Adjuvant radiotherapy and survival of patients with squamous cell carcinoma involving the entire tongue: The SEER database analysis

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The Surveillance, Epidemiology, and End Results database was applied to identify patients treated with or without aRT for tongue SCC. The Kaplan–Meier method and log-rank test assessed survival curves for SCC stages stratified by aRT. Hazard ratios were estimated for stage and aRT concerning overall survival (OS) and disease-specific survival (DSS). Propensity-score matching was performed to assess differences in baseline characteristics. We included 3322 cases. The total number of deaths and disease-specific deaths were 1234 (37.15%) and 938 (28.24%), respectively. The Kaplan–Meier curves for 5-year OS and DSS showed that patients receiving aRT had lower and higher survival probabilities during Stages I and IV, respectively (P<0.0001). On Cox regression analysis, aRT and 5-year OS and DSS were positively and negatively associated with Stage I and Stage IV patients, respectively. Sensitivity analysis results were consistent before and after PSM. OS and DSS of Stage II and III patients in the aRT and non-aRT groups were not significantly different (P<0.05). aRT WAS significantly associated with survival benefits and worse survival for Stage IV and I tongue SCC cases, respectively. Figures Figure 1 Figure 2 Figure 3 Introduction Annually, squamous cell carcinoma (SCC) affects more than 650,000 people worldwide, and 330,000 people die from the disease each year [ 1 – 3 ]. Several factors may contribute to the development of oral and oropharyngeal SCC, including tobacco use, alcohol consumption, and human papillomavirus infection [ 4 – 6 ]. In response to the national health campaign and public health awareness, the incidence of oral cancer has declined in general [ 5 , 7 ]. However, several studies have reported that head and neck cancer is becoming more common among young people and women, indicating an epidemiological shift from older adults and men to younger adults and women [ 5 , 8 – 10 ]. Moreover, public health concerns remain significant because of the disease burden. Cancers affecting the anterior two-thirds of the tongue are referred to as carcinomas of the tongue, whereas those affecting the posterior one-third are referred to as base of tongue cancers [ 6 ]. In SCC of the body of the tongue, the malignant clinical characteristics include rapid local invasion and lymph node metastasis, which can result in impaired speech and chewing and, ultimately, affect the patients’ quality of life [ 11 , 12 ]. Although diagnostic techniques and modalities have advanced dramatically in recent years, the overall survival (OS) rate for tongue SCC has been reduced owing to its clinicopathological features [ 13 – 16 ]. Over the past few decades, the therapeutic regimen for SCC has not changed significantly. Various treatments are currently used, including radiotherapy alone or in combination with adjuvant chemotherapy, resection of the primary tumor with or without adjuvant radiotherapy (aRT), and neck dissection [ 1 , 17 ]. Previous studies have found that head and neck cancer patients with high-risk features benefit from postoperative chemotherapy in terms of local-regional control and disease-free survival [ 18 , 19 ]. In contrast, short- and long-term radiation therapies are frequently associated with toxic side effects, including dysgeusia, dysphagia, aspiration, mucositis, soft tissue necrosis, carotid atherosclerosis, stroke, radiation fibrosis, osteoradionecrosis, and cranial neuropathy [ 4 , 20 ]. Radiation therapy regimens are currently topics of controversy. According to some evidence, aRT does not appear have considerable benefits for oral SCC at the early stage [ 21 – 24 ]. Other reports have suggested that aRT is effective, even during the early stages of head and neck SCC [ 25 – 29 ]. However, these studies have limitations. Sandhya et al. and Shim et al. conducted their studies with a limited number of patients [ 21 , 22 ] and Luryi et al. and Sowder et al. did not evaluate the benefits of radiotherapy for each subsite [ 23 , 24 ]. Therefore, there is a need to investigate appropriate groups for postoperative radiotherapy, which can alleviate the side effects of therapeutic regimens and provide patients with a better quality of life. The National Comprehensive Cancer Network treatment guidelines recommend a combination of surgery and radiotherapy as the primary treatment for early-stage oral SCC; however, reports on its effectiveness are limited [ 30 ]. Therefore, we extracted data from the Surveillance, Epidemiology, and End Results (SEER) database, funded by the National Cancer Institute, to address this knowledge gap regarding the effect of radiotherapy on survival in patients with entire tongue SCC. This study was designed to examine the effects of aRT on patients by using the SEER database with different stages of SCC involving the entire tongue body (including the frontal two-thirds of the tongue and base of the tongue), identify the most suitable group of patients for aRT, and reduce unnecessary therapeutic procedures. Results Patient characteristics Initially, the data of 13379 SCC patients were retrieved from the SEER database between 2004 and 2015. After excluding 6659 cases coded with surg prim site code 0 (none, no surgery of primary site; autopsy only), 446 patients with Tx, 29 patients with Nx, 36 patients with Mx, 17 patients with surg prim site code 99 (unknown if surgery was performed; death certificate only), 2749 patients with a follow-up duration < 5 years, and 121 cases recorded with missing data, a total of 3322 patients were enrolled for the final analysis (Fig. 1 ). Among them, 3322 cases had 5-year OS data and 3026 cases had 5-year disease-free survival (DSS) data. These patients were predominantly men (63.73%); 36.27% of the patients were women. The total number of deaths and disease-specific deaths (DSDs) were 1234 (37.15%) and 938 (28.24%), respectively. Based on the therapeutic regimens, we classified the included patients into two groups, surgery with and without aRT, and compared the baseline characteristics of the two groups. The differences in age, sex, race, primary site, grade, chemotherapy, stage, and TN classification were significant (P 0.05), in the initial data (Table 1 ). Table 1 Baseline characteristics of aRT receivers and non-aRT receivers (2004–2015) aRT P-value No (n = 1709) Yes (n = 1613) Age < 0.001 30–49 years 373 (21.83%) 352 (21.82%) 50–59 years 446 (26.10%) 570 (35.34%) 60–69 years 420 (24.58%) 446 (27.65%) ≥ 70 years 470 (27.50%) 245 (15.19%) Sex < 0.001 Female 717 (41.95%) 488 (30.25%) Male 992 (58.05%) 1125 (69.75%) Race 0.004 White 1468 (85.90%) 1370 (84.93%) Black 74 (4.33%) 109 (6.76%) others 167 (9.77%) 134 (8.31%) Primary site < 0.001 Base of tongue 266 (15.56%) 708 (43.89%) Dorsal surface of tongue 108 (6.32%) 68 (4.22%) Border of tongue 544 (31.83%) 338 (20.95%) Ventral surface of tongue 325 (19.02%) 164 (10.17%) Anterior 2/3 of tongue 466 (27.27%) 335 (20.77%) Grade < 0.001 I-Well differentiated 543 (31.77%) 134 (8.31%) II-Moderately differentiated 887 (51.90%) 847 (52.51%) III-Poorly differentiated 271 (15.86%) 613 (38.00%) IV-Undifferentiated 8 (0.47%) 19 (1.18%) Chemotherapy < 0.001 Yes 42 (2.46%) 855 (53.01%) No/Unknown 1667 (97.54%) 758 (46.99%) Stage < 0.001 I 1096 (64.13%) 181 (11.22%) II 272 (15.92%) 212 (13.14%) III 174 (10.18%) 393 (24.36%) IV 167 (9.78%) 827 (51.27%) T-classification < 0.001 T1 1203 (70.39%) 508 (31.49%) T2 355 (20.77%) 691 (42.84%) T3 95 (5.56%) 208 (12.90%) T4a 52 (3.04%) 189 (11.72%) T4b 4 (0.23%) 15 (0.93%) T4NOS 0 (0.00%) 2 (0.12%) N-classification < 0.001 N0 1442 (84.38%) 492 (30.50%) N1 144 (8.43%) 380 (23.56%) N2a 24 (1.40%) 108 (6.70%) N2b 71 (4.15%) 465 (28.83%) N2c 18 (1.05%) 120 (7.44%) N2NOS 3 (0.18%) 12 (0.74%) N3 7 (0.41%) 36 (2.23%) M-classification 0.138 M0 1694 (99.12%) 1590 (98.57%) M1 15 (0.88%) 23 (1.43%) aRT, adjuvant radiotherapy; NOS, not otherwise specified Kaplan–Meier survival curves for 5-year OS and DSS Kaplan–Meier survival analysis revealed that among Stage I patients, 14.27% received aRT, while 85.83% did not, compared with 16.8% non-aRT receivers and 83.2% aRT receivers among those with Stage IV disease (Table 1 ). Stage I patients undergoing aRT had a lower 5-year survival probability for both OS and DSS than non-aRT receivers. (P < 0.0001) (Fig. 2 a, e) In contrast, aRT showed significant benefits for the treatment of Stage IV tumors, with a 10–20% improvement in the OS and DSS survival probabilities (P 0.05). Impact of aRT on 5-year overall death and disease-specific death in patients with different tumor stages Cox regression analysis showed that among Stage I patients, the 5-year overall death (OD) risk in aRT receivers increased by 105% (Hazard ratio [HR], 2.05; 95% confidence interval [CI], 1.57–2.67) and the 5-year DSD risk in aRT receivers increased by 171% (HR, 2.71, 95% CI, 1.97–3.72) in contrast with those in non-aRT receivers in the non-adjusted model. Among Stage IV patients, the 5-year OD risk in aRT receivers decreased by 48% (HR, 0.52; 95% CI, 0.42–0.6), and the 5-year DSD risk in aRT receivers decreased by 49% (HR, 0.51; 95% CI, 0.41–0.6) compared to those in non-aRT receivers in the non-adjusted model. Stage II and III patients receiving aRT and those not receiving aRT did not differ significantly. Similar results were observed for the adjusted model (Table 2 ). Table 2 Impact of aRT on OD and DSD in patients with different tumor stages Stage I HR (95%CI) Stage II HR (95%CI) Stage III HR (95%CI) Stage IV HR (95%CI) OD ( 305/1277 ) DSD ( 187/1159 ) OD ( 181/484 ) DSD ( 121/424 ) OD ( 235/567 ) DSD ( 187/519 ) OD ( 513/994 ) DSD ( 443/924 ) Non-adjusted aRT No Reference Reference Reference Reference Reference Reference Reference Reference Yes 2.05 (1.57, 2.67) * 2.71 (1.97, 3.72) * 1.21 (0.90, 1.61) 1.22 (0.85, 1.74) 0.84 (0.64, 1.09) 0.84 (0.62, 1.15) 0.52 (0.42, 0.64) * 0.51 (0.41, 0.64) * Adjusted a aRT No Reference Reference Reference Reference Reference Reference Reference Reference Yes 1.72 (1.28, 2.33) * 2.07 (1.43, 2.98) * 1.18 (0.85, 1.63) 1.13 (0.75, 1.68) 1.00 (0.74, 1.36) 1.01 (0.72, 1.42) 0.58 (0.45, 0.74) * 0.59 (0.45, 0.77) * *indicates P < 0.05 a adjusted for age, sex, race, primary site, grade, and chemotherapy. aRT, adjuvant radiotherapy; CI, confidence interval; DSD, disease-specific death; HR, hazard ratio; OD, overall death Sensitivity analysis We matched 1502 cases in the aRT (n = 751) and non-aRT (n = 751) groups by propensity-score matching (PSM) totally. We failed to detect significant differences in age, sex, race, grade, and chemotherapy for these matched cases, except for the primary site (P < 0.05) (Table 3 ). In the Kaplan–Meier survival analysis, we obtained the same results as those before PSM; aRT showed a benefit for both 5-year OS and DSS in patients diagnosed with Stage IV tumors but a negative effect in those with Stage I tumors (P 0.05) (Fig. 3 b, c, f, g). Table 3 Baseline characteristics of aRT receivers and non-aRT receivers after propensity score matching Variables aRT Standardized diff. P value Yes(n = 751) No (n = 751) Age 0.0517 30–49 years 164 (21.8) 170 (22.6) 0.02 50–59 years 230 (30.6) 221 (29.4) 0.03 60–69 years 199 (26.5) 164 (21.8) 0.11 ≥ 70 years 158 (21) 196 (26.1) 0.12 Sex 0.02 0.7486 Female 275 (36.6) 282 (37.5) Male 476 (63.4) 469 (62.5) Race 0.8567 White 626 (83.4) 633 (84.3) 0.03 Black 53 (7.1) 52 (6.9) 0.01 Others 72 (9.6) 66 (8.8) 0.03 Primary site < 0.0001 Base of tongue 222 (29.6) 172 (22.9) 0.15 Dorsal surface of tongue 36 (4.8) 69 (9.2) 0.17 Border of tongue 190 (25.3) 296 (39.4) 0.31 Ventral surface of tongue 103 (13.7) 94 (12.5) 0.04 Anterior 2/3 of tongue 200 (26.6) 120 (16) 0.26 Grade 0.4739 I-Well differentiated 90 (12) 107 (14.2) 0.07 II-Moderately differentiated 451 (60.1) 434 (57.8) 0.05 III-Poorly differentiated 202 (26.9) 205 (27.3) 0.01 IV-Undifferentiated 8 (1.1) 5 (0.7) 0.04 Chemotherapy 0 1.0000 Yes 42 (5.6) 42 (5.6) No/Unknown 709 (94.4) 709 (94.4) aRT, adjuvant radiotherapy To eliminate bias from the primary site, we adjusted this variable in the HR analysis (Table 4 ). The Cox regression analysis showed that aRT was positively correlated with both 5-year OD (HR, 2.51; 95% CI, 1.77–3.55) and DSD (HR, 2.76l 95% CI, 1.82–4.19) in Stage I patients. aRT was negatively associated with both 5-year OD (HR, 0.55; 95% CI, 0.41–0.74) and DSD (HR, 0.55; 95% CI, 0.40–0.76) in Stage IV patients (Table 4 ). Similar results were observed for the adjusted model. The results before and after PSM were consistent. Table 4 Impact of aRT on OD and DSD in patients with different tumor stages in the matched cohort Stage I HR (95%CI) Stage II HR (95%CI) Stage III HR (95%CI) Stage IV HR (95%CI) OD (130/585) DSD (90/545) OD (105/280) DSD (77/252) OD (113/300) DSD (95/282) OD (190/337) DSD (164/311) Non-adjusted aRT No Reference Reference Reference Reference Reference Reference Reference Reference Yes 2.51 (1.77, 3.55) * 2.76 (1.82, 4.19) * 1.34 (0.90, 1.99) 1.08 (0.69, 1.70) 1.29 (0.85, 1.97) 1.23 (0.78, 1.93) 0.55 (0.41, 0.74) * 0.55 (0.40, 0.76) * Adjusted a aRT No Reference Reference Reference Reference Reference Reference Reference Reference Yes 2.55 (1.78, 3.67) * 2.86 (1.85, 4.42) * 1.28 (0.85, 1.92) 1.01 (0.63, 1.60) 1.24 (0.81, 1.90) 1.17 (0.74, 1.84) 0.52 (0.39, 0.70) * 0.53 (0.38, 0.72) * *indicates P < 0.05 a adjusted for primary site. aRT, adjuvant radiotherapy; CI, confidence interval; DSD, disease-specific death; HR, hazard ratio; OD, overall death Ethical approval The SEER research data files were downloaded using the account number 20161-Nov2020. The account is approved to access to the 1975-2018 SEER Research Plus Data (November 2020 Submission). The data released by the SEER database do not require informed patient consent. All experiments were performed in accordance with relevant guidelines and regulations. Discussion This study revealed that aRT is significantly associated with survival benefits in patients with Stage IV SCC of the tongue. aRT is commonly used after surgery in cases of unfavorable histological findings. For large tumors, several oncologists recommend aRT if the surgical margins are close to the tumor or involved or if several positive nodes persist after neck dissection. Previous studies have indicated that early tongue cancers are associated with 5-year survival rates of at least 80% [21,31,32], although cancers of the tongue have a worse prognosis than those affecting other oral areas. Rusthoven et al. revealed that Stage I and II tongue cancers have 60.9% and 83.5% 5-year OS and cause-specific survival rates, respectively; other oral subsites had rates of 64.7% and 94.1%, respectively, according to the SEER database [33]. Shim et al. attributed the high survival rate of tongue cancer to appropriate radiotherapy [21]. Thus, feasible and reasonable radiation therapy regimens are important for the survival status of patients. In this study, we analyzed the survival of patients with SCC of the tongue and sought to determine the impact of aRT use on survival. We discovered that aRT confers advanced survival in Stage IV SCC of the tongue, whereas it failed to improve survival status in Stage I to Stage III SCC patients. Furthermore, aRT for Stage I cancers has a negative impact on patient survival. To unequivocally establish the association between the tumor stage and aRT, we verified the results in the original and PSM cohorts and obtained the same conclusion. Our results contribute to the growing body of knowledge related to tongue SCC-related outcomes and reveal that survival and response to aRT vary with tumor stage. In this article, we report a number of observational associations that can provide motivation and set the stage for future mechanistic studies investigating the biological mechanisms that may underlie the observed differences in tongue body SCC prognosis and response to treatment. In our original data analysis, aRT served as a risk factor for patients with Stage I tumors in 5-year OS and DSS. In addition, it is worth noting that we could not detect any significant benefits of aRT for Stage II and Stage III patients. These results suggest that these early-stage patients do not benefit from aRT. There are reports [21–24] of findings similar to those of our study. Sandhya et al. analyzed a cohort of 103 cases and suggested that postoperative radiation therapy had no significant impact on the survival of patients with Stage I and II deep tongue cancers, with no less than a 4-mm tumor invasion depth [22]. According to Shim et al., 86 patients with early-stage tongue cancer were enrolled in the study, but no significant differences were observed in the OS rate after surgery alone and a combination of surgery and postoperative radiation therapy [21]. However, these studies included only a few patients, and it was difficult to adjust baselines. Focusing on oral cavity cancers generally, Luryi et al. and Sowder et al. analyzed the data from the SEER database with a large number of cases and revealed that treatment with adjuvants led to significantly worse OS and DSS than surgery alone for early-stage oral cancers [23,24]. However, they did not determine whether postoperative radiation therapy was beneficial for each subsite. Our results are consistent with those of previous studies that suggested that early-stage patients should not receive aRT after surgery. This would increase the cost of treatment and reduce the quality of life of these patients, and the radiation exposure to the oral cavity and oropharynx may lead to unfavorable complications. In contrast, some other reports have suggested that aRT is beneficial for early-stage head and neck SCC. Tsai et al. confirmed that aRT could improve neck control and survival status in patients with early oral cancers with a single nodal status in the Taiwan Cancer Registry database [25]. Furthermore, Schiff et al. suggested that aRT could improve regional failure in patients with pN1 tongue cancers, although the results were not significant (P=0.32) [26]. Torrecillas et al. confirmed significant survival benefit of aRT for patients with T1N1 and T2N2 oral cavity SCC [27]. Qian et al. suggested that aRT resulted in better survival in patients with pN0 [28]. Shrime et al. suggested that aRT was associated with the most significant improvements in cancers of the tongue after verifying its effects on T1N1 or T2N1 oral SCCs [29]. Several factors were responsible for these divergent conclusions: first, the sources of their data were variable, and the characteristics of patients and aRT modalities could be different; second, some studies have focused on the oral cavity or head and neck rather than a specific subsite, which may influence the survival status of patients; third, some early-stage patients may suffer from occult node metastases. We speculate that advanced benefits of aRT may be identified in larger cohorts with occult metastases. Compared with these studies, we conducted a more accurate study based on a large number of patients in the SEER database and included SCCs of the entire tongue body (anterior 2/3 and base of tongue). We also included various patient characteristics and treatment options. Considering that patients with different tumor stages could have different characteristics, we made some adjustments to the basic characteristics of the patients to reduce bias. We performed a subgroup analysis and conducted PSM based on baseline variables. For both the original and PSM groups, we explored the effects of postoperative radiation therapy on OS and DSS. After adjustment, we did not detect any significant changes in the results compared to the original data. We used PSM to match all variables at a 1:1 ratio between aRT and non-aRT receivers; 1502 cases were included. We discovered that aRT could worsen the survival of patients with Stage I SCC, even after adjustment and matching. In addition, we found that aRT could not always extend the duration of survival for late-stage tumors. aRT can only improve the survival of patients with Stage IV SCC of the tongue and is not significantly associated with survival benefits in the original and propensity-score matching populations. Our PSM and adjusted results provide dual authentication that patients with different stages of SCC cannot always benefit from aRT after surgery. The provision of appropriate therapeutic regimens is of great importance. This should be based on several factors, including patient characteristics, disease progression, and quality of life following surgery. Because of its retrospective nature, this study inevitably had several limitations. Due to the lack of therapeutic parameters of radiation (including definitive versus palliative intent, dose/fractionation) in the SEER database, we could not evaluate the effects of these factors on survival and prognosis. The list of variables included in our analysis was not exhaustive, and some potentially important factors (e.g., smoking status, alcohol drinking, and vascular invasion) were not available in the SEER database. Additionally, we do not have access to the information on various patient characteristics in the SEER database, including quality of life, complications, tumor resection margins, recurrence, and treatment of recurrence, all of which may have affected our aRT analysis. Advances have been made in radiotherapy technology; however, as a result of differences in selection criteria, techniques, and equipment, toxicity and quality of life within a given period of time can be compromised more than survival outcomes [34]. In conclusion, we suggested that there were significant survival benefits associated with aRT for Stage IV SCC of the tongue and that patients with Stage I SCC of the tongue cannot benefit from aRT. Thus, survival and other benefits of aRT for early-stage SCC need some further justification, especially for Stage I patients. Otherwise, these patients may not be subjected to unnecessary radiation and morbidity. Our results provide an orientation for research interest in the biological mechanism, and future researchers can provide reasonable explanations and feasible methods of improvements for aRT. Patients And Methods Data collection We retrieved the data of cases with SCC involving the anterior two-thirds of the tongue and base of the tongue from the SEER Stat 8.3.9. The data were part of the SEER 18 Regs Custom Data (with additional treatment fields), Nov 2018 Sub (1975–2016 varying). Relevant patient information in the SEER database includes demographic characteristics, histology, malignancy, therapeutic regimen, and survival duration, among others. Based on histology recode and the WHO definition of squamous cell tumors (8050–8089 squamous cell tumors), we ran the research modality in a cast-listing session. The selected neoplasms exhibited malignant behavior. The site and morphology (primary site-labeled) included C01.9-base of the tongue, not otherwise specified (NOS); C02.0-dorsal surface of tongue, NOS; C02.1-border of tongue; C02,2-ventral surface of tongue, NOS; and C02.3-anterior two-thirds of the tongue, NOS. These data were retrieved and analyzed as follows: age (30–49; 50–59; 60–69; ≥70 years); sex (male, female); race (white, black, American Indian/Alaska Native, Asian, or Pacific Islander); year of diagnosis; grade (I, II, III, IV); SEER Combined Summary Stage 2000 (2004+) (regional lymph nodes involved only, regional by direct extension only, regional by both direct extension and lymph node involvement, localized only, distant site(s)/node(s) involved); anatomic site (C01.9-base of the tongue, NOS; C02.0-dorsal surface of the tongue, NOS; C02.1-border of tongue; C02,2-ventral surface of the tongue, NOS; C02.3-anterior two-thirds of the tongue, NOS); derived American Joint Committee on Cancer (AJCC) TNM stage, 6 th edition (2004-2015); surgery; aRT; and DSS and OS, both measured in months. SCCs were staged based on the AJCC 6 th edition, effective 2004 and onward. The analysis did not include patients without surgery. We only included patients who underwent surgery alone or post-surgery radiotherapy. A 5-year OS and DSS were the study's endpoints. Based on months from the date of initial pathological diagnosis to the date of death or the end of 60 months, OS or DSS was calculated. Statistical analysis The Kaplan–Meier method and log-rank test were applied to calculate and assess the survival curves of patients diagnosed with different stages stratified by aRT. We estimated the association between the stage and aRT and OS and DSS using HRs and the corresponding 95% CIs was calculated via Cox regression models. Patients with similar baseline characteristics were identified via PSM. Based on a series of baseline covariates including age, sex, race, primary site, grade, and chemotherapy, a propensity score is calculated as the conditional probability of being exposed to a given exposure (aRT yes versus no). The 1:1 matching protocol was employed without replacement (greedy-matching algorithm); the caliper width was estimated to be equal to 0.01 of the standard deviation of the propensity score. For all baseline covariates, standardized differences were estimated before and after matching to assess the pre-match and post-match balance. Standardized differences <10.0% for a given covariate indicate a relatively small imbalance. Using the Kaplan–Meier method and a log-rank test, we could generate and compare survival curves of patients stratified by aRT in the matched cohort. The association between aRT, OS, and DSS of patients with different stages of cancer was also studied using a Cox proportional hazards regression model. All analyses were performed using the statistical software packages R (R Foundation for Statistical Computing, Vienna, Austria) and Empower Stats (X&Y Solutions, Inc., Boston, MA, USA). The significance level was determined by the two-tailed P-value of 0.05. Abbreviations aRT, adjuvant radiotherapy CI, confidence interval DSD, disease-specific death DSS, disease-specific survival HR, hazard ratio OD, overall death OS, overall survival PSM, propensity-score matching SCC, squamous cell carcinoma SEER, Surveillance, Epidemiology, and End Results Declarations Acknowledgments Authors’ contribution Zhenyu Ding designed the study and collected the data. Run Yao analyzed the data. Zhenyu Ding and Run Yao wrote the manuscript. Ning Li and Jun Zuo reviewed and edited the manuscript. Zhenyu Ding and Run Yao share first authorship. All authors have read and approved the final manuscript. Funding This study was supported by the Natural Science Foundation of Hunan Province (project no. 2018JJ2546) and the Scientific Research Project of Hunan Provincial Health Commission (project no. 202218013370). Availability of data and materials The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request. Consent for publication Not applicable. Role of the funding source Statistical analysis and language editing. Competing interests The authors declare no competing interests. References Christopherson K, Morris CG, Kirwan JM, et al. Radiotherapy alone or combined with chemotherapy for base of tongue squamous cell carcinoma. Laryngoscope. 2017;127(7):1589–1594. doi: 10.1002/lary.26460 Saba NF, Ward K. Gender and Ethnic Disparities in Incidence and Survival of Squamous Cell Carcinoma of the Oral Tongue, Base of Tongue, and Tonsils : A Surveillance, Epidemiology and End Results Program-Based Analysis. Published online 2011:12–20. doi: 10.1159/000330807 Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. 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Corrigendum to “MicroRNA-17/20a functions to inhibit cell migration and can be used a prognostic marker in oral squamous cell carcinoma” [Oral Oncol. 49(9) (2013) 923–931]. Oral Oncol . 2017;72:202–203. doi: 10.1016/J.ORALONCOLOGY.2017.06.021 Selek U, Garden AS, Morrison WH, El-Naggar AK, Rosenthal DI, Ang KK. Radiation therapy for early-stage carcinoma of the oropharynx. Int J Radiat Oncol Biol Phys. 2004;59(3):743–751. doi: 10.1016/j.ijrobp.2003.12.002 JS C, TF P, AA F, et al. Postoperative concurrent radiotherapy and chemotherapy for high-risk squamous-cell carcinoma of the head and neck. N Engl J Med. 2004;350(19):1937–1944. doi: 10.1056/NEJMOA032646 J B, C D, M O, et al. Postoperative irradiation with or without concomitant chemotherapy for locally advanced head and neck cancer. N Engl J Med. 2004;350(19):1945–1952. doi: 10.1056/NEJMOA032641 Monroe MM, Buchmann LO, Hunt JP, Hitchcock YJ, Lloyd S, Hashibe M. The Benefit of Adjuvant Radiation in Surgically-Treated T1-2 N1 Oropharyngeal Squamous Cell Carcinoma. Laryngoscope Investig Otolaryngol. 2017;2(2):57–62. doi: 10.1002/lio2.64 Shim SJ, Cha J, Koom WS, et al. Clinical outcomes for T1-2N0-1oral tongue cancer patients underwent surgery with and without postoperative radiotherapy. Radiat Oncol. 2010;5(1):1–7. doi: 10.1186/1748-717X-5-43 S G, N P, LM RS, R R, KV R, R C. Role of postoperative radiation therapy (PORT) in pT1-T2 N0 deep tongue cancers. Oral Surg Oral Med Oral Pathol Oral Radiol. 2015;120(6):e227-e231. doi: 10.1016/J.OOOO.2015.08.002 AL L, MM C, S M, SA R, JA S, BL J. Treatment Factors Associated With Survival in Early-Stage Oral Cavity Cancer: Analysis of 6830 Cases From the National Cancer Data Base. JAMA Otolaryngol Head Neck Surg. 2015;141(7):593–598. doi: 10.1001/JAMAOTO.2015.0719 Leoncini E, Ricciardi W, Cadoni G, et al. Treatment-related determinants of survival in early-stage (T1–2N0M0) oral cavity cancer: A population-based study. Head Neck. 2014;36(10):1391. doi: 10.1002/HED Tsai C-J, Kuo Y-H, Wu H-C, et al. Adjuvant Radiotherapy Significantly Increases Neck Control and Survival in Early Oral Cancer Patients with Solitary Nodal Involvement: A National Cancer Registry Database Analysis. Published online 2021. doi: 10.3390/cancers13153742 BA S, DB R, A E-N, AS G, JN M. Selective vs modified radical neck dissection and postoperative radiotherapy vs observation in the treatment of squamous cell carcinoma of the oral tongue. Arch Otolaryngol Head Neck Surg. 2005;131(10):874–878. doi: 10.1001/ARCHOTOL.131.10.874 Torrecillas V, Shepherd HM, Francis S, et al. Adjuvant radiation for T1-2N1 oral cavity cancer survival outcomes and utilization treatment trends: Analysis of the SEER database. Oral Oncol. 2018;85(May):1–7. doi: 10.1016/j.oraloncology.2018.07.019 Qian X, Sinikovic B, Schreiber · Frank, et al. HEAD & NECK pN status predicts outcomes in surgically treated pT1-pT2 patients of various disease stages with squamous cell carcinoma of the head and neck: a 17-year retrospective single center cohort study. Eur Arch Oto-Rhino-Laryngology . 2018;275(3):2787–2795. doi: 10.1007/s00405-018-5108-z Shrime MG, Gullane PJ, Dawson L, Kim J, Gilbert RW, Irish JC. The Impact of Adjuvant Radiotherapy on Survival in T1-2N1 Squamous Cell Carcinoma of the Oral Cavity . Vol 136.; 2010. https://jamanetwork.com/ DG P, S S, DM B, et al. Head and neck cancers, Version 2.2014. Clinical practice guidelines in oncology. J Natl Compr Canc Netw. 2014;12(10):1454–1487. doi: 10.6004/JNCCN.2014.0142 K R, A B, D R, C C. Poor prognosis in patients with stage I and II oral tongue squamous cell carcinoma. Cancer. 2008;112(2):345–351. doi: 10.1002/CNCR.23183 DS S, IA M. The radial forearm flap in intraoral reconstruction: the experience of 60 consecutive cases. Plast Reconstr Surg. 1986;78(1):1–8. doi: 10.1097/00006534-198607000-00001 K R, A B, D R, C C. Poor prognosis in patients with stage I and II oral tongue squamous cell carcinoma. Cancer. 2008;112(2):345–351. doi: 10.1002/CNCR.23183 Tasoulas J, Divaris K, Theocharis S, et al. Impact of tumor site and adjuvant radiotherapy on survival of patients with adenoid cystic carcinoma: A seer database analysis. Cancers (Basel). 2021;13(4):1–16. doi: 10.3390/cancers13040589 Additional Declarations No competing interests reported. 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. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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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-1406293","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":90548712,"identity":"a75ef220-ee2e-4da8-8581-4e5b7cf2a7bf","order_by":0,"name":"Zhenyu Ding","email":"","orcid":"","institution":"Central South University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Zhenyu","middleName":"","lastName":"Ding","suffix":""},{"id":90548713,"identity":"b1cbee71-4026-4243-b7d4-c08a31541ff5","order_by":1,"name":"Run Yao","email":"","orcid":"","institution":"Central South University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Run","middleName":"","lastName":"Yao","suffix":""},{"id":90548714,"identity":"452a8928-1456-4a70-8132-7d729339a2bb","order_by":2,"name":"Jun Zuo","email":"","orcid":"","institution":"Central South University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Jun","middleName":"","lastName":"Zuo","suffix":""},{"id":90548715,"identity":"f35dc668-78e9-4e5e-9071-c22eb8bff5e4","order_by":3,"name":"Ning Li","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA0UlEQVRIiWNgGAWjYBACPmYGhgMgBj+Ez0xYCxtMi2QD0VpgDIMDRGth5z14uODX4cTNx48/k2CosE5sYD97gIDD+BIOz+xLS9x2JsdMguFMemIDT14CAS08Bod5e2wSt93gYZNgbDuc2CDBY0CMFonEzTPYn0kw/iNWC88Pm8QNEgxmEowNRNvSkGY840yOsUXCsXTjNp4c/Fr4+c8Yf+b5c1i2v/34wxsfaqxl+9nP4NcCBoxtDI4NIEYCA1JM4Qd/GOyJUzgKRsEoGAUjEgAAHJA/Wb+8IGoAAAAASUVORK5CYII=","orcid":"","institution":"Central South University","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"Ning","middleName":"","lastName":"Li","suffix":""}],"badges":[],"createdAt":"2022-03-01 04:14:03","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-1406293/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-1406293/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":19261132,"identity":"81291f5b-37b4-4915-a071-68d9ef839685","added_by":"auto","created_at":"2022-03-15 19:03:40","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":46052,"visible":true,"origin":"","legend":"\u003cp\u003eFlowchart of selection and exclusion of patients with squamous cell carcinoma from the Surveillance, Epidemiology, and End Results (SEER) database (2004–2015).\u003c/p\u003e","description":"","filename":"Figure1.png","url":"https://assets-eu.researchsquare.com/files/rs-1406293/v1/e5c0daa388433f9564415e29.png"},{"id":19261363,"identity":"cd36c0a9-b7fe-450c-91a2-86372afa16e6","added_by":"auto","created_at":"2022-03-15 19:06:40","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":431057,"visible":true,"origin":"","legend":"\u003cp\u003eKaplan–Meier survival curves of patients for 5-year overall survival (\u003cstrong\u003ea\u003c/strong\u003e: Stage I, \u003cstrong\u003eb\u003c/strong\u003e: Stage II,\u003cstrong\u003e c\u003c/strong\u003e: Stage III, \u003cstrong\u003ed\u003c/strong\u003e: Stage IV) and disease-specific survival (\u003cstrong\u003ee\u003c/strong\u003e: Stage I, \u003cstrong\u003ef\u003c/strong\u003e: Stage II, \u003cstrong\u003eg\u003c/strong\u003e: Stage III, \u003cstrong\u003eh\u003c/strong\u003e: Stage IV).\u003c/p\u003e","description":"","filename":"Figure2.png","url":"https://assets-eu.researchsquare.com/files/rs-1406293/v1/216d36f18a02d610e5d4dadc.png"},{"id":19261131,"identity":"5241c50b-72ca-484b-a9bb-4222b0f64acc","added_by":"auto","created_at":"2022-03-15 19:03:40","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":426034,"visible":true,"origin":"","legend":"\u003cp\u003eKaplan–Meier survival curves of patients for 5-year overall survival (\u003cstrong\u003ea\u003c/strong\u003e: Stage I, \u003cstrong\u003eb\u003c/strong\u003e: Stage II, \u003cstrong\u003ec\u003c/strong\u003e: Stage III, \u003cstrong\u003ed\u003c/strong\u003e: Stage IV) and disease-specific survival (\u003cstrong\u003ee\u003c/strong\u003e: Stage I, \u003cstrong\u003ef\u003c/strong\u003e: Stage II, \u003cstrong\u003eg\u003c/strong\u003e: Stage III, \u003cstrong\u003eh\u003c/strong\u003e: Stage IV) in the matched cohort.\u003c/p\u003e","description":"","filename":"Figure3.png","url":"https://assets-eu.researchsquare.com/files/rs-1406293/v1/c134a1bb48731403254f82a1.png"},{"id":21851522,"identity":"43671d41-3550-49cd-b9d2-24be3a667c48","added_by":"auto","created_at":"2022-05-25 05:29:19","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":982652,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-1406293/v1/4d3f4fb0-1928-4171-ac71-0c6ce0541b0e.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"\u003cp\u003eAdjuvant radiotherapy and survival of patients with squamous cell carcinoma involving the entire tongue: The SEER database analysis\u003c/p\u003e","fulltext":[{"header":"Introduction","content":"\u003cp\u003eAnnually, squamous cell carcinoma (SCC) affects more than 650,000 people worldwide, and 330,000 people die from the disease each year [\u003cspan additionalcitationids=\"CR2\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Several factors may contribute to the development of oral and oropharyngeal SCC, including tobacco use, alcohol consumption, and human papillomavirus infection [\u003cspan additionalcitationids=\"CR5\" citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. In response to the national health campaign and public health awareness, the incidence of oral cancer has declined in general [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. However, several studies have reported that head and neck cancer is becoming more common among young people and women, indicating an epidemiological shift from older adults and men to younger adults and women [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan additionalcitationids=\"CR9\" citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. Moreover, public health concerns remain significant because of the disease burden. Cancers affecting the anterior two-thirds of the tongue are referred to as carcinomas of the tongue, whereas those affecting the posterior one-third are referred to as base of tongue cancers [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. In SCC of the body of the tongue, the malignant clinical characteristics include rapid local invasion and lymph node metastasis, which can result in impaired speech and chewing and, ultimately, affect the patients\u0026rsquo; quality of life [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. Although diagnostic techniques and modalities have advanced dramatically in recent years, the overall survival (OS) rate for tongue SCC has been reduced owing to its clinicopathological features [\u003cspan additionalcitationids=\"CR14 CR15\" citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eOver the past few decades, the therapeutic regimen for SCC has not changed significantly. Various treatments are currently used, including radiotherapy alone or in combination with adjuvant chemotherapy, resection of the primary tumor with or without adjuvant radiotherapy (aRT), and neck dissection [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. Previous studies have found that head and neck cancer patients with high-risk features benefit from postoperative chemotherapy in terms of local-regional control and disease-free survival [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. In contrast, short- and long-term radiation therapies are frequently associated with toxic side effects, including dysgeusia, dysphagia, aspiration, mucositis, soft tissue necrosis, carotid atherosclerosis, stroke, radiation fibrosis, osteoradionecrosis, and cranial neuropathy [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. Radiation therapy regimens are currently topics of controversy. According to some evidence, aRT does not appear have considerable benefits for oral SCC at the early stage [\u003cspan additionalcitationids=\"CR22 CR23\" citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]. Other reports have suggested that aRT is effective, even during the early stages of head and neck SCC [\u003cspan additionalcitationids=\"CR26 CR27 CR28\" citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e]. However, these studies have limitations. Sandhya et al. and Shim et al. conducted their studies with a limited number of patients [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e] and Luryi et al. and Sowder et al. did not evaluate the benefits of radiotherapy for each subsite [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e, \u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]. Therefore, there is a need to investigate appropriate groups for postoperative radiotherapy, which can alleviate the side effects of therapeutic regimens and provide patients with a better quality of life.\u003c/p\u003e \u003cp\u003eThe National Comprehensive Cancer Network treatment guidelines recommend a combination of surgery and radiotherapy as the primary treatment for early-stage oral SCC; however, reports on its effectiveness are limited [\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e]. Therefore, we extracted data from the Surveillance, Epidemiology, and End Results (SEER) database, funded by the National Cancer Institute, to address this knowledge gap regarding the effect of radiotherapy on survival in patients with entire tongue SCC. This study was designed to examine the effects of aRT on patients by using the SEER database with different stages of SCC involving the entire tongue body (including the frontal two-thirds of the tongue and base of the tongue), identify the most suitable group of patients for aRT, and reduce unnecessary therapeutic procedures.\u003c/p\u003e"},{"header":"Results","content":"\u003cdiv class=\"Section2\" id=\"Sec3\"\u003e\n \u003ch2\u003ePatient characteristics\u003c/h2\u003e\n \u003cp\u003eInitially, the data of 13379 SCC patients were retrieved from the SEER database between 2004 and 2015. After excluding 6659 cases coded with surg prim site code 0 (none, no surgery of primary site; autopsy only), 446 patients with Tx, 29 patients with Nx, 36 patients with Mx, 17 patients with surg prim site code 99 (unknown if surgery was performed; death certificate only), 2749 patients with a follow-up duration\u0026thinsp;\u0026lt;\u0026thinsp;5 years, and 121 cases recorded with missing data, a total of 3322 patients were enrolled for the final analysis (Fig. \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e). Among them, 3322 cases had 5-year OS data and 3026 cases had 5-year disease-free survival (DSS) data. These patients were predominantly men (63.73%); 36.27% of the patients were women. The total number of deaths and disease-specific deaths (DSDs) were 1234 (37.15%) and 938 (28.24%), respectively.\u003c/p\u003e\n \u003cp\u003eBased on the therapeutic regimens, we classified the included patients into two groups, surgery with and without aRT, and compared the baseline characteristics of the two groups. The differences in age, sex, race, primary site, grade, chemotherapy, stage, and TN classification were significant (P\u0026thinsp;\u0026lt;\u0026thinsp;0.05) of aRT and non-aRT receivers, but not M classification (P\u0026thinsp;\u0026gt;\u0026thinsp;0.05), in the initial data (Table \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e).\u0026nbsp;\u003c/p\u003e\u003ctable border=\"1\" id=\"Tab1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eBaseline characteristics of aRT receivers and non-aRT receivers (2004\u0026ndash;2015)\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\" rowspan=\"2\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003cth align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003eaRT\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003eP-value\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eNo (n\u0026thinsp;=\u0026thinsp;1709)\u003c/strong\u003e\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eYes (n\u0026thinsp;=\u0026thinsp;1613)\u003c/strong\u003e\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eAge\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e30\u0026ndash;49 years\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e373 (21.83%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e352 (21.82%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e50\u0026ndash;59 years\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e446 (26.10%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e570 (35.34%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e60\u0026ndash;69 years\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e420 (24.58%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e446 (27.65%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026ge;\u0026thinsp;70 years\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e470 (27.50%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e245 (15.19%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eSex\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eFemale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e717 (41.95%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e488 (30.25%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e992 (58.05%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1125 (69.75%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eRace\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.004\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eWhite\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1468 (85.90%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1370 (84.93%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBlack\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e74 (4.33%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e109 (6.76%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eothers\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e167 (9.77%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e134 (8.31%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003ePrimary site\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBase of tongue\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e266 (15.56%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e708 (43.89%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eDorsal surface of tongue\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e108 (6.32%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e68 (4.22%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBorder of tongue\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e544 (31.83%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e338 (20.95%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eVentral surface of tongue\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e325 (19.02%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e164 (10.17%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAnterior 2/3 of tongue\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e466 (27.27%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e335 (20.77%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eGrade\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eI-Well differentiated\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e543 (31.77%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e134 (8.31%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eII-Moderately differentiated\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e887 (51.90%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e847 (52.51%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eIII-Poorly differentiated\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e271 (15.86%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e613 (38.00%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eIV-Undifferentiated\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e8 (0.47%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e19 (1.18%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eChemotherapy\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e42 (2.46%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e855 (53.01%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNo/Unknown\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1667 (97.54%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e758 (46.99%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eStage\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1096 (64.13%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e181 (11.22%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eII\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e272 (15.92%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e212 (13.14%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eIII\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e174 (10.18%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e393 (24.36%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eIV\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e167 (9.78%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e827 (51.27%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eT-classification\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eT1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1203 (70.39%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e508 (31.49%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eT2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e355 (20.77%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e691 (42.84%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eT3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e95 (5.56%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e208 (12.90%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eT4a\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e52 (3.04%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e189 (11.72%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eT4b\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e4 (0.23%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e15 (0.93%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eT4NOS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0 (0.00%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e2 (0.12%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eN-classification\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eN0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1442 (84.38%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e492 (30.50%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eN1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e144 (8.43%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e380 (23.56%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eN2a\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e24 (1.40%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e108 (6.70%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eN2b\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e71 (4.15%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e465 (28.83%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eN2c\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e18 (1.05%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e120 (7.44%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eN2NOS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e3 (0.18%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e12 (0.74%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eN3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e7 (0.41%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e36 (2.23%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eM-classification\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.138\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eM0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1694 (99.12%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1590 (98.57%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eM1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e15 (0.88%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e23 (1.43%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003ctfoot\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"4\"\u003eaRT, adjuvant radiotherapy; NOS, not otherwise specified\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tfoot\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cdiv class=\"Section2\" id=\"Sec4\"\u003e\n \u003ch2\u003eKaplan\u0026ndash;Meier survival curves for 5-year OS and DSS\u003c/h2\u003e\n \u003cp\u003eKaplan\u0026ndash;Meier survival analysis revealed that among Stage I patients, 14.27% received aRT, while 85.83% did not, compared with 16.8% non-aRT receivers and 83.2% aRT receivers among those with Stage IV disease (Table \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e). Stage I patients undergoing aRT had a lower 5-year survival probability for both OS and DSS than non-aRT receivers. (P\u0026thinsp;\u0026lt;\u0026thinsp;0.0001) (Fig. \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003ea, e) In contrast, aRT showed significant benefits for the treatment of Stage IV tumors, with a 10\u0026ndash;20% improvement in the OS and DSS survival probabilities (P\u0026thinsp;\u0026lt;\u0026thinsp;0.0001) (Fig. \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003ed, h). In addition, there were no significant survival benefits of aRT for aRT and non-aRT receivers with Stage II and III tumors (Fig. \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003eb, c, f, g) (P\u0026thinsp;\u0026gt;\u0026thinsp;0.05).\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eImpact of aRT on 5-year overall death and disease-specific death in patients with different tumor stages\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eCox regression analysis showed that among Stage I patients, the 5-year overall death (OD) risk in aRT receivers increased by 105% (Hazard ratio [HR], 2.05; 95% confidence interval [CI], 1.57\u0026ndash;2.67) and the 5-year DSD risk in aRT receivers increased by 171% (HR, 2.71, 95% CI, 1.97\u0026ndash;3.72) in contrast with those in non-aRT receivers in the non-adjusted model. Among Stage IV patients, the 5-year OD risk in aRT receivers decreased by 48% (HR, 0.52; 95% CI, 0.42\u0026ndash;0.6), and the 5-year DSD risk in aRT receivers decreased by 49% (HR, 0.51; 95% CI, 0.41\u0026ndash;0.6) compared to those in non-aRT receivers in the non-adjusted model. Stage II and III patients receiving aRT and those not receiving aRT did not differ significantly. Similar results were observed for the adjusted model (Table \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e).\u0026nbsp;\u003c/p\u003e\u003ctable border=\"1\" id=\"Tab2\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eImpact of aRT on OD and DSD in patients with different tumor stages\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\" colspan=\"2\" rowspan=\"2\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003cth align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003eStage I\u003c/p\u003e\n \u003cp\u003eHR (95%CI)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003eStage II\u003c/p\u003e\n \u003cp\u003eHR (95%CI)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003eStage III\u003c/p\u003e\n \u003cp\u003eHR (95%CI)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003eStage IV\u003c/p\u003e\n \u003cp\u003eHR (95%CI)\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eOD\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e(\u003c/strong\u003e305/1277\u003cstrong\u003e)\u003c/strong\u003e\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eDSD\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e(\u003c/strong\u003e187/1159\u003cstrong\u003e)\u003c/strong\u003e\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eOD\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e(\u003c/strong\u003e181/484\u003cstrong\u003e)\u003c/strong\u003e\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eDSD\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e(\u003c/strong\u003e121/424\u003cstrong\u003e)\u003c/strong\u003e\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eOD\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e(\u003c/strong\u003e235/567\u003cstrong\u003e)\u003c/strong\u003e\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eDSD\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e(\u003c/strong\u003e187/519\u003cstrong\u003e)\u003c/strong\u003e\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eOD\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e(\u003c/strong\u003e513/994\u003cstrong\u003e)\u003c/strong\u003e\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eDSD\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e(\u003c/strong\u003e443/924\u003cstrong\u003e)\u003c/strong\u003e\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e\u003cstrong\u003eNon-adjusted\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003e\u003cstrong\u003eaRT\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eNo\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eReference\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eReference\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eReference\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eReference\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eReference\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eReference\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eReference\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eReference\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eYes\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.05 (1.57, 2.67) *\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.71 (1.97, 3.72) *\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.21 (0.90, 1.61)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.22 (0.85, 1.74)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.84 (0.64, 1.09)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.84 (0.62, 1.15)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.52 (0.42, 0.64) *\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.51 (0.41, 0.64) *\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e\u003cstrong\u003eAdjusted\u003c/strong\u003e \u003csup\u003e\u003cstrong\u003ea\u003c/strong\u003e\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003e\u003cstrong\u003eaRT\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eNo\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eReference\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eReference\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eReference\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eReference\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eReference\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eReference\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eReference\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eReference\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eYes\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.72 (1.28, 2.33) *\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.07 (1.43, 2.98) *\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.18 (0.85, 1.63)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.13 (0.75, 1.68)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.00 (0.74, 1.36)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.01 (0.72, 1.42)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.58 (0.45, 0.74) *\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.59 (0.45, 0.77) *\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003ctfoot\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"10\"\u003e*indicates P\u0026thinsp;\u0026lt;\u0026thinsp;0.05\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"10\"\u003e\u003csup\u003ea\u003c/sup\u003eadjusted for age, sex, race, primary site, grade, and chemotherapy.\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"10\"\u003eaRT, adjuvant radiotherapy; CI, confidence interval; DSD, disease-specific death; HR, hazard ratio; OD, overall death\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tfoot\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cdiv class=\"Section2\" id=\"Sec5\"\u003e\n \u003ch2\u003eSensitivity analysis\u003c/h2\u003e\n \u003cp\u003eWe matched 1502 cases in the aRT (n\u0026thinsp;=\u0026thinsp;751) and non-aRT (n\u0026thinsp;=\u0026thinsp;751) groups by propensity-score matching (PSM) totally. We failed to detect significant differences in age, sex, race, grade, and chemotherapy for these matched cases, except for the primary site (P\u0026thinsp;\u0026lt;\u0026thinsp;0.05) (Table \u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e). In the Kaplan\u0026ndash;Meier survival analysis, we obtained the same results as those before PSM; aRT showed a benefit for both 5-year OS and DSS in patients diagnosed with Stage IV tumors but a negative effect in those with Stage I tumors (P\u0026thinsp;\u0026lt;\u0026thinsp;0.001) (Fig. \u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003ea, e, d, h). The difference between Stage II and III disease was not significant (P\u0026thinsp;\u0026gt;\u0026thinsp;0.05) (Fig. \u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003eb, c, f, g).\u003c/p\u003e\u003ctable border=\"1\" id=\"Tab3\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eBaseline characteristics of aRT receivers and non-aRT receivers after propensity score matching\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003eVariables\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003eaRT\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colspan=\"2\" rowspan=\"2\"\u003e\n \u003cp\u003eStandardized diff.\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003eP value\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eYes(n\u0026thinsp;=\u0026thinsp;751)\u003c/strong\u003e\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eNo (n\u0026thinsp;=\u0026thinsp;751)\u003c/strong\u003e\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAge\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.0517\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e30\u0026ndash;49 years\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e164 (21.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e170 (22.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.02\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e50\u0026ndash;59 years\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e230 (30.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e221 (29.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.03\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e60\u0026ndash;69 years\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e199 (26.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e164 (21.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026ge;\u0026thinsp;70 years\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e158 (21)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e196 (26.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eSex\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.02\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.7486\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eFemale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e275 (36.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e282 (37.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e476 (63.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e469 (62.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eRace\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.8567\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eWhite\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e626 (83.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e633 (84.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.03\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBlack\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e53 (7.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e52 (6.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.01\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eOthers\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e72 (9.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e66 (8.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.03\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003ePrimary site\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.0001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBase of tongue\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e222 (29.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e172 (22.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eDorsal surface of tongue\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e36 (4.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e69 (9.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.17\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBorder of tongue\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e190 (25.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e296 (39.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.31\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eVentral surface of tongue\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e103 (13.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e94 (12.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.04\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAnterior 2/3 of tongue\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e200 (26.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e120 (16)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.26\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eGrade\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.4739\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eI-Well differentiated\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e90 (12)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e107 (14.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.07\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eII-Moderately differentiated\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e451 (60.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e434 (57.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.05\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eIII-Poorly differentiated\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e202 (26.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e205 (27.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.01\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eIV-Undifferentiated\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e8 (1.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e5 (0.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.04\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eChemotherapy\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.0000\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e42 (5.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e42 (5.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNo/Unknown\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e709 (94.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e709 (94.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003ctfoot\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"6\"\u003eaRT, adjuvant radiotherapy\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tfoot\u003e\n \u003c/table\u003e\n \u003cp\u003eTo eliminate bias from the primary site, we adjusted this variable in the HR analysis (Table \u003cspan class=\"InternalRef\"\u003e4\u003c/span\u003e). The Cox regression analysis showed that aRT was positively correlated with both 5-year OD (HR, 2.51; 95% CI, 1.77\u0026ndash;3.55) and DSD (HR, 2.76l 95% CI, 1.82\u0026ndash;4.19) in Stage I patients. aRT was negatively associated with both 5-year OD (HR, 0.55; 95% CI, 0.41\u0026ndash;0.74) and DSD (HR, 0.55; 95% CI, 0.40\u0026ndash;0.76) in Stage IV patients (Table \u003cspan class=\"InternalRef\"\u003e4\u003c/span\u003e). Similar results were observed for the adjusted model. The results before and after PSM were consistent.\u003c/p\u003e\n\u003c/div\u003e\u003ctable border=\"1\" id=\"Tab4\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eImpact of aRT on OD and DSD in patients with different tumor stages in the matched cohort\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\" colspan=\"2\" rowspan=\"2\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003cth align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003eStage I\u003c/p\u003e\n \u003cp\u003eHR (95%CI)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003eStage II\u003c/p\u003e\n \u003cp\u003eHR (95%CI)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003eStage III\u003c/p\u003e\n \u003cp\u003eHR (95%CI)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003eStage IV\u003c/p\u003e\n \u003cp\u003eHR (95%CI)\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eOD\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e(130/585)\u003c/strong\u003e\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eDSD\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e(90/545)\u003c/strong\u003e\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eOD\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e(105/280)\u003c/strong\u003e\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eDSD\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e(77/252)\u003c/strong\u003e\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eOD\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e(113/300)\u003c/strong\u003e\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eDSD\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e(95/282)\u003c/strong\u003e\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eOD\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e(190/337)\u003c/strong\u003e\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eDSD\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e(164/311)\u003c/strong\u003e\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e\u003cstrong\u003eNon-adjusted\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003e\u003cstrong\u003eaRT\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eNo\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eReference\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eReference\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eReference\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eReference\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eReference\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eReference\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eReference\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eReference\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eYes\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.51 (1.77, 3.55) *\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.76 (1.82, 4.19) *\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.34 (0.90, 1.99)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.08 (0.69, 1.70)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.29 (0.85, 1.97)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.23 (0.78, 1.93)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.55 (0.41, 0.74) *\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.55 (0.40, 0.76) *\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e\u003cstrong\u003eAdjusted\u003c/strong\u003e \u003csup\u003e\u003cstrong\u003ea\u003c/strong\u003e\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003e\u003cstrong\u003eaRT\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eNo\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eReference\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eReference\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eReference\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eReference\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eReference\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eReference\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eReference\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eReference\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eYes\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.55 (1.78, 3.67) *\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.86 (1.85, 4.42) *\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.28 (0.85, 1.92)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.01 (0.63, 1.60)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.24 (0.81, 1.90)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.17 (0.74, 1.84)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.52 (0.39, 0.70) *\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.53 (0.38, 0.72) *\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003ctfoot\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"10\"\u003e*indicates P\u0026thinsp;\u0026lt;\u0026thinsp;0.05\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"10\"\u003e\u003csup\u003ea\u003c/sup\u003eadjusted for primary site.\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"10\"\u003eaRT, adjuvant radiotherapy; CI, confidence interval; DSD, disease-specific death; HR, hazard ratio; OD, overall death\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tfoot\u003e\n \u003c/table\u003e\n\u003c/div\u003e\u003cp\u003e\u003cstrong\u003eEthical approval\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe SEER research data files were downloaded using the account number 20161-Nov2020. The account is approved to access to the 1975-2018 SEER Research Plus Data (November 2020 Submission). The data released by the SEER database do not require informed patient consent. All experiments were performed in accordance with relevant guidelines and regulations.\u0026nbsp;\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis study revealed that aRT is significantly associated with survival benefits in patients with Stage IV SCC of the tongue. aRT is commonly used after surgery in cases of unfavorable histological findings. For large tumors, several oncologists recommend aRT if the surgical margins are close to the tumor or involved\u0026nbsp;or if several\u0026nbsp;positive nodes persist after neck dissection. Previous studies have indicated that early tongue cancers are associated with 5-year survival rates of at least 80% [21,31,32], although cancers of the tongue have a worse prognosis than those affecting other oral areas. Rusthoven et al. revealed that Stage I and II tongue cancers have 60.9% and 83.5% 5-year OS and cause-specific survival rates, respectively; other oral subsites had rates of 64.7% and 94.1%, respectively, according to\u0026nbsp;the SEER database [33]. Shim et al. attributed the high survival rate of tongue cancer to appropriate radiotherapy [21]. Thus, feasible and reasonable radiation therapy regimens are important for the survival status of patients. In this study, we analyzed the survival of patients with SCC of the tongue and sought to determine the impact of aRT\u0026nbsp;use on survival. We discovered that aRT confers\u0026nbsp;advanced survival in Stage IV SCC of\u0026nbsp;the tongue, whereas it failed to improve survival status in Stage I to Stage III SCC patients. Furthermore, aRT for Stage I cancers has a negative\u0026nbsp;impact on patient survival. To unequivocally establish the association between the tumor stage and aRT, we verified the results in\u0026nbsp;the original and\u0026nbsp;PSM cohorts and obtained the same conclusion. Our results contribute to the growing body of knowledge related to tongue SCC-related outcomes and reveal that survival and response to aRT vary with tumor stage. In this article, we report a number of observational associations that can provide motivation and set the stage for future mechanistic studies investigating the biological mechanisms that may underlie the observed differences in tongue body SCC prognosis and response to treatment.\u003c/p\u003e\n\u003cp\u003eIn our original data analysis, aRT served as a risk factor for patients with Stage I tumors in 5-year OS and DSS. In addition, it is worth noting that we could not detect any significant benefits of aRT for Stage II and Stage III patients. These results suggest that these early-stage patients do not benefit from aRT. There are reports [21\u0026ndash;24] of findings similar to\u0026nbsp;those of our study. Sandhya et al. analyzed a cohort of 103 cases and suggested that postoperative radiation therapy had no significant impact on\u0026nbsp;the survival of patients with Stage I and II deep tongue cancers, with no less than a 4-mm tumor invasion depth [22]. According to Shim et al., 86 patients with early-stage tongue cancer were enrolled in the study, but no significant differences were observed in the OS rate after surgery alone and\u0026nbsp;a combination of surgery and postoperative radiation therapy [21]. However, these studies included only\u0026nbsp;a few patients, and it\u0026nbsp;was difficult to adjust baselines. Focusing on oral cavity cancers generally, Luryi et al. and Sowder et al. analyzed the data from\u0026nbsp;the SEER database with a large number of cases and revealed that treatment with adjuvants led to significantly worse OS and DSS\u0026nbsp;than surgery alone for early-stage oral cancers [23,24]. However, they did not determine whether postoperative radiation therapy was beneficial for each subsite. Our results are consistent with\u0026nbsp;those of previous studies that suggested that\u0026nbsp;early-stage patients should not receive aRT after surgery. This would increase the cost of treatment and reduce the quality of life of these patients, and the radiation exposure to the oral cavity and oropharynx may lead to unfavorable complications.\u003c/p\u003e\n\u003cp\u003eIn contrast, some other reports have suggested that aRT is beneficial for early-stage head and neck SCC. Tsai et al. confirmed that aRT could improve neck control and survival status in patients with early oral cancers with a single nodal status in the Taiwan Cancer Registry database [25]. Furthermore, Schiff et al. suggested that aRT could improve regional failure in patients with pN1 tongue cancers, although the results were not significant (P=0.32) [26]. Torrecillas et al. confirmed significant survival benefit of aRT for patients with T1N1 and T2N2 oral cavity SCC [27]. Qian et al. suggested that aRT resulted in better survival in patients with pN0 [28]. Shrime et al. suggested that aRT was associated with the most significant improvements in cancers of the tongue after verifying its effects on T1N1 or T2N1 oral SCCs [29]. Several factors were responsible for these divergent conclusions: first, the sources of their data were variable, and the characteristics of patients and aRT modalities could be different; second, some studies have focused on the oral cavity or head and neck rather than a specific subsite, which may influence the survival status of patients; third, some early-stage patients may suffer from occult node metastases. We speculate that advanced benefits of aRT may be identified in larger cohorts with occult metastases.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eCompared with these studies, we conducted a more accurate study based on a large number of patients in the SEER database and included SCCs of the entire tongue body (anterior 2/3 and base of tongue). We also included various patient characteristics and treatment options. Considering that patients with different tumor stages could have different characteristics, we made some adjustments to the basic characteristics of the patients to reduce bias. We performed a subgroup analysis and conducted PSM based on baseline variables. For both the original and PSM groups, we explored the effects of postoperative radiation therapy on OS and DSS. After adjustment, we did not detect any significant changes in the results compared to the original data. We used PSM to match all variables at a 1:1 ratio between aRT and non-aRT receivers; 1502 cases were included. We discovered that aRT could worsen the survival of patients with Stage I SCC, even after adjustment and matching. In addition, we found that aRT could not always extend the duration of survival for late-stage tumors. aRT can only improve the survival of patients with Stage IV SCC of the tongue and is not significantly associated with survival benefits in the original and propensity-score matching populations. Our PSM and adjusted results provide dual authentication that patients with different stages of SCC cannot always benefit from aRT after surgery. The provision of appropriate therapeutic regimens is of great importance. This should be based on several factors, including patient characteristics, disease progression, and quality of life following surgery.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eBecause of its retrospective nature, this study inevitably had several limitations. Due to the lack of therapeutic parameters of radiation (including definitive versus palliative intent, dose/fractionation) in\u0026nbsp;the SEER database, we could not evaluate the effects of these factors on survival and prognosis. The list of variables included in our analysis was not exhaustive, and some potentially important factors (e.g., smoking status, alcohol drinking, and vascular invasion) were not available in the SEER database. Additionally, we do not have access to the information on various patient characteristics in the SEER database, including quality of life, complications, tumor resection margins, recurrence, and\u0026nbsp;treatment of recurrence, all of which may have affected our aRT analysis. Advances have been made in radiotherapy technology; however, as a result of differences in selection criteria, techniques, and equipment, toxicity and quality of life within a given period of time can be compromised more than survival outcomes [34].\u003c/p\u003e\n\u003cp\u003eIn conclusion, we suggested that there were significant survival benefits associated with aRT for Stage IV SCC of the tongue and that patients with Stage I SCC of the tongue cannot benefit from aRT. Thus, survival and other benefits of aRT for early-stage SCC need some further justification, especially for Stage I patients. Otherwise, these patients may not be subjected to unnecessary radiation and morbidity. Our results provide an orientation for research interest in the biological mechanism, and future researchers can provide reasonable explanations and feasible methods of improvements for aRT.\u003c/p\u003e"},{"header":"Patients And Methods","content":"\u003cp\u003e\u003cstrong\u003eData collection\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe retrieved the data of cases with SCC involving\u0026nbsp;the\u0026nbsp;anterior two-thirds of\u0026nbsp;the tongue and\u0026nbsp;base of\u0026nbsp;the tongue from the SEER Stat 8.3.9. The data were part of\u0026nbsp;the SEER 18 Regs Custom Data (with additional treatment fields), Nov 2018 Sub (1975\u0026ndash;2016 varying). Relevant patient information in the SEER database includes demographic characteristics, histology, malignancy, therapeutic regimen, and survival duration, among others. Based on histology recode and the WHO definition of squamous cell tumors (8050\u0026ndash;8089 squamous cell tumors), we\u0026nbsp;ran the research modality in a cast-listing session. The selected neoplasms exhibited malignant behavior. The site and morphology (primary site-labeled) included C01.9-base of the tongue, not otherwise specified (NOS); C02.0-dorsal surface of tongue, NOS; C02.1-border of tongue; C02,2-ventral surface of tongue, NOS; and C02.3-anterior two-thirds of the tongue, NOS.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThese data were retrieved and analyzed as follows: age (30\u0026ndash;49; 50\u0026ndash;59; 60\u0026ndash;69;\u0026nbsp;\u0026ge;70 years); sex (male, female); race (white, black, American Indian/Alaska Native, Asian, or Pacific Islander); year of diagnosis; grade (I, II, III, IV); SEER Combined Summary Stage 2000 (2004+) (regional lymph nodes involved only, regional by direct extension only, regional by both direct extension and lymph node involvement, localized only, distant site(s)/node(s) involved); anatomic site (C01.9-base of the tongue, NOS; C02.0-dorsal surface of the tongue, NOS; C02.1-border of tongue; C02,2-ventral surface of the tongue, NOS; C02.3-anterior two-thirds of the tongue, NOS); derived American Joint Committee on Cancer (AJCC) TNM stage, 6\u003csup\u003eth\u003c/sup\u003e edition (2004-2015); surgery; aRT; and DSS and OS, both measured in months. SCCs were staged based on\u0026nbsp;the AJCC 6\u003csup\u003eth\u003c/sup\u003e edition, effective 2004\u0026nbsp;and onward. The analysis did not include patients without surgery. We only included patients who\u0026nbsp;underwent surgery alone or post-surgery radiotherapy. A 5-year OS and DSS were the study\u0026apos;s endpoints. Based on months from the date of initial pathological diagnosis to the date of death or the end of 60 months, OS or DSS was calculated.\u003c/p\u003e\n\u003ch2\u003eStatistical analysis\u003c/h2\u003e\n\u003cp\u003eThe Kaplan\u0026ndash;Meier method and log-rank test were applied to calculate and assess the survival curves of\u0026nbsp;patients diagnosed with\u0026nbsp;different stages stratified by aRT. We estimated the association between the stage and aRT and OS and DSS using HRs and the corresponding 95% CIs was calculated via Cox regression models. Patients with similar baseline characteristics were identified via PSM. Based on a series of baseline covariates including age, sex, race, primary site, grade, and chemotherapy, a propensity score is calculated as the conditional probability of being exposed to a given exposure (aRT yes versus no). The 1:1 matching protocol was employed without replacement (greedy-matching algorithm); the caliper width was estimated to be equal to 0.01 of the standard deviation of the propensity score. For all baseline covariates, standardized differences were estimated before and after matching to assess the pre-match and post-match balance. Standardized differences \u0026lt;10.0% for a given covariate indicate a relatively small imbalance. Using the Kaplan\u0026ndash;Meier method and a log-rank test, we could generate and compare survival curves of patients stratified by aRT in the matched cohort. The association between aRT, OS, and DSS of patients with different stages of cancer was also studied using a Cox proportional hazards regression model.\u003c/p\u003e\n\u003cp\u003eAll analyses were performed using the statistical software packages R (R Foundation for Statistical Computing, Vienna, Austria) and Empower Stats (X\u0026amp;Y Solutions, Inc., Boston, MA, USA). The significance level was determined by the two-tailed P-value of 0.05.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eaRT, adjuvant radiotherapy\u003c/p\u003e\n\u003cp\u003eCI, confidence interval\u003c/p\u003e\n\u003cp\u003eDSD, disease-specific death\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eDSS, disease-specific survival\u003c/p\u003e\n\u003cp\u003eHR, hazard ratio\u003c/p\u003e\n\u003cp\u003eOD, overall death\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eOS, overall survival\u0026nbsp;\u003c/p\u003e\n\u003cp\u003ePSM, propensity-score matching\u003c/p\u003e\n\u003cp\u003eSCC, squamous cell carcinoma\u003c/p\u003e\n\u003cp\u003eSEER, Surveillance, Epidemiology, and End Results\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgments\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026rsquo; contribution\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eZhenyu Ding designed the study and collected the data. Run Yao analyzed the data. Zhenyu Ding and Run Yao wrote the manuscript. Ning Li and Jun Zuo reviewed and edited the manuscript. Zhenyu Ding and Run Yao share first authorship. All authors have read and approved the final manuscript.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was supported by the Natural Science Foundation of Hunan Province\u0026nbsp;(project no. 2018JJ2546) and\u0026nbsp;the Scientific\u0026nbsp;Research Project of Hunan Provincial Health Commission (project no. 202218013370).\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eRole of the funding source\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eStatistical analysis and language editing.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare no competing interests.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eChristopherson K, Morris CG, Kirwan JM, et al. 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Cancers (Basel). 2021;13(4):1\u0026ndash;16. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.3390/cancers13040589\u003c/span\u003e\u003cspan address=\"10.3390/cancers13040589\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003c/ol\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":"","lastPublishedDoi":"10.21203/rs.3.rs-1406293/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-1406293/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eWe examined the benefits of adjuvant radiotherapy (aRT) for patients with tongue squamous cell carcinoma (SCC).\u003cstrong\u003e \u003c/strong\u003eThe Surveillance, Epidemiology, and End Results database was applied to identify patients treated with or without aRT for tongue SCC. The Kaplan–Meier method and log-rank test assessed survival curves for SCC stages stratified by aRT. Hazard ratios were estimated for stage and aRT concerning overall survival (OS) and disease-specific survival (DSS). Propensity-score matching was performed to assess differences in baseline characteristics. We included 3322 cases. The total number of deaths and disease-specific deaths were 1234 (37.15%) and 938 (28.24%), respectively. The Kaplan–Meier curves for 5-year OS and DSS showed that patients receiving aRT had lower and higher survival probabilities during Stages I and IV, respectively (P\u0026lt;0.0001). On Cox regression analysis, aRT and 5-year OS and DSS were positively and negatively associated with Stage I and Stage IV patients, respectively. Sensitivity analysis results were consistent before and after PSM. OS and DSS of Stage II and III patients in the aRT and non-aRT groups were not significantly different (P\u0026lt;0.05). aRT WAS significantly associated with survival benefits and worse survival for Stage IV and I tongue SCC cases, respectively.\u003c/p\u003e","manuscriptTitle":"Adjuvant radiotherapy and survival of patients with squamous cell carcinoma involving the entire tongue: The SEER database analysis","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2022-03-15 19:03:38","doi":"10.21203/rs.3.rs-1406293/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":"5a0ae937-1552-4252-917f-6df6f972afd1","owner":[],"postedDate":"March 15th, 2022","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2022-05-25T05:29:09+00:00","versionOfRecord":[],"versionCreatedAt":"2022-03-15 19:03:38","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-1406293","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-1406293","identity":"rs-1406293","version":["v1"]},"buildId":"7rjqhiLT3MXkJMwkYKINL","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}