© 2001 by Oxford University Press
Journal of the National Cancer Institute, Vol. 93, No. 11, 850-857,
June 6, 2001
© 2001 Oxford University Press
Age and Adjuvant Chemotherapy Use After Surgery for Stage III Colon Cancer
Affiliations of authors: D. Schrag, P. B. Bach (Department of Medicine and Department of Epidemiology and Biostatistics), L. D. Cramer, C. B. Begg (Department of Epidemiology and Biostatistics), Memorial Sloan-Kettering Cancer Center, New York, NY.
Correspondence to: Deborah Schrag, M.D., M.P.H., Health Outcomes Research Group, Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, 1275 York Ave., New York, NY 10021 (e-mail: schragd{at}mskcc.org).
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ABSTRACT |
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Background: Randomized trials have established that 5-fluorouracil-based adjuvant chemotherapy following resection of stage III colon cancer reduces subsequent mortality by as much as 30%. However, the extent to which adjuvant therapy is used outside the clinical trial setting, particularly among the elderly, is unknown. Methods: A retrospective cohort study utilizing the Surveillance, Epidemiology, and End Results/Medicare-linked database identified 6262 patients aged 65 years and older with resected stage III colon cancer. The primary outcome was chemotherapy use within 3 months of surgery, as ascertained from Medicare claims. We examined the extent to which age at diagnosis was associated with adjuvant chemotherapy usage, and we adjusted for potential confounding based on differences in other patient characteristics with the use of multiple logistic regression. All P values were two-sided. Results: Age at diagnosis was the strongest determinant of chemotherapy: 78% of patients aged 65–69 years, 74% of those aged 70–74 years, 58% of those aged 75–79 years, 34% of those aged 80–84 years, and 11% of those aged 85–89 years received postoperative chemotherapy. The age trend remained pronounced after adjustment for potential confounding based on variation in patients' demographic and clinical characteristics and after exclusion of patients with any evident comorbidity (all P values <.001). Conclusions: Adjuvant chemotherapy for stage III colon cancer is used extensively, especially for patients under the age of 75 years. However, treatment rates decline dramatically with chronologic age. Because patients in their 70s and even 80s have a reasonable life expectancy, further efforts are needed to ensure that elderly patients have the opportunity to make informed decisions regarding this potentially curative treatment.
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INTRODUCTION |
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Randomized controlled clinical trials conducted in the 1980s evaluated postoperative 5-fluorouracil (5-FU)-based chemotherapy for patients with stage III colon cancer and established that treatment reduces the risk of cancer recurrence and mortality by as much as 30% (1,2). Moreover, these studies demonstrated that adjuvant therapy can be administered with minimal toxicity and that the vast majority of patients are able to complete treatment (3). Consequently, since the publication of a National Institutes of Health (NIH) consensus statement in 1990 (4), 5-FU-based adjuvant therapy has represented the standard of care for patients in the United States following the complete resection of colon cancer that has spread to regional lymph nodes (stage III disease).
Although cancer is predominantly a disease of the elderly, older patients have been underrepresented in clinical trials; as a result, it can be difficult to determine whether the benefits realized by trial participants pertain to older patients with similar tumors (5). While the median ages in the large randomized adjuvant therapy trials for colon cancer ranged from 60 to 62 years, the median age at diagnosis for patients with stage III colon cancer in the United States is 70 years (6). A recent analysis from the Mayo Clinic (7) combining primary data for 3351 patients treated on one of seven randomized trials demonstrated that adjuvant treatment provides a statistically significant improvement in disease-free and overall survival for patients over age 70 years. The benefits realized by elderly patients diminished only slightly with increasing age (7). Although the NIH consensus statement on adjuvant therapy and other clinical guidelines do not recommend an upper age limit for treatment, the greater burden of comorbid disease in elderly patients provokes legitimate concern about whether the risks associated with adjuvant therapy justify the potential benefits. In practice, clinicians may also be reluctant to treat older patients because of the perception that 5-FU toxicity increases with age (8), even though studies of clinical trial participants (9,10) show that there is a minimal increase in toxicity risk for most chemotherapy agents in older patients without major comorbidity. In addition, clinicians may perceive that short remaining natural life expectancy curtails the potential benefits (11) or that older patients themselves are reluctant to receive chemotherapy.
We sought to evaluate the relationship between the patient's age at diagnosis and use of adjuvant chemotherapy outside the clinical trial setting. A 1993 analysis of the National Cancer Database (12) estimated that 43% of patients with stage III colon cancer receive adjuvant treatment, but usage among patients with varying age and comorbidity has not been well described. We expected to find that the likelihood of receiving adjuvant treatment decreases with age. However, our goal was to describe the magnitude of the association between age and treatment, as well as the extent to which comorbidity and toxicity might be greater for elderly patients.
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SUBJECTS AND METHODS |
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Data Sources
Linkage of the Surveillance, Epidemiology, and End Results (SEER)1 population-based cancer registries with the Medicare database of the Health Care Financing Administration (HCFA) containing health care claims for its enrollees enabled us to identify a cohort of elderly patients with stage III colon cancer and to determine whether or not they received adjuvant chemotherapy. The SEER registries, sponsored by the National Cancer Institute (NCI), ascertain all incident cancer cases diagnosed in five states and in six U.S. metropolitan areas, representing approximately 14% of the U.S. population (6). The SEER Program collects information on each incident cancer, including the primary site and histology classified according to the International Classification of Disease for Oncology, 2nd edition (ICD-O-2) (13), the tumor stage at diagnosis, and patient demographics.
The Medicare Program provides health insurance to 97% of the U.S. population aged 65 years and older. The Medicare Provider Analysis and Review (MEDPAR) files give details of all hospitalizations for persons eligible for Medicare Part A. To receive payment, hospitals submit medical claims coding up to 10 diagnoses and 10 procedures using the International Classification of Diseases, 9th revision, Clinical Modification (ICD-9-CM) classification (14). For the 96% of Medicare beneficiaries who opt for Part B coverage, claims for care delivered in hospital outpatient departments and physicians' offices are also recorded. For its beneficiaries, Medicare documents date of death based on information provided by the Social Security Administration. The SEER and Medicare data have been linked to facilitate population-based studies of the medical and economic outcomes of cancer treatment. Ninety-four percent of patients in SEER who are aged 65 years or older have been successfully linked to their Medicare records (15).
Cohort Definition
All Medicare-enrolled patients aged 65 years and older who were diagnosed with primary colon cancer in a SEER area during the years 1991 through 1996 were potentially eligible for inclusion in our study. Distal rectal cancer cases were excluded. Colon cancers were defined with the use of SEER codes for cancer sites 18.0–18.9 and 19.9; thus, tumors arising in the rectosigmoid region were classified as colon cancers. We restricted our cohort to patients with a histologic diagnosis consistent with adenocarcinoma (SEER histology codes 8140, 8210–1, 8220–1, 8260–3, 8470, 8480–1, and 8490). Diagnoses noted exclusively on death certificates or at autopsy were excluded, as were those where the month of diagnosis was unknown.
Claims detailing specific procedures and diagnoses are not reported to HCFA by risk-contract health maintenance organizations (HMOs). Thus, patients enrolled in these plans were excluded from our cohort. During the study years, 16.5% of the patients were enrolled in an HMO at diagnosis.
We searched Medicare claims records for patients who had colon cancer surgery performed within 3 months of primary diagnosis and had surgeries consistent with definitive tumor resection, according to the ICD-9-CM classification system (45.7x, 45.8, 48.4x, 48.5, and 48.6x). Patients whose claims indicated that they were operated on exclusively for local resection or creation of an ostomy were excluded. We further verified those who were diagnosed with stage III disease with the use of information on tumor size, lymph node involvement, and distant spread recorded in the SEER database and classified according to the American Joint Committee on Cancer staging schema (16). Because adjuvant chemotherapy is generally delivered in the outpatient setting and enrollment in Part B Medicare is necessary for coverage of outpatient care, we restricted our cohort to patients enrolled in both Medicare Part B and Part A during the 3-month period after surgery.
Identification of Adjuvant Chemotherapy Use
Utilization of adjuvant chemotherapy within 3 months of surgery was the primary study outcome. Because there is no reliable way to ascertain on the basis of claims whether chemotherapy is given with palliative or curative (adjuvant) intent, we assumed that patients who had stage III disease and had received chemotherapy within 3 months of primary surgery had adjuvant treatment. The date of hospitalization served as a proxy for the date of surgery, since it is more reliably coded in the Medicare database and the median interval from admission to surgery was 1 day. Patients with stage III disease who had claims for chemotherapeutic agents, chemotherapy administration, or medical supervision of chemotherapy in either the inpatient (MEDPAR), outpatient, or physician/supplier Medicare files at any point within the 3-month postoperative period were considered to be recipients of adjuvant therapy. The absence of such claims was assumed to indicate the lack of adjuvant treatment. Medicare claims for medical evaluation for chemotherapy (ICD-9-CM codes V58.1, V66.2, and V67.2), chemotherapy administration (ICD-9-CM code 99.25; Current Procedural Terminology codes 96408, 96410, 96412, 96414, 96520, 96530, and 96545; HCFA Common Procedure Coding System (HCPCS) codes Q0083–Q0085; and revenue center codes 0331, 0332, and 0335), and intravenous chemotherapy agents (HCPCS codes J9190 for 5-FU, J0640 for leucovorin, and J9200 for floxuridine) identified usage. Because oral 5-FU analogues were not available during the study period and oral levamisole is always administered as a companion to intravenous 5-FU, our claims-based method should not have missed any standard adjuvant regimens.
Adjuvant chemotherapy is clearly not warranted for patients whose prognosis is so poor that they will not survive the immediate postoperative period; thus, our analysis is restricted to patients who survived for at least 3 months following surgery. Patients diagnosed with a second malignancy during this interval were also excluded, since the second cancer could have limited either the feasibility or the anticipated benefits of adjuvant colon cancer treatment.
Patient Characteristics Associated With Adjuvant Chemotherapy Utilization
The patient's age at diagnosis was the primary predictor of interest for this analysis. To examine the possibility that other clinical and demographic variables confound the relationship between chemotherapy use and age at diagnosis, we evaluated the patient's sex, race, comorbidity, number of involved lymph nodes, year of diagnosis, and socioeconomic status (identified by the median income in the patient's census tract of residence).
To adjust for potential confounding based on the severity of noncancer medical illness, we used Romano's modification of the Charlson comorbidity index (17,18). The diagnoses included in the Charlson/Romano comorbidity index include myocardial infarction and diabetes, as well as moderate liver and moderate renal failure, and thus it captures many of the absolute or relative contraindications to administration of adjuvant chemotherapy. We examined all available inpatient Medicare claims for the 15-month period extending from 12 months before the index surgical admission until 3 months after surgery and assigned patients the maximal comorbidity observed. We also included comorbidity evident from outpatient and provider claims during the 3-month postoperative period and classified patients according to whether their Charlson/Romano comorbidity index was 0, 1, or greater than or equal to 2.
Outcomes of Adjuvant Chemotherapy
Although the primary study outcome was use of adjuvant chemotherapy within 3 months of surgery, we also examined treatment complications requiring hospitalization because we anticipated that this secondary endpoint might explain the association between chemotherapy use and age. To assess whether chemotherapy resulted in greater toxicity among the elderly, we compared hospitalization rates for complications attributable to 5-FU during the 6-month period subsequent to treatment initiation according to age at diagnosis. Specifically, we examined the frequency of neutropenia, mucositis, bacteremia, sepsis, diarrhea, and dehydration (ICD-9-CM codes 038.0–038.9, 790.7, 288.0, 528.0, 564.5, 787.91, and 276.5) as either a primary or a secondary diagnosis on any inpatient claim during this 6-month interval.
Statistical Analysis
To assess the overall association between chemotherapy use and age, we used the Mantel–Haenszel test for trend with the patient's age at diagnosis rounded to the nearest year. We performed stratified Mantel–Haenszel trend tests to identify potential confounders in univariate analysis. To examine the simultaneous effect of multiple variables, we performed logistic regression with adjuvant chemotherapy within 3 months of surgery as the outcome and the patient's age at diagnosis as the primary predictor of usage. Potential confounders were entered in the multivariable regression model based on known prognostic factors with the use of dummy variables according to the categories shown in Table 1
. P values are two-sided and were considered to be statistically significant at the .05 level; SAS software (version 6.12; SAS Institute, Cary, NC) was used for all statistical analyses. Overall survival was measured until death due to any cause, for 6 years, or until the censoring date of December 31, 1998. Cancer-specific survival was measured until death from cancer, for 6 years, or until December 31, 1996. Survival is illustrated with the use of the Kaplan–Meier method.
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RESULTS |
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We identified 6956 patients with stage III colon cancer enrolled in Medicare Part A and Part B and not in an HMO, who had surgical resection during the 6-year study interval. Of these 6956 patients, 562 died during the 3-month postoperative period and 132 were diagnosed with a second cancer. The remaining 6262 patients define the study cohort. Patients' ages at diagnosis and the relationship between age and other patient characteristics are shown in Table 1
. As expected, compared with younger patients, elderly patients had higher comorbidity, were more likely to be women and to reside in low-income areas, and were less likely to be black. Neither the number of involved lymph nodes nor the calendar year at diagnosis was related to age (Table 1). Age
Overall, 55% of the patients received adjuvant chemotherapy within 3 months of colon cancer resection, and a steep decline in receipt of such treatment was evident with increasing age at diagnosis (P<.001). For 50% of the patients, at least one claim for the drugs 5-FU or leucovorin indicated chemotherapy use. For an additional 5% of the patients, claims for chemotherapy administration provided evidence that adjuvant treatment was administered, even though the individual drugs were not specified in the claims.
Table 2 shows the frequency of chemotherapy use according to age at diagnosis for the entire cohort as well as for subgroups based on other patient characteristics. Whereas 78% of patients aged 65–69 years had adjuvant chemotherapy, only 58% of those aged 75–79 years and 11% of those aged 85–89 years did so. For the 3391 patients with no major comorbidity, age was also highly associated with treatment; utilization was 80%, 64%, and 13% for patients aged 65–69 years, 75–79 years, and 85–89 years, respectively. As shown in Table 2, the strong association between age and adjuvant treatment was evident among patients with similar sex, race, number of involved lymph nodes, median income, and calendar year of diagnosis (all P values <.001). The association between age and chemotherapy use remained statistically significant after simultaneous adjustment for all variables in multiple logistic regression (P<.001).
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Other Patient Characteristics Associated With Chemotherapy Use
We found statistically significant associations between adjuvant chemotherapy and patient characteristics other than age (Table 3). Higher comorbidity was associated with a lower probability of adjuvant treatment; 60%, 51%, and 42% of the patients with Charlson comorbidity index of 0, 1, or 2 and higher, respectively, received chemotherapy (adjusted P<.001). Sex, race, number of positive lymph nodes, median income, and year at diagnosis were also associated with treatment, although the relationships were less strong than for comorbidity and not nearly as dramatic as the association observed for age. Overall, 50% of the women were treated as compared with 61% of the men, but this difference was attenuated after adjustment for age because women predominate in the oldest age categories (P = .06).
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Blacks were less likely to receive chemotherapy (45% for blacks versus 55% for whites), even if they had no major comorbidity (49% for blacks versus 61% for whites; adjusted P<.001 for comparison between whites and blacks). Patients who were neither white nor black received chemotherapy at rates similar to those for white patients; however, the small numbers of members of each of the racial/ethnic groups constituting this category preclude meaningful analysis.
There was a trend toward greater utilization of adjuvant treatment among patients with higher socioeconomic status (60% for patients with median income in the top quartile versus 50% for patients with median income in the bottom quartile). Patients with a greater number of involved lymph nodes were more likely to receive adjuvant therapy. Chemotherapy use increased modestly during the study interval; 54% of the patients were treated in 1991, and 60% were treated in 1996.
We used the reporting SEER registry to evaluate geographic variation in treatment, but we excluded location from our multivariable model, since utilization varied minimally across registries. Urban (city) registries did not consistently report higher treatment rates than the statewide registries. For example, adjuvant chemotherapy use was low in both San Francisco and New Mexico (each 48%) and high in Atlanta (59%) and Iowa (57%). Chemotherapy utilization varied minimally based on primary tumor site within the colon. Treatment rates ranged from 52% for patients with transverse colon primary tumors to 61% for those with rectosigmoid primary tumors. Because these and other variables, such as tumor grade and the total number of lymph nodes in the surgical specimen, were not independently associated with chemotherapy utilization, they were excluded from our multivariate analysis.
Time to Initiation of Therapy Use
Consistent with the standard from clinical trials, both the median and the mean time to initiation of adjuvant therapy was 5–6 weeks. Of the 3437 treated patients, 542 (16%) had their first claim for chemotherapy dated more than 8 weeks after surgery; the degree to which such delay compromises efficacy is uncertain. Patients whose therapy started after more than an 8-week delay were older, had higher comorbidity, and had longer primary hospitalizations.
Complications of Chemotherapy
To explore the validity of the perception that adjuvant 5-FU causes excess toxicity in older patients, we examined hospitalization rates for 5-FU treatment complications according to patient age (Table 4). Whereas 7% of chemotherapy recipients aged 65–79 years were hospitalized for neutropenia, mucositis, diarrhea, bacteremia, sepsis, or dehydration, 9% of recipients aged 75–79 years and 13% of recipients aged 85–89 years were admitted for these treatment-associated morbidities. Overall, 23% of 65- to 69-year-old recipients, 27% of 75- to 79-year-old recipients, and 35% of 85- to 89-year-old recipients required hospitalization for any cause during the 6-month interval after initiation of chemotherapy.
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Survival
To consider the possibility that poor survival for untreated elderly colon cancer patients justifies omission of adjuvant chemotherapy, we examined overall survival and colon cancer-specific survival for 75- to 84-year-old patients with stage III colon cancer. The curves shown in Fig. 1 illustrate that these patients have sufficient life expectancy to warrant consideration of adjuvant therapy. Fig. 1 also demonstrates that cancer is the primary cause of death for this group. We have not separated survival for treated and untreated patients because, without randomization, this analysis would not yield an unbiased estimate of the effectiveness of adjuvant therapy.
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DISCUSSION |
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In a population-based sample of Medicare enrollees diagnosed with stage III colon cancer during the period from 1991 through 1996, we found that 55% received postoperative adjuvant chemotherapy. This estimate exceeds the 43% rate reported by the American College of Surgeons (12) based on patterns of care in 1993 among colon cancer patients of all ages. Our analysis provides a basis for optimism about the quality of cancer care because more than 70% of patients with stage III colon cancer who were aged 65–74 years initiated postoperative chemotherapy. However, it also characterizes those patients who went untreated and suggests that, in some instances, treatment may have been omitted for reasons unrelated to a patient's medical condition.
We found that chronologic age at diagnosis was highly associated with receipt of adjuvant treatment and that other patient characteristics, such as comorbidity, had much less of an influence on the decision to treat. Our results are consistent with those of other studies (19–25) that have examined the association between age and utilization of both curative and palliative cancer treatments. For example, use of radiation therapy after breast-conserving surgery (26) and palliative chemotherapy for metastatic lung cancer also decline sharply with age (27).
Why do elderly patients fail to receive potentially curative postoperative adjuvant chemotherapy? Chronologic age is an imperfect surrogate for physiologic age, and clinical guidelines do not include it as a treatment criterion. Plausible explanations for decreased utilization of chemotherapy in the elderly may include their high burden of comorbidity, financial and geographic barriers to care, physician knowledge and attitudes, and patient preferences (28–30).
Clearly, the incidence of conditions that may complicate or even preclude administration of adjuvant treatment increases with age. However, the low rates of utilization of adjuvant chemotherapy among elderly patients who were healthy enough to withstand colon resection and were free of cardiac, hepatic, renal, vascular, and neurologic disease strongly suggest that greater treatment toxicity is an insufficient explanation for the decline in usage seen with advancing age. Nonmedical barriers to care, such as financial status, could also explain why the elderly are less likely to receive treatment (31). However, since Medicare insured all patients for the full study period, lack of insurance coverage appears to be an insufficient explanation for the age-related decline in use.
Elderly patients themselves may choose not to receive adjuvant chemotherapy. However, the consistent finding from studies of treatment preferences is that no simple sociodemographic variable, such as chronologic age, is a reliable predictor of what patients actually want and that the only way to facilitate decisions that truly reflect preferences is to elicit them at the individual level. When surveyed, older cancer patients were just as likely as their younger counterparts to want chemotherapy, although after choosing to receive treatment, they were less likely to accept major toxicity in exchange for added survival (32). Furthermore, older patients have indicated that the primary determinant of their decisions regarding chemotherapy is their physician's advice (33). Thus, even if the elderly choose not to receive therapy, these decisions may be influenced by their physicians' attitudes toward treatment.
Physicians' knowledge and attitudes may explain the low utilization of adjuvant chemotherapy among the elderly. Our analysis of postoperative referral patterns suggests that many untreated patients did not have the opportunity for an individualized assessment of the risks and benefits of treatment from a medical oncologist. Our data do not permit ascertainment of whether this was because surgeons did not facilitate referrals for their elderly patients or because patients were uninterested or unable to attend postoperative consultations. Those elderly patients who do see a medical oncologist may be discouraged from pursuing adjuvant treatment (34). The perception that the elderly tolerate chemotherapy poorly likely accounts for some of the reluctance to administer adjuvant therapy. However, both randomized trials (7) and our comparison of the complication rates for younger and older Medicare patients reveal only a modest increase in the toxicity of chemotherapy with advancing age. There is a paucity of data on the quality of life for elderly patients who receive colon cancer chemotherapy, but available evidence suggests that treatment can be well tolerated even among the very old (3,35).
Physicians may perceive that their elderly patients' short natural life expectancy limits the potential benefits of treatment. However, the 5-year survival is 71% for 80-year-olds in the U.S. population, and total remaining life expectancy is 7.5 years for men and 9.1 years for women (36). These life-table estimates and the observation that median survival for 75- to 84-year-old patients with stage III colon cancer in our cohort was 3 years and 8 months (Fig. 1) indicate that they merit the opportunity to at least discuss the potential risks and benefits of adjuvant treatment.
Several limitations of our analysis must be noted. First, the potential for inaccurate coding exists for any claims-based analysis, and clinical information available from billing records is not as detailed as that available from chart review (37–40). Chemotherapy may be underreported in Medicare claims, compromising the sensitivity of our approach to ascertaining treatment (14,41). However, a comparison using medical record review and physician reporting as the gold standard among a cohort of 495 colon cancer patients in SEER–Medicare suggests that claims have 90% sensitivity (Warren J: Identification of chemotherapy administration from Medicare claims data. Unpublished data presented at the SEER–Medicare Data Users Workshop, Bethesda, MD; November 16–17, 2000). Specificity may be limited, if, for example, patients with stage III disease received postoperative chemotherapy for palliation of rapidly progressive metastatic disease that became manifest in the postoperative period. Second, although we used a clinically relevant method to assess comorbidity, we may have failed to identify patients who would be judged to be poor chemotherapy candidates on the basis of rare illnesses poorly captured by comorbidity indices or on the basis of poor functional status or minimal social supports (42). On the other hand, all of the patients in our cohort were deemed to be sufficiently fit to undergo major cancer surgery and recovered from their surgeries. Finally, our results are not generalizable to the approximately 16% of Medicare beneficiaries who received care in an HMO setting, where patterns of care may have been different (41).
Our claims-based analysis suggests that chemotherapy may not be optimally utilized among the elderly and that nonmedical factors influence treatment decisions. Neither comorbidity nor treatment toxicity nor short natural life expectancies appear to justify the sharp decline in utilization with increasing age. Further investigation is necessary to determine whether patients' preferences, their functional status, physicians' attitudes, or other barriers explain this care pattern (31,43). Because colon cancer is common and adjuvant chemotherapy is one of the most efficacious interventions in the oncology armamentarium, adjuvant chemotherapy usage is considered to be an indicator of high-quality cancer care. For such quality indicators to be useful and to thereby determine whether treatment is underused, overused, or appropriately used, further research that assesses physicians' and patients' knowledge and attitudes regarding treatment will be essential.
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NOTES |
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1 Editor's note: SEER is a set of geographically defined, population-based, central cancer registries in the United States, operated by local nonprofit organizations under contract to the National Cancer Institute (NCI). Registry data are submitted electronically without personal identifiers to the NCI on a biannual basis, and the NCI makes the data available to the public for scientific research.
Supported by Public Health Service career development award in preventive oncology K07CA83950 (to D. Schrag) from the National Cancer Institute, National Institutes of Health, Department of Health and Human Services.
This study used the linked SEER–Medicare database. We acknowledge the efforts of the Applied Research Program, NCI (Bethesda, MD); the Office of Information Services and the Office of Strategic Planning, Health Care Financing Administration (Baltimore, MD); Information Management Services, Inc. (Silver Spring, MD); and the Surveillance, Epidemiology, and End Results (SEER) Program tumor registries in the creation of the SEER–Medicare database. We also thank Dr. Joan Warren of the Applied Research Program, NCI, and Drs. Jane Weeks and Craig Earle of the Dana-Farber Cancer Institute (Boston, MA) for helpful discussions as well as Sofia Yakren and Sarah Gelfand of the Memorial Sloan-Kettering Cancer Center for their dedicated research assistance.
The interpretation and reporting of these data are the sole responsibility of the authors.
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