Among Medicare enrollees with metastatic colorectal cancer, the use of newer chemotherapy agents was lower for African American patients and for older patients.
Objectives: To test the hypotheses that African American patients and older patients with stage IV colorectal cancer were less likely to receive newer chemotherapy agents.
Study Design: Retrospective cohort design.
Methods: Among 5068 Surveillance, Epidemiology, and End Results—Medicare patients diagnosed as having stage IV colorectal cancer between 2000 and 2002, a total of 2466 received chemotherapy and were included in the analysis. Irinotecan hydrochloride was the first of the “newer” chemotherapy agents and was marketed in 2000 as a first-line add-on agent. Descriptive statistics were generated, and a multivariable logistic regression was run to estimate the odds of receiving irinotecan among African American patients and older patients and within 2 months of chemotherapy initiation.
Results: African American patients had lower odds of initiating treatment with a newer chemotherapy than white patients (adjusted odds ratio, 0.641; 95% confidence interval, 0.453-0.907). An age disparity was also found, with all older age groups being significantly less likely to initiate treatment with a newer chemotherapy than the youngest age group: the adjusted odds of receiving newer chemotherapy agents (relative to patients aged 66-70 years) were lower and significant among patients aged 71 to 75, 76 to 80, and older than 80 years (odds ratios, 0.708, 0.527, and 0.213, respectively).
Conclusions: Disparities in chemotherapy selection exist among patients receiving chemotherapy for stage IV colorectal cancer. On initiating chemotherapy, African American patients and older patients were less likely to receive a newer agent.
(Am J Manag Care. 2010;16(7):515-522)
In a population-based study of older Medicare patients with stage IV colorectal cancer, racial/ethnic and age disparities were detected in the receipt of newer chemotherapy agents (using irinotecan hydrochloride as an example of a newer therapy) for first-line management of the disease. The following specific findings were observed:
Studies1-8 have evaluated racial/ethnic and age disparities in whether patients receive chemotherapy for nonmetastatic colo-rectal cancer (CRC) treatment and have found that patients of nonwhite race/ethnicity and older patients are less likely to receive chemotherapy. However, these studies did not evaluate specific types of chemotherapy agents used.
Management of metastatic (stage IV) CRC historically has involved 5-fluorouracil—leucovorin as the standard chemotherapy,9-11 but the introduction of various novel add-on chemotherapies with improved efficacy has led to an increase in the chemotherapeutic options available to manage stage IV CRC.12,13 Irinotecan hydrochloride, approved in 1998 as a second-line agent for metastatic CRC treatment and approved in 2000 as a first-line agent for use with 5-fluorouracil—leucovorin,14 was the first of these novel agents to show improved efficacy relative to 5-fluorouracil—leucovorin alone.15,16 Irinotecan inhibits the enzyme necessary for the reversible breakage and relegation of DNA strands during DNA synthesis, leading to significant improvement in tumor progression slowing and median survival time (approximately 3 additional months relative to the 5-fluorouracil—leucovorin regimen).14 Its availability, as well as the subsequent availability of other novel agents such as oxaliplatin, bevacizumab, and cetuximab, has raised expectations for more efficacious regimens than 5-fluorouracil—leucovorin alone.17-20 Nevertheless, these novel agents also place patients at higher risk of experiencing adverse effects as a result of their increased toxic effects.15,16,17-20
Knowledge is scarce about racial/ethnic and age disparities in the receipt of newer chemotherapies. Addressing this gap by examining the first of the newer agents marketed for treatment of advanced CRC disease can provide an understanding of healthcare disparities among specific services for CRC management. In addition to knowing whether patients are receiving chemotherapy in real-world settings, it is important to know whether newer chemotherapies are being selectively utilized among chemotherapy users, particularly elderly patients in whom incidence of the disease is high.21
This study sought to determine whether racial/ethnic and age disparities existed in the selection of specific types of chemotherapy among elderly patients with stage IV CRC. Given that irinotecan was the first novel agent to be available at the start of the study period, newer therapy was designated as irinotecan-containing chemotherapy. It was hypothesized that patients of African American race/ethnicity and older patients with stage IV CRC would have a lower likelihood of receipt of newer chemotherapy than white patients and younger patients.
The linked Surveillance, Epidemiology, and End Results (SEER)-Medicare database was used for this study.22 SEER data provided clinical and demographic information about patients with cancer from SEER registries across the following 16 geographic areas: Connecticut, Detroit (Michigan), Hawaii, Iowa, New Mexico, Seattle (Washington), Utah, Atlanta (Georgia), rural Georgia, Kentucky, Louisiana, New Jersey, greater California, and Los Angeles, San Jose, and San Francisco (California). Health utilization information for these patients was obtained from their Medicare Part A and Part B claims, which include hospital services, physician and other noninstitutional provider services, and outpatient institutional providers.22
A total of 112,345 patients with at least 1 diagnosis of nonappendiceal colon or rectal cancer occurring between 1998 and 2002 were initially identified from SEER. Patients diagnosed at death were excluded (n = 1104 patients), as were patients diagnosed as having nonadenocarcinomas or a stage of disease that did not require any chemotherapy treatment (n = 39,755). Patients younger than 66 years also were excluded to allow a complete year of data during the year before CRC diagnosis to identify prediagnosis comorbidities (n = 10,600).
Patients who were ineligible for Medicare fee for service were excluded, as were those with no utilization information because of death or loss of Medicare eligibility occurring during the same month of diagnosis (n = 22,140). To ensure that chemotherapy use was specifically for stage IV CRC, patients with a history of cancer dating 5 years or earlier before the current CRC diagnosis or patients with a concurrent cancer occurring in the same year as the CRC diagnosis were excluded (n = 3883). The final sample was further refined to those eligible to receive first-line irinotecan-containing chemotherapy (ie, patients with stage IV disease diagnosed after 1999 [n = 5068]).
The main variable of interest was the receipt of newer chemotherapy (irinotecan vs all other chemotherapy) within 2 months of chemotherapy initiation. Chemotherapy administration was identified through specific chemotherapy-related medical codes in physician, outpatient facility, and durable medical equipment Medicare claims. Various resources and published studies3,7,23-26 that have measured chemotherapy through Medicare claims were used to identify the relevant codes that represented chemotherapy use. These codes are listed in .
Patients with any chemotherapy-related Medicare claim were identified as chemotherapy users, and the earliest chemotherapy-related claim on or after the first day of the diagnosis month was used to identify the chemotherapy start date. A 2-month window beginning on the chemotherapy start date was searched for any claims indicating irinotecan use (Healthcare Common Procedure Coding System code J9206). If no irinotecan claims were identified, the chemotherapy user was identified as having received “other” chemotherapy.
Explanatory and Control Variables
Clinical Variables. SEER-Medicare data were used to identify several clinical variables. Year of diagnosis was obtained from the SEER file. Other SEER clinical variables included a history of cancer that occurred at least 5 years before the cancer diagnosis under study. Furthermore, although all patients had stage IV disease, variability in tumor characteristics such as tumor site and lymph node involvement was observed, and these variables were included in the descriptive analysis.
The Charlson Comorbidity Index (CCI), a measure of disease burden, was used as a proxy for health status (prediagnosis). The index has been validated as a reliable tool for the prediction of morbidity in patients with cancer.27-30 Calculation of the index involved using physician and hospital claims in the year preceding cancer diagnosis to search medical codes that reflected the following: myocardial infarction, congestive heart failure, peripheral vascular disease, chronic obstructive pulmonary disease, dementia, paralysis, diabetes, chronic renal failure, liver disease, ulcers, rheumatoid arthritis, and AIDS.31 Because few patients had CCI scores exceeding 2, the final CCI obtained was used to categorize patients into the following 3 groups: 0 CCI, 1 CCI, or more than 1 CCI.
Other cancer-related procedures occurring within the first 4 months of diagnosis were measured. Codes reflecting surgery to the colorectal region, surgery to metastatic sites (eg, liver, lung), and radiation therapy were identified from published resources (Table 1).8,26,32-36
Demographic Variables. In addition to age at diagnosis and race/ethnicity, sex and marital status were obtained from the SEER-Medicare enrollment files. The following 4 age groups were created: 66 to 70, 71 to 75, 76 to 80, or older than 80 years. Race/ethnicity was categorized as white, African American, or other. A variable indicating whether the patient was married at the time of diagnosis was also available. Finally, SEER registry geographic information was available as a demographic variable.
Aggregate Socioeconomic Variables. Individual-level socioeconomic variables were unavailable. However, SEER data contained a group of aggregate zip code—level and census tract–level household income variables that were used to create a proxy variable for socioeconomic status.37 A compound median household income proxy variable for socioeconomic status was generated using an algorithm previously applied to SEER-Medicare data.38,39 In order of priority, the algorithm used information from the census tract median household income by race/ethnicity, by age, and by income, as well as the zip code median income.38,39 Patients were then ranked into quintiles based on the final composite median income value.
Patient residence in a metropolitan (vs rural) area was also measured. This tested whether proximity to an urban area might influence the receipt of newer agents if adoption occurs earlier in urban environments.
All analyses were conducted using commercially available software (SAS/STAT software version 9.1; SAS Institute Inc, Cary, NC). Bivariate descriptive statistics and likelihood ratio X2tests of significance were generated to compare patients initiating newer chemotherapy versus patients initiating any other chemotherapy with respect to demographic, socioeconomic, and clinical variables. Variables significantly associated with initiation of newer chemotherapy at the bivariate level (P <.05) were included in a multivariable logistic regression model to test the association between race/ethnicity or age and the odds of initiating on newer chemotherapy, while controlling for clinical and demographic factors.
The final sample among 5068 patients with stage IV CRC receiving chemotherapy was 2466 patients. Approximately 32% of the chemotherapy users initiated their therapy using an irinotecan-containing regimen. Based on healthcare claims,the patient group using non—irinotecan-containing chemotherapy primarily received (in approximately 93% of patients) 5-fluorouracil as the cytotoxic agent.
Results of the bivariate analysis comparing patients who initiated treatment with newer chemotherapy versus those who initiated treatment with other chemotherapy are given in . Race/ethnicity, sex, age, year of diagnosis, median household income, presence of comorbidities, marital status, surgery to the metastatic site, and radiation therapy were significantly associated with the receipt of newer chemotherapy agents (P <.05). Specifically, among patients initiating treatment with newer chemotherapy, there were higher proportions of white, male, and younger patients, as well as patients diagnosed in later years (2001 and 2002), patients in higher quintiles of median household income, patients with fewer comorbidities, and married patients, compared with patients not receiving irinotecan. With respect to clinical characteristics significantly associated with the receipt of newer chemotherapy agents, fewer patients who received radiation therapy or surgery to the metastatic site (within 4 months of diagnosis) received newer chemotherapeutic agents.
Results of the final model developed for the multivariable logistic regression analysis are given in . After simultaneously controlling for demographic and clinical variables significant at the bivariate level, African American race/ethnicity and older age remained significantly (P<.05) negatively associated with the receipt of newer chemotherapy agents in the logistic regression analysis. Specifically, African American patients were 35.9% less likely to initially receive newer chemotherapy than white patients (odds ratio, 0.641; 95% confidence interval, 0.453-0.907). Patients aged 71 to 75, 76 to 80, and older than 80 years were 29.2%, 47.3%, and 78.7%, respectively, less likely to initiate treatment with newer chemotherapy than patients aged 66 to 70 years (P<.05). Male patients remained significantly more likely to receive newer chemotherapy.
This study reveals important findings with regard to the receipt of general chemotherapy and specific chemotherapeutic agent use among a Medicare sample of older patients with stage IV CRC. Approximately 49% of the final patient sample received any chemotherapy. This estimate is not directly comparable to other SEER-Medicare data because of differences in staging, disease site (colon vs rectal), and period of study, but evidence nevertheless indicates that a substantial proportion of Medicare patients with CRC do not receive chemotherapy: studies23,40 of SEER-Medicare older patients with stage III CRC (among whom chemotherapy benefits are widely acknowledged) indicate that the receipt of chemotherapy ranges from only 54% to 70%.
Our study results also indicate that, among chemotherapy-receiving patients with stage IV CRC, African American patients and older patients were significantly less likely to initiate their chemotherapy with a newer agent such as irinotecan compared with white patients and younger patients. The direction of results is generally consistent with published studies1-3,5-8,23,25,40-43 that have evaluated racial/ethnic and age disparities among patients receiving treatment for locally advanced CRC.
Disparities in the receipt of chemotherapy among patients with stage IV CRC have not been as widely researched as disparities among patients with earlier stages of CRC. However, McKibbin et al44 evaluated the receipt of irinotecan, oxaliplatin, or bevacizumab in patients with advanced CRC from 10 cancer centers and detected a significant association between younger age (<65 years) and increased receipt of newer chemotherapeutic agents. Furthermore, compared with patients younger than 65 years, the receipt of newer agents decreased among older patients (ie, >70 and >75 years).44 In addition, the direction of racial/ethnic and age disparities observed in the present studywas consistent with that in other observational studies32,33 addressing surgical management of patients with stage IV CRC.
The existence of racial/ethnic and age differences in the receipt of newer chemotherapeutic agents among patients receiving chemotherapy indicates a persisting disparity even after selection into chemotherapy treatment. Because irinotecan was likely perceived during the study period to be a new agent with improved benefits (but with a more toxic profile), disparities in its use during that time warrant consideration. Arguably, the observed disparities may have been due to justifiable clinical or patient preference—related reasons. Conversely, these disparities may have been the result of access issues (eg, African American patients or older patients may be less able to afford a newer medication such as irinotecan) or other unmeasured factors.
With regard to the racial/ethnic disparity observed, identifying factors driving the observed difference is challenging. There is evidence to suggest that African
American patients are more likely to receive care from less trained primary care physicians who have fewer resources to offer patients.45 It is unknown if this finding extends to medical oncologists providing cancer care. Baldwin et al40 evaluated various patient, physician, hospital, and environmental characteristics in an attempt to identify why African American patients with stage III colon cancer were less likely to receive chemotherapy than white patients and found “no single or simple explanation.” Although African American patients and white patients were equally likely to see a medical oncologist, the authors noted that African American patients who saw a medical oncologist were less likely to receive chemotherapy. In their analyses, although oncologist characteristics such as years in practice and volume of consultations influenced the receipt of chemotherapy, disparities persisted even after accounting for these characteristics (as well as patient characteristics such as age, sex, and comorbidities).40 Almost half of the variation in the observed receipt of chemotherapy could not be accounted for. The authors suggest that other unmeasured factors such as supplemental insurance and affordability of care, as well as patient perceptions, may have a role in selection of patients into chemotherapy.40 Similar conclusions have been drawn in other analyses of the receipt of chemotherapy among patients with rectal cancer.46 It is unclear whether similar observations can be made with regard to disparities in specific types of chemotherapy selected among users, particularly patients with stage IV CRC.
The age disparity observed may be the result of a misconception that older patients are too frail to receive chemotherapy and should not be placed on a newer and more toxic regimen.47 Evidence suggests that chemotherapy treatment recommendations in older patients can be influenced by physician characteristics such as age (with younger physicians being more likely to recommend chemotherapy) and whether he or she practiced in a teaching hospital.48 Furthermore, older patients may have difficulty than their younger counterparts in accessing more intensive healthcare services. The age disparity warrants further study, particularly in older patients who are healthy enough to tolerate aggressive therapy, among whom data demonstrate derivation of clinical benefits similar to those of younger patients.49 Like racial/ethnic disparities, age disparities are likely multifaceted and driven by patient, physician, and health system characteristics.
Male patients were more likely to initiate treatment with newer chemotherapy than female patients. Evidence indicates that women experience more adverse effects with chemotherapy than men, a factor that may have lessened the use of the more toxic therapy in women.50 Our analysis also indicates that the receipt of newer chemotherapy was less likely to occur if the patient underwent surgery. This relationship was observed in unadjusted and adjusted analyses.
This study has some limitations. Although the analysis involved a large cohort of SEER-Medicare patients, the exclusion criteria resulted in a considerable loss of patients, particularly patients enrolled in health maintenance organizations. Therefore, the patients in this study may not be representative of all patients with stage IV CRC. Nevertheless, given that CRC is primarily a disease of older patients,21 the information obtained with regard to drug use in the selected group of Medicare patients with stage IV disease is important to learn more about how management of the disease in this group of Medicare enrollees is evolving.
In addition, as a result of relying on limited clinical information from SEER-Medicare data, certain variables were unavailable that may have contributed to variation in the receipt of newer chemotherapy. These include patient preferences, performance status, patient-level socioeconomic measures, and physician and hospital characteristics. Therefore, bias may exist as a result of unmeasured variables. It is difficult to state with certainty that the type of chemotherapy selected is the result of a real disparity or rather is the effect of an unobserved factor systematically distributed between racial/ethnic or age groups. Nevertheless, unobservable bias may be less pronounced between subgroups among patients who have been selected into chemotherapy. In other words, given selection into chemotherapy treatment, subgroups within chemotherapy-receiving patients are likely to be more homogeneous than broader groups of treated and untreated patients with CRC, among whom the receipt of any chemotherapy has been previously evaluated.1-8
Despite these limitations, this study is important in providing information about a topic (disparities in the use of novel chemotherapies) and a stage of disease (stage IV CRC) that have not been widely researched through population-based studies. Furthermore, although the study focus is on the receipt of irinotecan, information with regard to racial/ethnic and age disparities in irinotecan use is likely to be relevant to the use of newer agents with similar profiles (improved clinical efficacy but higher toxic effects, as well as costs) marketed after irinotecan.
In conclusion, our results support the existence of racial/ethnic and age disparities in the use of irinotecan, an agent representative of a newer trend in chemotherapy treatment for patients with stage IV CRC. The results are consistent with the literature, namely, lower health services utilization in patients of African American race/ethnicity and in older patients. This utilization trend, coupled with the association of minority races/ethnicities with lower survival outcomes,51,52 provides further rationale for continuing to investigate the cause and extent of disparities in cancer-related health services across all stages of CRC. Additional population-based research on disparities in the use of newer agents marketed after irinotecan (eg, oxaliplatin, bevacizumab) is recommended, particularly as advances in chemotherapy regimens are taking place that lead to the questions not only of “should chemotherapy be administered” but also of “what chemotherapy should be used given the decision to treat.” Medicare Demonstration Projects & Evaluation Reports provide an excellent example of how such investigations may be studied, as do large prospective observational studies such as the Cancer Care Outcomes Research & Surveillance Consortium.53,54
We acknowledge the Pharmaceutical Research Computing Center within the Department of Pharmaceutical Health Services Research, University of Maryland, for assistance with data management and consultation.
Author Affiliations: From the Department of Pharmaceutical Health Services Research (NAO, FGP, IHZ, FBP, CDM), the Department of Pharmacy Practice (JAT), and the Department of Pulmonary and Critical Care Medicine (SD), University of Maryland, Baltimore, MD; and the Veterans Affairs Medical Center (SD), Baltimore, MD. Dr Obeidat is now with the King Hussein Institute for Biotechnology and Cancer, Amman, Jordan.
Funding Source: This study was funded in part by sanofi-aventis.
Author Disclosure: Dr Obeidat reports receiving salary support for her doctoral and postdoctoral training from sanofi-aventis. Dr Zuckerman reports receiving grant support as a coinvestigator from sanofi-aventis. Dr Mullins reports receiving consulting income or honoraria from Amylin Pharmaceuticals, AHIMA Foundation, Bayer Pharmaceuticals, Bristol-Myers Squibb, Genentech, GlaxoSmithKline, Lilly, Merck, Novartis, Pfizer, and sanofi-aventis. Dr Mullins also reports receiving grant support from Pfizer and sanofi-aventis. The other authors (FGP, JAT, FBP, SD) report no relationship or financial interest with any entity that would pose a conflict of interest with the subject matter of this article.
Authorship Information: Concept and design (NAO, FGP, IHZ, JAT, FBP, SD, CDM); acquisition of data (CDM); analysis and interpretation of data (NAO, FGP, IHZ, CDM); drafting of the manuscript (NAO, FGP, CDM); critical revision of the manuscript for important intellectual content (NAO, FGP, IHZ, JAT, FBP, SD, CDM); statistical analysis (NAO); obtaining funding (CDM); administrative, technical, or logistic support (NAO); and supervision (FGP, IHZ, JAT, FBP, SD, CDM).
Address correspondence to: Nour A. Obeidat, PhD, King Hussein Institute for Biotechnology and Cancer, Amman, 11814, Jordan. E-mail: email@example.com.
1. Morris AM, Billingsley KG, Baxter NN, Baldwin LM. Racial disparities in rectal cancer treatment: a population-based analysis. Arch Surg. 2004;139(2):151-156.
2. Potosky AL, Harlan LC, Kaplan RS, Johnson KA, Lynch CF. Age, sex, and racial differences in the use of standard adjuvant therapy for colorectal cancer. J Clin Oncol. 2002;20(5):1192-1202.
3. Ayanian JZ, Zaslavsky AM, Fuchs CS, et al. Use of adjuvant chemotherapy and radiation therapy for colorectal cancer in a population-based cohort. J Clin Oncol. 2003;21(7):1293-1300.
4. Jessup JM, Stewart A, Greene FL, Minsky BD. Adjuvant chemotherapy for stage III colon cancer: implications of race/ethnicity, age, and differentiation. JAMA. 2005;294(21):2703-2711.
5. Neugut AI, Fleischauer AT, Sundararajan V, et al. Use of adjuvant chemotherapy and radiation therapy for rectal cancer among the elderly: a popula-tion-based study. J Clin Oncol. 2002;20(11):2643-2650.
6. Schrag D, Cramer LD, Bach PB, Begg CB. Age and adjuvant chemotherapy use after surgery for stage III colon cancer. J Natl Cancer Inst. 2001;93(11):850-857.
7. Dobie SA, Baldwin LM, Dominitz JA, Matthews B, Billingsley K, Barlow W. Completion of therapy by Medicare patients with stage III colon cancer. J Natl Cancer Inst. 2006;98(9):610-619.
8. Gross CP, Smith BD, Wolf E, Andersen M. Racial disparities in cancer therapy: did the gap narrow between 1992 and 2002? Cancer. 2008;112(4):900-908.
9. Ragnhammar P, Hafström L, Nygren P, Glimelius B; SBU-Group, Swedish Council of Technology Assessment in Health Care. A systematic overview of chemotherapy effects in colorectal cancer. Acta Oncol. 2001;40(2-3):282-308.
10. Kindler HL, Shulman KL. Metastatic colorectal cancer. Curr Treat Options Oncol. 2001;2(6):459-471.
11. International Multicentre Pooled Analysis of Colon Cancer Trials (IMPACT) Investigators. Efficacy of adjuvant fluorouracil and folinic acid in colon cancer. Lancet. 1995;345(8955):939-944.
12. National Comprehensive Cancer Network Web site. NCCN Clinical Practice Guidelines in Oncology: colon cancer. Version 2. 2006. http://www.nccn.org/professionals/physician_gls/PDF/colon.pdf. Accessed December 24, 2005.
13. Board RE, Valle JW. Metastatic colorectal cancer: current systemic treatment options. Drugs. 2007;67(13):1851-1867.
14. Drugs @ FDA: FDA Approved Drug Products Web site. Irinotecan approval history. http://www.accessdata.fda.gov/scripts/cder/drug satfda/index.cfm?fuseaction=Search.Label_ApprovalHistory#apphist. Accessed December 23, 2005.
15. Saltz LB, Cox JV, Blanke C, et al; Irinotecan Study Group. Irino-tecan plus fluorouracil and leucovorin for metastatic colorectal cancer. N Engl J Med. 2000;343(13):905-914.
16. Douillard JY, Cunningham D, Roth AD, et al. Irinotecan combined with fluorouracil compared with fluorouracil alone as first-line treatment for metas-tatic colorectal cancer: a multicentre randomised trial. Lancet. 2000;355(9209):1041-1047.
17. Goldberg RM, Sargent DJ, Morton RF, et al. A randomized controlled trial of fluorouracil plus leucovorin, irinotecan, and oxaliplatin combinations in patients with previously untreated metastatic colorectal cancer. J Clin Oncol. 2004;22(1):23-30.
18. de Gramont A, Figer A, Seymour M, et al. Leucovorin and fluoro-uracil with or without oxaliplatin as first-line treatment in advanced colorectal cancer. J Clin Oncol. 2000;18(16):2938-2947.
19. Hurwitz H, Fehrenbacher L, Novotny W, et al. Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med. 2004;350(23):2335-2342.
20. Cunningham D, Humblet Y, Siena S, et al. Cetuximab monotherapy and cetuximab plus irinotecan in irinotecan-refractory metastatic colorectal can-cer. N Engl J Med. 2004;351(4):337-345.
21. American Cancer Society Web site. Colorectal cancer facts & figures: special edition 2005. http://www.cancer.org/downloads/STT/CAFF2005CR4PWSecured.pdf. Accessed February 27, 2006.
22. Warren JL, Klabunde CN, Schrag D, Bach PB, Riley GF. Overview of the SEER-Medicare data: content, research applications, and generalizability to the United States elderly population. Med Care. 2002;40(8)(suppl):IV-3-IV-18.
23. Dobie SA, Warren JL, Matthews B, Schwartz D, Baldwin LM, Billingsley K. Survival benefits and trends in use of adjuvant therapy among elderly stage II and III rectal cancer patients in the general population. Cancer. 2008;112(4):789-799.
24. Warren JL, Harlan LC, Fahey A, et al. Utility of the SEER-Medicare data to identify chemotherapy use. Med Care. 2002;40(8)(suppl):IV-55-IV-61.
25. Schrag D, Gelfand SE, Bach PB, Guillem J, Minsky BD, Begg CB. Who gets adjuvant treatment for stage II and III rectal cancer? insight from Surveillance, Epidemiology, and End Results: Medicare. J Clin Oncol. 2001;19(17):3712-3718.
26. Cooper GS, Yuan Z, Stange KC, Dennis LK, Amini SB, Rimm AA. Agreement of Medicare claims and tumor registry data for assessment of cancer-related treatment. Med Care. 2000;38(4):411-421.
27. Klabunde CN, Legler JM, Warren JL, Baldwin LM, Schrag D. A refined comorbidity measurement algorithm for claims-based studies of breast, pros-tate, colorectal, and lung cancer patients. Ann Epidemiol. 2007;17(8):584-590.
28. Romano PS, Roos LL, Jollis JG. Adapting a clinical comorbidity index for use with ICD-9-CM administrative data: differing perspectives. J Clin Epide-miol. 1993;46(10):1075-1079, 1081-1090.
29. Baldwin LM, Klabunde CN, Green P, Barlow W, Wright G. In search of the perfect comorbidity measure for use with administrative claims data: does it exist? Med Care. 2006;44(8):745-753.
30. Charlson ME, Pompei P, Ales KL, MacKenzie CR. A new method of classifying prognostic comorbidity in longitudinal studies: development and vali-dation. J Chronic Dis. 1987;40(5):373-383.
31. National Cancer Institute Web site. SEER-Medicare: calculation of comorbidity weights. http://healthservices.cancer.gov/seermedicare/program/comorbidity.html. Accessed March 7, 2008.
32. Temple LK, Hsieh L, Wong WD, Saltz L, Schrag D. Use of surgery among elderly patients with stage IV colorectal cancer. J Clin Oncol. 2004;22(17):3475-3484.
33. Cook AD, Single R, McCahill LE. Surgical resection of primary tumors in patients who present with stage IV colorectal cancer: an analysis of Surveil-lance, Epidemiology, and End Results data, 1988 to 2000. Ann Surg Oncol. 2005;12(8):637-645.
34. Cummings LC, Payes JD, Cooper GS. Survival after hepatic resection in metastatic colorectal cancer: a population-based study. Cancer. 2007;109(4):718-726.
35. National Cancer Institute Web site. SEER-Medicare: identification of diagnosis & procedure codes. http://healthservices.cancer.gov/ seermedicare/considerations/identification.html. Accessed July 15, 2007.
36. Cooper GS, Virnig B, Klabunde CN, Schussler N, Freeman J, Warren JL. Use of SEER-Medicare data for measuring cancer surgery. Med Care. 2002;40(8)(suppl):IV-43-IV-48.
37. Bach PB, Guadagnoli E, Schrag D, Schussler N, Warren JL. Patient demographic and socioeconomic characteristics in the SEER-Medicare data-base applications and limitations. Med Care. 2002;40(8)(suppl): IV-19-IV-25.
38. Hershman D, Hall MJ, Wang X, et al. Timing of adjuvant chemotherapy initiation after surgery for stage III colon cancer. Cancer. 2006;107(11):2581-2588.
39. Punglia RS, Weeks JC, Neville BA, Earle CC. Radiation therapy after mastectomy between 1991 and 1999 in elderly women: response to clinical trial information. J Clin Oncol. 2006;24(21):3474-3482.
40. Baldwin LM, Dobie SA, Billingsley K, et al. Explaining black-white differences in receipt of recommended colon cancer treatment. J Natl Cancer Inst. 2005;97(16):1211-1220.
41. Cronin DP, Harlan LC, Potosky AL, Clegg LX, Stevens JL, Mooney MM. Patterns of care for adjuvant therapy in a random population-based sample of patients diagnosed with colorectal cancer. Am J Gastroenterol. 2006;101(10):2308-2318.
42. Neugut AI, Matasar M, Wang X, et al. Duration of adjuvant chemotherapy for colon cancer and survival among the elderly. J Clin Oncol. 2006;24(15):2368-2375.
43. Shavers VL, Brown ML. Racial and ethnic disparities in the receipt of cancer treatment. J Natl Cancer Inst. 2002;94(5):334-357.
44. McKibbin T, Frei CR, Greene RE, Kwan P, Simon J, Koeller JM. Disparities in the use of chemotherapy and monoclonal antibody therapy for elderly advanced colorectal cancer patients in the community oncology setting. Oncologist. 2008;13(8):876-885.
45. Bach PB, Pham HH, Schrag D, Tate RC, Hargraves JL. Primary care physicians who treat blacks and whites. N Engl J Med. 2004;351(6): 575-584.
46. Morris AM, Billingsley KG, Hayanga AJ, Matthews B, Baldwin LM, Birkmeyer JD. Residual treatment disparities after oncology referral for rectal cancer. J Natl Cancer Inst. 2008;100(10):738-744.
47. Lichtman SM. Management of advanced colorectal cancer in older patients. Oncology (Williston Park). 2005;19(5):597-602.
48. Keating NL, Landrum MB, Klabunde CN, et al. Adjuvant chemotherapy for stage III colon cancer: do physicians agree about the importance of pa-tient age and comorbidity? J Clin Oncol. 2008;26(15): 2532-2537.
49. Folprecht G, Seymour MT, Saltz L, et al. Irinotecan/fluorouracil combination in first-line therapy of older and younger patients with metastatic colorec-tal cancer: combined analysis of 2,691 patients in randomized controlled trials. J Clin Oncol. 2008;26(9):1443-1451.
50. Tsalic M, Bar-Sela G, Beny A, Visel B, Haim N. Severe toxicity related to the 5-fluorouracil/leucovorin combination (the Mayo Clinic regimen): a pro-spective study in colorectal cancer patients. Am J Clin Oncol. 2003;26(1):103-106.
51. Polite BN, Dignam JJ, Olopade OI. Colorectal cancer model of health disparities: understanding mortality differences in minority populations. J Clin Oncol. 2006;24(14):2179-2187.
52. Du XL, Meyer TE, Franzini L. Meta-analysis of racial disparities in survival in association with socioeconomic status among men and women with colon cancer. Cancer. 2007;109(11):2161-2170.
53. Centers for Medicare & Medicaid Services Web site. Medicare Demonstration Projects & Evaluation reports. http://www.cms.hhs.gov/DemoProjectsEvalRpts/01_Overview.asp#TopOfPage. Accessed December 3, 2009.
54. National Cancer Institute Web site. Cancer Care Outcomes Research & Surveillance Consortium. http://outcomes.cancer.gov/ cancors/. Accessed December 3, 2009.