Clinicopathologic Features of Epithelial Myoepithelial Carcinoma of the Head and Neck: Analysis of Demographics, Clinical Characteristics, and Treatment Modality

Clinicopathologic Features of Epithelial Myoepithelial Carcinoma of the Head and Neck: Analysis of Demographics, Clinical Characteristics, and Treatment Modality | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Clinicopathologic Features of Epithelial Myoepithelial Carcinoma of the Head and Neck: Analysis of Demographics, Clinical Characteristics, and Treatment Modality Kue Tylor Lee, Bisma Tareen, Victoria N. Huynh, Abdul Qahar Khan Yasinzai, and 6 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6265268/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Purpose: Epithelial myoepithelial carcinoma (EMC) is a rare salivary gland malignancy that accounts for less than 1% of salivary gland tumors. Our study evaluates clinicopathologic features of the largest known cohort reported in current literature. Methods: We queried the Surveillance, Epidemiology, and End Results (SEER) database for cases reported between 2000-2018. Demographic and clinicopathologic data were collected, and Cox proportional hazards survival analysis was performed to evaluate for factors impacting overall survival (OS) and cause-specific survival (CSS). Results: Three-hundred eighty-six cases with a median age of 66 were included. EMC was found to occur predominantly in females (56.5%) and in Caucasians (77.6%). Two-hundred forty-seven (71.4%) of cases were localized to the primary site, while 76 (22.0%) had regional disease, and 23 (6.6%) had distant metastases. The majority of patients received surgery monotherapy (51.6%) or surgery with radiation (41.7%). The treatment modality with the highest 5-year CSS was surgery monotherapy (90.9%, 95% Confidence Interval (CI) = 88.1-93.7, p = 0.780). Univariate analysis revealed that increased age, high grade, tumor size of >4.1cm, regional, and distant stage were independent factors that led to poorer prognosis in CSS. Multivariate analysis revealed that increasing age (HR=1.08, 95% CI=1.06-1.11, p <0.001), high grade (HR=11.35, 95% CI=3.35-38.45, p<0.001), and distant stage (HR=7.63, 95% CI=2.00-29.10, p = 0.003) negatively impacted survival is CSS. Conclusion: EMC mainly affects older Caucasian females. Independent variables that led to worse CSS were advanced age, high tumor grade, larger tumor size, and regional and distant stage. Five-year OS and CSS were generally favorable with surgical therapy. Epithelial Myoepithelial Carcinoma Salivary Gland Cancer Epidemiology Kaplan Meier Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Introduction Epithelial-myoepithelial carcinoma (EMC) is a rare, low-grade malignancy of the salivary glands that accounts for approximately 2% of malignant salivary gland epithelial neoplasms.[ 1 ] The majority of EMC cases (60% − 80%) affect the parotid glands while the remaining cases are split between the minor and submandibular salivary glands.[ 2 ] It shows a slight female predilection, and the average age of patients at diagnosis is 60.[ 1 ] Immunohistochemistry and histology are diagnostic of EMC as radiological manifestations are non-specific and cytology may favor a benign process. Histopathologically, EMC is a biphasic neoplasm with both epithelial and myoepithelial elements. 4 Some cases may also present with high-grade transformation, which is commonly associated with poor prognosis.[ 3 ] Generally a poorer prognosis is associated with minor salivary gland location, larger tumor size (> 4 cm), higher proliferation index, and margin status.[ 4 ] EMC is most often treated surgically with radiation traditionally reserved for the adjuvant setting depending on adverse risk factors on final pathology.[ 5 ] At this time, there are no explicit guidelines on the management of tumors that are locally advanced and inoperable.[ 6 ] Considering the histological variety with which EMC may present, further investigation of demographic and tumor characteristics will provide a more comprehensive understanding of prognostically significant clinicopathological features. In 1973, the National Cancer Institute began The Surveillance, Epidemiology, and End Results (SEER) database in order to overview around 28% of the United States (US) cancer patient population. This database was used for our study. Materials and Methods Between 2000–2018, a software known as the SEER*Stat (Version 8.4.0) was utilized in order to compile such data. Using the International Classification of Disease Version 3 (ICD-I-3), anatomical and histological code 8562/3, this particular cohort was able to be founded. Codes 8561, 8550, 8430, and 8200 were excluded. 18 registries in the SEER database were use in order to extract data. This data was then exported to Statistical Package for Social Sciences (SPSS) version 28.0.0.0 for analysis. In this study, both demographic factors and clinical data were included. Demographic and clinical data included age, race, sex, tumor grade, tumor size, lymph node status, metastasis, stage, and treatment received. Ethnicity was not available in the SEER database. Tumor grade was categorized as low (grade I & II) and high (grade III & IV). SEER has its own staging criteria. Localized stage defines cases confined to the organ of origin. Regional stage are cases where the cancer has spread by direct extension to adjacent organs or tissues, and/or spread to lymph nodes considered regional to the organ of origin with no further spread. Distant stage are cases where cancer has spread beyond adjacent organs or tissues, and/or metastasis to distant lymph nodes or tissues. The stage diagnosis is based on clinical diagnosis only with aid of radiography without microscopic confirmation. SPSS was used for demographics statistics and survival factors and trends. Cox proportional hazards regression analysis was utilized to examine associations among demographic factors, tumor characteristics, treatment modality, overall survival (OS), and cause-specific survival (CSS). Categorical data were expressed as proportions and analyzed using the Chi-squared test. Hazard ratios (HR) calculated by the Cox model for continuous variables were calculated by the study endpoint with a predefined unit of increase of the independent variable. Log-rank p values, HR, and 95% confidence intervals (CI) were calculated. Associations and comparisons were visualized graphically using Kaplan-Meier survival plots. Endpoints included OS and CSS. Univariate and multivariate survival analysis was performed to view such associations and assess for independent risk factors from known demographic, clinical, and treatment variables. Cases with unknown variables in multivariate analysis were censored. A two-tailed p-value < 0.05 was considered significant. Results A total of 386 cases were identified from 2000–2018 in the SEER database. 3.1 Demographic Data: The median age in this study was 66. The majority of patients in this study were between 70–79 years old (25.6%), and the majority of patients were females (56.5%), ( Table 1 ). With respect to race, the majority of patients were White (77.6%). 3.2 Tumor Characteristics Regarding grade, when provided, the majority were low grade (81.1%, Table 2 ) When size was provided, the majority of tumor size was between 2.1cm and 4.0cm (40.6%). When lymph node status was known, a small minority (4.7%) were positive while the majority was negative (90.9%). Of those with known tumor stage, the majority of cases were limited to local disease (71.4%). In cases where metastatic status was reported, distant metastasis to the brain, bone, liver, and lung were rare (< 1.5%). 3.3 Treatment Modality Of the total cases, 373 (96.6%) had an unknown chemotherapy status. The majority of cases underwent surgery only (51.6%), followed by both surgery and radiation (N = 161, 41.7%, Fig. 1 ) 3.4 Outcomes and Survival Analysis of Overall and Cause-Specific Survival The overall observed 5-years survival was 77.7% (95% CI = 75.2–80.2) and 5-years cause-specific survival (CSS) was 91.6% (95% CI = 89.9–93.3) (Fig. 2 , Supplemental Table 1) The 1-year and 5-year CSS with surgical resection of the tumor were 96.8% (95.5–98.1) and 93.6% (91.6–95.6). The 1-year and 5-year survival of surgery & radiation were 97.0% (95.5–98.5) and 90.9 (88.1–93.7). Life tables of "chemotherapy only" and "combination therapy" (surgery and adjuvant chemoradiation) were not analyzed due to the small number of cases skewing the data. There was no significant improvement in survival in any of the treatment modalities. There was no significant difference in improvement of OS nor CSS in both surgery and surgery & radiation (Fig. 3 a, b). Neither race nor sex bore significant impact on OS nor CSS (Fig. 4 a-d, Supplemental Table 2, 3). Upon Kaplan-Meier analysis, it was determined that nodal status whether negative or positive was not associated with better or worse outcomes in terms of overall survival (p = 0.321). High grade (p = 0.010), larger tumor size (p < 0.001), and higher stage (p < 0.001) were all associated with a worse OS (Fig. 5 a-d). Upon Kaplan-Meier analysis, higher grade (p < 0.001), larger tumor size (p < 0.001), positive nodal status (p = 0.032) and higher stage (p < 0.001) were all associated with a worse CSS (Fig. 6 a-d). Increasing age was associated with worse OS in both univariable (HR = 1.08, 95% CI = 1.06–1.11, p < 0.001) and multivariable analysis (H.R. = 1.06, 95% CI = (1.03–1.10), p < 0.001). ( Table 3 ) Increasing age was also associated with worse CSS in both univariable (HR = 1.04, 95% CI = 1.01–1.08, p = 0.009) and multivariable analysis (HR = 1.08, 95% CI = 1.02–1.13, p = 0.004). ( Table 4 ) High grade was significantly associated with worse outcomes in univariable (HR = 3.66, 95% CI = 1.60–8.37, p = 0.010) and multivariable analysis in OS (HR = 2.90, 95% CI = 1.53–5.50). ( Table 3 ) High grade was significantly associated with worse outcomes in univariable (HR = 7.60, 95% CI = 2.94–19.68, p < 0.001) and multivariable analysis (HR = 11.35, 95% CI = 3.35–38.45, p < 0.001) in CSS. ( Table 4 ) Greater than 4 cm tumor size was a significant negative prognostic factor in univariable (HR = 3.51, 95% CI = 1.85–6.66, p < 0.001), but not multivariable analysis in OS. ( Table 3 ) Greater than 4 cm tumor size was a significant negative prognostic factor in univariable (HR = 5.35, 95% CI = 1.64–17.4, p = 0.005), but not multivariable analysis in CSS. ( Table 4 ) Distant stage was a significant negative prognostic factor in univariable analysis only in OS (HR = 3.08, 95% CI = 1.61–5.92, p < 0.001). ( Table 3 ) Distant stage was a significant negative prognostic factor in univariable analysis (HR = 10.78, 95% CI = 4.00-29.05, p < 0.001) and multivariable analysis in CSS (HR = 7.63, 95% CI = 2.00-29.10, p = 0.003) ( Table 4 ) Discussion In this study, we performed univariate, multivariate, and Kaplan-Meyer survival analysis of 386 patients from the SEER database with EMC to evaluate for prognostic clinicopathologic factors. In our analysis, we found EMC to occur predominantly in Caucasian females with the majority of tumors localized to the primary site. The majority of patients received surgery monotherapy or surgery with radiation. The treatment modality with the highest 5-year CSS was surgery monotherapy. Multivariate analysis revealed only increasing age amongst factors to negatively impact survival Our analysis demonstrates that many of the demographic patterns observed in EMC align closely with findings from previous literature. The results of the Gore and Vasquez et al study show that EMC is more common in Caucasians, with most cases in their 60s.[ 7 , 8 ] Our study showed similar trends. Our findings also underscore the association between older age and poorer outcomes, a trend supported by existing literature. This correlation may be attributed to older patients exhibiting a higher rate of dedifferentiation, resulting in a rapid transition of the myoepithelial component into a high-grade component.[ 9 , 10 ] Our study did not find a correlation between sex and survival outcomes, consistent with literature suggesting that, morphologically and molecularly, sex does not influence the subsets of EMC, leading to similar EMC types among both males and females[ 4 ]. Furthermore, our analysis indicates no disparities in survival rates among different racial groups, although this observation may be influenced by limited statistical power. This finding is particularly noteworthy considering that race often impacts survival outcomes in other types of salivary gland tumors. For instance, in various head and neck cancers, African American patients typically experience significantly worse prognoses, possibly attributable to factors such as patient comorbidities, socioeconomic status, and treatment modalities[ 11 ]. Notably, Cheung et al. conducted a comprehensive analysis of parotid and salivary gland cancer, revealing that, when controlling for various patient factors, race and ethnicity did not significantly impact survival in salivary gland studies.[ 12 ] In the case of EMC salivary gland tumors, race did not emerge as a significant factor influencing survival outcomes. It should be noted that the value of race may be skewed due to the limited number of cases in Black Americans and other cases (Asian, Pacific Islander, American Indian or Alaska Native) in our study. In our study, we found an intriguing trend regarding tumor grade and its impact on survival. When comparing patient with high grade EMC (Grade III&IV) to one with lower grade EMC (Grade I&II), patients with high grade EMC tended to have a worse prognosis.[ 13 ] This represents a new discovery in studies using the SEER database, as previous studies, such as the 1973–2014 SEER database study by Gore and Vazquez, did not consider grade as a predictor of survival.[ 7 , 8 ] Similar to our study however, a retrospective study by Su et al. found that higher grade in EMC is often associated with the need for radiation therapy in addition to the recommended surgical treatment[ 14 ]. Disease stage and tumor size emerged as important prognostic factors in our analysis. In univariate analysis, we observed that an advanced disease stage and a tumor size greater than 4 cm were both associated with a poorer prognosis. This aligns with existing literature, which consistently shows that advanced stage and a tumor size exceeding 5 cm are unfavorable prognostic factors.[ 15 , 16 ] Of these, an NCDB study of EMC performed by Jo et al. also found that, similar to our findings, higher stage was the most significant predictor of survival in malignancies.[ 17 ] Considering our cohort's cutoff was > 4 centimeters and is still a predictor for survival, a 4-centimeter cutoff could potentially serve as a risk factor predictor. The use of surgical resection alone was the treatment method in the majority of cases included in this study. This finding is supported by existing literature, which presents a consensus that surgical resection is the preferred treatment modality for cases of EMC.[ 8 , 18 ] After surgery alone, surgery in combination with radiotherapy is the next most common treatment method followed by combination therapy (surgery, radiation, and chemotherapy). Currently, there are no universal second-line treatment guidelines or clinical trials.[ 19 ] In cases with positive surgical margins or tumor sizes > 4cm as well as cases of distant metastases, radiotherapy or chemotherapy in addition to surgery may also be considered.[ 8 , 20 – 24 ] There is currently no standard chemotherapy regimen for malignant salivary gland tumors or for EMC specifically, and the use of chemotherapy in cases of EMC is not well reported or documented[ 24 ]. Further, there is currently conflicting evidence about whether additional treatment with radiotherapy is beneficial. In this study, we found that while no one treatment method consistently resulted in a better prognosis, surgery with radiation had the highest 5-year survival rate. Similarly, limited evidence from Simpson 1991 suggests that surgical excision and immediate post-operation radiotherapy may be beneficial and decrease recurrence.[ 23 ] However, other studies report no significant survival benefit or poorer survival benefit associated with radiotherapy in addition to surgical resection.[ 1 , 8 ] , [ 24 ] In particular, Vasquez et al. indicated that there is no significant difference in 10-year survival between patients treated with surgery only and patients treated with surgery and radiotherapy.[ 8 ] Additionally, Wockner et al 2023 report radiotherapy and/or chemotherapy in addition to surgery to be associated with decreased rates of cause-free survival and overall survival, but this may be mediated by the use of these therapies in cases with initially poor prognosis.[ 24 ] In this study, in cases where metastatic status was known, 6.6% of cases presented with distant metastases and 1.5% of cases presented with metastases to the brain, bone, liver, and lung. These findings are within the range of previously reported rates of distant metastases. Specifically, existing literature reports that the cases of distant metastases in EMC ranges from 2.6–11%.[ 1 , 7 , 8 , 25 , 26 ] However, other reviews of cases from older iterations of the SEER database report lower rates of distant metastases compared to our findings. In the review of the 1973–2010 SEER database by Vasquez et al., rate of distant metastases was reported to be 4.5%.[ 8 ] Then, in the review of the 1973–2014 SEER database by Gore et al., rate of distant metastases was found to be at 2.6%.[ 7 ] The updated data in the present cohort suggest a reversal in the decrease in rates of distant metastases previously established in the literature. Our study's limitations stem from the incompleteness of information within the SEER database. Missing data in demographic and clinical characteristic categories limited our analysis to cases where data was available, which varied across categories. Comorbidities, which could impact outcomes, were not included in the database. Information on the specific types of surgery, radiotherapy, and chemotherapy administered was also lacking. Additionally, the grading criteria for EMC are not standardized, and many patients had missing grading data. The database did not include information on the type of surgery, whether lymph node dissection was performed, nor margin status reported. There was also no data on the specific chemotherapy regimens used, and details regarding the genomic profiles of the tumors could not be retrieved. Conclusion EMC represents a rare salivary cancer, predominantly affecting older Caucasian females. Our study, the largest in the literature, provides valuable insights into its prognostic clinicopathologic features. We found that older age, high grade, larger tumor size (> 4cm), and regional and distant stage are independent factors associated with a poorer prognosis in EMC patients. Interestingly, we did not observe a clear treatment modality that consistently led to a better prognosis. Surgery only showed the highest 5-year survival rate in our cohort, however. Nevertheless, patients who are appropriately treated with adjuvant radiation will have similar survival rates as those who do not need it, and thus patients meeting such indications should undergo adjuvant treatment. Given the rarity of EMC, it is imperative to continue collecting data and enrolling patients in registries prospectively. This will not only enhance our understanding of the pathogenesis and survival factors of EMC but also guide the development of more effective treatment modalities for this rare malignancy. Declarations Funding This study was not supported by any funding. Conflict of Interest The authors declare that they have no conflict of interest. Ethical Approval For this type of study formal consent is not required. Consent to Participate For this type of study informed consent is not required. Consent for Publication For this type of study consent for publication is not required. Availability to Data and Materials All data analyzed in this study is available publicly through the SEER database. Code Availability Code availability is not applicable for this study. References Okuyama K, Michi Y, Kashima Y, Tomioka H, Hirai H, Yokokawa M, et al. Epithelial-Myoepithelial Carcinoma of the Minor Salivary Glands: Case Series with Comprehensive Review. Diagn Basel Switz 2021;11. https://doi.org/10.3390/diagnostics11112124. Sedassari BT, dos Santos HT, Mariano FV, da Silva Lascane NA, Altemani A, Sousa S. 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Tables Table I: Demographic Factors Variable (n = 386) N (%) Demographic Factors Age (Years) <70 236 (61.2) ≥70 150 (38.8) Sex Female 218 (56.5) Male 168 (43.5) Race White 295 (76.4) Black 44 (11.4) Asian or Pacific Islander 38 (9.8) American Indian or Alaska Natives 3 (0.8) Unknown 6 (1.6) Table II: Tumor Characteristics Variable (n = 386) N (%) Tumor Characteristics Grade Low (Grade I&II) 159 (41.2) High (Grade III&IV) 37 (9.6) Unknown 190 (49.3) SEER Stage Localized 247 (64.0) Regional 76 (19.7) Distant 23 (6.0) Unknown 40 (10.4) Tumor Size 4.1 cm 53 (13.7) Unknown 130 (33.8) Lymph Node Status Negative 179 (46.4) Positive 18 (4.6) Unknown 189 (49.0) Table III: Univariable & Multivariable Analysis of Independent Factors Influencing Overall Survival. Univariable Multivariable Variable (n, %) H.R. (95% C.I) p-value H.R. (95% C.I) p-value Age (Years) 1.08 (1.06-1.11) <0.001* 1.06 (1.03-1.10) <0.001* Grade Low 159, 41.2 1 1 High 37, 9.6 2.24 (1.19-4.22) 0.013* 2.90 (1.53-5.50) 0.001* Size 4.1 cm 53, 13.7 3.51 (1.85-6.66) <0.001* 2.18 (0.81-5.85) 0.122 Stage Localized 247, 64.0 1 1 Regional 76, 19.7 1.21 (0.69-2.12) 0.501 0.15 (0.03-0.65) 0.160 Distant 23, 6.0 3.081 (1.61-5.92) <0.001* 2.06 (0.72-5.88) 0.086 Treatment Surgery Only 199, 51.6 1.39 (0.90-2.15) 0.135 1.44 (0.16-12.58) 0.744 Surgery + Radiation 161, 41.7 0.66 (0.42-1.03) 0.067 0.81 (0.10-6.69) 0.847 *Associated with worse survival outcomes + Associated with better survival outcomes Table IV: Univariable & Multivariable Analysis of Independent Factors Influencing Cause-Specific Survival Univariable Multivariable Variable (n, %) H.R. (95% C.I) p-value H.R. (95% C.I) p-value Age (Years) 1.04 (1.01-1.08) 0.009* 1.08 (1.02-1.13) 0.004* Grade Low 159, 41.2 1 1 High 37, 9.6 7.60 (2.94-19.68) <0.001* 11.35 (3.35-38.45) <0.001* Size 4.1 cm 53, 13.7 5.35 (1.64-17.4) 0.005* 1.98 (0.23-16.93) 0.532 Stage Localized 247, 64.0 1 1 Regional 76, 19.7 4.69 (1.94-11.33) <0.001* 1.60 (0.43-6.00) 0.483 Distant 23, 6.0 10.78 (4.00-29.05) <0.001* 7.63 (2.00-29.10) 0.003* Treatment Surgery Only 199, 51.6 0.78 (0.37-1.64) 0.509 1.52 (0.10-24.03) 0.765 Surgery + Radiation 161, 41.7 0.87 (0.41-1.85) 0.710 0.94 (0.10-9.30) 0.938 *Associated with worse survival outcomes Additional Declarations No competing interests reported. Supplementary Files SupplementalTables.docx Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-6265268","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":432103471,"identity":"324a5a48-4d21-4bbe-87c3-fb6cd8b23cdf","order_by":0,"name":"Kue Tylor Lee","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAz0lEQVRIiWNgGAWjYBACCQbmBgaGCoQAYwNhLSA1ZxCqidTC2EaKFskZiY0PPs6zS5wfkf78wQ8GG9kNBwhokZZIbDacuS05ceONHMPGHoY0Y4Ja5CQS26R5tzEnbpyRw9jAw3A4kRgt7b//zqkHakl/2PiH4T9hLUCHtTEzNhxOnC+RYNjMw3CAsBbJnofNkj3Hjhtv4HljOFvGINl4JiEtEseTD374UVMtO789/cHHNxV2sn2EtMCBAVilAbHKQUC+gRTVo2AUjIJRMKIAADTQSVHuHHrUAAAAAElFTkSuQmCC","orcid":"","institution":"Medical College of Georgia","correspondingAuthor":true,"prefix":"","firstName":"Kue","middleName":"Tylor","lastName":"Lee","suffix":""},{"id":432103472,"identity":"9e1ab2bd-c6b7-4d46-b07a-5b7d0bd5bde8","order_by":1,"name":"Bisma Tareen","email":"","orcid":"","institution":"Bolan Medical College","correspondingAuthor":false,"prefix":"","firstName":"Bisma","middleName":"","lastName":"Tareen","suffix":""},{"id":432103473,"identity":"676af651-adb5-49c2-91f2-fe83288a8c70","order_by":2,"name":"Victoria N. Huynh","email":"","orcid":"","institution":"Medical College of Georgia","correspondingAuthor":false,"prefix":"","firstName":"Victoria","middleName":"N.","lastName":"Huynh","suffix":""},{"id":432103474,"identity":"a921fcdc-4bfa-49f4-b8cb-ed5101df3087","order_by":3,"name":"Abdul Qahar Khan Yasinzai","email":"","orcid":"","institution":"Bolan Medical College","correspondingAuthor":false,"prefix":"","firstName":"Abdul","middleName":"Qahar Khan","lastName":"Yasinzai","suffix":""},{"id":432103475,"identity":"9a24d8a6-9d73-4ba9-b4c7-dda632a20822","order_by":4,"name":"Asif Iqbal","email":"","orcid":"","institution":"Mercy Hospital","correspondingAuthor":false,"prefix":"","firstName":"Asif","middleName":"","lastName":"Iqbal","suffix":""},{"id":432103476,"identity":"8cfac5d6-43c8-447f-b3fd-8c07258d1e07","order_by":5,"name":"Forest Weir","email":"","orcid":"","institution":"Medical College of Georgia at Wellstar MCG Health","correspondingAuthor":false,"prefix":"","firstName":"Forest","middleName":"","lastName":"Weir","suffix":""},{"id":432103477,"identity":"61487ceb-bfe8-450f-bd02-cbf2944ead24","order_by":6,"name":"Michael Groves","email":"","orcid":"","institution":"Medical College of Georgia at Wellstar MCG Health","correspondingAuthor":false,"prefix":"","firstName":"Michael","middleName":"","lastName":"Groves","suffix":""},{"id":432103478,"identity":"5a89e96a-3d18-4f6c-a97c-c4a6dec58fef","order_by":7,"name":"Kenneth Byrd","email":"","orcid":"","institution":"Medical College of Georgia at Wellstar MCG Health","correspondingAuthor":false,"prefix":"","firstName":"Kenneth","middleName":"","lastName":"Byrd","suffix":""},{"id":432103479,"identity":"6d9938bd-2d06-486d-ba1a-34c597ae8afe","order_by":8,"name":"Daniel Sharbel","email":"","orcid":"","institution":"Medical College of Georgia at Wellstar MCG Health","correspondingAuthor":false,"prefix":"","firstName":"Daniel","middleName":"","lastName":"Sharbel","suffix":""},{"id":432103480,"identity":"9883ac83-518e-4f87-9ec4-4e983c103bee","order_by":9,"name":"Asad Ullah","email":"","orcid":"","institution":"Texas Tech University Health Sciences Center","correspondingAuthor":false,"prefix":"","firstName":"Asad","middleName":"","lastName":"Ullah","suffix":""}],"badges":[],"createdAt":"2025-03-20 01:53:13","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6265268/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6265268/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":79176139,"identity":"a485e1c4-11d8-485b-b6f8-21380b5e0c9c","added_by":"auto","created_at":"2025-03-25 09:57:10","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":40043,"visible":true,"origin":"","legend":"\u003cp\u003ePie Chart of Treatment Characteristics\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-6265268/v1/ba3115d1895ad59c12053349.png"},{"id":79177377,"identity":"3a3d9a33-434c-4a98-8847-6da727d66db8","added_by":"auto","created_at":"2025-03-25 10:05:10","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":38907,"visible":true,"origin":"","legend":"\u003cp\u003e(a) Overall Survival (b) Cause-Specific Survival\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-6265268/v1/08018c3906671b0bdc8deabb.png"},{"id":79177374,"identity":"2139632b-d3ef-4012-9e15-c5c9faa42608","added_by":"auto","created_at":"2025-03-25 10:05:10","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":47927,"visible":true,"origin":"","legend":"\u003cp\u003e(a) Overall Survival and (b) Cause-Specific Survival Probabilities of Different Treatment Modalities\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-6265268/v1/51bb9bfa084de7b3c1928e91.png"},{"id":79179252,"identity":"cf529586-b688-42da-b1a4-dfca13852d22","added_by":"auto","created_at":"2025-03-25 10:13:10","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":111842,"visible":true,"origin":"","legend":"\u003cp\u003eSurvival Probability of (a) Overall Survival Race, (b) Overall Survival Sex, (c) Cause-Specific Survival Race, and (d) Cause-Specific Survival Sex\u003c/p\u003e","description":"","filename":"4.png","url":"https://assets-eu.researchsquare.com/files/rs-6265268/v1/f9e7c52570ef721fb7bf9f14.png"},{"id":79176149,"identity":"03e01912-deda-4f59-b232-8a51f76b52b2","added_by":"auto","created_at":"2025-03-25 09:57:10","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":108053,"visible":true,"origin":"","legend":"\u003cp\u003eOverall Survival of (a) Grade, (b) Tumor Size, (c) Lymph Node Status, and (d) Stage\u003c/p\u003e","description":"","filename":"5.png","url":"https://assets-eu.researchsquare.com/files/rs-6265268/v1/93fafe31a07abc2f1c5e878d.png"},{"id":79177372,"identity":"4e1179a7-eda8-4f5b-93a4-192c36022acc","added_by":"auto","created_at":"2025-03-25 10:05:10","extension":"png","order_by":6,"title":"Figure 6","display":"","copyAsset":false,"role":"figure","size":104928,"visible":true,"origin":"","legend":"\u003cp\u003eCause Specific Survival of (a) Grade, (b) Tumor Size, (c) Lymph Node Status, and (d) Stage\u003c/p\u003e","description":"","filename":"6.png","url":"https://assets-eu.researchsquare.com/files/rs-6265268/v1/8e8eac80a03a7fbb702218f3.png"},{"id":80721253,"identity":"65ff3fdd-11d5-4cd7-9045-bd0a58cc1881","added_by":"auto","created_at":"2025-04-16 11:01:44","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1217206,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6265268/v1/4c2da574-a0a9-4e1a-85fa-75c24958b90f.pdf"},{"id":79176141,"identity":"c10eae4a-d825-481e-979f-cf19039b4999","added_by":"auto","created_at":"2025-03-25 09:57:10","extension":"docx","order_by":0,"title":"","display":"","copyAsset":false,"role":"supplement","size":15982,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementalTables.docx","url":"https://assets-eu.researchsquare.com/files/rs-6265268/v1/90c911295be89a9066750927.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Clinicopathologic Features of Epithelial Myoepithelial Carcinoma of the Head and Neck: Analysis of Demographics, Clinical Characteristics, and Treatment Modality","fulltext":[{"header":"Introduction","content":"\u003cp\u003eEpithelial-myoepithelial carcinoma (EMC) is a rare, low-grade malignancy of the salivary glands that accounts for approximately 2% of malignant salivary gland epithelial neoplasms.[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e] The majority of EMC cases (60% \u0026minus;\u0026thinsp;80%) affect the parotid glands while the remaining cases are split between the minor and submandibular salivary glands.[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e] It shows a slight female predilection, and the average age of patients at diagnosis is 60.[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eImmunohistochemistry and histology are diagnostic of EMC as radiological manifestations are non-specific and cytology may favor a benign process. Histopathologically, EMC is a biphasic neoplasm with both epithelial and myoepithelial elements.\u003csup\u003e4\u003c/sup\u003e Some cases may also present with high-grade transformation, which is commonly associated with poor prognosis.[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e] Generally a poorer prognosis is associated with minor salivary gland location, larger tumor size (\u0026gt;\u0026thinsp;4 cm), higher proliferation index, and margin status.[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eEMC is most often treated surgically with radiation traditionally reserved for the adjuvant setting depending on adverse risk factors on final pathology.[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e] At this time, there are no explicit guidelines on the management of tumors that are locally advanced and inoperable.[\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eConsidering the histological variety with which EMC may present, further investigation of demographic and tumor characteristics will provide a more comprehensive understanding of prognostically significant clinicopathological features. In 1973, the National Cancer Institute began The Surveillance, Epidemiology, and End Results (SEER) database in order to overview around 28% of the United States (US) cancer patient population. This database was used for our study.\u003c/p\u003e"},{"header":"Materials and Methods","content":"\u003cp\u003eBetween 2000\u0026ndash;2018, a software known as the SEER*Stat (Version 8.4.0) was utilized in order to compile such data. Using the International Classification of Disease Version 3 (ICD-I-3), anatomical and histological code 8562/3, this particular cohort was able to be founded. Codes 8561, 8550, 8430, and 8200 were excluded. 18 registries in the SEER database were use in order to extract data. This data was then exported to Statistical Package for Social Sciences (SPSS) version 28.0.0.0 for analysis.\u003c/p\u003e \u003cp\u003eIn this study, both demographic factors and clinical data were included. Demographic and clinical data included age, race, sex, tumor grade, tumor size, lymph node status, metastasis, stage, and treatment received. Ethnicity was not available in the SEER database. Tumor grade was categorized as low (grade I \u0026amp; II) and high (grade III \u0026amp; IV). SEER has its own staging criteria. Localized stage defines cases confined to the organ of origin. Regional stage are cases where the cancer has spread by direct extension to adjacent organs or tissues, and/or spread to lymph nodes considered regional to the organ of origin with no further spread. Distant stage are cases where cancer has spread beyond adjacent organs or tissues, and/or metastasis to distant lymph nodes or tissues. The stage diagnosis is based on clinical diagnosis only with aid of radiography without microscopic confirmation.\u003c/p\u003e \u003cp\u003eSPSS was used for demographics statistics and survival factors and trends. Cox proportional hazards regression analysis was utilized to examine associations among demographic factors, tumor characteristics, treatment modality, overall survival (OS), and cause-specific survival (CSS). Categorical data were expressed as proportions and analyzed using the Chi-squared test. Hazard ratios (HR) calculated by the Cox model for continuous variables were calculated by the study endpoint with a predefined unit of increase of the independent variable. Log-rank p values, HR, and 95% confidence intervals (CI) were calculated. Associations and comparisons were visualized graphically using Kaplan-Meier survival plots. Endpoints included OS and CSS. Univariate and multivariate survival analysis was performed to view such associations and assess for independent risk factors from known demographic, clinical, and treatment variables. Cases with unknown variables in multivariate analysis were censored. A two-tailed p-value\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was considered significant.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eA total of 386 cases were identified from 2000\u0026ndash;2018 in the SEER database.\u003c/p\u003e\n\u003ch3\u003e3.1 Demographic Data:\u003c/h3\u003e\n\u003cp\u003eThe median age in this study was 66. The majority of patients in this study were between 70\u0026ndash;79 years old (25.6%), and the majority of patients were females (56.5%), (\u003cb\u003eTable\u0026nbsp;1\u003c/b\u003e). With respect to race, the majority of patients were White (77.6%).\u003c/p\u003e\n\u003ch3\u003e3.2 Tumor Characteristics\u003c/h3\u003e\n\u003cp\u003eRegarding grade, when provided, the majority were low grade (81.1%, \u003cb\u003eTable\u0026nbsp;2\u003c/b\u003e) When size was provided, the majority of tumor size was between 2.1cm and 4.0cm (40.6%). When lymph node status was known, a small minority (4.7%) were positive while the majority was negative (90.9%). Of those with known tumor stage, the majority of cases were limited to local disease (71.4%). In cases where metastatic status was reported, distant metastasis to the brain, bone, liver, and lung were rare (\u0026lt;\u0026thinsp;1.5%).\u003c/p\u003e\n\u003ch3\u003e3.3 Treatment Modality\u003c/h3\u003e\n\u003cp\u003eOf the total cases, 373 (96.6%) had an unknown chemotherapy status. The majority of cases underwent surgery only (51.6%), followed by both surgery and radiation (N\u0026thinsp;=\u0026thinsp;161, 41.7%, Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e1\u003c/span\u003e)\u003c/p\u003e\n\u003ch3\u003e3.4 Outcomes and Survival Analysis of Overall and Cause-Specific Survival\u003c/h3\u003e\n\u003cp\u003eThe overall observed 5-years survival was 77.7% (95% CI\u0026thinsp;=\u0026thinsp;75.2\u0026ndash;80.2) and 5-years cause-specific survival (CSS) was 91.6% (95% CI\u0026thinsp;=\u0026thinsp;89.9\u0026ndash;93.3) (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e2\u003c/span\u003e, Supplemental Table\u0026nbsp;1)\u003c/p\u003e \u003cp\u003eThe 1-year and 5-year CSS with surgical resection of the tumor were 96.8% (95.5\u0026ndash;98.1) and 93.6% (91.6\u0026ndash;95.6). The 1-year and 5-year survival of surgery \u0026amp; radiation were 97.0% (95.5\u0026ndash;98.5) and 90.9 (88.1\u0026ndash;93.7). Life tables of \"chemotherapy only\" and \"combination therapy\" (surgery and adjuvant chemoradiation) were not analyzed due to the small number of cases skewing the data. There was no significant improvement in survival in any of the treatment modalities. There was no significant difference in improvement of OS nor CSS in both surgery and surgery \u0026amp; radiation (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e3\u003c/span\u003ea, b).\u003c/p\u003e \u003cp\u003eNeither race nor sex bore significant impact on OS nor CSS\u003c/p\u003e \u003cp\u003e(Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e4\u003c/span\u003ea-d, Supplemental Table\u0026nbsp;2, 3).\u003c/p\u003e \u003cp\u003eUpon Kaplan-Meier analysis, it was determined that nodal status whether negative or positive was not associated with better or worse outcomes in terms of overall survival (p\u0026thinsp;=\u0026thinsp;0.321). High grade (p\u0026thinsp;=\u0026thinsp;0.010), larger tumor size (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), and higher stage (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) were all associated with a worse OS (Fig.\u0026nbsp;\u003cspan refid=\"Fig6\" class=\"InternalRef\"\u003e5\u003c/span\u003ea-d). Upon Kaplan-Meier analysis, higher grade (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), larger tumor size (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), positive nodal status (p\u0026thinsp;=\u0026thinsp;0.032) and higher stage (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) were all associated with a worse CSS (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e6\u003c/span\u003ea-d).\u003c/p\u003e \u003cp\u003eIncreasing age was associated with worse OS in both univariable (HR\u0026thinsp;=\u0026thinsp;1.08, 95% CI\u0026thinsp;=\u0026thinsp;1.06\u0026ndash;1.11, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) and multivariable analysis (H.R. = 1.06, 95% CI = (1.03\u0026ndash;1.10), p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). (\u003cb\u003eTable\u0026nbsp;3\u003c/b\u003e) Increasing age was also associated with worse CSS in both univariable (HR\u0026thinsp;=\u0026thinsp;1.04, 95% CI\u0026thinsp;=\u0026thinsp;1.01\u0026ndash;1.08, p\u0026thinsp;=\u0026thinsp;0.009) and multivariable analysis (HR\u0026thinsp;=\u0026thinsp;1.08, 95% CI\u0026thinsp;=\u0026thinsp;1.02\u0026ndash;1.13, p\u0026thinsp;=\u0026thinsp;0.004). (\u003cb\u003eTable\u0026nbsp;4\u003c/b\u003e)\u003c/p\u003e \u003cp\u003eHigh grade was significantly associated with worse outcomes in univariable (HR\u0026thinsp;=\u0026thinsp;3.66, 95% CI\u0026thinsp;=\u0026thinsp;1.60\u0026ndash;8.37, p\u0026thinsp;=\u0026thinsp;0.010) and multivariable analysis in OS (HR\u0026thinsp;=\u0026thinsp;2.90, 95% CI\u0026thinsp;=\u0026thinsp;1.53\u0026ndash;5.50). (\u003cb\u003eTable\u0026nbsp;3\u003c/b\u003e) High grade was significantly associated with worse outcomes in univariable (HR\u0026thinsp;=\u0026thinsp;7.60, 95% CI\u0026thinsp;=\u0026thinsp;2.94\u0026ndash;19.68, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) and multivariable analysis (HR\u0026thinsp;=\u0026thinsp;11.35, 95% CI\u0026thinsp;=\u0026thinsp;3.35\u0026ndash;38.45, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) in CSS. (\u003cb\u003eTable\u0026nbsp;4\u003c/b\u003e)\u003c/p\u003e \u003cp\u003eGreater than 4 cm tumor size was a significant negative prognostic factor in univariable (HR\u0026thinsp;=\u0026thinsp;3.51, 95% CI\u0026thinsp;=\u0026thinsp;1.85\u0026ndash;6.66, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), but not multivariable analysis in OS. (\u003cb\u003eTable\u0026nbsp;3\u003c/b\u003e) Greater than 4 cm tumor size was a significant negative prognostic factor in univariable (HR\u0026thinsp;=\u0026thinsp;5.35, 95% CI\u0026thinsp;=\u0026thinsp;1.64\u0026ndash;17.4, p\u0026thinsp;=\u0026thinsp;0.005), but not multivariable analysis in CSS. (\u003cb\u003eTable\u0026nbsp;4\u003c/b\u003e)\u003c/p\u003e \u003cp\u003eDistant stage was a significant negative prognostic factor in univariable analysis only in OS (HR\u0026thinsp;=\u0026thinsp;3.08, 95% CI\u0026thinsp;=\u0026thinsp;1.61\u0026ndash;5.92, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). (\u003cb\u003eTable\u0026nbsp;3\u003c/b\u003e) Distant stage was a significant negative prognostic factor in univariable analysis (HR\u0026thinsp;=\u0026thinsp;10.78, 95% CI\u0026thinsp;=\u0026thinsp;4.00-29.05, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) and multivariable analysis in CSS (HR\u0026thinsp;=\u0026thinsp;7.63, 95% CI\u0026thinsp;=\u0026thinsp;2.00-29.10, p\u0026thinsp;=\u0026thinsp;0.003) (\u003cb\u003eTable\u0026nbsp;4\u003c/b\u003e)\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eIn this study, we performed univariate, multivariate, and Kaplan-Meyer survival analysis of 386 patients from the SEER database with EMC to evaluate for prognostic clinicopathologic factors. In our analysis, we found EMC to occur predominantly in Caucasian females with the majority of tumors localized to the primary site. The majority of patients received surgery monotherapy or surgery with radiation. The treatment modality with the highest 5-year CSS was surgery monotherapy. Multivariate analysis revealed only increasing age amongst factors to negatively impact survival\u003c/p\u003e \u003cp\u003eOur analysis demonstrates that many of the demographic patterns observed in EMC align closely with findings from previous literature. The results of the Gore and Vasquez et al study show that EMC is more common in Caucasians, with most cases in their 60s.[\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e] Our study showed similar trends.\u003c/p\u003e \u003cp\u003eOur findings also underscore the association between older age and poorer outcomes, a trend supported by existing literature. This correlation may be attributed to older patients exhibiting a higher rate of dedifferentiation, resulting in a rapid transition of the myoepithelial component into a high-grade component.[\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e] Our study did not find a correlation between sex and survival outcomes, consistent with literature suggesting that, morphologically and molecularly, sex does not influence the subsets of EMC, leading to similar EMC types among both males and females[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. Furthermore, our analysis indicates no disparities in survival rates among different racial groups, although this observation may be influenced by limited statistical power. This finding is particularly noteworthy considering that race often impacts survival outcomes in other types of salivary gland tumors. For instance, in various head and neck cancers, African American patients typically experience significantly worse prognoses, possibly attributable to factors such as patient comorbidities, socioeconomic status, and treatment modalities[\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. Notably, Cheung et al. conducted a comprehensive analysis of parotid and salivary gland cancer, revealing that, when controlling for various patient factors, race and ethnicity did not significantly impact survival in salivary gland studies.[\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e] In the case of EMC salivary gland tumors, race did not emerge as a significant factor influencing survival outcomes. It should be noted that the value of race may be skewed due to the limited number of cases in Black Americans and other cases (Asian, Pacific Islander, American Indian or Alaska Native) in our study.\u003c/p\u003e \u003cp\u003eIn our study, we found an intriguing trend regarding tumor grade and its impact on survival. When comparing patient with high grade EMC (Grade III\u0026amp;IV) to one with lower grade EMC (Grade I\u0026amp;II), patients with high grade EMC tended to have a worse prognosis.[\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e] This represents a new discovery in studies using the SEER database, as previous studies, such as the 1973\u0026ndash;2014 SEER database study by Gore and Vazquez, did not consider grade as a predictor of survival.[\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e] Similar to our study however, a retrospective study by Su et al. found that higher grade in EMC is often associated with the need for radiation therapy in addition to the recommended surgical treatment[\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. Disease stage and tumor size emerged as important prognostic factors in our analysis. In univariate analysis, we observed that an advanced disease stage and a tumor size greater than 4 cm were both associated with a poorer prognosis. This aligns with existing literature, which consistently shows that advanced stage and a tumor size exceeding 5 cm are unfavorable prognostic factors.[\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e] Of these, an NCDB study of EMC performed by Jo et al. also found that, similar to our findings, higher stage was the most significant predictor of survival in malignancies.[\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e] Considering our cohort's cutoff was \u0026gt;\u0026thinsp;4 centimeters and is still a predictor for survival, a 4-centimeter cutoff could potentially serve as a risk factor predictor.\u003c/p\u003e \u003cp\u003eThe use of surgical resection alone was the treatment method in the majority of cases included in this study. This finding is supported by existing literature, which presents a consensus that surgical resection is the preferred treatment modality for cases of EMC.[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e] After surgery alone, surgery in combination with radiotherapy is the next most common treatment method followed by combination therapy (surgery, radiation, and chemotherapy). Currently, there are no universal second-line treatment guidelines or clinical trials.[\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e] In cases with positive surgical margins or tumor sizes\u0026thinsp;\u0026gt;\u0026thinsp;4cm as well as cases of distant metastases, radiotherapy or chemotherapy in addition to surgery may also be considered.[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan additionalcitationids=\"CR21 CR22 CR23\" citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e] There is currently no standard chemotherapy regimen for malignant salivary gland tumors or for EMC specifically, and the use of chemotherapy in cases of EMC is not well reported or documented[\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]. Further, there is currently conflicting evidence about whether additional treatment with radiotherapy is beneficial. In this study, we found that while no one treatment method consistently resulted in a better prognosis, surgery with radiation had the highest 5-year survival rate. Similarly, limited evidence from Simpson 1991 suggests that surgical excision and immediate post-operation radiotherapy may be beneficial and decrease recurrence.[\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e] However, other studies report no significant survival benefit or poorer survival benefit associated with radiotherapy in addition to surgical resection.[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]\u003csup\u003e,\u003c/sup\u003e[\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e] In particular, Vasquez et al. indicated that there is no significant difference in 10-year survival between patients treated with surgery only and patients treated with surgery and radiotherapy.[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e] Additionally, Wockner et al 2023 report radiotherapy and/or chemotherapy in addition to surgery to be associated with decreased rates of cause-free survival and overall survival, but this may be mediated by the use of these therapies in cases with initially poor prognosis.[\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eIn this study, in cases where metastatic status was known, 6.6% of cases presented with distant metastases and 1.5% of cases presented with metastases to the brain, bone, liver, and lung. These findings are within the range of previously reported rates of distant metastases. Specifically, existing literature reports that the cases of distant metastases in EMC ranges from 2.6\u0026ndash;11%.[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e, \u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e] However, other reviews of cases from older iterations of the SEER database report lower rates of distant metastases compared to our findings. In the review of the 1973\u0026ndash;2010 SEER database by Vasquez et al., rate of distant metastases was reported to be 4.5%.[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e] Then, in the review of the 1973\u0026ndash;2014 SEER database by Gore et al., rate of distant metastases was found to be at 2.6%.[\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e] The updated data in the present cohort suggest a reversal in the decrease in rates of distant metastases previously established in the literature.\u003c/p\u003e \u003cp\u003eOur study's limitations stem from the incompleteness of information within the SEER database. Missing data in demographic and clinical characteristic categories limited our analysis to cases where data was available, which varied across categories. Comorbidities, which could impact outcomes, were not included in the database. Information on the specific types of surgery, radiotherapy, and chemotherapy administered was also lacking. Additionally, the grading criteria for EMC are not standardized, and many patients had missing grading data. The database did not include information on the type of surgery, whether lymph node dissection was performed, nor margin status reported. There was also no data on the specific chemotherapy regimens used, and details regarding the genomic profiles of the tumors could not be retrieved.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eEMC represents a rare salivary cancer, predominantly affecting older Caucasian females. Our study, the largest in the literature, provides valuable insights into its prognostic clinicopathologic features. We found that older age, high grade, larger tumor size (\u0026gt;\u0026thinsp;4cm), and regional and distant stage are independent factors associated with a poorer prognosis in EMC patients. Interestingly, we did not observe a clear treatment modality that consistently led to a better prognosis. Surgery only showed the highest 5-year survival rate in our cohort, however. Nevertheless, patients who are appropriately treated with adjuvant radiation will have similar survival rates as those who do not need it, and thus patients meeting such indications should undergo adjuvant treatment. Given the rarity of EMC, it is imperative to continue collecting data and enrolling patients in registries prospectively. This will not only enhance our understanding of the pathogenesis and survival factors of EMC but also guide the development of more effective treatment modalities for this rare malignancy.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cem\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eThis study was not supported by any funding.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cem\u003e\u003cstrong\u003eConflict of Interest\u003c/strong\u003e\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no conflict of interest.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cem\u003e\u003cstrong\u003eEthical Approval\u003c/strong\u003e\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eFor this type of study formal consent is not required.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cem\u003e\u003cstrong\u003eConsent to Participate\u003c/strong\u003e\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eFor this type of study informed consent is not required.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cem\u003e\u003cstrong\u003eConsent for Publication\u003c/strong\u003e\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eFor this type of study consent for publication is not required.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cem\u003e\u003cstrong\u003eAvailability to Data and Materials\u003c/strong\u003e\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eAll data analyzed in this study is available publicly through the SEER database.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003e\u003cstrong\u003eCode Availability\u0026nbsp;\u003c/strong\u003e\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eCode availability is not applicable for this study.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eOkuyama K, Michi Y, Kashima Y, Tomioka H, Hirai H, Yokokawa M, et al. Epithelial-Myoepithelial Carcinoma of the Minor Salivary Glands: Case Series with Comprehensive Review. Diagn Basel Switz 2021;11. https://doi.org/10.3390/diagnostics11112124.\u003c/li\u003e\n\u003cli\u003eSedassari BT, dos Santos HT, Mariano FV, da Silva Lascane NA, Altemani A, Sousa S. Carcinoma ex pleomorphic adenoma of minor salivary glands with major epithelial-myoepithelial component: clinicopathologic and immunohistochemical study of 3 cases. Ann Diagn Pathol 2015;19:164\u0026ndash;8. https://doi.org/10.1016/j.anndiagpath.2015.03.011.\u003c/li\u003e\n\u003cli\u003eUrano M, Nakaguro M, Yamamoto Y, Hirai H, Tanigawa M, Saigusa N, et al. Diagnostic Significance of HRAS Mutations in Epithelial-Myoepithelial Carcinomas Exhibiting a Broad Histopathologic Spectrum. Am J Surg Pathol 2019;43.\u003c/li\u003e\n\u003cli\u003eEl Hallani S, Udager AM, Bell D, Fonseca I, Thompson LDR, Assaad A, et al. 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BMC Ear Nose Throat Disord 2018;18:15. https://doi.org/10.1186/s12901-018-0063-2.\u003c/li\u003e\n\u003cli\u003eV\u0026aacute;zquez A, Patel TD, D\u0026rsquo;Aguillo CM, Abdou RY, Farver W, Baredes S, et al. Epithelial-Myoepithelial Carcinoma of the Salivary Glands: An Analysis of 246 Cases. Otolaryngol Neck Surg Off J Am Acad Otolaryngol-Head Neck Surg 2015;153:569\u0026ndash;74. https://doi.org/10.1177/0194599815594788.\u003c/li\u003e\n\u003cli\u003eRoy P, Bullock MJ, Perez-Ordo\u0026ntilde;ez B, Dardick I, Weinreb I. Epithelial-myoepithelial carcinoma with high grade transformation. Am J Surg Pathol 2010;34:1258\u0026ndash;65. https://doi.org/10.1097/PAS.0b013e3181e366d2.\u003c/li\u003e\n\u003cli\u003eNagao T. \u0026ldquo;Dedifferentiation\u0026rdquo; and high-grade transformation in salivary gland carcinomas. Head Neck Pathol 2013;7 Suppl 1:S37-47. https://doi.org/10.1007/s12105-013-0458-8.\u003c/li\u003e\n\u003cli\u003eMolina MA, Cheung MC, Perez EA, Byrne MM, Franceschi D, Moffat FL, Livingstone AS, Goodwin WJ, Gutierrez JC, Koniaris LG. African American and poor patients have a dramatically worse prognosis for head and neck cancer: an examination of 20,915 patients. Cancer. 2008 Nov 15;113(10):2797-806. doi: 10.1002/cncr.23889. PMID: 18839393. n.d.\u003c/li\u003e\n\u003cli\u003eCheung MC, Franzmann E, Sola JE, Pincus DJ, Koniaris LG. A comprehensive analysis of parotid and salivary gland cancer: worse outcomes for male gender. J Surg Res 2011;171:151\u0026ndash;8. https://doi.org/10.1016/j.jss.2009.11.721.\u003c/li\u003e\n\u003cli\u003eEllis G.L., Auclair P. Tumors of the Salivary Glands (AFIP Atlas of Tumor Pathology: Series 4) American Registry of Pathology; Washington, DC, USA: 2008. Epithelial-myoepithelial carcinoma; pp. 309\u0026ndash;322. n.d.\u003c/li\u003e\n\u003cli\u003eSu Y-X, Roberts DB, Hanna EY, El-Naggar A, Saylam G, Frank SJ, et al. Risk Factors and Prognosis for Myoepithelial Carcinoma of the Major Salivary Glands. Ann Surg Oncol 2015;22:3701\u0026ndash;7. https://doi.org/10.1245/s10434-015-4389-3.\u003c/li\u003e\n\u003cli\u003eGiridhar P, Gupta P, Mallick S, Upadhyay AD, Rath GK. Impact of adjuvant therapy on survival in patients with myoepithelial carcinoma: A systematic review and individual patient data analysis of 691 patients. Radiother Oncol J Eur Soc Ther Radiol Oncol 2019;140:125\u0026ndash;30. https://doi.org/10.1016/j.radonc.2019.06.017.\u003c/li\u003e\n\u003cli\u003eXiao CC, Baker AB, White-Gilbertson SJ, Day TA. Prognostic Factors in Myoepithelial Carcinoma of the Major Salivary Glands. Otolaryngol Neck Surg Off J Am Acad Otolaryngol-Head Neck Surg 2016;154:1047\u0026ndash;53. https://doi.org/10.1177/0194599816637605.\u003c/li\u003e\n\u003cli\u003eJo V. Myoepithelial Tumors: An Update. Surg Pathol Clin. 2015 Sep;8(3):445-66. doi: 10.1016/j.path.2015.05.005. PMID: 26297065. n.d.\u003c/li\u003e\n\u003cli\u003eYamazaki H, Ota Y, Aoki T, Kaneko A. Lung metastases of epithelial-myoepithelial carcinoma of the parotid gland successfully treated with chemotherapy: a case report. J Oral Maxillofac Surg Off J Am Assoc Oral Maxillofac Surg 2013;71:220\u0026ndash;6. https://doi.org/10.1016/j.joms.2012.03.031.\u003c/li\u003e\n\u003cli\u003eM\u0026auml;kel\u0026auml; R, Arjonen A, Suryo Rahmanto A, H\u0026auml;rm\u0026auml; V, Lehti\u0026ouml; J, Kuopio T, et al. Ex vivo assessment of targeted therapies in a rare metastatic epithelial-myoepithelial carcinoma. Neoplasia N Y N 2020;22:390\u0026ndash;8. https://doi.org/10.1016/j.neo.2020.06.007.\u003c/li\u003e\n\u003cli\u003eCerda T, Sun XS, Vignot S, Marcy P-Y, Baujat B, Baglin A-C, et al. A rationale for chemoradiation (vs radiotherapy) in salivary gland cancers? On behalf of the REFCOR (French rare head and neck cancer network). Crit Rev Oncol Hematol 2014;91:142\u0026ndash;58. https://doi.org/10.1016/j.critrevonc.2014.02.002.\u003c/li\u003e\n\u003cli\u003eCorio RL, Sciubba JJ, Brannon RB, Batsakis JG. Epithelial-myoepithelial carcinoma of intercalated duct origin. A clinicopathologic and ultrastructural assessment of sixteen cases. Oral Surg Oral Med Oral Pathol 1982;53:280\u0026ndash;7. https://doi.org/10.1016/0030-4220(82)90304-8.\u003c/li\u003e\n\u003cli\u003eHamper K, Br\u0026uuml;gmann M, Koppermann R, Caselitz J, Arps H, Askensten U, et al. Epithelial-myoepithelial duct carcinoma of salivary glands: a follow-up and cytophotometric study of 21 cases. J Oral Pathol Med Off Publ Int Assoc Oral Pathol Am Acad Oral Pathol 1989;18:299\u0026ndash;304. https://doi.org/10.1111/j.1600-0714.1989.tb00401.x.\u003c/li\u003e\n\u003cli\u003eSimpson RH, Clarke TJ, Sarsfield PT, Gluckman PG. Epithelial-myoepithelial carcinoma of salivary glands. J Clin Pathol 1991;44:419\u0026ndash;23.\u003c/li\u003e\n\u003cli\u003eWockner RS, Seethala RR, Emeto TI, McCaul JA, Subramaniam SS. Epithelial-myoepithelial carcinoma of the maxillofacial and sinonasal region: a systematic review of presenting characteristics, treatment modalities, and associated outcomes. Int J Oral Maxillofac Surg 2023;52:1\u0026ndash;12. https://doi.org/10.1016/j.ijom.2022.05.005.\u003c/li\u003e\n\u003cli\u003eDimitrijevic MV, Tomanovic NR, Jesic SD, Arsovic NA, Mircic ALJ, Krstic AM. Epithelial-myoepithelial carcinoma--review of clinicopathological and immunohistochemical features. Arch Iran Med 2015;18:218\u0026ndash;22.\u003c/li\u003e\n\u003cli\u003eSeethala RR, Barnes EL, Hunt JL. Epithelial-myoepithelial carcinoma: a review of the clinicopathologic spectrum and immunophenotypic characteristics in 61 tumors of the salivary glands and upper aerodigestive tract. Am J Surg Pathol 2007;31:44\u0026ndash;57. https://doi.org/10.1097/01.pas.0000213314.74423.d8.\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003e\u003cstrong\u003eTable I:\u003c/strong\u003e Demographic Factors\u0026nbsp;\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 310px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eVariable (n = 386)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 137px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;N (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 447px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eDemographic Factors\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 310px;\"\u003e\n \u003cp\u003eAge (Years)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 137px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 310px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026lt;70\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 137px;\"\u003e\n \u003cp\u003e236 (61.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 310px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026ge;70\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 137px;\"\u003e\n \u003cp\u003e150 (38.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 310px;\"\u003e\n \u003cp\u003eSex\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 137px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 310px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;Female\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 137px;\"\u003e\n \u003cp\u003e218 (56.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 310px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;Male\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 137px;\"\u003e\n \u003cp\u003e168 (43.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 310px;\"\u003e\n \u003cp\u003eRace\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 137px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 310px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;White\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 137px;\"\u003e\n \u003cp\u003e295 (76.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 310px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;Black\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 137px;\"\u003e\n \u003cp\u003e44 (11.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 310px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;Asian or Pacific Islander\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 137px;\"\u003e\n \u003cp\u003e38 (9.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 310px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;American Indian or Alaska Natives\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 137px;\"\u003e\n \u003cp\u003e3 (0.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 310px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;Unknown\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 137px;\"\u003e\n \u003cp\u003e6 (1.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cstrong\u003eTable II:\u003c/strong\u003e Tumor Characteristics\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 310px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eVariable (n = 386)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 137px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;N (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 447px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTumor Characteristics\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 310px;\"\u003e\n \u003cp\u003eGrade\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 137px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 310px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;Low (Grade I\u0026amp;II)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 137px;\"\u003e\n \u003cp\u003e159\u0026nbsp;(41.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 310px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;High (Grade III\u0026amp;IV)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 137px;\"\u003e\n \u003cp\u003e37\u0026nbsp;(9.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 310px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;Unknown\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 137px;\"\u003e\n \u003cp\u003e190\u0026nbsp;(49.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 310px;\"\u003e\n \u003cp\u003eSEER Stage\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 137px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 310px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;Localized\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 137px;\"\u003e\n \u003cp\u003e247\u0026nbsp;(64.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 310px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;Regional\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 137px;\"\u003e\n \u003cp\u003e76\u0026nbsp;(19.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 310px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;Distant\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 137px;\"\u003e\n \u003cp\u003e23\u0026nbsp;(6.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 310px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;Unknown\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 137px;\"\u003e\n \u003cp\u003e40\u0026nbsp;(10.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 310px;\"\u003e\n \u003cp\u003eTumor Size\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 137px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 310px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026lt;2.1 cm\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 137px;\"\u003e\n \u003cp\u003e99\u0026nbsp;(25.6)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 310px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;2.1 \u0026ndash; 4.0 cm\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 137px;\"\u003e\n \u003cp\u003e104\u0026nbsp;(26.9)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 310px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026gt;4.1 cm\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 137px;\"\u003e\n \u003cp\u003e53\u0026nbsp;(13.7)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 310px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;Unknown\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 137px;\"\u003e\n \u003cp\u003e130\u0026nbsp;(33.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 310px;\"\u003e\n \u003cp\u003eLymph Node Status\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 137px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 310px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;Negative\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 137px;\"\u003e\n \u003cp\u003e179\u0026nbsp;(46.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 310px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;Positive\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 137px;\"\u003e\n \u003cp\u003e18\u0026nbsp;(4.6)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 310px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;Unknown\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 137px;\"\u003e\n \u003cp\u003e189\u0026nbsp;(49.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable III:\u003c/strong\u003e Univariable \u0026amp; Multivariable Analysis of Independent Factors Influencing Overall Survival.\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"648\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 196px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 72px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 188px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eUnivariable\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMultivariable\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 196px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eVariable\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 72px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e(n, %)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 122px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eH.R. (95% C.I)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ep-value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 126px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eH.R. (95% C.I)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ep-value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 196px;\"\u003e\n \u003cp\u003eAge (Years)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 72px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 122px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 126px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 196px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 72px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 122px;\"\u003e\n \u003cp\u003e1.08 (1.06-1.11)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e\u0026lt;0.001*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 126px;\"\u003e\n \u003cp\u003e1.06 (1.03-1.10)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e\u0026lt;0.001*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 196px;\"\u003e\n \u003cp\u003eGrade\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 72px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 122px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 126px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 196px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;Low\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 72px;\"\u003e\n \u003cp\u003e159, 41.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 122px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 126px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 196px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;High \u0026nbsp; \u0026nbsp;\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 72px;\"\u003e\n \u003cp\u003e37, 9.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 122px;\"\u003e\n \u003cp\u003e2.24 (1.19-4.22)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e0.013*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 126px;\"\u003e\n \u003cp\u003e2.90 (1.53-5.50)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e0.001*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 196px;\"\u003e\n \u003cp\u003eSize\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 72px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 122px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 126px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 196px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026lt;2.1 cm\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003e99, 25.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 122px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 126px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 196px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;2.1 \u0026ndash; 4.0 cm\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003e104, 26.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 122px;\"\u003e\n \u003cp\u003e1.43 (0.75-2.75)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e0.279\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 126px;\"\u003e\n \u003cp\u003e1.31 (0.56-3.04)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e0.534\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 196px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026gt;4.1 cm\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003e53, 13.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 122px;\"\u003e\n \u003cp\u003e3.51 (1.85-6.66)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e\u0026lt;0.001*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 126px;\"\u003e\n \u003cp\u003e2.18 (0.81-5.85)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e0.122\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 196px;\"\u003e\n \u003cp\u003eStage\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 72px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 122px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 126px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 196px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;Localized\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 72px;\"\u003e\n \u003cp\u003e247, 64.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 122px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 126px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 196px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;Regional\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 72px;\"\u003e\n \u003cp\u003e76, 19.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 122px;\"\u003e\n \u003cp\u003e1.21 (0.69-2.12)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e0.501\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 126px;\"\u003e\n \u003cp\u003e0.15 (0.03-0.65)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e0.160\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 196px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;Distant\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 72px;\"\u003e\n \u003cp\u003e23, 6.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 122px;\"\u003e\n \u003cp\u003e3.081 (1.61-5.92)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e\u0026lt;0.001*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 126px;\"\u003e\n \u003cp\u003e2.06 (0.72-5.88)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e0.086\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 196px;\"\u003e\n \u003cp\u003eTreatment\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 72px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 122px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 126px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 196px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;Surgery Only\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 72px;\"\u003e\n \u003cp\u003e199, 51.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 122px;\"\u003e\n \u003cp\u003e1.39 (0.90-2.15)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e0.135\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 126px;\"\u003e\n \u003cp\u003e1.44 (0.16-12.58)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e0.744\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 196px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;Surgery + Radiation\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 72px;\"\u003e\n \u003cp\u003e161, 41.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 122px;\"\u003e\n \u003cp\u003e0.66 (0.42-1.03)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e0.067\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 126px;\"\u003e\n \u003cp\u003e0.81 (0.10-6.69)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e0.847\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e*Associated with worse survival outcomes\u003c/p\u003e\n\u003cp\u003e\u003csup\u003e+\u003c/sup\u003eAssociated with better survival outcomes\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable IV:\u003c/strong\u003e Univariable \u0026amp; Multivariable Analysis of Independent Factors Influencing Cause-Specific Survival\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"648\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 180px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 198px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eUnivariable\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMultivariable\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 180px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eVariable\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e(n, %)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eH.R. (95% C.I)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ep-value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 126px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eH.R. (95% C.I)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ep-value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 180px;\"\u003e\n \u003cp\u003eAge (Years)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 126px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 180px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e1.04 (1.01-1.08)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e0.009*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 126px;\"\u003e\n \u003cp\u003e1.08 (1.02-1.13)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e0.004*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 180px;\"\u003e\n \u003cp\u003eGrade\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 126px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 180px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;Low\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e159, 41.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 126px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 180px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;High \u0026nbsp; \u0026nbsp;\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e37, 9.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e7.60 (2.94-19.68)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e\u0026lt;0.001*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 126px;\"\u003e\n \u003cp\u003e11.35 (3.35-38.45)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e\u0026lt;0.001*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 180px;\"\u003e\n \u003cp\u003eSize\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 126px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 180px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026lt;2.1 cm\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003e99, 25.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 126px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 180px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;2.1 \u0026ndash; 4.0 cm\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003e104, 26.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e1.63 (0.46-5.77)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e0.450\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 126px;\"\u003e\n \u003cp\u003e1.30 (0.20-8.60)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e0.783\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 180px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026gt;4.1 cm\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003e53, 13.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e5.35 (1.64-17.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e0.005*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 126px;\"\u003e\n \u003cp\u003e1.98 (0.23-16.93)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e0.532\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 180px;\"\u003e\n \u003cp\u003eStage\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 126px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 180px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;Localized\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e247, 64.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 126px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 180px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;Regional\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e76, 19.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e4.69 (1.94-11.33)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e\u0026lt;0.001*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 126px;\"\u003e\n \u003cp\u003e1.60 (0.43-6.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e0.483\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 180px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;Distant\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e23, 6.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e10.78 (4.00-29.05)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e\u0026lt;0.001*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 126px;\"\u003e\n \u003cp\u003e7.63 (2.00-29.10)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e0.003*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 180px;\"\u003e\n \u003cp\u003eTreatment\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 126px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 180px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;Surgery Only\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e199, 51.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e0.78 (0.37-1.64)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e0.509\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 126px;\"\u003e\n \u003cp\u003e1.52 (0.10-24.03)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e0.765\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 180px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;Surgery + Radiation\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e161, 41.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e0.87 (0.41-1.85)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e0.710\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 126px;\"\u003e\n \u003cp\u003e0.94 (0.10-9.30)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e0.938\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e*Associated with worse survival outcomes\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Epithelial Myoepithelial Carcinoma, Salivary Gland, Cancer, Epidemiology, Kaplan Meier","lastPublishedDoi":"10.21203/rs.3.rs-6265268/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6265268/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003ePurpose:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eEpithelial myoepithelial carcinoma (EMC) is a rare salivary gland malignancy that accounts for less than 1% of salivary gland tumors. Our study evaluates clinicopathologic features of the largest known cohort reported in current literature.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe queried the Surveillance, Epidemiology, and End Results (SEER) database for cases reported between 2000-2018. Demographic and clinicopathologic data were collected, and Cox proportional hazards survival analysis was performed to evaluate for factors impacting overall survival (OS) and cause-specific survival (CSS).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThree-hundred eighty-six cases with a median age of 66 were included. EMC was found to occur predominantly in females (56.5%) and in Caucasians (77.6%). Two-hundred forty-seven (71.4%) of cases were localized to the primary site, while 76 (22.0%) had regional disease, and 23 (6.6%) had distant metastases. The majority of patients received surgery monotherapy (51.6%) or surgery with radiation (41.7%). The treatment modality with the highest 5-year CSS was surgery monotherapy (90.9%, 95% Confidence Interval (CI) = 88.1-93.7, p = 0.780). Univariate analysis revealed that increased age, high grade, tumor size of \u0026gt;4.1cm, regional, and distant stage were independent factors that led to poorer prognosis in CSS. Multivariate analysis revealed that increasing age (HR=1.08, 95% CI=1.06-1.11, \u003cem\u003ep\u003c/em\u003e\u0026lt;0.001), high grade (HR=11.35, 95% CI=3.35-38.45, p\u0026lt;0.001), and distant stage (HR=7.63, 95% CI=2.00-29.10, p = 0.003) negatively impacted survival is CSS.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eEMC mainly affects older Caucasian females. Independent variables that led to worse CSS were advanced age, high tumor grade, larger tumor size, and regional and distant stage. Five-year OS and CSS were generally favorable with surgical therapy.\u003c/p\u003e","manuscriptTitle":"Clinicopathologic Features of Epithelial Myoepithelial Carcinoma of the Head and Neck: Analysis of Demographics, Clinical Characteristics, and Treatment Modality","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-03-25 09:57:05","doi":"10.21203/rs.3.rs-6265268/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"d3a55db6-430b-4791-8059-9a631628084f","owner":[],"postedDate":"March 25th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-04-16T10:53:33+00:00","versionOfRecord":[],"versionCreatedAt":"2025-03-25 09:57:05","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-6265268","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6265268","identity":"rs-6265268","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}