Download Changes in treatment patterns for patients with locally advanced

Original Article
Changes in Treatment Patterns for Patients With Locally
Advanced Rectal Cancer in the United States Over the Past
Decade: An Analysis From the National Cancer Data Base
Helmneh M. Sineshaw, MD, MPH1; Ahmedin Jemal, DVM, PhD1; Charles R. Thomas Jr, MD2; and Timur Mitin, MD, PhD2
BACKGROUND: In the United States, neoadjuvant chemoradiotherapy (NACRT) is widely accepted as the standard of care in the
treatment of patients with locally advanced rectal cancer. In the current study, the authors attempted to examine patterns of treatment in the United States over the past decade. METHODS: Using the National Cancer Data Base, a total of 66,197 patients who were
diagnosed with American Joint Committee on Cancer stage II to III rectal adenocarcinoma and treated between 2004 and 2012 were
identified. The authors described trends in the receipt of treatment for 3 time periods (2004-2006, 2007-2009, and 2010-2012) and
analyzed 5-year overall survival probabilities for 28,550 patients treated between 2004 and 2007. RESULTS: Receipt of NACRT
increased significantly from 42.9% between 2004 and 2006 to 50.0% between 2007 and 2009, and to 55.0% between 2010 and
2012 (P <.0001). In contrast, the use of adjuvant chemoradiotherapy (CRT) decreased from 16.7% between 2004 and 2006 to 10.5%
between 2007 and 2009, and to 6.7% between 2010 and 2012 (P <.0001). Similarly, the use of surgery alone decreased from 13.1%
between 2004 and 2006 to 8.7% between 2010 and 2012 (P <.0001). Older age, the presence of comorbidities, larger primary tumor
size, lymph node involvement, not being of non-Hispanic white race/ethnicity, lack of private insurance, and treatment at a facility
that did not have a high case volume were associated with a significantly lower possibility of receiving NACRT. The 5-year overall survival rates for patients treated with NACRT, surgery and adjuvant CRT, surgery alone, and definitive CRT were 72.4%, 70.9%, 44.9%,
and 48.8%, respectively. CONCLUSIONS: The use of NACRT before surgery in US patients with rectal cancer has substantially
increased over the past decade. However, only approximately one-half of patients currently receive this standard therapy, which could
be explained in part by socioeconomic factors. Trimodality therapy is associated with the best outcomes for these patients. Cancer
C 2016 American Cancer Society.
2016;000:000–000. V
KEYWORDS: health disparities, National Cancer Data Base, neoadjuvant chemoradiotherapy, patterns of care, rectal cancer, trimodality therapy.
INTRODUCTION
Rectal cancer is a common disease in the United States, with an estimated 40,000 new cases expected to have been diagnosed in 2015,1 and a worrisome increase in incidence rates in the younger population.2 The management of rectal cancer
has become more complex, with a greater chance of variation by patient-associated, physician-associated, and treatment
facility-associated factors.3,4 Trimodality therapy, incorporating total mesorectal excision (TME), pelvic radiotherapy
(RT), and systemic chemotherapy, is an established treatment paradigm for patients with American Joint Committee on
Cancer stage II and III rectal adenocarcinoma, based on several randomized clinical trials.5,6 A previous analysis of the
National Cancer Data Base (NCDB) regarding the patterns of care in the United States7 encompassed the period between
1985 and 1995 and revealed a dramatic increase in the receipt of trimodality therapy: from 9.5% between 1985 and 1986
to 31% between 1989 and 1990, and again to 46% between 1994 and 1995. This trend was based, in part, on a National
Cancer Institute consensus statement that was published in 1990.8 In addition, the publication of the phase 3 randomized
trial of the German Rectal Cancer Study Group in 20049 established neoadjuvant chemoradiotherapy (NACRT) followed
by TME as a standard of care in the United States, based on improvements in local control, decreased toxicity, and a
Corresponding author: Timur Mitin, MD, PhD, Department of Radiation Medicine, Oregon Health and Science University, 3181 SW Sam Jackson Park Rd,
KPV4010, Portland, OR 97239-3098; Fax: (503) 681-4210; [email protected]
1
Surveillance and Health Services Research Program, American Cancer Society, Atlanta, Georgia; 2Department of Radiation Medicine, Oregon Health and Science
University, Portland, Oregon.
The data used in the study are derived from a limited data set of the National Cancer Data Base (NCDB). The authors acknowledge the efforts of the American
College of Surgeons, the Commission on Cancer, and the American Cancer Society in the creation of the NCDB. The American College of Surgeons and the
Commission on Cancer have not verified and are not responsible for the analytic or statistical methodology used, or the conclusions drawn from these data by
the authors.
DOI: 10.1002/cncr.29993, Received: January 27, 2016; Accepted: February 16, 2016, Published online Month 00, 2016 in Wiley Online Library
(wileyonlinelibrary.com)
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Month 00, 2016
1
Original Article
possibly increased rate of sphincter preservation, in
comparison with TME followed by adjuvant chemoradiotherapy (CRT). In the current study, we examined contemporary patterns of and factors associated with the
receipt of NACRT in the United States.
MATERIALS AND METHODS
Study Population
The NCDB, which is jointly sponsored by the American
College of Surgeons Commission on Cancer and the
American Cancer Society, is a hospital-based registry that
serves as a comprehensive clinical surveillance resource
that derives its data from approximately 1500 Commission on Cancer–accredited programs in the United States.
As such, the NCDB captures approximately 70% of incident cancers in the United States each year, making it one
of the most powerful and generalizable cancer databases in
the world.10 Ongoing validation of the accuracy and quality of the NCDB data is performed through internal monitoring, site surveys, and data quality reviews.11 Data
coding methods have been described previously.12
We extracted data regarding patients aged >18 years
who were diagnosed with a single primary or first primary
American Joint Committee on Cancer stage II to III rectal
adenocarcinoma and received all or part of their treatment
at an accredited NCDB facility between January 1, 2004
and December 31, 2012. Rectal carcinoma cases include
cancers topographically coded as C20.9, according to the
International Classification of Diseases for Oncology, 3rd
Edition (ICD-O-3).13 Treatment of all cases was analyzed
using the clinical stage of disease (pathologic stage was
used if the clinical stage was missing) at the time of diagnosis. Management strategies for rectal carcinoma include
surgery, chemotherapy, RT, and combinations of these
modalities. Disease histology was limited to rectal adenocarcinomas (ICD-0-3 histology codes 8140, 8210, 826063, 8470, 8480, and 8481), including adenocarcinoma,
not otherwise specified; adenocarcinoma in adenomatous
polyps; papillary adenocarcinoma, not otherwise specified; villous adenocarcinoma; adenocarcinoma in tubulovillous adenoma; mucinous adenocarcinoma; and mucinproducing adenocarcinoma. Tumors recorded as other
carcinomas or with unspecified histology codes were
excluded from the current analysis. Information retrieved
included type of surgery, patient age, patient sex, patient
race (categorized as non-Hispanic [NH] white, NH black,
Hispanic, or other/missing data/unknown), patient insurance (private, Medicaid, Medicare, uninsured, or other/
missing data), facility type, facility volume (tertiles of
2
facility case volume were ranked into low, medium, and
high case volumes by counting the number of cases treated
at the facility), educational attainment (defined as the percentage of residents per ZIP code without a high school
diploma), date of diagnosis, date of surgery, date chemotherapy was initiated, date RT was initiated, receipt of
chemotherapy, receipt of RT, number of RT fractions,
lymph node status, tumor grade, tumor size, and comorbidity score. We defined adjuvant therapy as when treatment was administered within 6 months after surgical
resection, and also defined neoadjuvant therapy as when
treatment was administered within 6 months before surgical resection. Receipt of NACRT and adjuvant CRT were
categorized based on receipt of chemotherapy and RT
within the specified time frame. For the trend analysis, all
patients were grouped according to predetermined time
periods of diagnosis: 2004 to 2006, 2007 to 2009, and
2010 to 2012. For 5-year survival analysis, data were limited to cancer diagnoses made between 2004 and 2007.
Statistical Analysis
We used SAS statistical software (version 9.4; SAS Institute Inc, Cary, NC) to perform the statistical analysis. We
performed descriptive analysis to demonstrate patterns of
NACRT using chi-square tests to test significance for categorical variables and the Cochran-Armitage test for trend
to determine trends over time in the use of NACRT for 3
time periods (2004-2006, 2007-2009, and 2010-2012).
Variables likely to be associated with the receipt of preoperative treatment and the type of preoperative treatment
were included in the multivariable logistic regression
model. All-cause, unadjusted, 5-year survival rates were
calculated using the Kaplan-Meier method. Follow-up
time for calculating survival rates was from the date of
diagnosis until the date the study ended (December 31,
2012), last contact date, or death (whichever occurred
first). Cox proportional hazards models were used to estimate the 5-year risk of all-cause mortality and to identify
independent predictors of survival. The proportional hazards assumption test did not show violations for variables
included in the model. Statistical significance was considered when the 2-sided P value was < .05.
RESULTS
Patient Demographics
We identified 68,182 patients in the NCDB who received a
diagnosis of stage II or III rectal cancer between 2004 and
2012. No significant differences were evident with regard to
the sociodemographic and clinical characteristics of the
patients (age, ethnicity, comorbidity score, insurance,
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Treatment Patterns for Rectal Cancer in US/Sineshaw et al
income, or education) among the 3 diagnosis periods
(Table 1). The majority of patients (>70%) diagnosed with
locally advanced rectal cancer were aged 50 to 79 years, and
the vast majority had excellent performance status with a
comorbidity score (Charlson/Deyo) of 0.
Tumor Characteristics
Overall, the quality of documentation of tumor characteristics was good, with no apparent changes between 2004
and 2012. Approximately 10% of patients were missing
information regarding tumor grade and 20% were missing information regarding tumor size. No significant
changes in tumor characteristics were observed among the
3 diagnosis-year cohorts (Table 1), and there was a nearly
equal split between patients with stage II and stage III
disease at the time of diagnosis.
Patterns of Treatment
The majority of patients were treated at comprehensive
community cancer programs, and the percentage of
patients treated at facilities with low case volumes substantially decreased from 12.3% between 2004 and 2006 to
6.8% between 2010 and 2102 (Table 2). Of the patients
who underwent surgery, few received local excision. The
percentage of patients who underwent surgery alone for
stage II or III rectal cancer declined from 13.1% between
2004 and 2006 to 8.7% between 2010 and 2012, whereas
the percentage of patients who received treatment with definitive CRT and did not undergo surgery increased from
9.4% to 12.3% during these same time periods. The
receipt of adjuvant CRT appears to have steadily declined
from 16.7% between 2004 and 2006 to 10.5% between
2007 and 2009 to 6.7% between 2010 and 2012, whereas
receipt of NACRT increased from 42.9% to 50.6% and
then to 55% over the 3 time periods (P for trend < .0001)
(Fig. 1). Less than 1% of patients received short-course
RT, defined as 5 sessions. The majority of patients
received standard fractionation RT (between 25 and 33
fractions).
Factors Associated With Receipt of NACRT
Patients who were diagnosed with more advanced disease
(larger tumors and involved pelvic lymph nodes) were
more likely to undergo either surgery alone or surgery followed by adjuvant CRT and less likely to receive
NACRT. Patients treated at facilities that did not have a
high case volume (as defined earlier) were less likely to
receive NACRT. Several social factors were found to be
associated with a lower likelihood of receiving NACRT:
nonwhite ethnicity, lack of private medical insurance, and
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residing in a neighborhood with a low educational background (Table 3).
Survival Outcomes
A total of 28,550 patients diagnosed with stage II or III
rectal cancer between 2004 and 2007 were analyzed for
5-year survival outcomes. The 5-year unadjusted overall
survival (OS) rate was 72.4%, 70.9%, 44.9%, and 48.8%,
respectively, among patients who received NACRT, adjuvant CRT, surgery alone, and definitive CRT (Fig. 2).
When compared with patients who received NACRT, the
adjusted hazard ratio for risk of death at 5 years was 1.66
(95% confidence interval, 1.56-1.77) for surgery alone
and 1.48 (95% confidence interval, 1.37-1.59) for definitive CRT (Table 4). Black race, older age at the time of
diagnosis, high tumor grade, increased tumor size,
involved lymph nodes, higher comorbidity score, treatment facilities that did not have a high case volume, nonprivate insurance, and lower median income were found
to be associated with a higher risk of death at 5 years after
treatment for stage II or III rectal cancer.
DISCUSSION
The treatment paradigm for locally advanced rectal cancer
has been shifting continuously over the past 30 years to
incorporate 3 treatment modalities (surgery, chemotherapy, and RT) to achieve best treatment outcomes. An earlier report concerning patterns of care for rectal cancer in
the United States based on an analysis of NCDB data
revealed the receipt of trimodality therapy (with no information regarding the sequencing of these modalities) in
9.5% of patients with stage II or III rectal cancer between
1985 and 1986, which increased to 31% between 1989
and 1990 and further increased to 46% between 1994
and 1995 (calculated from Table 4 in Jessup et al7). This
trend could be attributed in part to the publication of the
National Cancer Institute consensus statement in 1990.8
We extended this analysis through 2012 and demonstrated
that the percentage of US patients receiving trimodality
therapy (either NACRT followed by surgery or surgery
followed by adjuvant CRT) has been steady at approximately 60% over the past decade. We also demonstrated
that, in keeping with several randomized clinical trials, the
use of trimodality therapy is associated with the best OS
rate of >70%.
A randomized trial of NACRT versus adjuvant CRT,
published in 2004, established NACRT as a standard of care
in Europe and North America. Although there was no survival difference noted, NACRT led to improved local control, decreased severe acute and long-term treatment-related
3
Original Article
TABLE 1. Descriptive Characteristics of Patients With Locally Advanced Rectal Cancer and Their Tumor
Characteristics By 3 Diagnosis-Year Periods, Shown as Percentage
2004 to 2006
N 5 21,302
2007 to 2009
N521,808
2010 to 2012
N523,087
18-49
50-64
65-79
80
16.5
36.8
34.7
11.9
18.4
38.8
31.8
11.1
17.8
41.2
30.2
10.7
NH white
NH black
Hispanic
Other/missing data
73.3
7.7
5.5
13.6
73.5
8.2
5.9
12.4
75.3
8.6
6.4
9.7
0
1
2
78.6
16.2
5.1
77.1
16.5
6.4
76.2
17.1
6.7
Uninsured
Medicaid
Medicare
Private
Other/missing data
4.0
4.5
42.1
45.6
3.7
4.6
6.0
39.4
47.0
3.1
5.9
7.3
38.2
45.5
3.0
13.9
18.1
27.3
36.3
4.5
14.2
18.8
27.4
35.5
4.1
13.3
19.1
26.9
37.1
3.7
17.4
23.2
23.2
31.7
4.5
17.6
23.4
23.4
31.3
4.1
17.4
23.3
23.8
31.9
3.7
6.8
14.3
20.6
18.4
6.6
8.6
8.5
4.7
11.5
5.4
13.8
20.5
18.5
6.6
8.7
9.4
4.8
12.3
5.3
14.5
20.6
18.1
6.6
9.0
9.3
5.2
11.4
48.8
51.2
48.6
51.4
47.1
52.9
7.5
67.2
13.8
0.7
10.8
7.0
66.6
13
1.0
12.6
7.5
67.2
10.4
1.2
13.8
7.7
40.1
29.6
22.6
9.5
39.7
28.4
22.5
9.0
40.0
31.5
19.4
Variable
Category
Age group, y
Race/ethnicity
Comorbidity score
Insurance
Median incomea
<$30,000
$30,000-$34,999
$35,000-$45,999
$46,000
Missing data
Median with no high school diplomab
29%
20%-28.9%
14%-19.9%
<14%
Missing data
US region
New England
Middle Atlantic
South Atlantic
East North Central
East South Central
West North Central
West South Central
Mountain
Pacific
c
AJCC clinical stage
II
III
Tumor grade
1
2
3
4
Missing data
Tumor size, cm
<2
2 to < 5
5
Missing data/unknown
Abbreviations: AJCC, American Joint Committee on Cancer; NH, non-Hispanic.
a
Area-level median household income quartiles were derived from the 2000 US Census data.
b
Area-level quartiles for the percentage of adults without a high school diploma were derived from the 2000 US Census data.
c
Pathologic stage of disease was used if the clinical stage was missing.
4
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Treatment Patterns for Rectal Cancer in US/Sineshaw et al
TABLE 2. Percentage of Patients With Locally Advanced Rectal Cancer by Type of Treatment Facility and
Treatment in 3 Diagnosis-Year Periods, Shown As Percentage
Variable
Category
2004 to 2006
N 5 21,302
2007 to 2009
N521,808
2010 to 2012
N523,087
11.1
49.3
22.6
9.9
11.1
47.4
22.6
10.8
11.2
46.3
24.1
11
12.3
21.6
66.1
7.5
27.3
65.2
6.8
26.9
66.3
10.7
3
83.7
2.6
13.4
2.8
81.4
2.4
14.2
2.8
80.7
2.3
13.1
3.9
0.6
16.7
0.1
1.6
42.9
0.8
1.2
9.4
9.8
3.1
0.7
10.5
0.1
1
50.6
1
1.4
11.7
8.7
3
0.6
6.7
0.1
0.6
55
1.4
1.2
12.3
19.6
0.3
59.2
20.9
16
0.4
62.9
20.7
14.7
0.7
66.8
17.9
Facility type
Community cancer program
Comprehensive community cancer program
Teaching/research center
NCI program/network
Facility case volume
Low
Medium
High
Surgery type
None
Local excision
Proctectomy/proctocolectomy
Unknown/missing data
Treatment types and sequences
Surgery alone
Surgery with adjuvant chemotherapy
Neoadjuvant chemotherapy with surgery
Surgery with adjuvant chemoRT
Neoadjuvant chemotherapy with surgery and adjuvant RT
Surgery with adjuvant RT
Neoadjuvant chemoRT with surgery
Neoadjuvant RT with surgery and adjuvant chemotherapy
Neoadjuvant RT and surgery
ChemoRT with no surgery
No. of radiation fractions
None
5
25-33
Other/unknown
Abbreviations: chemoRT, chemoradiotherapy; NCI, National Cancer Institute, RT, radiotherapy.
Figure 1. Trends in receipt of trimodality therapy for patients
with locally advanced rectal cancer diagnosed between 2004
and 2012.
toxicities, and possibly improved the rate of sphincter preservation, in comparison with adjuvant CRT.9 Over the past
decade, since the publication of the randomized trial by the
German Rectal Cancer Study Group,9 we have observed an
increase in the rate of adoption of NACRT in the management of patients with locally advanced rectal cancer in the
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United States, with the parallel decrease in the use of adjuvant
CRT. Unfortunately, with only 55% of US patients receiving
the standard of treatment in recent years, one must address
the gap between the guidelines and the variable penetrance
into routine clinical practice. The results of the current study
indicate that facilities with low or medium case volumes are
less likely to offer patients the standard treatment, and that
socioeconomic factors such as not being of NH white race/
ethnicity, a lack of private insurance, and residence in a neighborhood with a lower educational background are independent factors associated with a lower probability of receiving the
standard national guidelines-supported therapies.
The standard trimodality therapy in the United
States involves a fractionated RT treatment course over 5
weeks with concurrent chemotherapy, followed by surgery. This treatment paradigm is costly for the health care
system to support. Conversely, short-course RT of 25 Gy
delivered in 5 fractions followed by immediate surgery,
without concurrent chemotherapy, has a long history of
evaluation in Europe. Recently, 2 randomized trials compared long-course CRT with short-course RT. A Polish
randomized trial demonstrated no benefit from the long5
Original Article
TABLE 3. Adjusted ORs Predicting Receipt of
NACRT for Locally Advanced Rectal Cancera
TABLE 3. Continued
Variable
Variable
Category
OR
Race/ethnicity
NH white (reference)
NH black
Hispanic
Other/missing data/unknown
Diagnosis age group, y
18-49 (reference)
50-64
65-79
80
Diagnosis year
2004-2006 (reference)
2007-2009
2010-2012
AJCC clinical stageb
II (reference)
III
Tumor grade
1 (reference)
2
3
4
Missing data
Tumor size, cm
<2 (reference)
2 to < 5
5
Missing data/unknown
Comorbidity score
0 (reference)
1
2
Region
East North Central (reference)
East South Central
Middle Atlantic
Mountain
New England
Pacific
South Atlantic
West North Central
West South Central
Facility category
Teaching/research
center (reference)
Community cancer program
Comprehensive community
cancer program
NCI program/network
Other programs
Facility case volume
High (reference)
Low
Medium
Insurance
Private (reference)
Uninsured
Medicaid
Medicare
Other/missing data
Median with no high school diplomac
<14% (reference)
29%
20%-28.9%
14%-19.9%
6
1.00
0.85
0.86
0.88
Category
OR
95% CI
1.00
1.05
1.08
1.04
1.00-1.10
1.02-1.15
0.97-1.12
95% CI
0.80-0.91
0.80-0.93
0.83-0.93
1.00
0.86
0.69
0.26
0.82-0.91
0.65-0.74
0.24-0.28
1.00
1.36
1.64
1.31-1.42
1.58-1.72
1.00
1.23
1.18-1.28
1.00
0.99
0.92
0.78
1.49
0.92-1.06
0.85-1.00
0.65-0.94
1.37-1.62
1.00
0.57
0.45
0.94
0.53-0.61
0.42-0.48
0.87-1.01
1.00
0.96
0.69
0.91-1.00
0.64-0.74
1.00
0.74
0.85
0.76
1.02
0.60
0.95
1.11
0.77
0.69-0.81
0.80-0.90
0.69-0.83
0.94-1.11
0.56-0.64
0.90-1.01
1.03-1.19
0.72-0.83
1.00
0.98
1.00
0.92-1.06
0.95-1.05
1.21
1.07
1.13-1.29
1.00-1.15
1.00
0.71
0.83
0.66-0.76
0.79-0.87
1.00
0.93
0.90
0.85
0.44
0.86-1.01
0.83-0.97
0.81-0.90
0.39-0.49
1.00
0.82
0.88
0.97
0.77-0.88
0.83-0.93
0.92-1.02
Median incomed
$46,000 (reference)
$35,000-$45,999
$30,000-$34,999
<$30,000
Abbreviations: 95% CI, 95% confidence interval; AJCC, American Joint
Committee on Cancer; NACRT, neoadjuvant chemoradiotherapy; NCI,
National Cancer Institute; NH, non-Hispanic; OR, odds ratio.
a
Adjusted for race/ethnicity, age at diagnosis, year of diagnosis, stage of
disease, tumor grade, tumor size, lymph node status, comorbidity score,
US region, facility case volume, facility category, insurance status, median
with no high school diploma, and median income quartile.
b
Pathologic stage of disease was used if the clinical stage was missing.
c
Area-level quartiles for the percentage of adults without a high school
diploma were derived from the 2000 US Census data.
d
Area-level median household income quartiles were derived from the
2000 US Census data.
Figure 2. Overall 5-year survival probability for patients with
locally advanced rectal cancer by treatment received. “Other”
includes the following treatments: surgery with adjuvant chemotherapy, neoadjuvant chemotherapy with surgery, neoadjuvant chemotherapy with surgery and adjuvant radiotherapy
(RT), surgery with adjuvant RT, neoadjuvant RT with surgery
and adjuvant chemotherapy, and neoadjuvant RT and surgery.
chemoRT indicates chemoradiotherapy.
course CRT in terms of sphincter preservation, local control, or survival, while the local control trend actually
favored short-course RT.14 A more recent Trans-Tasman
Radiation Oncology Group trial compared short-course
RT with long-course CRT in patients with T3 rectal cancer defined on ultrasound or magnetic resonance imaging,
with all patients receiving chemotherapy with 5-fluorouracil.15 This trial did not demonstrate any difference in
local control or OS. The results of the current study demonstrate that <1% of US patients over the past decade
received short-course RT, defined as 5 fractions, usually
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Treatment Patterns for Rectal Cancer in US/Sineshaw et al
TABLE 4. Adjusted HRs of 5-Year Survival for
Patients Treated for Locally Advanced Rectal Cancer Between 2004 and 2007a
TABLE 4. Continued
Variable
Insurance
Category
HR
95% CI
Treatment
Neoadjuvant chemoRT (reference)
Adjuvant chemoRT
Definitive chemoRT
Surgery alone
Other
Race/ethnicity
NH white (reference)
NH black
Hispanic
Other/missing data/unknown
Diagnosis age group, y
18-49 (reference)
50-64
65-79
80
Diagnosis year
2004 (reference)
2005
2006
2007
AJCC clinical stageb
II (reference)
III
Tumor grade
1 (reference)
2
3
4
Missing data
Tumor size, cm
<2(reference)
2 to < 5
5
Missing data/unknown
Lymph node status
Negative (reference)
Positive
Missing data/unknown
Comorbidity score
0 (reference)
1
2
Region
East North Central (reference)
East South Central
Middle Atlantic
Mountain
New England
Pacific
South Atlantic
West North Central
West South Central
Facility category
Teaching/research center (reference)
Community cancer program
Comprehensive community
cancer program
NCI program/network
Other programs
Facility case volume
High (reference)
Low
Medium
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1.00
0.84
1.48
1.66
1.36
1.00
1.21
1.00
1.00
0.78-0.90
1.37-1.59
1.56-1.77
1.28-1.44
1.13-1.30
0.91-1.10
0.94-1.07
1.00
1.19
1.68
3.11
1.10-1.28
1.54-1.83
2.83-3.42
1.00
0.97
0.97
0.94
0.92-1.03
0.91-1.02
0.89-1.00
1.00
0.96
0.91-1.01
1.00
1.06
1.54
1.57
1.07
0.98-1.15
1.41-1.69
1.27-1.94
0.97-1.18
1.00
1.22
1.57
1.39
1.12-1.33
1.43-1.71
1.26-1.52
1.00
1.79
2.09
1.69-1.91
1.96-2.23
1.00
1.33
1.82
1.27-1.40
1.70-1.95
1.00
1.08
0.98
0.95
0.99
0.89
1.02
0.99
0.95
0.99-1.18
0.91-1.05
0.85-1.06
0.90-1.08
0.83-0.97
0.95-1.08
0.91-1.08
0.87-1.04
1.00
1.02
1.02
0.95-1.11
0.96-1.07
0.80
0.92
0.74-0.88
0.84-1.00
1.00
1.14
1.11
1.07-1.22
1.06-1.17
Variable
Category
HR
95% CI
Private (reference)
Uninsured
Medicaid
Medicare
Other/missing data
Median with no high school diplomac
<14% (reference)
29%
20%-28.9%
14%-19.9%
Median incomed
$46,000 (reference)
$35,000-$45,999
$30,000-$34,999
<$30,000
1.00
1.53
1.55
1.27
1.05
1.38-1.70
1.41-1.71
1.18-1.35
0.93-1.18
1.00
1.10
1.03
1.05
1.01-1.19
0.97-1.11
0.99-1.12
1.00
1.14
1.12
1.18
1.07-1.20
1.04-1.20
1.09-1.28
Abbreviations: 95% CI, 95% confidence interval; AJCC, American Joint
Committee on Cancer; chemoRT, chemoradiotherapy; HR, hazard ratio;
NCI, National Cancer Institute; NH, non-Hispanic.
a
Adjusted for race/ethnicity, age at diagnosis, year of diagnosis, stage of
disease, tumor grade, tumor size, lymph node status, comorbidity score,
US region, facility case volume, facility category, insurance status, median
with no high school diploma, and median income quartile.
b
Pathologic stage of disease was used if the clinical stage was missing.
c
Area-level quartiles for the percentage of adults without a high school
diploma were derived from the 2000 US Census data.
d
Area-level median household income quartiles were derived from the
2000 US Census data.
given within a span of 1 week. This is in stark contrast to
Sweden, where approximately 80% of patients were
reported to receive short-course RT and only 20% of
patients received long-course CRT, based on a recent
analysis of the Swedish National Patient Register.16
Because access to health care, such as the availability of
transportation, and treatment costs prevent US patients
from receiving the standard trimodality therapy,17,18
short-course neoadjuvant RT should be strongly considered as a reasonable and evidence-based alternative. In
general, as the debate over the cost-effectiveness of oncology care in the United States continues, many health care
systems are searching for ways to minimize expensive
treatments in areas in which clinical evidence exists to support the alternative, less costly treatment approaches.
The NCDB is a comprehensive national oncologic
database with detailed information available regarding sociodemographic, tumor, and treatment characteristics.19 Several comparison studies have documented the validity of
NCDB-based analysis.20,21 However, the current study has
several limitations. Despite the fact that the clinical and demographic characteristics of patients in the NCDB have
been shown to be similar to those of patients in the
population-based Surveillance, Epidemiology, and End
Results database,22 the NCDB remains a hospital-based
7
Original Article
cancer registries database and the results may not be generalizable to the US population. There could be underreporting
of the receipt of chemotherapy and RT because these therapies could be administered in the outpatient setting. The
NCDB does not collect information regarding provider/
patient preferences and individual socioeconomic factors,
which could influence receipt of treatment. Finally, an
unadjusted all-cause mortality was used for survival outcomes because the NCDB does not collect cancer-specific
mortality, which may not be reflective of treatment effectiveness but rather dependent on patient selection.
Conclusions
In a large national database, the results of the current
study demonstrated that the use of NACRT before surgery in US patients diagnosed with locally advanced rectal
cancer has substantially increased over the past decade.
However, only approximately one-half of these patients
currently receive the standard therapy as recommended by
national guidelines, which in part could be explained by
socioeconomic barriers. Trimodality therapy is associated
with the best outcomes for these patients, and surgery
alone or definitive CRT should only be reserved for
patients who are unable to tolerate trimodality therapy, or
for carefully selected patients taking part in clinical trials.
FUNDING SUPPORT
Supported by the American Cancer Society Intramural Research
Program.
CONFLICT OF INTEREST DISCLOSURES
Timur Mitin is a practicing radiation oncologist and has received
travel honorarium as a member of the advisory board for Novocure
Inc and has received royalties as a chapter author for UpToDate Inc
for work performed outside of the current study.
AUTHOR CONTRIBUTIONS
Helmneh M. Sineshaw: Study planning, analysis of data,
and article preparation and review. Ahmedin Jemal:
Study planning and article preparation and review.
Charles R. Thomas Jr: Study planning and article preparation and review. Timur Mitin: Study planning, article
preparation and review, and responsibility for the overall
content as guarantor.
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