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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) Cancer 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, Cancer Month 00, 2016 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 Cancer Month 00, 2016 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 Cancer Month 00, 2016 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 Cancer Month 00, 2016 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 Cancer Month 00, 2016 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 Cancer Month 00, 2016 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. REFERENCES 1. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2015. CA Cancer J Clin. 2015;65:5-29. 2. Siegel RL, Jemal A, Ward EM. Increase in incidence of colorectal cancer among young men and women in the United States. 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