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Social determinants of health and survivorship in parotid cancer: An analysis of the National Cancer Database
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Social determinants of health and survivorship in parotid cancer: An analysis of the National Cancer Database ⁎
Vanessa C. Stubbsa, ,1, Karthik Rajasekarana, Steven B. Cannadya, Jason G. Newmana, Said A. Ibrahimb, Jason A. Branta a b
Department of Otorhinolaryngology: Head and Neck Surgery, University of Pennsylvania, Philadelphia, PA 19104, United States of America Department of Healthcare Policy & Research, Division of Healthcare Delivery Science & Innovation, Weill Cornell Medicine, New York, NY, United States of America
A R T I C LE I N FO
A B S T R A C T
Keywords: National Cancer Database Parotid gland Parotid neoplasms Parotid cancer Survival Demographics Socioeconomic status Prognostic factors Multivariate analysis
Background: Given the rarity of parotid cancer, there is relatively few data published regarding outcomes. Utilizing the large sample population of the National Cancer Database (NCDB), we aim to examine the relationship between two key social determinants of health, demographics and socioeconomic status (SES), and parotid malignancy survival rates. Methods: Our analytic sample consists of patients with a diagnosis of primary malignancy of the parotid gland between 2004 and 2012 in the NCDB. We used univariable and multivariable Cox proportional hazard models to evaluate the relationship between overall survival rate and two key social determinants of health: demographics and SES. Results: 15,815 cases met inclusion criteria. Average age was 60.1 years and 8255 were male (52.2%). Median overall survival was 121 months with 5-year overall survival of 67.4%. Male sex and older age at diagnosis were associated with poorer overall survival (p < 0.0001). We found that Asian Americans compared to whites had better overall survival (HR 0.75; 95% CI [0.58–0.95]). Black patients had improved survival compared to whites on univariate (HR 0.71; 95% CI [0.64–0.79]); but not multivariate analysis. Hispanic ethnicity and higher education level were protective (HR 0.76 95% CI [0.63–0.91] and HR 0.84 95% CI [0.74–0.96], respectively). We found no significant survival association based on income level. Conclusion: In this national sample of patients with parotid malignancy, a rare form of cancer, we found a significant correlation between important social determinants of health and overall survival rate. Females, Asian-Americans, Hispanics, and patients with higher education level have better overall survival.
1. Introduction Malignancies of the parotid gland comprise a diverse group of rare neoplasms that, as a whole, account for < 6% of head and neck cancers [1]. With its relatively low incidence and wide diversity in histopathological subtypes, parotid malignancy traditionally has been difficult to research on a large scale, leading to a lack of generalizable data regarding epidemiology, diagnosis, treatment and survival outcomes [2]. However, several recent studies have reported an increase in incidence of parotid malignancy, noting an annual percent change of 1.13 between the years of 1973 and 2009, with incidence approximately 8 per 1,000,000 [3,4]. As a consequence of this trend and a rising population of patients affected, the lack of comprehensive data is
becoming more problematic. With increased access to healthcare brought forth by the Affordable Care Act and increasing recognition of the impact of social determinants of health on population outcomes, large national databases that contain data from multiple institutions offer new opportunities to examine variations in healthcare. For rare malignancies such as parotid cancer, these data allow us to examine large numbers of patients over long periods of time while minimizing selection or treatment biases associated with single institutional care. Among social determinants of health, age, sex, race, and socioeconomic status (SES) have previously been found to impact survival in the head and neck cancer population [5–8]. For example, analysis of the Surveillance, Epidemiology, and End Results (SEER) Program for head
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Corresponding author at: Department of Otorhinolaryngology - Head and Neck Surgery, 3400 Spruce Street, 5th Floor Silverstein Building, Philadelphia, PA 19104, United States of America. E-mail address: [email protected] (V.C. Stubbs). 1 Present Address: 1120 NW 14th Street, 5th Floor Department of Otolaryngology, Miami, FL 33139 https://doi.org/10.1016/j.amjoto.2019.102307 Received 19 August 2019 0196-0709/ © 2019 Elsevier Inc. All rights reserved.
Please cite this article as: Vanessa C. Stubbs, et al., Am J Otolaryngol, https://doi.org/10.1016/j.amjoto.2019.102307
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the percentage of people in an area without high school diplomas. Regional composition was defined as ‘Metro’, ‘Urban’, ‘Rural’, and ‘Unknown/unable to be obtained’. Tumor characteristics analyzed included histologic subtype, clinical TNM stage according to the 7th Edition American Joint Committee on Cancer classification, and treatment modality (surgery, radiation, and/ or chemotherapy).
and neck cancer has reported that black patients have a higher proportion of regional and distant spread at diagnosis, less frequently receive a cancer directed treatment, and have poorer overall and relative survival than whites [5,9,10]. While head and neck cancer has been evaluated as a whole, there have been relatively few studies that have examined rare head and neck cancers such as parotid malignancy. To address this knowledge gap, we sought use the National Cancer Database to investigate the impact of social determinants of health on rare cancer survivor rates. We hypothesized that racial/ethnic minorities and patients with low SES would have worse survival rates compared to white patients and those with high SES.
2.3. Statistical analysis Univariate analysis was performed using Pearson χ2 for categorical variables. Unadjusted Kaplan-Meier estimates and log-rank tests were used for univariate comparison of overall survival outcomes, and multivariable Cox proportional hazard models were generated for multivariable comparisons. Variables included in the final multivariable Cox proportional hazard model were: age, sex, race, ethnicity, insurance status, treatment modality, income, comorbidity score, facility type, facility location, education, clinical N stage, clinical T stage, and histological subtype. All data processing and analysis was performed with Microsoft Open R v. 3.3.2 (https://mran.microsoft.com/open/) via RStudio v. 1.1.23 (RStudio, Boston, MA, USA). This study was determined to be exempt by the Institutional Review Board of the institution of the primary author.
2. Methods 2.1. Study sample The National Cancer Database (NCDB) was utilized to obtain overall survival information for patients included with a diagnosis of parotid malignancy. Information for tumors involving the head and neck diagnosed between 2004 and 2012 was obtained from the NCDB on March 4th, 2016. The NCDB is jointly sponsored by the American College of Surgeons and the American Cancer Society and is a clinical oncology database with data collected from > 1500 Commission on Cancer accredited facilities. The NCDB, established in 1989, is a nationwide, facility-based, comprehensive clinical surveillance resource oncology data set that includes > 34 million records and represents > 70% of newly diagnosed cancer cases in the United States (www.facs.org/quality%20programs/cancer/ncdb). The NCDB uses the International Classification of Diseases for Oncology for topography (primary site), and morphology (histology) definitions (WHO, ICD-O). The National Cancer Data Base (NCDB) is a joint project of the Commission on Cancer (CoC) of the American College of Surgeons and the American Cancer Society. The CoC's NCDB and the hospitals participating in the CoC NCDB are the source of the de-identified data used herein; they have not verified and are not responsible for the statistical validity of the data analysis or the conclusions derived by the authors.
3. Results 3.1. Sample characteristics Baseline demographic characteristics are summarized in Table 1. Briefly, the average age was 60.1 years with a slight male predominance (52.2%). The majority of patients were white (83.4%), with black patients comprising 10.5%, Asians making up 3.2%, and unknown or other race with 2.9%. Non-Hispanic patients also composed a majority (88.0%) of patients, with Hispanic patients representing 5.0%. A diverse group of histological subtypes were found, with mucoepidermoid carcinoma representing the most common malignant neoplasm (28.0%), followed by acinic cell carcinoma (17.3%) and adenocarcinoma (10.8%). In the population of patients identified, there was a wide distribution of education levels. Most of the patients in our identified population are from areas in which 7–12.9% of people did not have high school diplomas (32.9%), followed by < 7% (26.1%), then 13–20.9% (23.9%), and 21% or more (15.5%).
2.2. Study measures The primary outcome of interest was overall survival following a diagnosis of parotid malignancy. The NCDB was queried for cases with a primary site of the parotid gland (C07.9). Only cases with behavior code of ‘/3’ were included: ‘Malignant neoplasms stated or presumed to be primary’. Cases were not included if they were recorded as having had surgery at a distant site. For comparison of survival outcomes by tumor type, all histological subtypes representing < 5% of the overall total were grouped as “Other.” Squamous cell carcinoma (SCC) was excluded from our primary analysis as it is unknown whether these lesions were regional metastasis from a cutaneous origin or were truly a primary parotid cancer. Demographic information collected and analyzed included age, sex, race, ethnicity, and comorbid conditions. Race was grouped as ‘White’, ‘Black’, ‘Asian’, and ‘Other/Unknown’. Ethnicity was grouped as ‘Hispanic’, ‘Non-Hispanic’, and ‘Unknown’. Comorbid conditions were measured using the Charlson/Deyo score, a cumulative weighted point value given for the following comorbidities: myocardial infarction, congestive heart failure, peripheral vascular disease, dementia, chronic pulmonary disease, rheumatologic disease, peptic ulcer disease, liver disease, diabetes, hemiplegia or paraplegia, renal disease, and AIDS. Due to the small proportion of cases with a Charlson/Deyo score that exceeds 2, the NCDB truncated the data to 0, 1 and 2 –the later representing > 1. Additional socioeconomic variables obtained included income level, education level, and regional composition of facility type. Income level was recorded as annual income. The NCDB records education level by
3.2. Results from univariate models Univariate analysis of overall survival is displayed in Table 2. Median overall survival was 121 months with a 5-year survival of 67.4% (95% CI [66.5%–68.2%]). On univariate analysis, the overall survival was found to be higher for women than for men (HR 0.54; 95% CI [0.51–0.57]). Younger age at diagnosis was also associated with improved survival with those ages 75 to 100 with a hazard ratio of 6.60 (95% CI [6.05–7.19]) compared to those under 55. Unadjusted KaplanMeier overall survival based on sex and age are shown in Fig. 1. Analysis of race showed significantly lower overall survival in the white population with median 5 and 10 year survival 65.7% (95% CI [64.8–66.7]) and 48.5% (95% CI [46.5–50.6]), respectively. This compared to 5 and 10 year overall survival of 73.8% (95% CI [71.3–76.3]) and 60.6% (95% CI [55.7–65.9]), respectively, for black patients and 81.3% (95% CI [77.2–85.6]) and 74.2% (95% CI [68.1–80.8]), respectively, for Asian patients. Hispanic ethnicity was found to have a higher overall survival rate when compared to the nonHispanic population (HR 0.63 [0.54–0.74]). Unadjusted Kaplan-Meier overall survival based on race and ethnicity are shown in Fig. 1. When examining education level, those from the most educated 2
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areas (< 7% without high school diplomas) were found to have the best overall survival, with hazard ratio of 0.80 [0.73–0.88], p < 0.0001) when compared to the least educated. Compared to the lowest income group (less than $38,000), both those with incomes between $48,000 and $62,999 and above $63,000 had significantly higher 5 and 10 year survival rates with hazard ratios of 0.89 (95% CI [0.82–0.98]) and 0.77 (95% CI [0.71–0.84]), respectively. Unadjusted Kaplan-Meier overall survival based on education and income level are shown in Fig. 2.
Table 1 Demographics and tumor characteristics for all patients. Characteristic
n (%)
Total n Mean age (SD) Sex Male Female Race White Black Asian Other/Unknown Ethnicity Hispanic Non-Hispanic Unknown Histologya Mucoepidermoid carcinoma Acinic cell carcinoma Adenocarcinoma Intraepithelial carcinoma Adenoid cystic carcinoma Carcinoma ex pleomorphic adenoma Epithelial-myoepithelial carcinoma Income Less than $38,000 $38,000–$47,999 $48,000–$62,999 $63,000 and greater NA Education levelb 21% or more 13%–20.9% 7–12.9% Less than 7% NA Regional composition Metro Urban Rural NA Comorbidities (Charlson/Deyo Score) 0 1 2 Clinical T stage T0 T1 T2 T3 T4 (unspecified) T4a T4b Tx NA Clinical N stage N0 N1 N2 (unspecified) N2a N2b N2c N3 NX NA Clinical M stage M0 M1 NA
15,815 60.1 (18.04) 8255 (52.2) 7560 (47.8) 13,188 (83.4) 1663 (10.5) 513 (3.2) 451 (2.9)
3.3. Results from multivariable models Multivariable cox proportional hazard analysis of overall survival is found in Table 3. Female sex remained a significant protective factor for overall survival on multivariate analysis (HR 0.77; 95% CI [0.72–0.82]). Older age at diagnosis was again associated with poorer survival outcomes. As compared to those diagnosed below the age of 55, patients diagnosed between the ages of 55 and 64 had worse overall survival (HR 1.33; 95% CI [1.19–1.49]). With increasing age, this hazard ratio grows, finding a hazard ratio of 1.62 (95% CI [1.43–1.84]) for those diagnosed between the ages of 65 and 74 and 2.94 (95% CI [2.59–3.32]) for those diagnosed over the age of 74. Multivariate analysis found a significant survival advantage of Asian race (HR 0.75; 95% CI [0.60–0.93]), while the difference in survival of the black population compared to whites was not found to be significant (HR 0.90; 95% CI [0.80–1.01]; p = 0.076). There was also no significant difference in survival for those with other/unknown race. Hispanic patients showed better survival outcomes than their nonHispanic counterparts with a hazard ratio 0.76 (95% CI [0.63–0.91]). While a survival advantage persisted on multivariate analysis for the most educated population, there were no significant differences in survival outcomes among different income levels. A survival advantage was seen for these patients in the most educated areas versus those from the least educated areas (> 21% without high school degree) with a hazard ratio of 0.84 (95% CI [0.74–0.96]). There was no significant difference among the intermediate groups compared to the least educated group.
796 (5.0) 13,922 (88.0) 1097 (6.9) 4431 (28.0) 2729 (17.3) 1711 (10.8) 1272 (8.0) 1231 (7.8) 553 (3.5) 395 (2.5) 2468 (15.6) 3579 (22.6) 4040 (25.5) 5459 (34.5) 269 (1.7) 2450 (15.5) 3773 (23.9) 5159 (32.9) 4132 (26.1) 262 (1.7) 12,884 (81.50 2126 (13.4) 281 (1.80 524 (3.3) 13,137 (83.1) 2146 (13.6) 532 (3.4)
4. Discussion In this national sample of patients with parotid malignancy, we found that demographic and socioeconomic disparities exist, with female sex, younger age at diagnosis, Asian race, Hispanic ethnicity, and higher education level associated with improved survival. By utilizing the NCDB, this present study is the largest study focusing on parotid malignancy to date with 15,815 patients included. Due to its rarity, survival outcomes in parotid malignancy have been most often studied in combination with malignancies of all salivary glands, rather than as a separate entity [11–14]. The large database provided by the NCDB has not only allowed for discrete analysis of this rare disease, but also limits the selection and treatment biases that are inherent of single institution studies. Both sex and age have been shown previously to be significant factors in survival in head and neck malignancy, where older age at diagnosis and male sex have had worse survival [5,7,15]. While a study by Wahlberg et al. in 2002 of the National Swedish Cancer Registry also found that females and younger patients with mucoepidermoid carcinoma had higher relative survival rates than males and older patients, the study only had 2465 patients and included both parotid and submandibular gland malignancies as a single entity [11]. A recent NCDB analysis of adenoid cystic carcinoma of all salivary glands by Lee et al. also found that female sex and younger patients had improved overall survival, corresponding to our findings [12]. In the present study, as information on overall survival was obtained, rather than disease-specific survival, it should be noted that other causes of mortality may have preferentially contributed to the lower survival rates in those older at diagnosis.
42 (0.3) 3478 (22.0) 3112 (19.7) 1509 (9.5) 46 (0.3) 1092 (6.9) 323 (2.0) 5749 (36.4) 263 (1.7) 8175 (51.7) 804 (5.1) 228 (1.4) 44 (0.3) 878 (5.6) 76 (0.5) 38 (0.2) 5120 (32.4) 201 (1.3) 14,426 (91.2) 549 (3.5) 200 (1.3)
Abbreviations: SD, standard deviation. a Histologies listed are those representing at least 2% of the sample. b Education level designated as percent in area without high school diploma.
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Table 2 Univariate Cox proportional hazard analysis for overall survival. Characteristic
3-year survival [95% CI]
5-year survival [95% CI]
10-year survival [95% CI]
All Age 0–54 55–64 65–74 75–100 Sex Male Female Race White Black Asian Other/Unknown Ethnicity Non-Hispanic Hispanic Unknown Income Less than $38,000 $38,000–$47,999 $48,000–$62,999 $63,000 and greater Education levela 21% or more 13%–20.9% 7–12.9% Less than 7% Regional composition Metro Urban Rural Comorbiditiesb 0 1 2 Histology Mucoepidermoid carcinoma Acinic cell carcinoma Adenocarcinoma Intraepithelial carcinoma Adenoid cystic carcinoma Other
76.0 [75.3–76.7]
67.4 [66.5–68.2]
50.8 [49.0–52.7]
90.7 81.1 73.2 53.4
86.6 73.6 63.0 39.4
77.8 61.9 41.5 15.0
[89.9–91.5] [79.6–82.5] [71.6–74.9] [52.8–55.1]
[85.6–87.7] [71.9–75.4] [61.0–65.0] [37.6–41.2]
Hazard ratio [95% CI]
p value
[75.2–80.4] [58.9–65.1] [37.1–46.4] [12.1–18.6]
1 (ref) 2.05 [1.86–2.28] 3.22 [2.93–3.55] 6.60 [6.05–7.19]
< 0.0001 < 0.0001 < 0.0001
69.8 [68.7–70.8] 82.7 [81.8–83.7]
59.8 [58.6–61.0] 75.6 [74.5–76.8]
41.6 [39.2–44.2] 61.0 [58.3–63.7]
1 (ref) 0.54 [0.51–0.57]
< 0.0001
74.5 81.1 87.3 87.0
65.7 73.8 81.3 77.9
48.5 60.6 74.2 69.1
[46.5–50.6] [55.7–65.9] [68.1–80.8] [62.5–76.4]
1 (ref) 0.71 [0.64–0.79] 0.48 [0.38–0.59] 0.56 [0.45–0.69]
< 0.0001 < 0.0001 < 0.0001
[73.8–75.3] [79.1–83.1] [84.2–90.6] [83.7–90.4]
[64.8–66.7] [71.3–76.3] [77.2–85.6] [73.5–82.7]
75.4 [74.6–76.2] 83.7 [80.9–86.5] 77.7 [75.2–80.3]
66.8 [65.9–67.7] 77.1 [73.7–80.6] 68.3 [65.4–71.5]
50.4 [48.6–52.4] 63.3 [54.3–73.9] 49.1 [42.6–56.7]
1 (ref) 0.63 [0.54–0.74] 0.94 [0.85–1.05]
< 0.0001 0.29
73.1 74.8 76.2 78.5
[71.2–75.0] [73.3–76.3] [74.8–77.6] [77.4–79.7]
65.3 65.2 66.9 70.9
[63.2–67.5] [63.4–67.1] [65.3–68.6] [69.6–72.3]
46.2 48.9 49.8 56.5
[41.5–51.4] [45.6–52.5] [46.1–53.8] [53.6–59.7]
1 (ref) 0.97 [0.89–1.06] 0.89 [0.82–0.98] 0.77 [0.71–0.84]
0.525 0.014 < 0.0001
74.3 75.4 75.6 78.9
[72.5–76.2] [73.9–76.8] [74.4–76.9] [77.5–80.2]
65.7 66.5 66.9 70.9
[63.6–68.0] [64.8–68.3] [65.4–68.4] [69.4–72.5]
49.4 49.1 49.0 57.3
[44.6–54.7] [45.5–53.0] [45.9–52.3] [54.0–60.8]
1 (ref) 0.97 [0.89–1.06] 0.96 [0.88–1.04] 0.80 [0.73–0.88]
0.53 0.32 < 0.0001
76.8 [76.0–77.5] 73.5 [71.5–75.5] 68.7 [63.1–74.8]
68.3 [67.3–69.2] 65.1 [62.8–67.4] 59.4 [53.0–66.5]
52.0 [50.0–54.0] 47.1 [42.5–52.2] 50.8 [42.3–60.9]
1 (ref) 1.15 [1.06–1.25] 1.30 [1.06–1.58]
< 0.001 0.011
78.0 [77.3–78.8] 68.6 [66.5–70.7] 53.9 [49.5–58.6]
69.9 [69.0–70.8] 57.6 [55.2–60.1] 43.2 [38.4–48.6]
53.9 [51.9–56.0 38.3 [34.1–43.2] 21.4 [14.2–32.3]
1 (ref) 1.57 [1.46–1.70] 2.53 [2.24–2.86]
< 0.0001 < 0.0001
81.5 91.7 60.6 54.1 84.9 68.8
75.2 87.1 48.5 42.0 77.0 57.8
59.1 75.5 31.5 21.3 55.8 40.4
1 (ref) 0.48 [0.42–0.54] 2.45 [2.23–2.68] 3.17 [2.88–3.49] 0.95 [0.83–1.08] 1.78 [1.65–1.92]
< 0.0001 < 0.0001 < 0.0001 0.43 < 0.0001
[80.3–82.8] [90.5–92.8] [58.2–63.0] [51.3–57.1] [82.8–87.1] [69.3–72.2]
[73.8–76.7] [85.7–88.6] [45.9–51.3] [39.0–45.3] [74.3–79.7] [57.8–61.2]
[55.5–62.9] [71.9–79.2] [26.5–37.6] [15.7–29.0] [49.3–63.3] [39.9–46.0]
Abbreviations: CI, confidence interval. Bolded values are statistically significant, p < 0.05. a Education level designated as percent in area without high school diploma. b Comorbidities defined by Charlson/Deyo Score.
at presentation, higher 5 year cumulative incidence of disease progression, higher incidence of distant-stage tumors at diagnosis, as well as a lower likelihood of receiving cancer-directed treatment or cancerdirected surgery when treatment was undergone [10,17,18]. Findings in our study suggest that parotid malignancy, given its diverse histologic composition, may have a different survival profile with regard to race than other cancers of the head and neck that are predominately squamous cell carcinoma. Previous studies examining racial factors on salivary malignancy survival have shown similar results. While evaluating malignancy of all salivary glands using the SEER database, Olarte et al. found that black patients were at a survival disadvantage on univariate analysis, but no significant difference on multivariate analysis. Similarly, in a NCDB study by Lee et al. looking at adenoid cystic carcinoma specifically, no significant difference in survival based on race was found [12]. Although Patel et al. found slightly higher 5-, 10-, 15- and 20-year survival rates for black patients when compared to white patients with acinic cell carcinoma in a SEER analysis, these differences were not statistically significant [14]. This lack of significant difference in black versus white survival by race within the parotid is consistent with our
When looking at race impact in head and neck cancer, this study found improved survival in Asian patients compared to white patients. With the exception of studies focusing on nasopharyngeal carcinoma, in which Asians have been found to have a higher risk of developing the disease, few large studies have looked at impact of Asian race in the head and neck. A retrospective study carried out in British Columbia by Kim et al. examined Asian compared to non-Asian survival outcomes in head and neck non-nasopharyngeal squamous cell carcinoma. In this study of 3036 patients, Asians had larger tumors and were less likely to receive multimodality therapy; however, they did have better overall survival than non-Asians [16]. Within large datasets focusing on parotid malignancy, our study is unique in examining impact of Asian race specifically, rather than grouping Asian race with other non-white/nonblack races. Unlike previous studies examining race effects in head and neck cancer, no difference in overall survival between black and white patients was found in this study. Previously, black race has been associated with a negative survival impact in the head and neck in both single institutional studies and large database studies [6,8,9,15]. Black patients have been found to have higher rates of advanced tumor stage 4
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Fig. 1. Unadjusted Kaplan-Meier overall survival based demographic variables of sex (a), age (b), race (c), and ethnicity (d).
Fig. 2. Unadjusted Kaplan-Meier overall survival based on socioeconomic variables of education level (a) and income (b). Education measured as percentage in the area without high school diploma.
findings. Our study also showed improved overall survival outcomes in the Hispanic population compared to non-Hispanic patients. For parotid malignancy, no significant ethnic differences have been previously
reported in the literature to our knowledge. In head and neck cancer in general, Shavers et al. noted a trend toward decreased survival rates for Hispanics with 2-year overall survival at 47.8% compared to 65.4% for whites, but no statistically significant difference was found [10]. No 5
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where to focus healthcare improvement efforts. A first step in improving quality and scope of care is identifying existing health care disparities. Awareness that these disparities exist can aid health care providers in their counseling and treatment of patients with parotid malignancy, in addition to guiding endeavors to improve care for those specifically at a survival disadvantage. There are several limitations to consider in interpreting our findings. First, while the NCDB is the largest cancer registry in the world and maintenance of data integrity is highly prioritized with standardization of all data reporting, the data is collected retrospectively [21]. The data is limited to characteristics collected in the database. Furthermore, there is lack of verification for coding or misclassification errors in the system. Lastly, even though this study is the largest of its nature, there are still relatively small numbers of patients in certain socioeconomic groups and a non-trivial number of patients whose data is unknown.
Table 3 Multivariable Cox proportional hazard analysis for overall survival. Characteristic Age 0–54 55–64 65–74 75–100 Sex Male Female Race White Black Asian Other/Unknown Ethnicity Non-Hispanic Hispanic Unknown Regional composition Metro Urban Rural Education levela 21% or more 13%–20.9% 7–12.9% Less than 7% Comorbiditiesb 0 1 2 Histology Mucoepidermoid carcinoma Acinic cell carcinoma Adenocarcinoma Intraepithelial carcinoma Adenoid cystic carcinoma Other
Hazard ratio [95% CI]
p value
1 (ref) 1.33 [1.19–1.49] 1.62 [1.43–1.84] 2.94 [2.59–3.32]
< 0.0001 < 0.0001 < 0.0001
1 (ref) 0.77 [0.72–0.82]
< 0.0001
1 (ref) 0.90 [0.80–1.01] 0.75 [0.58–0.95] 0.85 [0.67–1.07]
0.076 0.019 0.159
1 (ref) 0.76 [0.63–0.91] 0.94 [0.84–1.06]
0.003 0.302
1 (ref) 0.97 [0.89–1.07] 0.94 [0.76–1.16]
0.581 0.568
1 (ref) 0.91 [0.83–1.01] 0.95 [0.85–1.06] 0.84 [0.74–0.96]
0.086 0.352 0.011
1 (ref) 1.32 [1.22–1.43] 1.63 [1.44–1.85]
< 0.0001 < 0.0001
1 (ref) 0.61 [0.53–0.69] 1.29 [1.17–1.42] 1.38 [1.25–1.54] 0.82 [0.71–0.95] 1.05 [0.97–1.15]
< 0.0001 < 0.0001 < 0.0001 0.007 0.212
5. Conclusion In summary, in this analysis of a large national cancer dataset we found that female sex, younger age at diagnosis, Asian race, Hispanic ethnicity, and higher education level are significantly associated with improved overall survival in patients with parotid malignancy. Furthermore, we found no significant survival difference for black patients. Future studies are needed to examine the mechanism by which key social determinants of health such as demographics and SES shape survival rates in rare malignancies such as parotid cancer. Such information combined with genotypic data might help lead to more effective treatments against rare cancers. Funding This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. References
Abbreviations: CI, confidence interval. Bolded values are statistically significant, p < 0.05. a Education level designated as percent in area without high school diploma. b Comorbidities defined by Charlson/Deyo Score.
[1] Stenner M, Klussmann JP. Current update on established and novel biomarkers in salivary gland carcinoma pathology and the molecular pathways involved. Eur Arch Otorhinolaryngol 2009;266(3):333–41. [2] Davies L, Welch HG. Epidemiology of head and neck cancer in the United States. Otolaryngol Head Neck Surg 2006;135(3):451–7. [3] Del Signore AG, Megwalu UC. The rising incidence of major salivary gland cancer in the United States. Ear Nose Throat J 2017;96(3):E13–6. [4] Boukheris H, Curtis RE, Land CE, Dores GM. Incidence of carcinoma of the major salivary glands according to the World Health Organization (WHO) classification, 1992–2006: a population-based study in the United States. Cancer Epidemiol Biomarkers Prev 2009;18(11):2899–906. [5] Osazuwa-Peters N, Massa ST, Christopher KM, Walker RJ, Varvares MA. Race and sex disparities in long-term survival of oral and oropharyngeal cancer in the United States. J Cancer Res Clin Oncol 2016;142(2):521–8. [6] Piccirillo JF. Importance of comorbidity in head and neck cancer. Laryngoscope 2000;110(4):593–602. [7] Arbes SJ, Olshan AF, Caplan DJ, Schoenbach VJ, Slade GD, Symons MJ. Factors contributing to the poorer survival of black Americans diagnosed with oral cancer (United States). Cancer Causes Control 1999;10(6):513–23. [8] Ragin CC, Langevin SM, Marzouk M, Grandis J, Taioli E. Determinants of head and neck cancer survival by race. Head Neck 2011;33(8):1092–8. [9] Shiboski CH, Schmidt BL, Jordan RCK. Racial disparity in stage at diagnosis and survival among adults with oral cancer in the US. Community Dent Oral Epidemiol 2007;35(3):233–40. [10] Shavers VL, Harlan LC, Winn D, Davis WW. Racial/ethnic patterns of care for cancers of the oral cavity, pharynx, larynx, sinuses, and salivary glands. Cancer Metastasis Rev 2003;22(1):25–38. [11] Wahlberg P, Anderson H, Biörklund A, Möller T, Perfekt R. Carcinoma of the parotid and submandibular glands—a study of survival in 2465 patients. Oral Oncol 2002;38(7):706–13. [12] Lee A, Givi B, Osborn VW, Schwartz D, Schreiber D. Patterns of care and survival of adjuvant radiation for major salivary adenoid cystic carcinoma. Laryngoscope 2017;127(9):2057–62. [13] Olarte LS, Megwalu UC. The impact of demographic and socioeconomic factors on major salivary gland cancer survival. Otolaryngol Head Neck Surg 2014;150(6):991–8. [14] Patel NR, Sanghvi S, Khan MN, Husain Q, Baredes S, Eloy JA. Demographic trends
disease specific survival difference was found in Hispanic patients compared to white patients in nasopharyngeal cancer [19]. In cancer in general, Hispanics have cancer mortality rates that are similar to nonHispanic whites, with the exception of higher rates in cervical and gastric cancers [20]. The survival advantage noted in our paper is unique. Both education level and income had an impact on survival in this study. Patients from areas with the most high school graduates had a survival advantage over areas with the lowest percentage of graduates on both univariate and multivariate analysis. Higher income was associated with better overall survival on univariate analysis, but did not persist after multivariate correction. This is consistent with findings noted by Olarte et al. in their SEER analysis of major salivary gland malignancies showing a survival impact for both education level and income but only on univariate analysis [13]. There previously had been little data on socioeconomic factors and survival impact in salivary glands specifically; however, Arbes et al. did find a significant impact in oral cancer. Lower education level, lower median household and per capita income, and higher percentages of people below poverty and in the working class were associated with worse overall and disease specific 5-year survival estimates [7]. Our study extends these socioeconomic differences in survival to the parotid gland specifically. By using the NCDB, our study demonstrates that disparities exist within the rare parotid malignancy population. While our findings are likely related to interactions of among different socioeconomic factors as well as access of care, they offer providers crucial information as to 6
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[15] [16]
[17] [18]
National Cancer Database (1998–2012). J Cancer Res Clin Oncol 2016;142(8):1715–26. [19] Patel VJ, Chen N-W, Resto VA. Racial and ethnic disparities in nasopharyngeal cancer survival in the United States. Otolaryngol Head Neck Surg 2017;156(1):122–31. [20] Shavers VL, Brown ML. Racial and ethnic disparities in the receipt of cancer treatment. J Natl Cancer Inst 2002;94(5):334–57. [21] Mohanty S, Bilimoria KY. Comparing national cancer registries: the National Cancer Data Base (NCDB) and the surveillance, epidemiology, and end results (SEER) program. J Surg Oncol 2014;109(7):629–30.
and disease-specific survival in salivary acinic cell carcinoma: an analysis of 1129 cases. Laryngoscope 2014;124(1):172–8. Goodwin WJ, Thomas GR, Parker DF, et al. Unequal burden of head and neck cancer in the United States. Head Neck 2008;30(3):358–71. Kim JD, Chang JT, Moghaddamjou A, et al. Asian and non-Asian disparities in outcomes of non-nasopharyngeal head and neck cancer. Laryngoscope 2017;127(11):2528–33. Zakeri K, MacEwan I, Vazirnia A, et al. Race and competing mortality in advanced head and neck cancer. Oral Oncol 2014;50(1):40–4. Peterson CE, Khosla S, Chen LF, et al. Racial differences in head and neck squamous cell carcinomas among non-Hispanic black and white males identified through the
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Contents lists available at ScienceDirect
Am J Otolaryngol journal homepage: www.elsevier.com/locate/amjoto
Social determinants of health and survivorship in parotid cancer: An analysis of the National Cancer Database ⁎
Vanessa C. Stubbsa, ,1, Karthik Rajasekarana, Steven B. Cannadya, Jason G. Newmana, Said A. Ibrahimb, Jason A. Branta a b
Department of Otorhinolaryngology: Head and Neck Surgery, University of Pennsylvania, Philadelphia, PA 19104, United States of America Department of Healthcare Policy & Research, Division of Healthcare Delivery Science & Innovation, Weill Cornell Medicine, New York, NY, United States of America
A R T I C LE I N FO
A B S T R A C T
Keywords: National Cancer Database Parotid gland Parotid neoplasms Parotid cancer Survival Demographics Socioeconomic status Prognostic factors Multivariate analysis
Background: Given the rarity of parotid cancer, there is relatively few data published regarding outcomes. Utilizing the large sample population of the National Cancer Database (NCDB), we aim to examine the relationship between two key social determinants of health, demographics and socioeconomic status (SES), and parotid malignancy survival rates. Methods: Our analytic sample consists of patients with a diagnosis of primary malignancy of the parotid gland between 2004 and 2012 in the NCDB. We used univariable and multivariable Cox proportional hazard models to evaluate the relationship between overall survival rate and two key social determinants of health: demographics and SES. Results: 15,815 cases met inclusion criteria. Average age was 60.1 years and 8255 were male (52.2%). Median overall survival was 121 months with 5-year overall survival of 67.4%. Male sex and older age at diagnosis were associated with poorer overall survival (p < 0.0001). We found that Asian Americans compared to whites had better overall survival (HR 0.75; 95% CI [0.58–0.95]). Black patients had improved survival compared to whites on univariate (HR 0.71; 95% CI [0.64–0.79]); but not multivariate analysis. Hispanic ethnicity and higher education level were protective (HR 0.76 95% CI [0.63–0.91] and HR 0.84 95% CI [0.74–0.96], respectively). We found no significant survival association based on income level. Conclusion: In this national sample of patients with parotid malignancy, a rare form of cancer, we found a significant correlation between important social determinants of health and overall survival rate. Females, Asian-Americans, Hispanics, and patients with higher education level have better overall survival.
1. Introduction Malignancies of the parotid gland comprise a diverse group of rare neoplasms that, as a whole, account for < 6% of head and neck cancers [1]. With its relatively low incidence and wide diversity in histopathological subtypes, parotid malignancy traditionally has been difficult to research on a large scale, leading to a lack of generalizable data regarding epidemiology, diagnosis, treatment and survival outcomes [2]. However, several recent studies have reported an increase in incidence of parotid malignancy, noting an annual percent change of 1.13 between the years of 1973 and 2009, with incidence approximately 8 per 1,000,000 [3,4]. As a consequence of this trend and a rising population of patients affected, the lack of comprehensive data is
becoming more problematic. With increased access to healthcare brought forth by the Affordable Care Act and increasing recognition of the impact of social determinants of health on population outcomes, large national databases that contain data from multiple institutions offer new opportunities to examine variations in healthcare. For rare malignancies such as parotid cancer, these data allow us to examine large numbers of patients over long periods of time while minimizing selection or treatment biases associated with single institutional care. Among social determinants of health, age, sex, race, and socioeconomic status (SES) have previously been found to impact survival in the head and neck cancer population [5–8]. For example, analysis of the Surveillance, Epidemiology, and End Results (SEER) Program for head
⁎
Corresponding author at: Department of Otorhinolaryngology - Head and Neck Surgery, 3400 Spruce Street, 5th Floor Silverstein Building, Philadelphia, PA 19104, United States of America. E-mail address: [email protected] (V.C. Stubbs). 1 Present Address: 1120 NW 14th Street, 5th Floor Department of Otolaryngology, Miami, FL 33139 https://doi.org/10.1016/j.amjoto.2019.102307 Received 19 August 2019 0196-0709/ © 2019 Elsevier Inc. All rights reserved.
Please cite this article as: Vanessa C. Stubbs, et al., Am J Otolaryngol, https://doi.org/10.1016/j.amjoto.2019.102307
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the percentage of people in an area without high school diplomas. Regional composition was defined as ‘Metro’, ‘Urban’, ‘Rural’, and ‘Unknown/unable to be obtained’. Tumor characteristics analyzed included histologic subtype, clinical TNM stage according to the 7th Edition American Joint Committee on Cancer classification, and treatment modality (surgery, radiation, and/ or chemotherapy).
and neck cancer has reported that black patients have a higher proportion of regional and distant spread at diagnosis, less frequently receive a cancer directed treatment, and have poorer overall and relative survival than whites [5,9,10]. While head and neck cancer has been evaluated as a whole, there have been relatively few studies that have examined rare head and neck cancers such as parotid malignancy. To address this knowledge gap, we sought use the National Cancer Database to investigate the impact of social determinants of health on rare cancer survivor rates. We hypothesized that racial/ethnic minorities and patients with low SES would have worse survival rates compared to white patients and those with high SES.
2.3. Statistical analysis Univariate analysis was performed using Pearson χ2 for categorical variables. Unadjusted Kaplan-Meier estimates and log-rank tests were used for univariate comparison of overall survival outcomes, and multivariable Cox proportional hazard models were generated for multivariable comparisons. Variables included in the final multivariable Cox proportional hazard model were: age, sex, race, ethnicity, insurance status, treatment modality, income, comorbidity score, facility type, facility location, education, clinical N stage, clinical T stage, and histological subtype. All data processing and analysis was performed with Microsoft Open R v. 3.3.2 (https://mran.microsoft.com/open/) via RStudio v. 1.1.23 (RStudio, Boston, MA, USA). This study was determined to be exempt by the Institutional Review Board of the institution of the primary author.
2. Methods 2.1. Study sample The National Cancer Database (NCDB) was utilized to obtain overall survival information for patients included with a diagnosis of parotid malignancy. Information for tumors involving the head and neck diagnosed between 2004 and 2012 was obtained from the NCDB on March 4th, 2016. The NCDB is jointly sponsored by the American College of Surgeons and the American Cancer Society and is a clinical oncology database with data collected from > 1500 Commission on Cancer accredited facilities. The NCDB, established in 1989, is a nationwide, facility-based, comprehensive clinical surveillance resource oncology data set that includes > 34 million records and represents > 70% of newly diagnosed cancer cases in the United States (www.facs.org/quality%20programs/cancer/ncdb). The NCDB uses the International Classification of Diseases for Oncology for topography (primary site), and morphology (histology) definitions (WHO, ICD-O). The National Cancer Data Base (NCDB) is a joint project of the Commission on Cancer (CoC) of the American College of Surgeons and the American Cancer Society. The CoC's NCDB and the hospitals participating in the CoC NCDB are the source of the de-identified data used herein; they have not verified and are not responsible for the statistical validity of the data analysis or the conclusions derived by the authors.
3. Results 3.1. Sample characteristics Baseline demographic characteristics are summarized in Table 1. Briefly, the average age was 60.1 years with a slight male predominance (52.2%). The majority of patients were white (83.4%), with black patients comprising 10.5%, Asians making up 3.2%, and unknown or other race with 2.9%. Non-Hispanic patients also composed a majority (88.0%) of patients, with Hispanic patients representing 5.0%. A diverse group of histological subtypes were found, with mucoepidermoid carcinoma representing the most common malignant neoplasm (28.0%), followed by acinic cell carcinoma (17.3%) and adenocarcinoma (10.8%). In the population of patients identified, there was a wide distribution of education levels. Most of the patients in our identified population are from areas in which 7–12.9% of people did not have high school diplomas (32.9%), followed by < 7% (26.1%), then 13–20.9% (23.9%), and 21% or more (15.5%).
2.2. Study measures The primary outcome of interest was overall survival following a diagnosis of parotid malignancy. The NCDB was queried for cases with a primary site of the parotid gland (C07.9). Only cases with behavior code of ‘/3’ were included: ‘Malignant neoplasms stated or presumed to be primary’. Cases were not included if they were recorded as having had surgery at a distant site. For comparison of survival outcomes by tumor type, all histological subtypes representing < 5% of the overall total were grouped as “Other.” Squamous cell carcinoma (SCC) was excluded from our primary analysis as it is unknown whether these lesions were regional metastasis from a cutaneous origin or were truly a primary parotid cancer. Demographic information collected and analyzed included age, sex, race, ethnicity, and comorbid conditions. Race was grouped as ‘White’, ‘Black’, ‘Asian’, and ‘Other/Unknown’. Ethnicity was grouped as ‘Hispanic’, ‘Non-Hispanic’, and ‘Unknown’. Comorbid conditions were measured using the Charlson/Deyo score, a cumulative weighted point value given for the following comorbidities: myocardial infarction, congestive heart failure, peripheral vascular disease, dementia, chronic pulmonary disease, rheumatologic disease, peptic ulcer disease, liver disease, diabetes, hemiplegia or paraplegia, renal disease, and AIDS. Due to the small proportion of cases with a Charlson/Deyo score that exceeds 2, the NCDB truncated the data to 0, 1 and 2 –the later representing > 1. Additional socioeconomic variables obtained included income level, education level, and regional composition of facility type. Income level was recorded as annual income. The NCDB records education level by
3.2. Results from univariate models Univariate analysis of overall survival is displayed in Table 2. Median overall survival was 121 months with a 5-year survival of 67.4% (95% CI [66.5%–68.2%]). On univariate analysis, the overall survival was found to be higher for women than for men (HR 0.54; 95% CI [0.51–0.57]). Younger age at diagnosis was also associated with improved survival with those ages 75 to 100 with a hazard ratio of 6.60 (95% CI [6.05–7.19]) compared to those under 55. Unadjusted KaplanMeier overall survival based on sex and age are shown in Fig. 1. Analysis of race showed significantly lower overall survival in the white population with median 5 and 10 year survival 65.7% (95% CI [64.8–66.7]) and 48.5% (95% CI [46.5–50.6]), respectively. This compared to 5 and 10 year overall survival of 73.8% (95% CI [71.3–76.3]) and 60.6% (95% CI [55.7–65.9]), respectively, for black patients and 81.3% (95% CI [77.2–85.6]) and 74.2% (95% CI [68.1–80.8]), respectively, for Asian patients. Hispanic ethnicity was found to have a higher overall survival rate when compared to the nonHispanic population (HR 0.63 [0.54–0.74]). Unadjusted Kaplan-Meier overall survival based on race and ethnicity are shown in Fig. 1. When examining education level, those from the most educated 2
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areas (< 7% without high school diplomas) were found to have the best overall survival, with hazard ratio of 0.80 [0.73–0.88], p < 0.0001) when compared to the least educated. Compared to the lowest income group (less than $38,000), both those with incomes between $48,000 and $62,999 and above $63,000 had significantly higher 5 and 10 year survival rates with hazard ratios of 0.89 (95% CI [0.82–0.98]) and 0.77 (95% CI [0.71–0.84]), respectively. Unadjusted Kaplan-Meier overall survival based on education and income level are shown in Fig. 2.
Table 1 Demographics and tumor characteristics for all patients. Characteristic
n (%)
Total n Mean age (SD) Sex Male Female Race White Black Asian Other/Unknown Ethnicity Hispanic Non-Hispanic Unknown Histologya Mucoepidermoid carcinoma Acinic cell carcinoma Adenocarcinoma Intraepithelial carcinoma Adenoid cystic carcinoma Carcinoma ex pleomorphic adenoma Epithelial-myoepithelial carcinoma Income Less than $38,000 $38,000–$47,999 $48,000–$62,999 $63,000 and greater NA Education levelb 21% or more 13%–20.9% 7–12.9% Less than 7% NA Regional composition Metro Urban Rural NA Comorbidities (Charlson/Deyo Score) 0 1 2 Clinical T stage T0 T1 T2 T3 T4 (unspecified) T4a T4b Tx NA Clinical N stage N0 N1 N2 (unspecified) N2a N2b N2c N3 NX NA Clinical M stage M0 M1 NA
15,815 60.1 (18.04) 8255 (52.2) 7560 (47.8) 13,188 (83.4) 1663 (10.5) 513 (3.2) 451 (2.9)
3.3. Results from multivariable models Multivariable cox proportional hazard analysis of overall survival is found in Table 3. Female sex remained a significant protective factor for overall survival on multivariate analysis (HR 0.77; 95% CI [0.72–0.82]). Older age at diagnosis was again associated with poorer survival outcomes. As compared to those diagnosed below the age of 55, patients diagnosed between the ages of 55 and 64 had worse overall survival (HR 1.33; 95% CI [1.19–1.49]). With increasing age, this hazard ratio grows, finding a hazard ratio of 1.62 (95% CI [1.43–1.84]) for those diagnosed between the ages of 65 and 74 and 2.94 (95% CI [2.59–3.32]) for those diagnosed over the age of 74. Multivariate analysis found a significant survival advantage of Asian race (HR 0.75; 95% CI [0.60–0.93]), while the difference in survival of the black population compared to whites was not found to be significant (HR 0.90; 95% CI [0.80–1.01]; p = 0.076). There was also no significant difference in survival for those with other/unknown race. Hispanic patients showed better survival outcomes than their nonHispanic counterparts with a hazard ratio 0.76 (95% CI [0.63–0.91]). While a survival advantage persisted on multivariate analysis for the most educated population, there were no significant differences in survival outcomes among different income levels. A survival advantage was seen for these patients in the most educated areas versus those from the least educated areas (> 21% without high school degree) with a hazard ratio of 0.84 (95% CI [0.74–0.96]). There was no significant difference among the intermediate groups compared to the least educated group.
796 (5.0) 13,922 (88.0) 1097 (6.9) 4431 (28.0) 2729 (17.3) 1711 (10.8) 1272 (8.0) 1231 (7.8) 553 (3.5) 395 (2.5) 2468 (15.6) 3579 (22.6) 4040 (25.5) 5459 (34.5) 269 (1.7) 2450 (15.5) 3773 (23.9) 5159 (32.9) 4132 (26.1) 262 (1.7) 12,884 (81.50 2126 (13.4) 281 (1.80 524 (3.3) 13,137 (83.1) 2146 (13.6) 532 (3.4)
4. Discussion In this national sample of patients with parotid malignancy, we found that demographic and socioeconomic disparities exist, with female sex, younger age at diagnosis, Asian race, Hispanic ethnicity, and higher education level associated with improved survival. By utilizing the NCDB, this present study is the largest study focusing on parotid malignancy to date with 15,815 patients included. Due to its rarity, survival outcomes in parotid malignancy have been most often studied in combination with malignancies of all salivary glands, rather than as a separate entity [11–14]. The large database provided by the NCDB has not only allowed for discrete analysis of this rare disease, but also limits the selection and treatment biases that are inherent of single institution studies. Both sex and age have been shown previously to be significant factors in survival in head and neck malignancy, where older age at diagnosis and male sex have had worse survival [5,7,15]. While a study by Wahlberg et al. in 2002 of the National Swedish Cancer Registry also found that females and younger patients with mucoepidermoid carcinoma had higher relative survival rates than males and older patients, the study only had 2465 patients and included both parotid and submandibular gland malignancies as a single entity [11]. A recent NCDB analysis of adenoid cystic carcinoma of all salivary glands by Lee et al. also found that female sex and younger patients had improved overall survival, corresponding to our findings [12]. In the present study, as information on overall survival was obtained, rather than disease-specific survival, it should be noted that other causes of mortality may have preferentially contributed to the lower survival rates in those older at diagnosis.
42 (0.3) 3478 (22.0) 3112 (19.7) 1509 (9.5) 46 (0.3) 1092 (6.9) 323 (2.0) 5749 (36.4) 263 (1.7) 8175 (51.7) 804 (5.1) 228 (1.4) 44 (0.3) 878 (5.6) 76 (0.5) 38 (0.2) 5120 (32.4) 201 (1.3) 14,426 (91.2) 549 (3.5) 200 (1.3)
Abbreviations: SD, standard deviation. a Histologies listed are those representing at least 2% of the sample. b Education level designated as percent in area without high school diploma.
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Table 2 Univariate Cox proportional hazard analysis for overall survival. Characteristic
3-year survival [95% CI]
5-year survival [95% CI]
10-year survival [95% CI]
All Age 0–54 55–64 65–74 75–100 Sex Male Female Race White Black Asian Other/Unknown Ethnicity Non-Hispanic Hispanic Unknown Income Less than $38,000 $38,000–$47,999 $48,000–$62,999 $63,000 and greater Education levela 21% or more 13%–20.9% 7–12.9% Less than 7% Regional composition Metro Urban Rural Comorbiditiesb 0 1 2 Histology Mucoepidermoid carcinoma Acinic cell carcinoma Adenocarcinoma Intraepithelial carcinoma Adenoid cystic carcinoma Other
76.0 [75.3–76.7]
67.4 [66.5–68.2]
50.8 [49.0–52.7]
90.7 81.1 73.2 53.4
86.6 73.6 63.0 39.4
77.8 61.9 41.5 15.0
[89.9–91.5] [79.6–82.5] [71.6–74.9] [52.8–55.1]
[85.6–87.7] [71.9–75.4] [61.0–65.0] [37.6–41.2]
Hazard ratio [95% CI]
p value
[75.2–80.4] [58.9–65.1] [37.1–46.4] [12.1–18.6]
1 (ref) 2.05 [1.86–2.28] 3.22 [2.93–3.55] 6.60 [6.05–7.19]
< 0.0001 < 0.0001 < 0.0001
69.8 [68.7–70.8] 82.7 [81.8–83.7]
59.8 [58.6–61.0] 75.6 [74.5–76.8]
41.6 [39.2–44.2] 61.0 [58.3–63.7]
1 (ref) 0.54 [0.51–0.57]
< 0.0001
74.5 81.1 87.3 87.0
65.7 73.8 81.3 77.9
48.5 60.6 74.2 69.1
[46.5–50.6] [55.7–65.9] [68.1–80.8] [62.5–76.4]
1 (ref) 0.71 [0.64–0.79] 0.48 [0.38–0.59] 0.56 [0.45–0.69]
< 0.0001 < 0.0001 < 0.0001
[73.8–75.3] [79.1–83.1] [84.2–90.6] [83.7–90.4]
[64.8–66.7] [71.3–76.3] [77.2–85.6] [73.5–82.7]
75.4 [74.6–76.2] 83.7 [80.9–86.5] 77.7 [75.2–80.3]
66.8 [65.9–67.7] 77.1 [73.7–80.6] 68.3 [65.4–71.5]
50.4 [48.6–52.4] 63.3 [54.3–73.9] 49.1 [42.6–56.7]
1 (ref) 0.63 [0.54–0.74] 0.94 [0.85–1.05]
< 0.0001 0.29
73.1 74.8 76.2 78.5
[71.2–75.0] [73.3–76.3] [74.8–77.6] [77.4–79.7]
65.3 65.2 66.9 70.9
[63.2–67.5] [63.4–67.1] [65.3–68.6] [69.6–72.3]
46.2 48.9 49.8 56.5
[41.5–51.4] [45.6–52.5] [46.1–53.8] [53.6–59.7]
1 (ref) 0.97 [0.89–1.06] 0.89 [0.82–0.98] 0.77 [0.71–0.84]
0.525 0.014 < 0.0001
74.3 75.4 75.6 78.9
[72.5–76.2] [73.9–76.8] [74.4–76.9] [77.5–80.2]
65.7 66.5 66.9 70.9
[63.6–68.0] [64.8–68.3] [65.4–68.4] [69.4–72.5]
49.4 49.1 49.0 57.3
[44.6–54.7] [45.5–53.0] [45.9–52.3] [54.0–60.8]
1 (ref) 0.97 [0.89–1.06] 0.96 [0.88–1.04] 0.80 [0.73–0.88]
0.53 0.32 < 0.0001
76.8 [76.0–77.5] 73.5 [71.5–75.5] 68.7 [63.1–74.8]
68.3 [67.3–69.2] 65.1 [62.8–67.4] 59.4 [53.0–66.5]
52.0 [50.0–54.0] 47.1 [42.5–52.2] 50.8 [42.3–60.9]
1 (ref) 1.15 [1.06–1.25] 1.30 [1.06–1.58]
< 0.001 0.011
78.0 [77.3–78.8] 68.6 [66.5–70.7] 53.9 [49.5–58.6]
69.9 [69.0–70.8] 57.6 [55.2–60.1] 43.2 [38.4–48.6]
53.9 [51.9–56.0 38.3 [34.1–43.2] 21.4 [14.2–32.3]
1 (ref) 1.57 [1.46–1.70] 2.53 [2.24–2.86]
< 0.0001 < 0.0001
81.5 91.7 60.6 54.1 84.9 68.8
75.2 87.1 48.5 42.0 77.0 57.8
59.1 75.5 31.5 21.3 55.8 40.4
1 (ref) 0.48 [0.42–0.54] 2.45 [2.23–2.68] 3.17 [2.88–3.49] 0.95 [0.83–1.08] 1.78 [1.65–1.92]
< 0.0001 < 0.0001 < 0.0001 0.43 < 0.0001
[80.3–82.8] [90.5–92.8] [58.2–63.0] [51.3–57.1] [82.8–87.1] [69.3–72.2]
[73.8–76.7] [85.7–88.6] [45.9–51.3] [39.0–45.3] [74.3–79.7] [57.8–61.2]
[55.5–62.9] [71.9–79.2] [26.5–37.6] [15.7–29.0] [49.3–63.3] [39.9–46.0]
Abbreviations: CI, confidence interval. Bolded values are statistically significant, p < 0.05. a Education level designated as percent in area without high school diploma. b Comorbidities defined by Charlson/Deyo Score.
at presentation, higher 5 year cumulative incidence of disease progression, higher incidence of distant-stage tumors at diagnosis, as well as a lower likelihood of receiving cancer-directed treatment or cancerdirected surgery when treatment was undergone [10,17,18]. Findings in our study suggest that parotid malignancy, given its diverse histologic composition, may have a different survival profile with regard to race than other cancers of the head and neck that are predominately squamous cell carcinoma. Previous studies examining racial factors on salivary malignancy survival have shown similar results. While evaluating malignancy of all salivary glands using the SEER database, Olarte et al. found that black patients were at a survival disadvantage on univariate analysis, but no significant difference on multivariate analysis. Similarly, in a NCDB study by Lee et al. looking at adenoid cystic carcinoma specifically, no significant difference in survival based on race was found [12]. Although Patel et al. found slightly higher 5-, 10-, 15- and 20-year survival rates for black patients when compared to white patients with acinic cell carcinoma in a SEER analysis, these differences were not statistically significant [14]. This lack of significant difference in black versus white survival by race within the parotid is consistent with our
When looking at race impact in head and neck cancer, this study found improved survival in Asian patients compared to white patients. With the exception of studies focusing on nasopharyngeal carcinoma, in which Asians have been found to have a higher risk of developing the disease, few large studies have looked at impact of Asian race in the head and neck. A retrospective study carried out in British Columbia by Kim et al. examined Asian compared to non-Asian survival outcomes in head and neck non-nasopharyngeal squamous cell carcinoma. In this study of 3036 patients, Asians had larger tumors and were less likely to receive multimodality therapy; however, they did have better overall survival than non-Asians [16]. Within large datasets focusing on parotid malignancy, our study is unique in examining impact of Asian race specifically, rather than grouping Asian race with other non-white/nonblack races. Unlike previous studies examining race effects in head and neck cancer, no difference in overall survival between black and white patients was found in this study. Previously, black race has been associated with a negative survival impact in the head and neck in both single institutional studies and large database studies [6,8,9,15]. Black patients have been found to have higher rates of advanced tumor stage 4
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Fig. 1. Unadjusted Kaplan-Meier overall survival based demographic variables of sex (a), age (b), race (c), and ethnicity (d).
Fig. 2. Unadjusted Kaplan-Meier overall survival based on socioeconomic variables of education level (a) and income (b). Education measured as percentage in the area without high school diploma.
findings. Our study also showed improved overall survival outcomes in the Hispanic population compared to non-Hispanic patients. For parotid malignancy, no significant ethnic differences have been previously
reported in the literature to our knowledge. In head and neck cancer in general, Shavers et al. noted a trend toward decreased survival rates for Hispanics with 2-year overall survival at 47.8% compared to 65.4% for whites, but no statistically significant difference was found [10]. No 5
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where to focus healthcare improvement efforts. A first step in improving quality and scope of care is identifying existing health care disparities. Awareness that these disparities exist can aid health care providers in their counseling and treatment of patients with parotid malignancy, in addition to guiding endeavors to improve care for those specifically at a survival disadvantage. There are several limitations to consider in interpreting our findings. First, while the NCDB is the largest cancer registry in the world and maintenance of data integrity is highly prioritized with standardization of all data reporting, the data is collected retrospectively [21]. The data is limited to characteristics collected in the database. Furthermore, there is lack of verification for coding or misclassification errors in the system. Lastly, even though this study is the largest of its nature, there are still relatively small numbers of patients in certain socioeconomic groups and a non-trivial number of patients whose data is unknown.
Table 3 Multivariable Cox proportional hazard analysis for overall survival. Characteristic Age 0–54 55–64 65–74 75–100 Sex Male Female Race White Black Asian Other/Unknown Ethnicity Non-Hispanic Hispanic Unknown Regional composition Metro Urban Rural Education levela 21% or more 13%–20.9% 7–12.9% Less than 7% Comorbiditiesb 0 1 2 Histology Mucoepidermoid carcinoma Acinic cell carcinoma Adenocarcinoma Intraepithelial carcinoma Adenoid cystic carcinoma Other
Hazard ratio [95% CI]
p value
1 (ref) 1.33 [1.19–1.49] 1.62 [1.43–1.84] 2.94 [2.59–3.32]
< 0.0001 < 0.0001 < 0.0001
1 (ref) 0.77 [0.72–0.82]
< 0.0001
1 (ref) 0.90 [0.80–1.01] 0.75 [0.58–0.95] 0.85 [0.67–1.07]
0.076 0.019 0.159
1 (ref) 0.76 [0.63–0.91] 0.94 [0.84–1.06]
0.003 0.302
1 (ref) 0.97 [0.89–1.07] 0.94 [0.76–1.16]
0.581 0.568
1 (ref) 0.91 [0.83–1.01] 0.95 [0.85–1.06] 0.84 [0.74–0.96]
0.086 0.352 0.011
1 (ref) 1.32 [1.22–1.43] 1.63 [1.44–1.85]
< 0.0001 < 0.0001
1 (ref) 0.61 [0.53–0.69] 1.29 [1.17–1.42] 1.38 [1.25–1.54] 0.82 [0.71–0.95] 1.05 [0.97–1.15]
< 0.0001 < 0.0001 < 0.0001 0.007 0.212
5. Conclusion In summary, in this analysis of a large national cancer dataset we found that female sex, younger age at diagnosis, Asian race, Hispanic ethnicity, and higher education level are significantly associated with improved overall survival in patients with parotid malignancy. Furthermore, we found no significant survival difference for black patients. Future studies are needed to examine the mechanism by which key social determinants of health such as demographics and SES shape survival rates in rare malignancies such as parotid cancer. Such information combined with genotypic data might help lead to more effective treatments against rare cancers. Funding This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. References
Abbreviations: CI, confidence interval. Bolded values are statistically significant, p < 0.05. a Education level designated as percent in area without high school diploma. b Comorbidities defined by Charlson/Deyo Score.
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disease specific survival difference was found in Hispanic patients compared to white patients in nasopharyngeal cancer [19]. In cancer in general, Hispanics have cancer mortality rates that are similar to nonHispanic whites, with the exception of higher rates in cervical and gastric cancers [20]. The survival advantage noted in our paper is unique. Both education level and income had an impact on survival in this study. Patients from areas with the most high school graduates had a survival advantage over areas with the lowest percentage of graduates on both univariate and multivariate analysis. Higher income was associated with better overall survival on univariate analysis, but did not persist after multivariate correction. This is consistent with findings noted by Olarte et al. in their SEER analysis of major salivary gland malignancies showing a survival impact for both education level and income but only on univariate analysis [13]. There previously had been little data on socioeconomic factors and survival impact in salivary glands specifically; however, Arbes et al. did find a significant impact in oral cancer. Lower education level, lower median household and per capita income, and higher percentages of people below poverty and in the working class were associated with worse overall and disease specific 5-year survival estimates [7]. Our study extends these socioeconomic differences in survival to the parotid gland specifically. By using the NCDB, our study demonstrates that disparities exist within the rare parotid malignancy population. While our findings are likely related to interactions of among different socioeconomic factors as well as access of care, they offer providers crucial information as to 6
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National Cancer Database (1998–2012). J Cancer Res Clin Oncol 2016;142(8):1715–26. [19] Patel VJ, Chen N-W, Resto VA. Racial and ethnic disparities in nasopharyngeal cancer survival in the United States. Otolaryngol Head Neck Surg 2017;156(1):122–31. [20] Shavers VL, Brown ML. Racial and ethnic disparities in the receipt of cancer treatment. J Natl Cancer Inst 2002;94(5):334–57. [21] Mohanty S, Bilimoria KY. Comparing national cancer registries: the National Cancer Data Base (NCDB) and the surveillance, epidemiology, and end results (SEER) program. J Surg Oncol 2014;109(7):629–30.
and disease-specific survival in salivary acinic cell carcinoma: an analysis of 1129 cases. Laryngoscope 2014;124(1):172–8. Goodwin WJ, Thomas GR, Parker DF, et al. Unequal burden of head and neck cancer in the United States. Head Neck 2008;30(3):358–71. Kim JD, Chang JT, Moghaddamjou A, et al. Asian and non-Asian disparities in outcomes of non-nasopharyngeal head and neck cancer. Laryngoscope 2017;127(11):2528–33. Zakeri K, MacEwan I, Vazirnia A, et al. Race and competing mortality in advanced head and neck cancer. Oral Oncol 2014;50(1):40–4. Peterson CE, Khosla S, Chen LF, et al. Racial differences in head and neck squamous cell carcinomas among non-Hispanic black and white males identified through the
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