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Original Investigation Research

Survival in Carcinoma of the Minor Salivary Gland

fined as α < .05. For the survival analysis, days fromdiagnosis to death or the end of the study period were used to measure person-time. We used Kaplan-Meier survival curves to assess unadjusted 5- and 10-year CSS rates and log-rank statistics to assess differences in survival curves. We used multivariable Cox proportional hazards regression models to assess factors related to 5- and 10-year CSS rates. All variables were entered into a singlemodel to test for violations in theproportional haz- ards assumption. Becausehistologic subtype, radiotherapy, and stage violated the proportional hazards assumption andwere adjusted for in our multivariablemodel, we canmake no con- clusions regarding the association between these factors and survival. For 10-year survival analyses, grade also violated the proportional hazards assumption and was adjusted for in the STRATA statement. Of the 5334patientswithMSGcarcinoma included in the study, 2662 were men (49.9%) and 2672 were women (50.1%). Most of the patients were white (3426 [64.2%]) and aged 45 to 74 years (3267 [61.2%]). A nearly even distribution of cases from countieswith high (2869 [53.8%]) and low (2464 [46.2%]) lev- els of poverty was found. When the tumor stage was strati- fied by subsite, the proportion of patients with regional dis- easewas the highest for carcinomas of the nasal cavity and/or paranasal sinus (495 of 843 [58.7%]) and the pharynx (561 of 1130 [49.6%]). Tumors in the larynx (26 of 229 [11.4%]) and na- sal cavity and/or paranasal sinus (111 of 843 [13.2%]) had the highest rate of distant metastases. In terms of histologic sub- type, the 1228 patients with ACC had the highest frequency of regional (600 [48.9%]) and distant (156 [12.7%]) disease. We performed analyses to identify any differences in sur- gical treatment and radiotherapy trends during the study pe- riod. Overall, most of the patients received a form of surgical therapy (3604 [67.6%]). By specifically focusing on surgical trends over time, we found a significant difference between 2005 to 2009 and 1988 to 1994, with adjustment for other fac- tors (odds ratio, 1.35; 95% CI, 1.11-1.67). Therefore, we found more frequent surgical intervention at the end of the study pe- riod comparedwith the initial years. We found no differences in surgical treatment between the other periods and 1988 to 1994. In terms of radiotherapy, we identifiedno significant dif- ferences among the 5-year periods. Overall, patients withACC weremore likely to receive postoperative radiotherapy (816 of 1228 [66.4%]) than were patients with other subtypes. In terms of pathologic characteristics,MEC (1568 [29.4%]), ACC (1228 [23.0%]), and adenocarcinoma (1313 [24.6%]) were the most common histologic subtypes. The number of cases of adenocarcinoma NOS totaled 682 (12.8%). Low- and high- grade adenocarcinoma NOS totaled 493 (9.2%) and 189 (3.5%) cases, respectively. The most frequent sites of primary tumor were the oral cavity (3132 [58.7%]) and pharynx (1130 [21.2%]). Lymph node examination was not performed in most of the cases (4184 [78.4%]). Thesedata are stratifiedbyhistologic sub- type in the Table . Results Demographic and Clinicopathologic Findings

Survival Results Patientswith a primary tumor of the oral cavityhad the highest 5- and 10-year unadjustedCSS rates at 90.1%and84.7%, respec- tively. Thosewith a primary site in the larynx had the lowest 5- and10-yearCSSs,at52.6%and45.3%,respectively.Patientswith MEChad the highest unadjusted 5-year CSS (90.7%) compared with patients with ACC (79.1%), adenocarcinoma (80.8%), and other rare carcinomas (70.1%). Ten-year CSSpatternswere simi- lar to those of 5-year CSS for patientswithMEC (88.6%), adeno- carcinoma (75.5%), andother rarecarcinomas (62.1%); however, the 10-year CSS for patients with ACCwas much lower (62.4%) ( Figure 1 ). Intermsof SEERstage, patientswith isolated local dis- easehada 5-year CSSof 95.3%anda 10-year CSSof 93.0%. Five- and 10- year CSSs for patientswith regional diseasewere 74.9% and 63.4%, respectively; for those with distant disease, 44.8% and 28.8%, respectively. Patientswith low- and high-grade ad- enocarcinomaNOS had 5-year CSSs of 87.1%and47.1%, respec- tively, and 10-year CSSs of 83.8%and 35.3%, respectively. Five- year CSS among patientswho received radiotherapywas 72.9% comparedwith89.1%amongpatientswhodidnot receive radio- therapy. Five-year unadjusted CSSs for patients who received surgery vs surgery with radiotherapy were 93.5% and 79.4%, respectively ( Figure 2 ). We used multivariable Cox proportional hazards regres- sionmodels stratified by histologic subtype, radiotherapy, and stage because these variables did not meet the proportional hazards assumption. For 10-year survival analyses, grade also violated the proportional hazard assumption and was ad- justed for in themodel. Referent categories included oral cav- ity, white race, male sex, being younger than 45 years, not un- dergoing surgery, noLNE, low-grade adenocarcinomaNOS, low poverty areas, and a diagnosis year from 1988 to 1994. The 5-year CSS stratified by histologic subtype was poor- est in patients with MEC located in the larynx (hazard ratio [HR], 5.09; 95% CI, 2.13-12.16), followed by tumors in the na- sal cavity and/or paranasal sinus (HR, 2.84; 95% CI, 1.59- 5.08). Patients 75 years or older also had decreased CSS (HR, 2.98; 95% CI, 1.44-6.18). Compared with patients with MEC who did not undergo surgery, improved CSS was found in pa- tients withMECwho underwent local tumor destruction (HR, 0.20; 95% CI, 0.09-0.47), partial surgery (HR, 0.15; 95% CI, 0.07-0.33), and total surgery (HR, 0.28; 95% CI, 0.15-0.52). The 5-year CSS for patients with ACC stratified by site was worse in patients with ACC located in the pharynx (HR, 2.08; 95% CI, 1.20-3.61), followed by those with tumors located in the nasal cavity and/or paranasal sinus (HR, 1.85; 1.29-2.65). Patients 75 years or older also had decreased CSS (HR, 2.08; 95%CI, 1.28-3.38). Comparedwith patients with ACCwho did not undergo surgery, improvedCSSwas found in patientswith ACC who underwent local tumor destruction (HR, 0.26; 95% CI, 0.14-0.49), partial surgery (HR, 0.29; 95% CI, 0.17-0.47), and total surgery (HR, 0.38; 95% CI, 0.25-0.58). The 5-year CSS for patients with adenocarcinoma strati- fied by site was worse for patients with tumors located in the nasal cavity and/or paranasal sinus (HR, 1.60; 95% CI, 1.03- 2.49). Patients 75 years or older also had significantly de- creased CSS (HR, 5.07; 95%CI, 2.24-11.45). Comparedwith pa- tients with adenocarcinoma who did not undergo surgery,

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