| PART I:Effect of Metabolic Syndrome and Its Components on Recurrence and Survival in Colon Cancer PatientsBACKGROUND:Although epidemiologic studies suggest that metabolic syndrome (MetS) increases the risk of colorectal cancer, its effect on cancer mortality remains controversial.METHODS:We conducted a retrospective cohort study, using the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database (1998-2006), of 36,079 patients with colon cancer to determine the independent effect of MetS and its components on overall survival (OS) and disease-free survival (DFS). Data on MetS and its components was ascertained from Medicare claims. OS and DFS in patients with/without MetS and its components were compared using multivariate Cox models.RESULTS:MetS had no apparent effect on OS or DFS. Both elevated glucose/diabetes mellitus (DM) and hypertension were associated with worse OS (adjusted hazard ratios [aHR],1.17; 95% confidence internal [CI],1.13-1.21 and aHR, 1.08; 95% CI,1.03-1.12, respectively) and DFS (aHR,1.25; 95%CI,1.16-1.34 and aHR,1.22; 95% CI,1.12-1.33, respectively). In contrast, dyslipidemia was associated with improved survival (aHR,0.77; 95% Cl,0.75-0.80) and reduced recurrence (aHR, 0.71; 95%CI,0.66-0.75). These effects were consistent across gender and more pronounced in early-stage patients.CONCLUSION:MetS has no apparent effect on colon cancer outcomes, likely due to the combined adverse effects of elevated glucose/DM and hypertension and protective effect of dyslipidemia in patients with nonmetastatic disease. Early-stage, colon cancer patients with elevated glucose/DM and/or hypertension may benefit from more intensive surveillance and/or broader use of adjuvant therapy; clinical trials of low fat diets, insulin-lowering agents, and statins to reduce recurrence/improve survival in nonmetastatic colon cancer are warranted.PART II:Adjuvant Chemotherapy for Stage II Colon CancerBACKGROUND:Despite data suggesting that failure to meet a benchmark of 12-13 lymph nodes in resection specimens is associated with worse prognosis in patients with stage Ⅱ colon cancer, and may be an indication for adjuvant therapy, its use in this setting remains controversial. The objective of this study was to determine the benefit of chemotherapy in patients with stage II colon cancer according to the number of lymph nodes examined.METHODS:Using the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database, we identified 9,651 patients aged 66 and older with resected stage Ⅱ colon cancer diagnosed between 1999-2004. Use of chemotherapy within 3 months of surgery was ascertained from Medicare claims. The relationships between patient/tumor characteristics (including number of lymph nodes examined) and use of adjuvant chemotherapy were analyzed using chi square tests and logistic regression. Survival for treated and untreated patients was compared using multivariate Cox proportional hazard models.RESULTS:The majority (54.8%) of patients had only 1-12 nodes examined, while only 41.6% of had>12 nodes examined. Overall,20.9% of patients received adjuvant chemotherapy; there was no association between number of lymph nodes examined and chemotherapy use (P=0.984). Presence of 12 or less nodes in the surgical specimen was associated with worse overall survival (adjusted hazard ration [aHR]: 1.31; 95% confidence internal [CI]:1.21-1.41). Although adjuvant chemotherapy was associated with improved outcomes in our cohort, its beneficial effect on overall survival (aHR:0.73; 95% CI:0.64-0.83) and disease-free survival (aHR:0.71; 95% CI:0.60-0.85) was limited solely to patients with 0-12 nodes examined.CONCLUSION:Retrieval of 12 or fewer nodes in surgical specimens is associated with worse prognosis and survival benefit with use of adjuvant chemotherapy in patients with stage Ⅱ colon cancer. A greater emphasis on achieving recommended benchmarks for lymph node dissection is needed to help identify patients who may truly benefit from adjuvant chemotherapy after colectomy.PART Ⅲ-1:Racial/Ethnic Differences in Use of Surgery and Adjuvant Chemotherapy for Nonmetastatic Colon CancerBACKGROUND:Disparities in receipt of recommended medical therapy for colon cancer have been reported. The objective of this study was to determine the independent effect of black race and Hispanic ethnicity on use of surgery/adjuvant therapy in patients with nonmetastatic colon cancer, controlling for surgical/medical oncology consultation.METHODS:Using the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database, we identified 26,946 patients aged 66 and older with resected stage Ⅰ-Ⅲ colon cancer diagnosed between 1999-2004. Surgical/medical oncology consultation and receipt of chemotherapy were ascertained from Medicare claims. The relationships between patient/tumor characteristics, surgical/medical oncology consultation, and use of surgery/adjuvant therapy were analyzed using chi square tests. Odds ratios (OR) of receipt of surgery/chemotherapy were calculated using logistic regression analysis.RESULTS:We identified 23,834 white,2,022 black, and 1,090 Hispanic patients with stage I (7,965 pts), stage Ⅱ (10,735 pts), and stage Ⅲ (8,246 pts) colon cancer. Blacks and Hispanics were more likely to be younger, less educated, of lower income, and have greater comorbidity compared to whites. Rates of surgical resection were lower among blacks than Hispanics (86.6% versus 88.8% versus 92.0% in whites, all P＜0.001). Blacks with stage III colon cancer (but not Hispanics) were also less likely to receive adjuvant chemotherapy (48.2% versus 54.7% in whites,.P＜0.001). After controlling for socioeconomic status, comorbidity, and surgical/medical oncology consultation, black race (but not Hispanic ethnicity) was independently associated with underuse of surgery (adjusted OR [aOR],0.517; 95% confidence interval [CI], 0.432-0.620) and adjuvant chemotherapy (aOR,0.668; 95% CI,0.570-0.770).CONCLUSION:Black race, but not Hispanic ethnicity, is a powerful, independent predictor of underuse of surgery and adjuvant chemotherapy in patients with nonmetastatic colon cancer. Qualitative studies are needed to determine whether patient misperceptions about colon cancer surgery/chemotherapy or suboptimal physician-patient interactions may underlie these observations.PART Ⅲ-2:Racial/Ethnic Differences in Use of Surgery for Nonmetastatic Rectal CancerBACKGROUND:Stage-specific, racial disparities in rectal cancer survival persist; underuse of surgical resection among black patients have been reported. The objective of this study was to determine the independent effect of black race/Hispanic ethnicity on surgical consultation/subsequent surgical resection/overall survival in patients with nonmetastatic rectal cancer.METHODS:Using the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database, we identified 8,251 patients aged 66 and older with resected stage Ⅰ-Ⅲ rectal cancer diagnosed between 1999-2004. Surgical consultation/receipt of (neo)adjuvant therapy was ascertained from Medicare claims. Relationships between patient/tumor characteristics, surgical consultation, and use of surgery were analyzed using chi square tests. Odds ratios (OR) of receipt of surgery were calculated using logistic regression analysis; the effects of race/ethnicity/surgical consultation/surgery on survival were analyzed using multivariate Cox models.RESULTS:We identified 7,400 white,442 black, and 409 Hispanic patients. After controlling for other patient/socioeconomic/tumor factors, black race (but not Hispanic ethnicity) was independently associated with underuse of surgery (72.9% versus 80.0%, P＜0.001). Although black race was associated with lower rates of surgical consultation (91.4% versus 94.9%, P＜0.001), resection rates were similar in patients who received surgical consultation (79.7% versus 81.1%, P=0.020). Of note, receipt of surgery completely eradicated black-white differences in survival.CONCLUSION:Racial disparities in rectal cancer survival are largely explained by underuse of surgery. Efforts by the gastroenterology/surgical community are needed to optimize access to qualified surgeons. In the interim, patient navigation programs may overcome barriers to care and ensure that patients undergo prompt surgical consultation and subsequent resection.PART IV:Effect of Metabolic Syndrome and Its Components on Recurrence and Survival in Patients with Early Stage, non-Small Cell Lung CancerBACKGROUND:Epidemiologic studies suggest that metabolic syndrome (MetS) or its components may independently increase the risk of lung cancer, yet its effect on cancer mortality remains controversial. The objective of this study is to analyze the effect of MetS and its various components on cancer mortality in large, national cohort of patients with early stage non-small cell lung cancer (NSCLC), controlling for patient/tumor characteristics and treatment.METHODS:Using the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database, we identified 11,190 patients aged 66 and older with stage Ⅰ-Ⅱ NSCLC diagnosed between 1999-2004. Patients/tumor characteristics were obtained from the SEER dataset, data on MetS and its components and cancer treatment was ascertained from Medicare claims. Relationships between the various patients/tumor characteristics and MetS and its components status were analyzed using chi square test and t test. Kaplan-Meier survival curves for overall survival (OS) and disease-free survival (DFS) stratified by MetS and its components status were generated. Survival in patients with/without MetS and its components was compared using multivariate Cox proportional hazard models.RESULTS:A significant proportion of patients had MetS (19.0%), elevated glucose/ diabetes mellitus (DM) (26.6%), hypertension (74.0%) and dyslipidemia (55.7%). Patients with MetS were more likely to be younger, non-white, less educated, and have greater comorbidity (all P＜0.001). There was no association between tumor stage, histology, or grade and MetS. MetS had no apparent effect on survival. When the effect of its individual components was analyzed, however, elevated glucose/DM and hypertension were found to be independently associated with worse outcomes (adjusted hazard ratios [aHR],1.18; 95% confidence internal [CI],1.11-1.25 and aHR, 1.15; 95% CI:1.09-1.22, respectively) after adjusting for all other patient/tumor/treatment factors. In contrast, dyslipidemia was associated with significantly improved survival on both univariate (5-year survival:41%versus 29%, P0.001) and multivariate analyses (aHR,0.82; 95% CI,0.78-0.86).CONCLUSION:Elevated glucose/DM and hypertension have independent adverse effects on survival in patients with early stage NSCLC, whereas dyslipidemia appears to have a protective effect. Trials are needed to determine if use of metformin (in diabetic patients) and/or statins in the adjuvant setting improves long term outcomes in this patient population. |
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