patterns of use of non-recommended tests. Methods: We used Texas Cancer Registry-Medicare linked data (2001-2006) to identify physician visits, CEA testing, colonoscopy, abdominal CT, and PET/PET CT scans in patients 66 and older with stage I-III colorectal cancer who underwent curative resection. Adherence to guidelines was assessed with a composite measure of physician visits (>2 per year x 3 years), CEA tests (>2 per year x 2 years), and colonoscopy use (>1 in three years) from start of surveillance (90 days after surgery). Results: In patients who survived 3 years (N¼8080), the overall adherence to guidelines was 25.1%. 85.4% had physician visits, 29.5% had CEA testing, and 75.3% had colonoscopy as defined above. Adherence to guidelines was increased in younger, healthier patients and those with regional disease or poorly differentiated tumors. 57.5% of patients saw a medical oncologist in the 3 years after surgery and 38.2% saw a medical oncologist at least once a year for the 3 years. In patients seen by a medical oncologist after surgery, adherence to guidelines increased to 41.6%. It improved to 56.7% in those who saw a medical oncologist at least once a year. For those who did not see a medical oncologist, guideline adherence was only 2.9% (P<0.0001). For those with regular medical oncology visits, 48.6% met CEA recommendations, and 83.1% met colonoscopy recommendations. While guideline adherence remained fairly constant, the use of abdominal CT and PET/PET CT increased from 57.5% and 9.5%, respectively, for patients diagnosed in 2001 to 65.8% and 24.6% (P<0.0001) for patients diagnosed in 2006 Patients who saw a medical oncologist were more likely to get abdominal CT (79.1% vs. 41.0%, P<0.0001) and PET/ PET CT (30.5% vs. 3.5%, P<0.0001) than those who did not. Conclusions: Overall compliance with current minimum guidelines for post-treatment surveillance of resected colorectal cancer remains low and the use of non-recommended testing has increased over time. Adherence to guidelines and use of non-recommended tests are markedly increased in patients who have regular follow-up by a medical oncologist. Improved awareness of recommendations
Introduction: Preoperative chemoradiation is the standard of care for locally advanced rectal cancer. Patients who achieve a complete pathological response have improved oncologic outcomes, but unfortunately this only occurs in approximately 20% of cases. Identifying factors associated with poor response could help understand the underlying biology of treatment resistance. The goal of this study was to identify rectal cancer gene expression patterns relevant to therapy response. Methods: Pretreatment rectal adenocarcinoma biopsies were obtained and snap frozen within an IRB-approved protocol. Patients underwent neoadjuvant standard long course 5-FU based chemoradiation (CRT) and post-treatment responses were determined on the surgical resection specimen based on American Joint Committee on Cancer (AJCC) criteria. Total tumor mRNA was extracted from pretreatment specimens and run on an Illumina platform for microarray analysis. The study population was divided into 23 samples for discovery of the signature, and 10 samples for verification of the signature. Non-responders were compared to complete or incomplete responders by gene using non-parametric Wilcoxon t-test. Results were verified in the verification set using Prediction Analysis for Microarrays (PAM). Genes found to be differentially expressed were analyzed for functional analysis using the Ingenuity Pathway Analysis (IPA) software. In addition, unsupervised hierarchical clustering was performed using the significant gene lists from each nonparametric comparison and was visualized with heatmaps using the R package ‘‘gplots’’. Results: 33 patients were included between the years 20062009. A total 25,034 genes were analyzed. Non-responders (AJCC 3) were compared with complete or incomplete responders (AJCC 0-2) and 919 genes were differentially expressed. IPA canonical pathway analysis revealed a significant ratio of differentially expressed genes in the ‘‘DNA double strand break repair by homologous recombination’’ pathway. Key genes involved in this pathway included Rad50 and BRCA2, which were both down-regulated in the chemoradiation-resistant group. Validation of the differences between non-responders and responders using PAM, showed a sensitivity of 100% and specificity of 71.4% for predicting non-responders. Conclusions: Distinct rectal cancer gene profiles associated with poor response to chemoradiation identify alterations in the DNA double strand break repair pathway. Further work and validation is necessary, but this pathway could be a potential target to improve treatment response. 28.10. Signet Ring Cells in Pseudomyxoma Peritonei’s a Marker for Poor Survival. P. K. Shah,1 K. Lohani,1 S. Shetty,1 P. Thomas,2 G. Venkatesh,2 B. Natarajan,1 P. Sharma,3 B. Loggie1; 1Creighton University Medical Center, Omaha, NE; 2Creighton University Medical Center, Omaha, NE; 3Creighton University Medical Center, Omaha, N/A Introduction: Pseudomyxoma peritonei (PMP) is a rare but unique tumor known to arise out of an appendiceal tumor in majority of the patients. Various clinical and radiological criteria that predict a poor