Prognostic impact of extended neck dissection in oral squamous cell carcinoma: a retrospective study

Prognostic impact of extended neck dissection in oral squamous cell carcinoma: a retrospective study | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Prognostic impact of extended neck dissection in oral squamous cell carcinoma: a retrospective study Takuma Kugimoto, Yu Oikawa, Yoshihisa Kashima, Toshimitsu Ohsako, and 4 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-2101471/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background: Cervical lymph node metastasis with extranodal extension (ENE) is a poor prognostic factor for oral squamous cell carcinoma (OSCC). This study aimed to evaluate the treatment outcomes of OSCC patients who underwent extended neck dissection (ND), requiring resection of non-lymphatic structures for invasive nodal disease. Methods: Patients who underwent extended ND for OSCC at the Department of Oral and Maxillofacial Surgery, Tokyo Medical and Dental University between April 2001 and December 2018 were retrospectively analyzed. Regional recurrence and complication were assessed. The primary outcome variable was 5-year disease-specific survival. Results: A total of 49 patients were included, and regional recurrence was found 18 patients (36.7%). There was no significant difference in the regional recurrence rate, regardless of whether the non-lymphatic structure requiring resection was single or multiple (29.6% vs 45.4%, P = 0.398). The regional recurrence rate was significantly higher in patients who required resection of neurovascular structures than in patients who did not require resection of these structures (64.3% vs 25.7%, P = 0.028). Cox proportional-hazards regression models indicated that types of resected non-lymphatic structures (with neurovascular structures) was the most risk factor for predicting the risk of regional recurrence ( P = 0.048, hazard ratio = 2.59, 95% confidence interval: 1.01–6.66). Cox regression analysis to determine independent predictive factors for DSS, revealing that types of resected non-lymphatic structures ( P =0.038, HR = 2.58, 95% CI: 1.05–6.33) was independent predictive factors for DSS. Patients who required resection of neurovascular structures had significantly worse the 5-year DSS rate than those who did not (23.4% vs 63.1%; P = 0.014). Complications after extended ND included recurrent nerve paralysis in three patients, facial nerve paralysis in two patients, and chyle leak, fracture of mandible, and urgent tracheostomy due to larynx edema in a patient, respectively. Conclusion: This study suggests that adhesion of metastatic lymph nodes to neurovascular structures is a significant poor prognostic factor for regional recurrence after extended ND. Patients with OSCC with adhesion of metastatic lymph nodes to neurovascular structures require an adequate safety resection margin and intensive postoperative treatment. oral squamous cell carcinoma extended neck dissection regional recurrence non-lymphatic structure neurovascular structure Figures Figure 1 Figure 2 1 Background Metastasis to cervical lymph nodes is a major determinant prognosis factor in oral squamous cell carcinoma (OSCC). Neck dissection (ND) is the best treatment for patients with cervical lymph node metastasis in OSCC. Extranodal extension (ENE) is considered a high-risk factor for regional recurrence in OSCC ( 1 ). Regional recurrence is frequent in patients with advanced cervical lymph node metastasis because tumor cells may be disseminated and may have already involved the non-lymphatic tissues at the time of surgery ( 2 ). These involved structures must be removed to perform an oncologically complete resection. Extended ND refers to the removal of non-lymphatic structures not included in the radical ND ( 3 ). Examples of non-lymphatic structures include the carotid artery, hypoglossal nerve, vagus nerve, and paraspinal muscles. The surgical treatment of OSCC patients with ENE, who require removal of major muscular or neurovascular structures, has not been well investigated ( 4 – 6 ). In addition to treatment outcomes, postoperative complications should be considered in patients who underwent extended ND ( 7 ). The purpose of this study was to analyze the risk factors affecting the prognosis and regional recurrence of patients with OSCC requiring resection of non-lymphatic structures during ND due to ENE. . 2 Methods Patients This retrospective study evaluated patients with OSCC who underwent extended ND from April 2001 to December 2018 at the Department of Oral and Maxillofacial Surgery of Tokyo Medical and Dental University. Of those, adult patients aged > 20 years who were diagnosed with OSCC by biopsy and underwent extended ND were included. Patients who had a history of head and neck cancer, prior surgery in the targeted neck region, uncontrolled primary tumor, or involvement of cervical non-lymphatic structures by direct extension of the primary tumor were excluded. This study followed the Declaration of Helsinki on medical protocol and ethics and the Institutional Review Board of the Faculty of Dental Hospital of Tokyo Medical and Dental Hospital approved this clinicopathological study and waived the requirement for written informed patient consent, owing to the retrospective study design (approval No. D2015-600). Treatment The areas of ND were determined by comprehensively examining regional metastasis. Extended ND was defined as a resection of non-lymphatic tissue that was not resected by radical ND, as a result of ENE. In our department, the stylohyoid and digastric muscles were routinely sacrificed during any type of ND; therefore, these structures were excluded from non-lymphatic tissues. Non-lymphatic tissues included other muscular, osseous, cutaneous, and neurovascular structures. The structures requiring resection were determined by preoperative and intraoperative findings based on nodal invasion. Adjuvant chemoradiotherapy was conducted for patients with cervical lymph node metastasis of ≥ 4 nodes or presence of pathological ENE. The radiotherapy schedule comprised of 2.0 Gy per fraction, at one fraction per day, 5 days per week. The patients underwent postoperative radiotherapy for a total dose of 50–60 Gy ( 8 ). Platinum-based anticancer agents were basically used for postoperative concurrent chemoradiotherapy. Follow-up After extended ND, patients were followed up every 4 weeks for 1 year, every 2 months for the next year, with follow-up intervals gradually increasing thereafter. Surveillance included CT or positron emission tomography-computed tomography (PET-CT) performed 6 months after treatment and every year thereafter. Variables We evaluated the patients for age, sex, primary tumor site, TN stage, the initial treatment for the primary tumor, the period of extended ND, dissected nodal levels, the number of pathologically metastatic lymph nodes, presence of pathological ENE, resected non-lymphatic structures, and treatment outcomes. Tumors were clinically staged using the Union International Centre le Cancer Tumor-Node- Metastasis staging system (8th edition). Clinicopathological risk factors (age, sex, primary tumor site, TN stage, initial treatment for the primary tumor, extended ND period, the number of pathologically metastatic lymph nodes, contralateral node metastasis presence, pathological ENE presence, extended ND status and adjuvant therapy) represented the predictive variables. Extended ND status were types and number of resected non-lymphatic structures for adhesions. Types of resected non-lymphatic structures for adhesions (binary variable: with or without neurovascular structure) and number of resected non-lymphatic structures for adhesions (binary variable: multiple or single) defined as extended ND status. Disease-specific survival (DSS) was defined as the primary outcome variable. DSS was measured from the date of surgery to the date of death from uncontrolled OSCC. Regional recurrence was defined as the secondary outcome variable. Statistical analysis The regional recurrence rate was calculated for each non-lymphatic structure. The associations between regional recurrence and categorical variables were assessed using Fisher’s exact test or Pearson’s chi-square test. Multivariate analysis using Cox proportional hazards models was subsequently performed to evaluate variables that were significantly different in the univariate analysis and identify significant risk factors for regional recurrence. Cox regression analysis (both univariate and multivariate) was performed to identify independent predictive factors for DSS. Survival analysis was estimated using the Kaplan–Meier method, and groups were compared using the log-rank test. All statistical analyses were performed using R-3.5.3 statistical software ( https://www.r-project.org/ ). A P value of < 0.05 was considered statistically significant. 3 Results Patient characteristics A total of 1,547 patients with OSCC were treated at the Department of Oral and Maxillofacial Surgery of Tokyo Medical and Dental University. ND was performed on 931 neck sides in 794 patients. Of these, 544 neck sides in 477 patients (30.8%) demonstrated cervical lymph node metastases on pathological examination. Among these patients, we retrospectively reviewed 49 patients had underwent extended ND (35 men and 14 women; age range, 23–83 years; median age, 63.0 years). The median follow-up period was 63 months (range, 1–179 months). In the 49 extended ND patients, the primary tumor affected the tongue in 29 patients, buccal mucosa in 10 patients, lower gingiva in 6 patients, upper gingiva in 3 patients, and floor of the mouth in a patient. Clinical T stage classification was as follows: 13 patients for cT1, 21 patients for cT2, 9 patients for cT3, 5 patients for cT4a, and a patient for cT4b. With respect to the histological differentiation of primary tumor, we found well differentiation in 17 patients, moderate differentiation in 7 patients, poor differentiation in 12 patients, and differentiation was unknown in 13 patients. The initial treatment for the primary tumor was surgery in 38 patients and brachytherapy (Cs-137, Ir-192, or Au-198) in 11 patients. Clinicopathological variables among patients who underwent extended ND are described in Table 1 . Table 1 Univariate analyses of correlation between clinicopathological characteristics and regional recurrence in patients with extended ND Clinicopathological characteristics Without regional recurrence (n = 31) With regional recurrence (n = 18) P value Sex Male 23 12 0.815* Female 8 6 Age < 60 years 16 11 0.729* ≥ 60 years 15 7 Primary site Tongue 16 13 0.230** Others 15 5 cT stage T1-2 22 12 1.000* T3-4 9 6 Initial treatment for primary tumor Surgery 24 14 1.000** Brachytherapy 7 4 Period of extended ND Initial 8 3 0.724** Subsequent 23 15 pN stage N1-2 11 5 0.754** N3b 20 13 Number of positive nodes < 4 20 9 0.487* ≥ 4 11 9 Contralateral node metastasis Absent 29 13 0.084** Present 2 5 ENE Absent in pN 5 1 0.393** Present in pN 26 17 Number of resected non-lymphatic structures Single 19 8 0.398* Multiple 12 10 Types of resected non-lymphatic structures Without neurovascular structure 26 9 0.028* With Neurovascular structure 5 9 Adjuvant therapy Not performed 14 2 0.025** Performed 17 16 *Chi-square test. **Fisher’s exact test. Extended ND Extended ND was performed in 11 patients at the initial surgery combined with a primary resection, in 38 patients at subsequent cervical lymph node metastasis. The ipsilateral extended ND was performed in 43 patients and the contralateral in 6 patients. Dissected nodal levels included a patient with level I, a patient with levels I and II, 3 patients with levels I–III, 5 patients with levels I–IV, and 39 patients with levels I–V. The average number of the dissected nodes from surgical specimen was 50.8 (range, 8–141) and a median number of 3 metastatic lymph nodes (range, 1–17). Pathological ENE was found in 43 patients (87.8%). Table 2 shows the resected non-lymphatic structures and regional recurrence rate. Most frequently sacrificed tissues were as follows; mandible, mylohyoid muscle, platysma, and external carotid artery, with the regional recurrence rates of 29.4%, 31.3%, 27.3%, and 71.4%, respectively. There was no significant difference in the regional recurrence rate, regardless of whether the non-lymphatic structure requiring resection was single or multiple (29.6% vs 45.4%, P = 0.398). The regional recurrence rate was significantly higher in patients who required resection of neurovascular structures (neurovascular resection group) than in patients who did not require resection of these structures (neurovascular non-resection group) (64.3% vs 25.7%, P = 0.028) (Table 1 ). Table 2 Resected non-lymphatic structures and regional recurrence rate Non-lymphatic structure No. of patients (n = 49) Patients with regional recurrence Mandible 17 5 (29.4%) Mylohyoid muscle 16 5 (31.3%) Platysma 11 3 (27.3%) External carotid artery 7 5 (71.4%) Skin 7 3 (42.9%) Hypoglossal nerve 6 2 (33.3%) Masseter muscle 5 2 (40.0%) Lingual artery 2 2 (100%) Lingual nerve 2 1 (50.0%) Hyoglossus muscle 2 1 (50.0%) Superior thyroid artery 1 1 (100%) Glossopharyngeal nerve 1 1 (100%) Vagus nerve 1 1 (100%) Sternohyoid muscle 1 1 (100%) Geniohyoid muscle 1 1 (100%) Genioglossus muscle 1 1 (100%) Medial pterygoid muscle 1 0 (0%) Thyrohyoid muscle 1 0 (0%) Hyoid bone 1 0 (0%) Complications of extended ND Complications after extended ND included recurrent nerve paralysis in three patients, facial nerve paralysis in two patients, and chyle leak, fracture of mandible, and urgent tracheostomy due to larynx edema in a patient, respectively. At last follow-up, a patient had persistent gastrostomy and tracheostomy tube. Treatment outcome Twenty-four patients developed recurrence, specifically regional recurrence in 12 patients, distant metastasis in 6 patients, and regional recurrence and distant metastasis in 6 patients. The median interval from surgery to regional recurrence was 4.1 (interquartile range, 51.5–190) months. As shown Fig. 1 , the DSS rate was much lower for patients with regional recurrence (5.9% vs 79.6%, P < 0.001). Independent predictive factors for regional recurrence Univariate analysis was demonstrated that types of resected non-lymphatic structures ( P = 0.028) and adjuvant therapy ( P = 0.025) were significantly associated with regional recurrence. Then, by accomplishing multivariate Cox regression analysis, we identified that types of resected non-lymphatic structures ( P = 0.048, HR = 2.59, 95% CI: 1.01–6.66) was independent predictive factor for regional recurrence, which was demonstrated in Table 3 . Table 3 Multivariate analysis using Cox proportional-hazard regression for regional recurrence Clinicopathological factors Hazard ratio (95% CI) P value Types of resected non-lymphatic structures Without neurovascular structure 1.00 (Reference) 0.048 With Neurovascular structure 2.59 (1.01–6.66) Adjuvant therapy Not performed 1.00 (Reference) 0.053 Performed 4.38 (0.98–19.5) Independent predictive factors for DSS Analyses of the clinicopathologic predictors of DSS were performed using a Cox proportion hazard model. Initially, univariate Cox regression was performed to identify variables significantly associated with DSS, demonstrating that number of positive nodes ( P = 0.048, HR = 2.36, 95% CI: 1.01–5.54), contralateral node metastasis ( P = 0.046, HR = 2.78, 95% CI: 1.02–7.59), types of resected non-lymphatic structures ( P = 0.018, HR = 2.77, 95% CI: 1.19–6.43), and adjuvant therapy ( P = 0.017, HR = 5.91, 95% CI: 1.38–25.4) were significantly associated with DSS (Table 4 ). Subsequently, those variables significantly associated with DSS mentioned above were included in multivariate Cox regression analysis to determine independent predictive factors for DSS, revealing that types of resected non-lymphatic structures ( P = 0.038, HR = 2.58, 95% CI: 1.05–6.33) was independent predictive factors for DSS (Table 4 ). The 5-year DSS rate was significantly lower in neurovascular resection group than in neurovascular non-resection group (23.4% vs 63.1%, P = 0.014, Fig. 2 ). Table 4 Cox proportional-hazard regression for DSS Clinicopathologic factors Univariate analysis Multivariate analysis Hazard ratio (95% CI) P value Hazard ratio (95% CI) P value Sex Male 1.00 (Reference) 0.723 Female 1.18 (0.48–2.89) Age < 60 years 1.00 (Reference) 0.929 ≥ 60 years 0.96 (0.41–2.25) Primary site Tongue 1.00 (Reference) 0.320 Others 1.53 (0.66–3.56) cT stage T1-2 1.00 (Reference) 0.923 T3-4 1.05 (0.43–2.57) Initial treatment for primary tumor Surgery 1.00 (Reference) 0.179 Brachytherapy 0.43 (0.13–1.47) Period of extended ND Initial 1.00 (Reference) 0.609 Subsequent 1.33 (0.45–3.91) pN stage N1-2 1.00 (Reference) 0.136 N3b 2.14 (0.79–5.81) Number of positive nodes < 4 1.00 (Reference) 0.048 1.00 (Reference) 0.625 ≥ 4 2.36 (1.01–5.54) 1.27 (0.49–3.26) Contralateral node metastasis Absent 1.00 (Reference) 0.046 1.00 (Reference) 0.154 Present 2.78 (1.02–7.59) 2.28 (0.73–7.09) ENE Absent in pN 1.00 (Reference) 0.203 Present in pN 3.69 (0.49–27.5) Number of resected non-lymphatic structures Single 1.00 (Reference) 0.296 Multiple 1.57 (0.68–3.62) Types of resected non-lymphatic structures Without neurovascular structure 1.00 (Reference) 0.018 1.00 (Reference) 0.038 With neurovascular structure 2.77 (1.19–6.43) 2.58 (1.05–6.33) Adjuvant therapy Not performed 1.00 (Reference) 0.017 1.00 (Reference) 0.097 Performed 5.91 (1.38–25.4) 3.72 (0.79–17.6) 4 Discussion The regional recurrence rate after ND for OSCC has been reported to be 7.1–14.4% ( 9 – 11 ), and 5-year locoregional control rate in the patients with ENE and/or the presence of positive or close margin was 54.3% ( 12 ). Carew et al ( 5 ). reported that the regional recurrence rate after extended radical ND for head and neck cancer was 32%. Selective ND including the removal of non-lymphatic structures has been called an extended selective ND ( 4 ). Among patients who underwent extended selective ND, Dhiwakar et al ( 4 ). reported that the regional recurrence rate was 14.0%. In the present study, the regional recurrence rate after extended radical ND and extended selective ND was 34.7%. However, the present study contains both, extended radical ND and extended selective ND; therefore, it is impossible to simply compare it with past reports. This study aimed to identify risk factors for regional recurrence after extended ND at our hospital. To the best of our knowledge, this retrospective study included the largest cohort studied for this cancer type in the oral and maxillofacial surgery literature. Neurovascular structure adhesion was identified as a significant risk factor for regional recurrence after extended ND and was the most potent predictor of survival after extended ND. It represents an independent adverse prognostic factor for OSCC. Regarding association between combined resected tissue and regional recurrence, Shaha ( 6 ) reported that large metastatic lymph nodes in the mastoid process or posterior cervical triangle and those with skin invasion were risk factors of neck recurrence. On the other hand, Carew et al ( 5 ). reported that survival rate was significantly affected by positive nodes at levels IV or V (or multiple levels), not by the specific structure or number of structures sacrificed during extended ND. In our study, neurovascular resection group developed significantly higher regional recurrence. Nerves along with blood vessels, immune cells, fibroblasts, and the extracellular matrix are part of the tumor microenvironment, an established contributor to tumor progression ( 13 ). As such, vascular and perineural invasion make local and regional control particularly difficult by allowing tumor extension beyond the expected treatment margins ( 14 ). Our results suggest that if the neurovascular structures must be resected for ENE, the tumor cells may have already spread along the neurovascular structures. Most significant element in predicting the 5-year DSS was adhesion of metastatic lymph nodes to neurovascular structures. Patients requiring resection of neurovascular structures had a 23.4% 5-year survival, compared with 63.1% for those who had did not. More effective adjuvant therapies, such as concurrent chemoradiotherapy (CCRT), need to be performed in patients with head and neck squamous cell carcinoma (HNSCC) with ENE and multiple positive nodes after ND for more effective regional control ( 15 ). Some international guidelines recommend postoperative CCRT with high-dose cisplatin (every 3 weeks) as the standard treatment for patients with resectable advanced HNSCC who are at high risk of recurrence ( 1 , 16 ). Previous investigations have found that compared to patients with other types of HNSCC, those with OSCC have worse prognoses because of inadequate response to chemotherapy and radiotherapy ( 17 , 18 ). Recently, the usefulness of immune checkpoint inhibitors (ICIs) for recurrent or metastatic HNSCC has been reported ( 19 , 20 ). Furthermore, combination therapy with ICIs and radiation might be used in the future ( 21 – 23 ). Our retrospective study had some limitations. First, it included a very small cohort; moreover, there may be potential bias associated with its retrospective design. Second, the outcome measures for detailed swallowing and quality-of-life were absent. Moreover, this study examined the prognosis primarily associated with the resection of non-lymphatic structures. Therefore, metastatic lymph nodes requiring resection of neurovascular structures were considered as a risk factor for regional recurrence. The ability to infer an association with prognosis from this result is limited due to the retrospective study design. In addition, it is necessary to pathologically evaluate the appropriate range of resection of non-lymphatic structures. Further prospective studies will be warranted to elucidate the application of those parameters in assessing the risk of OSCC regional recurrence. 5 Conclusion This study suggests that patients with metastatic lymph nodes presenting ENE to non-lymphatic structures, especially neurovascular structures, are considered to have advanced nodal disease and are at a high risk for regional recurrence and distant metastasis. Therefore, extended ND with adequate safety margins and adjuvant therapy, particularly with new drugs, such as ICIs, are essential. Further prospective studies are required to investigate the application of this parameter in risk assessment for regional recurrence in OSCC. Abbreviations OSCC oral squamous cell carcinoma ND neck dissection ENE extranodal extension PET-CT positron emission tomography-computed tomography DSS disease-specific survival CCRT concurrent chemoradiotherapy HNSCC head and neck squamous cell carcinoma ICIs immune checkpoint inhibitors Declarations 1 Acknowledgments Not applicable. 2 Funding This research received no specific grant from any funding agencies in the public, commercial, or not-for-profit sectors. 3 Availability of data and materials Not applicable. 4 Authors’ Contributions TKugimoto designed this study. HHirai, HT and HHarada supervised this study. YO, TO and YK collected the data. YO, TKuroshima, and HT accomplished the statistical analyses in this study. TKugimoto prepared the manuscript. All authors read and approved the final manuscript. 5 Ethics approval and consent to participate The Institutional Review Board of Tokyo Medical and Dental Hospital approved the study (D2015-600), and all the patients included in this study had given his or her informed consent. 6 Consent for publication Not applicable. 7 Competing interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. 8 Publisher’s Note Springer Nature remains neural with regard to jurisdictional claims in published maps and institutional affiliations. 9 Author details Department of Oral and Maxillofacial Surgery, Division of Oral Health Science, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8549, Japan References Colevas AD, Yom SS, Pfister DG, Spencer S, Adelstein D, Adkins D, et al. 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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-2101471","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":139812386,"identity":"1869b9d8-eab5-4db8-91bf-88756165b712","order_by":0,"name":"Takuma Kugimoto","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA2ElEQVRIiWNgGAWjYBACCSA+AGLwQzkMjA3EapFsI0ULGBgcQ+LgBZIz0i8e+PDncL7x/e7EGww1dgzMswlYIy2RU3BwZtthy23HeDdbMBxLZmCccwC/FjmJnITDvA2HDcyO8W6TYGA7wMA4I4EILTx/DhsYt4G0/CNCi7RE+oHDPGyHDQzYgFoY24jQItnzhgHol3QDiWO5my0S+5J5CPpF4nj64w8f/lgb8Def3Xjjwzc7OUNCIcbAwGOAYAOdxGM4g5AOBvYHqHx54iJ0FIyCUTAKRhAAANM2RNiULQlSAAAAAElFTkSuQmCC","orcid":"","institution":"Tokyo Medical and Dental University","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"Takuma","middleName":"","lastName":"Kugimoto","suffix":""},{"id":139812387,"identity":"684e424b-26d5-488d-b18c-76e5ffef43cb","order_by":1,"name":"Yu Oikawa","email":"","orcid":"","institution":"Tokyo Medical and Dental University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Yu","middleName":"","lastName":"Oikawa","suffix":""},{"id":139812388,"identity":"cfea1b4f-da08-4770-b794-4204ac6d6c96","order_by":2,"name":"Yoshihisa Kashima","email":"","orcid":"","institution":"Tokyo Medical and Dental University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Yoshihisa","middleName":"","lastName":"Kashima","suffix":""},{"id":139812389,"identity":"1cbd374b-2ae6-42ae-be67-aa51c6fe64c2","order_by":3,"name":"Toshimitsu Ohsako","email":"","orcid":"","institution":"Tokyo Medical and Dental University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Toshimitsu","middleName":"","lastName":"Ohsako","suffix":""},{"id":139812390,"identity":"903219da-3ae1-4a7c-86dc-6b3b866a5091","order_by":4,"name":"Takeshi Kuroshima","email":"","orcid":"","institution":"Tokyo Medical and Dental University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Takeshi","middleName":"","lastName":"Kuroshima","suffix":""},{"id":139812391,"identity":"67a36524-2bdc-422a-a3b8-a64d5a34ca6a","order_by":5,"name":"Hideaki Hirai","email":"","orcid":"","institution":"Tokyo Medical and Dental University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Hideaki","middleName":"","lastName":"Hirai","suffix":""},{"id":139812392,"identity":"2bfcfaae-9dcc-4fdf-8855-a0c8180a8c3e","order_by":6,"name":"Hirofumi Tomioka","email":"","orcid":"","institution":"Tokyo Medical and Dental University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Hirofumi","middleName":"","lastName":"Tomioka","suffix":""},{"id":139812393,"identity":"77f76e12-8f1f-4298-8dfe-2ddda9460d29","order_by":7,"name":"Hiroyuki Harada","email":"","orcid":"","institution":"Tokyo Medical and Dental University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Hiroyuki","middleName":"","lastName":"Harada","suffix":""}],"badges":[],"createdAt":"2022-09-25 13:14:21","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-2101471/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-2101471/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":27110279,"identity":"d4536ae5-cb3b-402e-90ee-36d992153903","added_by":"auto","created_at":"2022-09-28 22:16:30","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":106287,"visible":true,"origin":"","legend":"\u003cp\u003eKaplan–Meier estimates of DSS among extended ND patients with (dashed line) or without (solid line) regional recurrence.\u003c/p\u003e","description":"","filename":"OnlineFigure1.png","url":"https://assets-eu.researchsquare.com/files/rs-2101471/v1/5452e2ba532fa3aac38569a7.png"},{"id":27110278,"identity":"1b254ec6-f718-4ef7-b57c-b656e3b48b2f","added_by":"auto","created_at":"2022-09-28 22:16:30","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":121223,"visible":true,"origin":"","legend":"\u003cp\u003eKaplan–Meier estimates of DSS of neurovascular resection group (dashed line) versus neurovascular non-resection group (solid line).\u003c/p\u003e","description":"","filename":"OnlineFigure2.png","url":"https://assets-eu.researchsquare.com/files/rs-2101471/v1/9b65dfe4663bcb3641ef5daa.png"},{"id":28403900,"identity":"7aa6678d-e3d3-42b5-ba4c-8545e547bd5a","added_by":"auto","created_at":"2022-10-29 14:29:24","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":616088,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-2101471/v1/1b65785f-5406-4982-b24c-7fbf1f6899fd.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Prognostic impact of extended neck dissection in oral squamous cell carcinoma: a retrospective study","fulltext":[{"header":"1 Background","content":"\u003cp\u003eMetastasis to cervical lymph nodes is a major determinant prognosis factor in oral squamous cell carcinoma (OSCC). Neck dissection (ND) is the best treatment for patients with cervical lymph node metastasis in OSCC. Extranodal extension (ENE) is considered a high-risk factor for regional recurrence in OSCC (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e). Regional recurrence is frequent in patients with advanced cervical lymph node metastasis because tumor cells may be disseminated and may have already involved the non-lymphatic tissues at the time of surgery (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e). These involved structures must be removed to perform an oncologically complete resection. Extended ND refers to the removal of non-lymphatic structures not included in the radical ND (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e). Examples of non-lymphatic structures include the carotid artery, hypoglossal nerve, vagus nerve, and paraspinal muscles. The surgical treatment of OSCC patients with ENE, who require removal of major muscular or neurovascular structures, has not been well investigated (\u003cspan additionalcitationids=\"CR5\" citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e). In addition to treatment outcomes, postoperative complications should be considered in patients who underwent extended ND (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e). The purpose of this study was to analyze the risk factors affecting the prognosis and regional recurrence of patients with OSCC requiring resection of non-lymphatic structures during ND due to ENE.\u003c/p\u003e \u003cp\u003e.\u003c/p\u003e"},{"header":"2 Methods","content":"\u003cp\u003e \u003cb\u003ePatients\u003c/b\u003e \u003c/p\u003e \u003cp\u003eThis retrospective study evaluated patients with OSCC who underwent extended ND from April 2001 to December 2018 at the Department of Oral and Maxillofacial Surgery of Tokyo Medical and Dental University. Of those, adult patients aged\u0026thinsp;\u0026gt;\u0026thinsp;20 years who were diagnosed with OSCC by biopsy and underwent extended ND were included. Patients who had a history of head and neck cancer, prior surgery in the targeted neck region, uncontrolled primary tumor, or involvement of cervical non-lymphatic structures by direct extension of the primary tumor were excluded. This study followed the Declaration of Helsinki on medical protocol and ethics and the Institutional Review Board of the Faculty of Dental Hospital of Tokyo Medical and Dental Hospital approved this clinicopathological study and waived the requirement for written informed patient consent, owing to the retrospective study design (approval No. D2015-600).\u003c/p\u003e \u003cp\u003e \u003cb\u003eTreatment\u003c/b\u003e \u003c/p\u003e \u003cp\u003eThe areas of ND were determined by comprehensively examining regional metastasis. Extended ND was defined as a resection of non-lymphatic tissue that was not resected by radical ND, as a result of ENE. In our department, the stylohyoid and digastric muscles were routinely sacrificed during any type of ND; therefore, these structures were excluded from non-lymphatic tissues. Non-lymphatic tissues included other muscular, osseous, cutaneous, and neurovascular structures. The structures requiring resection were determined by preoperative and intraoperative findings based on nodal invasion. Adjuvant chemoradiotherapy was conducted for patients with cervical lymph node metastasis of \u0026ge;\u0026thinsp;4 nodes or presence of pathological ENE. The radiotherapy schedule comprised of 2.0 Gy per fraction, at one fraction per day, 5 days per week. The patients underwent postoperative radiotherapy for a total dose of 50\u0026ndash;60 Gy (\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e). Platinum-based anticancer agents were basically used for postoperative concurrent chemoradiotherapy.\u003c/p\u003e \u003cp\u003e \u003cb\u003eFollow-up\u003c/b\u003e \u003c/p\u003e \u003cp\u003eAfter extended ND, patients were followed up every 4 weeks for 1 year, every 2 months for the next year, with follow-up intervals gradually increasing thereafter. Surveillance included CT or positron emission tomography-computed tomography (PET-CT) performed 6 months after treatment and every year thereafter.\u003c/p\u003e \u003cp\u003e \u003cb\u003eVariables\u003c/b\u003e \u003c/p\u003e \u003cp\u003eWe evaluated the patients for age, sex, primary tumor site, TN stage, the initial treatment for the primary tumor, the period of extended ND, dissected nodal levels, the number of pathologically metastatic lymph nodes, presence of pathological ENE, resected non-lymphatic structures, and treatment outcomes. Tumors were clinically staged using the \u003cem\u003eUnion International Centre le Cancer\u003c/em\u003e Tumor-Node- Metastasis staging system (8th edition). Clinicopathological risk factors (age, sex, primary tumor site, TN stage, initial treatment for the primary tumor, extended ND period, the number of pathologically metastatic lymph nodes, contralateral node metastasis presence, pathological ENE presence, extended ND status and adjuvant therapy) represented the predictive variables. Extended ND status were types and number of resected non-lymphatic structures for adhesions. Types of resected non-lymphatic structures for adhesions (binary variable: with or without neurovascular structure) and number of resected non-lymphatic structures for adhesions (binary variable: multiple or single) defined as extended ND status. Disease-specific survival (DSS) was defined as the primary outcome variable. DSS was measured from the date of surgery to the date of death from uncontrolled OSCC. Regional recurrence was defined as the secondary outcome variable.\u003c/p\u003e \u003cp\u003e \u003cb\u003eStatistical analysis\u003c/b\u003e \u003c/p\u003e \u003cp\u003eThe regional recurrence rate was calculated for each non-lymphatic structure. The associations between regional recurrence and categorical variables were assessed using Fisher\u0026rsquo;s exact test or Pearson\u0026rsquo;s chi-square test. Multivariate analysis using Cox proportional hazards models was subsequently performed to evaluate variables that were significantly different in the univariate analysis and identify significant risk factors for regional recurrence. Cox regression analysis (both univariate and multivariate) was performed to identify independent predictive factors for DSS. Survival analysis was estimated using the Kaplan\u0026ndash;Meier method, and groups were compared using the log-rank test. All statistical analyses were performed using R-3.5.3 statistical software (\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://www.r-project.org/\u003c/span\u003e\u003cspan address=\"https://www.r-project.org/\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e). A \u003cem\u003eP\u003c/em\u003e value of \u0026lt;\u0026thinsp;0.05 was considered statistically significant.\u003c/p\u003e"},{"header":"3 Results","content":"\u003cp\u003e \u003cb\u003ePatient characteristics\u003c/b\u003e \u003c/p\u003e \u003cp\u003eA total of 1,547 patients with OSCC were treated at the Department of Oral and Maxillofacial Surgery of Tokyo Medical and Dental University. ND was performed on 931 neck sides in 794 patients. Of these, 544 neck sides in 477 patients (30.8%) demonstrated cervical lymph node metastases on pathological examination. Among these patients, we retrospectively reviewed 49 patients had underwent extended ND (35 men and 14 women; age range, 23\u0026ndash;83 years; median age, 63.0 years). The median follow-up period was 63 months (range, 1\u0026ndash;179 months). In the 49 extended ND patients, the primary tumor affected the tongue in 29 patients, buccal mucosa in 10 patients, lower gingiva in 6 patients, upper gingiva in 3 patients, and floor of the mouth in a patient. Clinical T stage classification was as follows: 13 patients for cT1, 21 patients for cT2, 9 patients for cT3, 5 patients for cT4a, and a patient for cT4b. With respect to the histological differentiation of primary tumor, we found well differentiation in 17 patients, moderate differentiation in 7 patients, poor differentiation in 12 patients, and differentiation was unknown in 13 patients. The initial treatment for the primary tumor was surgery in 38 patients and brachytherapy (Cs-137, Ir-192, or Au-198) in 11 patients. Clinicopathological variables among patients who underwent extended ND are described in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eUnivariate analyses of correlation between clinicopathological characteristics and regional recurrence in patients with extended ND\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eClinicopathological characteristics\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eWithout regional recurrence\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;31)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eWith regional recurrence\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;18)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eSex\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e23\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.815*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eAge\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;60 years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e16\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.729*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026ge;\u0026thinsp;60 years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003ePrimary site\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTongue\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e16\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.230**\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eOthers\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003ecT stage\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eT1-2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e22\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e1.000*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eT3-4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eInitial treatment for primary tumor\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSurgery\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e24\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e1.000**\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eBrachytherapy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003ePeriod of extended ND\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eInitial\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.724**\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSubsequent\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e23\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e15\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003epN stage\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eN1-2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.754**\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eN3b\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e13\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eNumber of positive nodes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.487*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026ge;\u0026thinsp;4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eContralateral node metastasis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAbsent\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e29\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.084**\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePresent\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eENE\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAbsent in pN\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.393**\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePresent in pN\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e26\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e17\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eNumber of resected non-lymphatic structures\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSingle\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e19\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.398*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMultiple\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eTypes of resected non-lymphatic structures\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eWithout neurovascular structure\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e26\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.028*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eWith Neurovascular structure\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eAdjuvant therapy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNot performed\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.025**\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePerformed\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e17\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e16\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003e*Chi-square test. **Fisher\u0026rsquo;s exact test.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cb\u003eExtended ND\u003c/b\u003e \u003c/p\u003e \u003cp\u003eExtended ND was performed in 11 patients at the initial surgery combined with a primary resection, in 38 patients at subsequent cervical lymph node metastasis. The ipsilateral extended ND was performed in 43 patients and the contralateral in 6 patients. Dissected nodal levels included a patient with level I, a patient with levels I and II, 3 patients with levels I\u0026ndash;III, 5 patients with levels I\u0026ndash;IV, and 39 patients with levels I\u0026ndash;V. The average number of the dissected nodes from surgical specimen was 50.8 (range, 8\u0026ndash;141) and a median number of 3 metastatic lymph nodes (range, 1\u0026ndash;17). Pathological ENE was found in 43 patients (87.8%). Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e shows the resected non-lymphatic structures and regional recurrence rate. Most frequently sacrificed tissues were as follows; mandible, mylohyoid muscle, platysma, and external carotid artery, with the regional recurrence rates of 29.4%, 31.3%, 27.3%, and 71.4%, respectively. There was no significant difference in the regional recurrence rate, regardless of whether the non-lymphatic structure requiring resection was single or multiple (29.6% \u003cem\u003evs\u003c/em\u003e 45.4%, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.398). The regional recurrence rate was significantly higher in patients who required resection of neurovascular structures (neurovascular resection group) than in patients who did not require resection of these structures (neurovascular non-resection group) (64.3% \u003cem\u003evs\u003c/em\u003e 25.7%, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.028) (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eResected non-lymphatic structures and regional recurrence rate\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"3\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNon-lymphatic structure\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNo. of patients\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;49)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003ePatients with regional recurrence\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMandible\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e17\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5 (29.4%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMylohyoid muscle\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e16\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5 (31.3%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePlatysma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3 (27.3%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eExternal carotid artery\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5 (71.4%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSkin\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3 (42.9%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHypoglossal nerve\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (33.3%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMasseter muscle\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (40.0%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLingual artery\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (100%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLingual nerve\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (50.0%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHyoglossus muscle\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (50.0%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSuperior thyroid artery\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (100%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGlossopharyngeal nerve\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (100%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVagus nerve\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (100%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSternohyoid muscle\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (100%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGeniohyoid muscle\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (100%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGenioglossus muscle\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (100%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMedial pterygoid muscle\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0 (0%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eThyrohyoid muscle\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0 (0%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHyoid bone\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0 (0%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cb\u003eComplications of extended ND\u003c/b\u003e \u003c/p\u003e \u003cp\u003eComplications after extended ND included recurrent nerve paralysis in three patients, facial nerve paralysis in two patients, and chyle leak, fracture of mandible, and urgent tracheostomy due to larynx edema in a patient, respectively. At last follow-up, a patient had persistent gastrostomy and tracheostomy tube.\u003c/p\u003e \u003cp\u003e \u003cb\u003eTreatment outcome\u003c/b\u003e \u003c/p\u003e \u003cp\u003eTwenty-four patients developed recurrence, specifically regional recurrence in 12 patients, distant metastasis in 6 patients, and regional recurrence and distant metastasis in 6 patients. The median interval from surgery to regional recurrence was 4.1 (interquartile range, 51.5\u0026ndash;190) months. As shown Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e, the DSS rate was much lower for patients with regional recurrence (5.9% \u003cem\u003evs\u003c/em\u003e 79.6%, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003cb\u003eIndependent predictive factors for regional recurrence\u003c/b\u003e \u003c/p\u003e \u003cp\u003eUnivariate analysis was demonstrated that types of resected non-lymphatic structures (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.028) and adjuvant therapy (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.025) were significantly associated with regional recurrence. Then, by accomplishing multivariate Cox regression analysis, we identified that types of resected non-lymphatic structures (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.048, HR\u0026thinsp;=\u0026thinsp;2.59, 95% CI: 1.01\u0026ndash;6.66) was independent predictive factor for regional recurrence, which was demonstrated in Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eMultivariate analysis using Cox proportional-hazard regression for regional recurrence\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eClinicopathological factors\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eHazard ratio (95% CI)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eTypes of resected non-lymphatic structures\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eWithout neurovascular structure\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.00 (Reference)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.048\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eWith Neurovascular structure\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.59 (1.01\u0026ndash;6.66)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eAdjuvant therapy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNot performed\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.00 (Reference)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.053\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePerformed\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4.38 (0.98\u0026ndash;19.5)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cb\u003eIndependent predictive factors for DSS\u003c/b\u003e \u003c/p\u003e \u003cp\u003eAnalyses of the clinicopathologic predictors of DSS were performed using a Cox proportion hazard model. Initially, univariate Cox regression was performed to identify variables significantly associated with DSS, demonstrating that number of positive nodes (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.048, HR\u0026thinsp;=\u0026thinsp;2.36, 95% CI: 1.01\u0026ndash;5.54), contralateral node metastasis (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.046, HR\u0026thinsp;=\u0026thinsp;2.78, 95% CI: 1.02\u0026ndash;7.59), types of resected non-lymphatic structures (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.018, HR\u0026thinsp;=\u0026thinsp;2.77, 95% CI: 1.19\u0026ndash;6.43), and adjuvant therapy (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.017, HR\u0026thinsp;=\u0026thinsp;5.91, 95% CI: 1.38\u0026ndash;25.4) were significantly associated with DSS (Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e). Subsequently, those variables significantly associated with DSS mentioned above were included in multivariate Cox regression analysis to determine independent predictive factors for DSS, revealing that types of resected non-lymphatic structures (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.038, HR\u0026thinsp;=\u0026thinsp;2.58, 95% CI: 1.05\u0026ndash;6.33) was independent predictive factors for DSS (Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e). The 5-year DSS rate was significantly lower in neurovascular resection group than in neurovascular non-resection group (23.4% \u003cem\u003evs\u003c/em\u003e 63.1%, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.014, Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eCox proportional-hazard regression for DSS\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"6\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colspan=\"2\" morerows=\"1\" nameend=\"c2\" namest=\"c1\" rowspan=\"2\"\u003e \u003cp\u003eClinicopathologic factors\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003eUnivariate analysis\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003eMultivariate analysis\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003eHazard ratio (95% CI)\u003c/b\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cspan type=\"BoldItalic\" class=\"BoldItalic\" name=\"Emphasis\"\u003eP\u003c/span\u003e \u003cb\u003evalue\u003c/b\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003eHazard ratio (95% CI)\u003c/b\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cspan type=\"BoldItalic\" class=\"BoldItalic\" name=\"Emphasis\"\u003eP\u003c/span\u003e \u003cb\u003evalue\u003c/b\u003e\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eSex\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.00 (Reference)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.723\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.18 (0.48\u0026ndash;2.89)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eAge\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;60 years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.00 (Reference)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.929\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026ge;\u0026thinsp;60 years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.96 (0.41\u0026ndash;2.25)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003ePrimary site\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTongue\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.00 (Reference)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.320\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eOthers\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.53 (0.66\u0026ndash;3.56)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003ecT stage\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eT1-2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.00 (Reference)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.923\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eT3-4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.05 (0.43\u0026ndash;2.57)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eInitial treatment for primary tumor\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSurgery\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.00 (Reference)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.179\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eBrachytherapy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.43 (0.13\u0026ndash;1.47)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003ePeriod of extended ND\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eInitial\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.00 (Reference)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.609\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSubsequent\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.33 (0.45\u0026ndash;3.91)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003epN stage\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eN1-2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.00 (Reference)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.136\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eN3b\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.14 (0.79\u0026ndash;5.81)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eNumber of positive nodes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.00 (Reference)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.048\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.00 (Reference)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.625\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026ge;\u0026thinsp;4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.36 (1.01\u0026ndash;5.54)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.27 (0.49\u0026ndash;3.26)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eContralateral node metastasis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAbsent\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.00 (Reference)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.046\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.00 (Reference)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.154\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePresent\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.78 (1.02\u0026ndash;7.59)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2.28 (0.73\u0026ndash;7.09)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eENE\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAbsent in pN\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.00 (Reference)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.203\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePresent in pN\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3.69 (0.49\u0026ndash;27.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eNumber of resected non-lymphatic structures\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSingle\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.00 (Reference)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.296\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMultiple\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.57 (0.68\u0026ndash;3.62)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eTypes of resected non-lymphatic structures\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eWithout neurovascular structure\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.00 (Reference)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.018\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.00 (Reference)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.038\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eWith neurovascular structure\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.77 (1.19\u0026ndash;6.43)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2.58 (1.05\u0026ndash;6.33)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eAdjuvant therapy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNot performed\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.00 (Reference)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.017\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.00 (Reference)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.097\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePerformed\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5.91 (1.38\u0026ndash;25.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e3.72 (0.79\u0026ndash;17.6)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e"},{"header":"4 Discussion","content":"\u003cp\u003eThe regional recurrence rate after ND for OSCC has been reported to be 7.1\u0026ndash;14.4% (\u003cspan additionalcitationids=\"CR10\" citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e), and 5-year locoregional control rate in the patients with ENE and/or the presence of positive or close margin was 54.3% (\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e). Carew et al (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e). reported that the regional recurrence rate after extended radical ND for head and neck cancer was 32%. Selective ND including the removal of non-lymphatic structures has been called an extended selective ND (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e). Among patients who underwent extended selective ND, Dhiwakar et al (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e). reported that the regional recurrence rate was 14.0%. In the present study, the regional recurrence rate after extended radical ND and extended selective ND was 34.7%. However, the present study contains both, extended radical ND and extended selective ND; therefore, it is impossible to simply compare it with past reports. This study aimed to identify risk factors for regional recurrence after extended ND at our hospital. To the best of our knowledge, this retrospective study included the largest cohort studied for this cancer type in the oral and maxillofacial surgery literature. Neurovascular structure adhesion was identified as a significant risk factor for regional recurrence after extended ND and was the most potent predictor of survival after extended ND. It represents an independent adverse prognostic factor for OSCC.\u003c/p\u003e \u003cp\u003eRegarding association between combined resected tissue and regional recurrence, Shaha (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e) reported that large metastatic lymph nodes in the mastoid process or posterior cervical triangle and those with skin invasion were risk factors of neck recurrence. On the other hand, Carew et al (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e). reported that survival rate was significantly affected by positive nodes at levels IV or V (or multiple levels), not by the specific structure or number of structures sacrificed during extended ND. In our study, neurovascular resection group developed significantly higher regional recurrence. Nerves along with blood vessels, immune cells, fibroblasts, and the extracellular matrix are part of the tumor microenvironment, an established contributor to tumor progression (\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e). As such, vascular and perineural invasion make local and regional control particularly difficult by allowing tumor extension beyond the expected treatment margins (\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e). Our results suggest that if the neurovascular structures must be resected for ENE, the tumor cells may have already spread along the neurovascular structures. Most significant element in predicting the 5-year DSS was adhesion of metastatic lymph nodes to neurovascular structures. Patients requiring resection of neurovascular structures had a 23.4% 5-year survival, compared with 63.1% for those who had did not.\u003c/p\u003e \u003cp\u003eMore effective adjuvant therapies, such as concurrent chemoradiotherapy (CCRT), need to be performed in patients with head and neck squamous cell carcinoma (HNSCC) with ENE and multiple positive nodes after ND for more effective regional control (\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e). Some international guidelines recommend postoperative CCRT with high-dose cisplatin (every 3 weeks) as the standard treatment for patients with resectable advanced HNSCC who are at high risk of recurrence (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e). Previous investigations have found that compared to patients with other types of HNSCC, those with OSCC have worse prognoses because of inadequate response to chemotherapy and radiotherapy (\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e). Recently, the usefulness of immune checkpoint inhibitors (ICIs) for recurrent or metastatic HNSCC has been reported (\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e). Furthermore, combination therapy with ICIs and radiation might be used in the future (\u003cspan additionalcitationids=\"CR22\" citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eOur retrospective study had some limitations. First, it included a very small cohort; moreover, there may be potential bias associated with its retrospective design. Second, the outcome measures for detailed swallowing and quality-of-life were absent. Moreover, this study examined the prognosis primarily associated with the resection of non-lymphatic structures. Therefore, metastatic lymph nodes requiring resection of neurovascular structures were considered as a risk factor for regional recurrence. The ability to infer an association with prognosis from this result is limited due to the retrospective study design. In addition, it is necessary to pathologically evaluate the appropriate range of resection of non-lymphatic structures. Further prospective studies will be warranted to elucidate the application of those parameters in assessing the risk of OSCC regional recurrence.\u003c/p\u003e"},{"header":"5 Conclusion","content":"\u003cp\u003eThis study suggests that patients with metastatic lymph nodes presenting ENE to non-lymphatic structures, especially neurovascular structures, are considered to have advanced nodal disease and are at a high risk for regional recurrence and distant metastasis. Therefore, extended ND with adequate safety margins and adjuvant therapy, particularly with new drugs, such as ICIs, are essential. Further prospective studies are required to investigate the application of this parameter in risk assessment for regional recurrence in OSCC.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cdiv class=\"DefinitionList\"\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eOSCC\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eoral squamous cell carcinoma\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eND\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eneck dissection\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eENE\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eextranodal extension\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003ePET-CT\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003epositron emission tomography-computed tomography\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eDSS\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003edisease-specific survival\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eCCRT\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003econcurrent chemoradiotherapy\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eHNSCC\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003ehead and neck squamous cell carcinoma\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eICIs\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eimmune checkpoint inhibitors\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003c/div\u003e"},{"header":"Declarations","content":"\u003ch2\u003e1 Acknowledgments\u003c/h2\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003ch2\u003e2 Funding\u003c/h2\u003e\n\u003cp\u003eThis research received no specific grant from any funding agencies in the public, commercial, or not-for-profit sectors.\u003c/p\u003e\n\u003ch2\u003e3 Availability of data and materials\u003c/h2\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003ch2\u003e4 Authors\u0026rsquo; Contributions\u003c/h2\u003e\n\u003cp\u003eTKugimoto designed this study. HHirai, HT and HHarada supervised this study. YO, TO and YK collected the data. YO, TKuroshima, and HT accomplished the statistical analyses in this study. TKugimoto prepared the manuscript. All authors read and approved the final manuscript.\u003c/p\u003e\n\u003ch2\u003e5 Ethics approval and consent to participate\u003c/h2\u003e\n\u003cp\u003eThe Institutional Review Board of Tokyo Medical and Dental Hospital approved the study (D2015-600), and all the patients included in this study had given his or her informed consent.\u003c/p\u003e\n\u003ch2\u003e6 Consent for publication\u003c/h2\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003ch2\u003e7 Competing interest\u003c/h2\u003e\n\u003cp\u003eThe authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.\u003c/p\u003e\n\u003ch2\u003e8 Publisher\u0026rsquo;s Note\u003c/h2\u003e\n\u003cp\u003eSpringer Nature remains neural with regard to jurisdictional claims in published maps and institutional affiliations.\u003c/p\u003e\n\u003ch2\u003e9 Author details\u003c/h2\u003e\n\u003cp\u003eDepartment of Oral and Maxillofacial Surgery, Division of Oral Health Science, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8549, Japan\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eColevas AD, Yom SS, Pfister DG, Spencer S, Adelstein D, Adkins D, et al. NCCN Guidelines Insights: Head and Neck Cancers, Version 1.2018. J Natl Compr Canc Netw. 2018;16:479\u0026ndash;490.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKalnins IK, Leonard AG, Sako K, Razack MS, Shedd DP. Correlation between prognosis and degree of lymph node involvement in carcinoma of the oral cavity. Am J Surg. 1977;134:450\u0026ndash;454.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFerlito A, Robbins KT, Shah JP, Medina JE, Silver CE, Al-Tamimi S, et al. Proposal for a rational classification of neck dissections. Head Neck. 2011;33:445\u0026ndash;450.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDhiwakar M, Robbins KT, Rao K, Vieira F, Malone J. Efficacy of selective neck dissection for nodal metastasis with involvement of nonlymphatic structures. Head Neck. 2011;33:1099\u0026ndash;1105.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCarew JF, Spiro RH. Extended neck dissection. Am J Surg. 1997;174:485\u0026ndash;489.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eShaha AR. Extended neck dissection. J Surg Oncol. 1990;45:229\u0026ndash;233.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZenga J, Pipkorn P, Graboyes EM, Martin EJ, Rich JT, Moore EJ, et al. Oncologic outcomes of extended neck dissections in human papillomavirus-related oropharyngeal squamous cell carcinoma. Head Neck. 2018;40:955\u0026ndash;962.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHirai H, Ohsako T, Kugimoto T, Tomioka H, Michi Y, Kayamori K, et al. Comparison of 50- and 66-Gy total irradiation dose for postoperative cervical treatment of patients with oral squamous cell carcinoma. Oral Oncol. 2020;107:104708.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKowalski LP. Results of salvage treatment of the neck in patients with oral cancer. Arch Otolaryngol Head Neck Surg. 2002;128:58\u0026ndash;62.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSharma K, Ahlawat P, Gairola M, Tandon S, Sachdeva N, Sharief MI. Prognostic factors, failure patterns and survival analysis in patients with resectable oral squamous cell carcinoma of the tongue. Radiat Oncol J. 2019;37:73\u0026ndash;81.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKoo BS, Lim YC, Lee JS, Choi EC. Recurrence and salvage treatment of squamous cell carcinoma of the oral cavity. Oral Oncol. 2006;42:789\u0026ndash;794.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eYamamoto S, Denda Y, Ota Y, Hasegawa T, Akashi M, Okura M, et al. Postoperative adjuvant therapy for patients with loco-regionally advanced oral squamous cell carcinoma who are at high risk of recurrence. 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Lancet Oncol. 2019;20:e404-e416.\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":"oral squamous cell carcinoma, extended neck dissection, regional recurrence, non-lymphatic structure, neurovascular structure","lastPublishedDoi":"10.21203/rs.3.rs-2101471/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-2101471/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground:\u003c/strong\u003e Cervical lymph node metastasis with extranodal extension (ENE) is a poor prognostic factor for oral squamous cell carcinoma (OSCC). This study aimed to evaluate the treatment outcomes of OSCC patients who underwent extended neck dissection (ND), requiring resection of non-lymphatic structures for invasive nodal disease.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods:\u003c/strong\u003e Patients who underwent extended ND for OSCC at the Department of Oral and Maxillofacial Surgery, Tokyo Medical and Dental University between April 2001 and December 2018 were retrospectively analyzed. Regional recurrence and complication were assessed. The primary outcome variable was 5-year disease-specific survival.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults: \u003c/strong\u003eA total of 49 patients were included, and regional recurrence was found 18 patients (36.7%). There was no significant difference in the regional recurrence rate, regardless of whether the non-lymphatic structure requiring resection was single or multiple (29.6% \u003cem\u003evs\u003c/em\u003e 45.4%, \u003cem\u003eP\u003c/em\u003e = 0.398). The regional recurrence rate was significantly higher in patients who required resection of neurovascular structures than in patients who did not require resection of these structures (64.3% \u003cem\u003evs\u003c/em\u003e 25.7%, \u003cem\u003eP \u003c/em\u003e= 0.028). Cox proportional-hazards regression models indicated that types of resected non-lymphatic structures (with neurovascular structures) was the most risk factor for predicting the risk of regional recurrence (\u003cem\u003eP\u003c/em\u003e = 0.048, hazard ratio = 2.59, 95% confidence interval: 1.01–6.66). Cox regression analysis to determine independent predictive factors for DSS, revealing that types of resected non-lymphatic structures (\u003cem\u003eP\u003c/em\u003e=0.038, HR = 2.58, 95% CI: 1.05–6.33) was independent predictive factors for DSS. Patients who required resection of neurovascular structures had significantly worse the 5-year DSS rate than those who did not (23.4% vs 63.1%; \u003cem\u003eP\u003c/em\u003e = 0.014). Complications after extended ND included recurrent nerve paralysis in three patients, facial nerve paralysis in two patients, and chyle leak, fracture of mandible, and urgent tracheostomy due to larynx edema in a patient, respectively.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion:\u003c/strong\u003e This study suggests that adhesion of metastatic lymph nodes to neurovascular structures is a significant poor prognostic factor for regional recurrence after extended ND. Patients with OSCC with adhesion of metastatic lymph nodes to neurovascular structures require an adequate safety resection margin and intensive postoperative treatment.\u003c/p\u003e","manuscriptTitle":"Prognostic impact of extended neck dissection in oral squamous cell carcinoma: a retrospective study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2022-09-28 22:16:28","doi":"10.21203/rs.3.rs-2101471/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":"18e423e9-7e88-4994-9f27-4e36cb0f84c8","owner":[],"postedDate":"September 28th, 2022","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2022-10-29T14:29:13+00:00","versionOfRecord":[],"versionCreatedAt":"2022-09-28 22:16:28","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-2101471","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-2101471","identity":"rs-2101471","version":["v1"]},"buildId":"7rjqhiLT3MXkJMwkYKINL","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}