Impact of Postoperative Radiotherapy and Radiochemotherapy on Survival Outcomes in Oral Squamous Cell Carcinoma Patients with pN1 Neck

Impact of Postoperative Radiotherapy and Radiochemotherapy on Survival Outcomes in Oral Squamous Cell Carcinoma Patients with pN1 Neck | 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 Impact of Postoperative Radiotherapy and Radiochemotherapy on Survival Outcomes in Oral Squamous Cell Carcinoma Patients with pN1 Neck Ann-Kristin Struckmeier, Ralf Smeets, Cordula Petersen, Christian Betz, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6324918/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 The lymph node management of oral squamous cell carcinoma (OSCC) patients with pN1 neck remains a clinical challenge. This study investigates the impact of different treatment modalities – surgery alone, surgery with postoperative radiotherapy (PORT), and surgery with radiochemotherapy (RCT) – on recurrence and survival outcomes in OSCC patients with pN1 neck. Methods A retrospective cohort study was conducted on 98 patients who underwent tumor resection and neck dissection, with a subset receiving adjuvant therapy, between 2011 and 2020. Clinicopathological characteristics were examined for associations with treatment modality using chi-square test. Kaplan-Meier survival curves for overall survival (OS) and recurrence-free survival (RFS), along with the log-rank test, were employed to assess survival over a 10-year period. The prognostic significance of clinicopathological factors and treatment modalities was evaluated using Cox proportional hazards models. Results The addition of PORT following surgery significantly reduced the risk of recurrence (OR = 0.280, p = 0.010) and notably enhanced RFS, particularly at 10 years (p = 0.010). PORT was also associated with a statistically significant improvement in 5-year-OS (p = 0.031) compared to surgery alone, with a trend toward improved OS at 10 years (p = 0.175). In contrast, surgery alone did not yield comparable 10-year survival outcomes. Additionally, the inclusion of RCT did not show a distinct survival advantage over the combination of surgery and PORT. Conclusion Our results indicate that PORT should be considered the standard adjuvant treatment for these patients, as it improves RFS, particularly in the long term, while the addition of chemotherapy does not provide significant additional benefits over PORT alone. oral squamous cell carcinoma head and neck squamous cell carcinoma neck dissection lymph node metastases radiotherapy radiochemotherapy Figures Figure 1 Introduction Oral squamous cell carcinoma (OSCC) is one of the most common malignancies worldwide, accounting for a significant proportion of head and neck cancers ( 1 ). Approximately 30%-40% of patients with OSCC develop lymph node metastases, with the presence of cervical metastases significantly correlating with a substantial reduction in survival rates ( 2 , 3 ). Currently, the surgical management of OSCC typically involves radical resection of the primary tumor in combination with appropriate neck dissection, which is regarded as the standard treatment approach ( 2 ). The decision to administer postoperative radiotherapy (PORT) remains a topic of ongoing debate, particularly in cases of pN1 neck, defined by a single ipsilateral lymph node metastasis without extranodal extension (ENE), as outlined in the 8th UICC classification ( 4 ). Although the American Society of Clinical Oncology (ASCO) guidelines recommend adjuvant radiotherapy for patients with higher-risk features, such as multiple nodal metastases or ENE, the benefits of PORT in low-risk cases, such as patients with pN1 neck, are not clearly defined ( 5 , 6 ). However, some studies suggest that PORT could potentially improve locoregional control and survival in pN1 neck cases, while others report no clear survival advantage ( 7 , 8 ). Nonetheless, the impact of PORT on the quality of life in these patients remains a critical consideration, as the potential side effects and long-term consequences of treatment may outweigh the benefits of improved survival outcomes ( 9 – 12 ). The role of chemotherapy, particularly in combination with radiotherapy, is another important factor in the management of OSCC, though its role in patients with pN1 neck remains less clear. Chemotherapy is often employed as part of adjuvant radiochemotherapy (RCT) for more advanced or high-risk cases, such as those with ENE or multiple nodal metastases ( 13 – 17 ). While chemotherapy in combination with radiotherapy has demonstrated survival benefits in higher-risk OSCC patients ( 14 ), its potential role in patients with pN1 neck without adverse features remains uncertain. This study aims to evaluate the role of different treatment regimes in patients with OSCC and a single ipsilateral cervical lymph node metastasis without ENE (pN1) regarding survival outcomes and recurrence. By comparing patients treated with surgery alone versus those receiving PORT or adjuvant RCT, we aim to provide evidence to guide clinical decisions in this patient cohort. Materials and Methods Study design and participants This retrospective study included patients diagnosed with primary OSCC who underwent radical tumor resection and neck dissection at a high-volume tertiary center in Germany between January 1, 2011, and December 31, 2020. The treatment protocol adhered to the current German guidelines, and all procedures were performed following recommendations from multidisciplinary oncology board meetings. Neck dissection was conducted according to a standardized protocol. For patients without clinically detectable neck metastases, a unilateral selective neck dissection (SND) involving levels I to IV was performed. In cases with tumors located at or near the midline, a bilateral SND was carried out. If ipsilateral lymph node metastases were identified preoperatively, intraoperatively (via frozen section), or postoperatively, a modified radical neck dissection (MRND) was performed on the affected side, along with a contralateral SND. In patients with contralateral lymph node metastases, bilateral MRND was performed. The decision for adjuvant therapy was based on individual patient risk factors, in accordance with the German treatment guidelines. The exclusion criteria included patients with recurrent OSCC, squamous cell carcinoma of the lip, those who had received neoadjuvant immunotherapy, patients who declined neck dissection, individuals who underwent sentinel lymph node biopsy, and those who had limited neck dissection due to severe comorbidities. The study protocol was approved by the Ethics Committee of the Ärztekammer Hamburg (ethics vote: 2024-101379-BO-ff), and written informed consent was not required per national and institutional regulations. The manuscript adhered to STROBE guidelines. Clinicopathological characteristics Clinicopathological data were extracted from patient medical records, including age, sex, tumor localization, TNM classification, depth of invasion, ENE, grading, resection margins, and the presence of perineural, vascular, and lymphovascular invasion. We also recorded the dates of surgery, last follow-up, recurrence, and death. During the study period, the TNM classification was updated from the 7th to the 8th edition. Patients initially classified according to the 7th edition were reclassified according to the 8th edition to ensure consistency ( 4 ). As ENE was not considered in the 7th TNM classification, some patients classified as pN1 under this system had to be excluded due to the presence of ENE (n = 11). Statistical analysis Data analysis was conducted using SPSS software, version 28.0 (SPSS, Chicago, IL, USA). Correlation analysis was performed utilizing the chi-square test. Recurrence-free survival (RFS) and overall survival (OS) were estimated using the Kaplan-Meier method, and comparisons of survival outcomes between patients undergoing different treatment modalities were analyzed using the log-rank test. RFS was defined as the interval from surgery to the occurrence of local or regional recurrence, with data censored at the last follow-up in cases without recurrence. OS was defined as the time from surgical resection to death from any cause, with data censored at the last follow-up for patients who were still alive. For identifying prognostic factors of survival, univariate Cox analysis was performed, followed by a multivariate Cox analysis that incorporated factors showing significance in the univariate analysis. Figures were generated using SPSS. A p-value of < 0.05 was considered statistically significant. Results Clinicopathological characteristics of the cohort The study included 98 patients, with a slightly higher proportion of males (57; 58.2%) than females (41; 41.8%). The median age at surgery was evenly distributed, with 53 patients (54.1%) under 65 years and 45 (45.9%) aged 65 years or older. Pathological staging revealed that T2 was the most common T stage, observed in 37 patients (37.8%), followed by T4a in 28 patients (28.6%), T1 in 21 patients (21.4%), and T3 in 12 patients (12.2%). Clinically, T2 was also the most frequent stage, present in 37 cases (37.8%). Other clinical T stages included T1 in 12 cases (12.2%), T3 in 7 cases (7.1%), T4a in 22 cases (22.5%), and T4b in a single case (1.0%). Regarding clinical N stage, nearly half of the patients (46; 46.9%) were node-negative (N0). Among the remaining patients, N1 was observed in 20 cases (20.4%), N2b in 9 cases (9.18%), N2c in 4 cases (4.1%), and N2a and N3b in 1 case each (1.0%). All patients in the cohort were classified as M0, indicating the absence of distant metastases at the time of diagnosis. Tumor grading showed that the majority of cases (67; 68.4%) were moderately differentiated (G2), while 23 (23.5%) were poorly differentiated (G3), and 3 (3.1%) were well-differentiated (G1). Lymphovascular invasion was identified in 37 patients (37.8%), while 61 patients (62.2%) showed no evidence of such invasion. Vascular invasion was rare, occurring in only 3 cases (3.1%). Perineural invasion was present in 20 patients (20.0%), whereas 78 patients (79.6%) had no signs of perineural involvement. Resection margins were negative (R0) in 96 cases (99.0%), with only 2 patients (2.0%) having positive margins (R1). The clinical outcomes demonstrated a recurrence rate of 26.5%, with 26 patients experiencing recurrence, while 72 patients (73.5%) showed no signs of recurrence during follow-up. Distant metastases during follow-up were rare, occurring in only 5 patients (5.1%). Regarding treatment, 35 patients (35.7%) underwent surgery alone, 19 patients (19.4%) received surgery with RCT, and 44 patients (44.9%) underwent surgery followed by PORT. Correlation between clinicopathological characteristics and pN1 neck Chi-square test was performed to assess the associations between clinicopathological characteristics and therapy types. In terms of sex, females and males were evenly distributed across therapy types, with no significant association observed (p = 0.745). Age at surgery was significantly associated with therapy type (p = 0.046). Patients under 65 years of age were more likely to receive surgery only (34.0%) or surgery with RCT (28.3%), while those aged 65 years or older predominantly received PORT (53.3%). Pathological T stage showed a significant association with therapy type (p = 0.049). Patients with T1 tumors most frequently underwent surgery only (61.9%), while those with advanced stages, such as T3 and T4a, were more likely to receive PORT (58.3% and 57.1%, respectively). Grading did not show a significant relationship with therapy type (p = 0.342), although poorly differentiated tumors (G3) tended toward PORT (65.2%). Other histopathological features, including lymphovascular invasion (p = 0.477), vascular invasion (p = 0.816), and perineural invasion (p = 0.188), did not show significant associations with therapy type. However, patients with perineural invasion were slightly more likely to receive PORT (50.0%). Similarly, resection margins did not demonstrate a significant association (p = 0.376), though patients with positive margins tended toward PORT (50.0%). Recurrence was significantly associated with therapy type (p = 0.033). Patients with no recurrence were more likely to receive PORT (52.8%), whereas those with recurrence were more likely to have undergone surgery only (50.0%). The presence of distant metastases during follow-up did not show a significant association with therapy type (p = 0.385). Regarding tumor localization, no significant association was found with therapy type (p = 0.879). Tumors located in the floor of the mouth or lower jaw were evenly distributed across all therapy types, while those in the hard palate showed a slight preference for surgery only (50.0%) and PORT (30.0%). Univariate and multivariate analysis for recurrence-free survival The univariate analysis demonstrated that the type of therapy, vascular invasion, and resection margin were significantly associated with RFS (p < 0.05). Patients treated with surgery followed by PORT had a significantly lower risk of recurrence compared to those treated with surgery alone (HR = 0.280, 95% CI: 0.106–0.737, p = 0.010). Similarly, the presence of vascular invasion was associated with a markedly increased risk of recurrence (HR = 13.004, 95% CI: 2.727–62.002, p = 0.001). Positive resection margins also showed a strong association with recurrence, with a HR of 24.987 (95% CI: 4.175-149.567, p < 0.001). Other factors, including age, sex, pathological T category, tumor grading, lymphovascular invasion, and perineural invasion, did not reach statistical significance in the univariate analysis (p > 0.05). In the multivariate analysis, PORT remained independently associated with improved RFS (HR = 0.279, 95% CI: 0.098–0.789, p = 0.016), confirming its protective effect. Although vascular invasion and resection margins were significant in univariate analysis, their association with RFS was attenuated in the multivariate model, with p-values of 0.251 and 0.072, respectively. Univariate and multivariate analysis for overall survival The univariate analysis revealed that type of therapy and resection margins were significantly associated with OS (p < 0.05). Patients treated with surgery followed by PORT exhibited a trend toward improved survival compared to those treated with surgery alone (HR = 0.504, 95% CI: 0.240–1.058, p = 0.050). Additionally, positive resection margins were associated with a markedly worse OS (HR = 9.386, 95% CI: 2.042–43.136, p = 0.004). Other clinicopathological factors, including age, sex, pathological T category, tumor grading, lymphovascular invasion, vascular invasion, and perineural invasion, were not significantly associated with OS in the univariate analysis (p > 0.05). In the multivariate analysis, the protective effect of PORT on OS became more pronounced and reached statistical significance (HR = 0.361, 95% CI: 0.165–0.790, p = 0.011), confirming its independent role in improving survival outcomes. Furthermore, positive resection margins remained a significant predictor of worse survival in the adjusted model (HR = 14.036, 95% CI: 2.886–68.258, p = 0.001). Recurrence-free survival The 5-year-RFS was highest among patients who underwent surgery followed by PORT. However, this outcome only demonstrated a trend toward improved survival in the surgery plus PORT group, without reaching statistical significance when compared to the surgery-alone group (p = 0.092) or the surgery combined with RCT group (p = 0.096). Additionally, no significant difference in RFS at 5 years was found between the surgery-alone group and the surgery with RCT group (p > 0.05). At 10 years, a significant improvement in RFS was observed in the surgery + PORT group compared to both the surgery-alone group (p = 0.010) and the surgery + RCT group (p = 0.030). However, no significant difference in RFS was found between the surgery-alone group and the surgery + RCT group (p = 0.855). Overall survival Regarding 5-year-OS, a significant difference was observed between the surgery with PORT group and the surgery-alone group (p = 0.038). No significant differences in OS were found between the surgery-alone group and the surgery with RCT group (p = 0.412), or between the surgery with PORT group and the surgery with RCT group (p = 0.426). At 10 years, no significant differences in OS were observed between the treatment groups (p > 0.05). However, a trend toward slightly better survival was noted in the surgery with PORT group compared to the surgery-alone group, with a p-value of 0.175. Discussion The role of PORT in the management of OSCC patients with pN1 neck, particularly in the absence of other adverse pathological features, remains a subject of ongoing debate. Additionally, the potential benefits of RCT in improving survival outcomes are also under investigation. This study examines the efficacy of different treatment strategies – surgery alone, surgery with PORT, and surgery with adjuvant RCT – for managing the pN1 neck in OSCC patients. The results highlight significant differences in the effects of these treatment modalities on recurrence and survival, providing valuable insights for clinical decision-making in this patient population. Initially, we assessed the factors influencing treatment selection. Age at surgery and pathological T stage emerged as significant predictors of treatment modality. Notably, patients under 65 years of age were more likely to undergo surgery alone or surgery with RCT, while those aged 65 or older were predominantly treated with PORT, especially in cases with advanced tumor stages such as T3 or T4a (p < 0.05). Additionally, recurrence was strongly associated with treatment choice. Patients who did not experience recurrence were more likely to have received PORT, whereas those who experienced recurrence were more likely to have been treated with surgery alone (p < 0.05). In terms of RFS, the addition of PORT to surgery demonstrated the most favorable long-term outcomes, particularly at 10 years. At this time point, patients who underwent surgery with PORT had significantly better RFS compared to those treated with surgery alone (p = 0.010) or surgery with RCT (p = 0.030). These findings suggest that PORT provides a substantial long-term benefit in preventing recurrence. In contrast, at 5 years, no significant differences in RFS were observed between the treatment groups (p > 0.05). Furthermore, no significant difference in 5-Year-RFS was found between the surgery-only and surgery with RCT groups (p > 0.05), suggesting that the addition of chemotherapy to radiotherapy does not provide a clear advantage over surgery alone in the medium term. Univariate analysis confirmed that PORT significantly reduced the risk of recurrence compared to surgery alone (HR = 0.280, p = 0.010). Multivariate analysis further supported this finding, with PORT remaining independently associated with improved RFS (HR = 0.279, p = 0.016). Additionally, while factors such as vascular invasion and positive resection margins were significant in the univariate analysis, their impact on RFS was diminished in the multivariate model, highlighting the moderating role of PORT in improving outcomes. Consistent with our findings, most studies on pN1 neck in OSCC patients suggest that PORT reduces the risk of regional recurrence. Barry et al. performed a matched-pair analysis on 90 OSCC patients, including 30 with pN1, comparing those who received surgery with PORT to those treated with surgery alone. Their study demonstrated a significant improvement in locoregional tumor control in the PORT group ( 11 ). Similarly, Liu et al. evaluated the treatment outcomes in a cohort of 432 OSCC patients, 216 of whom received surgery alone and 216 received surgery with PORT. They observed a significantly improved RFS in patients who underwent surgery with PORT, with a higher 5-year RFS rate in this group compared to the surgery-only group ( 18 ). Kämmerer et al., in a multicenter trial involving 209 patients, found that PORT had a positive impact on progression-free survival, delaying disease progression relative to non-RT treatment. However, they also noted that patients who received PORT reported a significantly reduced quality of life up to three years post-treatment compared to the observation group ( 19 ). In contrast to the previously described findings and our own results, Tsai et al. found no significant differences in neck recurrence rates or RFS between patients who underwent surgery alone and those treated with surgery and PORT (7.7% vs. 15.8%, p > 0.05) ( 7 ). Regarding OS, patients who received surgery followed by PORT demonstrated significantly better survival at 5 years compared to those who underwent surgery alone (p = 0.038). However, no significant differences in OS were observed between the surgery-only and surgery with RCT groups (p = 0.412) or between the surgery with PORT and surgery with RCT groups (p = 0.426). These results suggest that PORT provides a survival advantage over surgery alone, but the addition of chemotherapy does not significantly enhance survival at this early time point. At 10 years, while no statistically significant differences in OS were observed (p > 0.05), a trend toward improved survival in the surgery + PORT group compared to surgery alone persisted, though it did not reach statistical significance (p = 0.175). Univariate analysis showed that PORT was associated with a trend toward improved survival compared to surgery alone (HR = 0.504, p = 0.050). In multivariate analysis, PORT significantly improved OS (HR = 0.361, p = 0.011), confirming its beneficial impact on survival outcomes. However, positive resection margins emerged as a strong predictor of poor survival (HR = 14.036, p = 0.001), underscoring the importance of achieving negative margins to improve prognosis. The addition of RCT did not demonstrate a clear survival benefit in the multivariate analysis (HR = 0.423, p = 0.087), suggesting that while RCT may offer some advantages, it does not provide significant improvements in OS over PORT alone. In contrast to our findings, several studies have failed to demonstrate a significant difference in OS. For instance, Liu et al. found no substantial difference in OS between patients who underwent surgery alone and those treated with surgery plus PORT, with similar 5-year OS rates in both groups ( 18 ). Similarly, in a multicenter trial involving 209 patients, Kämmerer et al. reported that PORT did not significantly affect OS in this cohort ( 19 ). On the contrary, Barry et al. observed that the addition of PORT suggested a survival benefit; however, this finding did not reach statistical significance ( 11 ). These inconsistencies may stem from variations in patient populations and treatment protocols. For example, Chen et al. analyzed a cohort of 1,467 OSCC patients and found that PORT was associated with improved OS, with a hazard ratio of 0.76 (95% CI, 0.63–0.92). Notably, a survival benefit was observed in patients younger than 70 years, and those with pT2 disease also benefitted from PORT. In contrast, no significant survival advantage was noted for patients aged 70 years or older ( 20 ). Moreover, Shrime et al. demonstrated that PORT conferred survival benefits only in patients with T2 tongue and tumors located at the floor of the mouth, with no observed benefit in other subsites ( 21 ). Additionally, an analysis by Suresh and Crameri, which included 1,909 patients (898 of whom received PORT), indicated a survival benefit in the overall cohort, with an adjusted hazard ratio of 0.82 (95% CI 0.72–0.94). This benefit was evident regardless of the adequacy of neck dissection, and patients with lymph node metastases larger than 10 mm experienced greater benefit from PORT compared to those with smaller metastases ( 22 ). While the benefits of PORT in reducing regional recurrence are well-documented, it is essential to consider the associated implications for patients' quality of life. Several studies, including those by Bekiroglu et al. and Barry et al., have highlighted the significant short-term and long-term functional impairments that patients may experience following PORT. These impairments include pain, dysphagia, speech disturbances, xerostomia, and restricted mouth opening, all of which can substantially affect patients' daily functioning and overall well-being ( 10 , 11 , 18 ). The benefit of adding chemotherapy to radiotherapy remains a topic of debate. In contrast to our findings, a cohort study by Lee et al., which included 1,598 patients with pT1/2 N1 HNSCC without positive margins or ENE, demonstrated that patients receiving adjuvant RCT had a 13.8% improvement in survival compared to those treated with PORT. However, no significant difference in survival was observed between patients treated with PORT and those treated with surgery alone ( 23 ). Similarly, Chang et al. reported that 5-year-OS rates for patients treated with surgery alone, PORT, and RCT were 62.2%, 58.7%, and 71.1%, respectively (P = 0.03). Adjuvant RCT was associated with significantly improved survival compared to PORT in the overall group (p = 0.008). However, this benefit was particularly evident in the pT2 group, where RCT resulted in significantly better survival rates than PORT (p = 0.001). In contrast, no significant survival differences were observed between the two treatment approaches for patients with pT1 disease ( 24 ). Limitations of this study While this study offers valuable insights into the management of the pN1 neck in patients with OSCC, several limitations should be considered. The retrospective nature of the study, along with the relatively small sample size, may limit the generalizability of the findings. Additionally, the study did not account for certain patient factors, such as performance status or comorbidities, which may also influence treatment decisions and outcomes. Further studies with larger cohorts, including prospective trials, are needed to confirm these findings and better understand the role of PORT and RCT in improving long-term survival in this patient population. Nevertheless, the strengths of our study may lie in the fact that all patients were classified according to the 8th UICC staging system, and the cohort was thoroughly characterized in terms of pathological characteristics. Conclusion In the management of OSCC patients with pN1 neck, PORT is associated with improved RFS and OS, especially in the long term. Surgery combined with PORT provides the most significant survival benefit, while the addition of RCT does not show a clear advantage over surgery alone or surgery with PORT. Our results indicate that PORT should be considered the preferred adjuvant treatment for OSCC patients with pN1 neck, while RCT may be reserved for those with specific high-risk characteristics. Nonetheless, impairments in quality of life should be taken into account. Abbreviations ASCO - American Society of Clinical Oncology CI - confidence interval ENE - extranodal extension HR - hazard ratio MRND - modified radical neck dissection OS - overall survival OSCC - oral squamous cell carcinoma PORT - postoperative radiotherapy PFS - progression-free survival RFS - recurrence-free survival RCT - radiochemotherapy SND - selective neck dissection SLNB - sentinel lymph node biopsy UICC - Union for International Cancer Control Declarations Data availability statement The data that support the findings of this study are available from the corresponding author upon reasonable request. Competing interests The authors declare no competing interests. Ethics approval This study was performed in line with the principles of the 1964 Helsinki Declaration and its later amendments. The Ethics Committee of the Ärztekammer Hamburg approved the study’s design and methods (2024-101379-BO-ff). In accordance with national regulations and institutional regulations, written informed consent was not required from the participating patients. Conflict of interest The authors have no financial or non-financial conflicts of interest to disclose. Author contribution AS: conception and design of the study, acquisition, analysis and interpretation of data, drafting the manuscript, and revising it critically for important intellectual content and scientific integrity. RS, CP, CB, WW and MG: reading and revising the manuscript critically for important intellectual content and scientific integrity. All authors read and agreed to the final version of the manuscript. References Ferlay J, Colombet M, Soerjomataram I, Mathers C, Parkin DM, Pineros M, et al. Estimating the global cancer incidence and mortality in 2018: GLOBOCAN sources and methods. Int J Cancer. 2019;144(8):1941-53. https://doi.org/10.1002/ijc.31937 Struckmeier AK, Buchbender M, Lutz R, Kesting M. 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N Engl J Med. 2004;350(19):1945-52. https://doi.org/10.1056/NEJMoa032641 Cooper JS, Zhang Q, Pajak TF, Forastiere AA, Jacobs J, Saxman SB, et al. Long-term follow-up of the RTOG 9501/intergroup phase III trial: postoperative concurrent radiation therapy and chemotherapy in high-risk squamous cell carcinoma of the head and neck. Int J Radiat Oncol Biol Phys. 2012;84(5):1198-205. https://doi.org/10.1016/j.ijrobp.2012.05.008 Mohamad I, Glaun MDE, Prabhash K, Busheri A, Lai SY, Noronha V, et al. Current Treatment Strategies and Risk Stratification for Oral Carcinoma. Am Soc Clin Oncol Educ Book. 2023;43:e389810. https://doi.org/10.1200/EDBK_389810 Liu T, David M, Batstone M, Clark J, Low TH, Goldstein D, et al. The utility of postoperative radiotherapy in intermediate-risk oral squamous cell carcinoma. Int J Oral Maxillofac Surg. 2021;50(2):143-50. https://doi.org/10.1016/j.ijom.2020.06.006 Kammerer PW, Tribius S, Cohrs L, Engler G, Ettl T, Freier K, et al. Adjuvant Radiotherapy in Patients with Squamous Cell Carcinoma of the Oral Cavity or Oropharynx and Solitary Ipsilateral Lymph Node Metastasis (pN1)-A Prospective Multicentric Cohort Study. Cancers (Basel). 2023;15(6). https://doi.org/10.3390/cancers15061833 Chen MM, Harris JP, Hara W, Sirjani D, Divi V. Association of Postoperative Radiotherapy With Survival in Patients With N1 Oral Cavity and Oropharyngeal Squamous Cell Carcinoma. JAMA Otolaryngol Head Neck Surg. 2016;142(12):1224-30. https://doi.org/10.1001/jamaoto.2016.3519 Shrime MG, Gullane PJ, Dawson L, Kim J, Gilbert RW, Irish JC, et al. The impact of adjuvant radiotherapy on survival in T1-2N1 squamous cell carcinoma of the oral cavity. Arch Otolaryngol Head Neck Surg. 2010;136(3):225-8. https://doi.org/10.1001/archoto.2010.22 Suresh K, Cramer JD. Postoperative radiation therapy vs observation for pN1 oral cavity squamous cell carcinoma. Head Neck. 2019;41(12):4136-42. https://doi.org/10.1002/hed.25958 Lee A, Givi B, Roden DF, Tam MM, Wu SP, Gerber NK, et al. Utilization and Survival of Postoperative Radiation or Chemoradiation for pT1-2N1M0 Head and Neck Cancer. Otolaryngol Head Neck Surg. 2018;158(4):677-84. https://doi.org/10.1177/0194599817746391 Chang CC, Wu YT, Lu HH, Cheng YJ, Tsai MH. The role of postoperative radiotherapy or chemoradiation in pT1-2N1M0 oral squamous cell carcinoma. J Formos Med Assoc. 2024. https://doi.org/10.1016/j.jfma.2024.03.005 Tables Table 1. Clinicopathological characteristics of the cohort Variable Category n (%) Sex Female 41 (41.8) Male 57 (58.2) Age at surgery < 65 years 53 (54.1) ≥ 65 years 45 (45.9) Pathological T stage T1 21 (21.4) T2 37 (37.8) T3 12 (12.2) T4a 28 (28.6) Clinical T stage T1 12 (12.2) T2 37 (37.8) T3 7 (7.1) T4a 22 (22.5) T4b 1 (1.0) Missing 19 (19.3) Clinical N stage N0 46 (46.9) N1 20 (20.4) N2a 1 (1.0) N2b 9 (9.2) N2c 4 (4.1) N3b 1 (1.0) Missing 17 (17.4) M stage M0 98 (100.0) Grading G1 3 (3.1) G2 67 (68.4) G3 23 (23.5) Gx 5 (5.1) Lymphovascular invasion L0 61 (62.2) L1 37 (37.8) Vascular invasion V0 95 (96.9) V1 3 (3.1) Perineural invasion Pn0 78 (79.6) Pn1 20 (20.4) Resection margin R0 96 (99.0) R1 2 (2.0) Recurrence No 72 (73.5) Yes 26 (26.5) Occurrence of distant metastases during observation period No 93 (94.9) Yes 5 (5.1) Therapy Surgery only 35 (35.7) Surgery + RCT 19 (19.4) Surgery + PORT 44 (44.9) Abbreviations : T stage – tumor stage, N stage – node stage, M – metastasis, RCT – radiochemotherapy, PORT – postoperative radiotherapy. Table 2. Association between clinicopathological variables and type of therapy Variable Characteristic Type of therapy Surgery only n (%) Surgery + RCT n (%) Surgery + PORT n (%) p value Sex Female 13 (31.7) 9 (22.0) 19 (46.3) 0.745 Male 22 (38.6) 10 (17.5) 25 (43.9) Age at surgery < 65 years 18 (34.0) 15 (28.3) 20 (37.8) 0.046* ≥ 65 years 17 (37.8) 4 (9.0) 24 (53.3) Pathological T stage T1 13 (61.9) 3 (14.3) 5 (23.8) 0.049* T2 15 (40.5) 6 (16.2) 16 (43.2) T3 2 (16.7) 3 (25.0) 7 (58.3) T4a 5 (17.9) 7 (25.0) 16 (57.1) Grading G1 1 (33.3) 1 (33.3) 1 (33.3) 0.342 G2 26 (38.8) 13 (19.4) 28 (41.8) G3 6 (26.1) 2 (8.7) 15 (65.2) Lymphovascular invasion L0 21 (34.4) 10 (16.4) 30 (49.2) 0.477 L1 14 (37.8) 9 (24.3) 14 (37.8) Vascular invasion V0 34 (35.8) 18 (19.0) 43 (45.3) 0.816 V1 1 (33.3) 1 (33.3) 1 (33.3) Perineural invasion Pn0 31 (39.7) 13 (16.7) 34 (43.6) 0.188 Pn1 4 (20.0) 6 (30.0) 10 (50.0) Resection margin R0 29 (34.1) 14 (16.5) 42 (49.4) 0.376 R1 0 (0.0) 1 (50.0) 1 (50.0) Recurrence No 22 (30.6) 12 (16.7) 38 (52.8) 0.033* Yes 13 (50.0) 7 (26.9) 6 (23.1) Distant metastases during follow-up No 33 (35.5) 17 (16.3) 43 (46.2) 0.385 Yes 2 (40.0) 2 (40.0) 1 (20.0) Localization Floor of the mouth 21 (37.5) 11 (19.6) 24 (42.9) 0.879 Lower jaw 6 (31.6) 4 (21.1) 9 (43.4) Upper jaw 1 (25.0) 0 (0.0) 3 (75.0) Hard palate 5 (50.0) 2 (20.0) 3 (30.0) Buccal plane 2 (22.2) 2 (22.2) 5 (55.6) A p value < 0.05 was considered statistically significant. Statistically significant differences are marked with an asterisk. Abbreviations : RCT – radiochemotherapy, PORT – postoperative radiotherapy. Table 3. Univariate and multivariate analysis of recurrence-free survival Clinicopathological characteristics Univariate analysis Multivariate analysis OR 95% CI p value OR 95% CI p value Age < 65 vs. ≥ 65 years 0.984 0.435-2.066 0.894 Sex 2.189 0.993-4.827 0.052 pT category T1 1 T2 2.202 0.621-7.810 0.222 T3 2.146 0.429-10.743 0.353 T4a 1.848 0.490-6.969 0.364 Type of therapy Surgery only 1 1 Surgery + adjuvant RCT 0.793 0.316-1.989 0.621 0.318 0.076-1.327 0.116 Surgery + PORT 0.280 0.106-0.737 0.010* 0.279 0.098-0.789 0.016* Grading 0.501 0.172-1.461 0.206 Lymphovascular invasion 1.458 0.630-3.376 0.379 Vascular invasion 13.004 2.727-62.002 0.001* 4.822 0.328-70.822 0.251 Perineural invasion 1.189 0.428-3.304 0.739 Resection margin 24.987 4.175-149.567 <0.001* 13.514 0.792-230.700 0.072 A p value < 0.05 was considered statistically significant. Statistically significant differences are marked with an asterisk. Abbreviations : CI – confidence interval, HR – hazard ratio, PORT – postoperative radiotherapy, RCT – radiochemotherapy, RFS – recurrence-free survival. Table 4. Univariate and multivariate analysis of overall survival Clinicopathological characteristics Univariate analysis Multivariate analysis HR 95% CI p value HR 95% CI p value Age < 65 vs. ≥ 65 years 1.572 0.823-3.003 0.171 Sex 1.202 0.629-2.297 0.577 pT category T1 1 T2 0.935 0.403-2.171 0.876 T3 1.045 0.317-3.450 0.942 T4a 0.639 0.253-1.612 0.343 Type of therapy Surgery only 1 1 Surgery + adjuvant RCT 0.759 0.327-1.763 0.521 0.423 0.158-1.132 0.087 Surgery + PORT 0.504 0.240-1.058 0.050 0.361 0.165-0.790 0.011* Grading 1.150 0.543-2.437 0.715 Lymphovascular invasion 1.063 0.536-2.109 0.861 Vascular invasion 5.542 0.680-45.136 0.110 Perineural invasion 1.1355 0.623-2.945 0.443 Resection margin 9.386 2.042-43.136 0.004* 14.036 2.886-68.258 0.001* A p value < 0.05 was considered statistically significant. Statistically significant differences are marked with an asterisk. Abbreviations : HR – hazard ratio, CI – confidence interval, PORT – postoperative radiotherapy, RCT – radiochemotherapy, OS – overall survival. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. 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-6324918","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":435741533,"identity":"3833881d-a14a-4194-b83f-fb29903d6e95","order_by":0,"name":"Ann-Kristin Struckmeier","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA4klEQVRIie3OsQrCMBCA4SuCXQKu7aJPIDQUzsFSn6U4+ACCKDgkFNLRWRDfwaVzJGCX1tlNSwdXu+kmVVyDbg75IHCE/OQADOOPeQAWA5g3w+toNU8/Sf5b0ozii6TD7Gu1EKHfT2JeLbbK70Brd9EljiSUF2KMmO9jWqQKXdae6r+RxOJcyABPkXB5qgJPEnR0RU/a5Ts5l8mDb1QwkmRw1yWeBNokiCdLWJwp9ICgdi+qCF2z49jHPIpddpj4jmpPtYt1s+RSs1lI0ywra7Yc0lUS727ab1pf3BiGYRi/egJGo0xCkea1awAAAABJRU5ErkJggg==","orcid":"","institution":"University Medical Center Hamburg-Eppendorf","correspondingAuthor":true,"prefix":"","firstName":"Ann-Kristin","middleName":"","lastName":"Struckmeier","suffix":""},{"id":435741534,"identity":"5457f687-3c0d-4830-adcc-0c951038a289","order_by":1,"name":"Ralf Smeets","email":"","orcid":"","institution":"University Medical Center Hamburg-Eppendorf","correspondingAuthor":false,"prefix":"","firstName":"Ralf","middleName":"","lastName":"Smeets","suffix":""},{"id":435741535,"identity":"ac09a42e-e9be-4222-85c8-321a0d0d8128","order_by":2,"name":"Cordula Petersen","email":"","orcid":"","institution":"University Medical Center Hamburg-Eppendorf","correspondingAuthor":false,"prefix":"","firstName":"Cordula","middleName":"","lastName":"Petersen","suffix":""},{"id":435741536,"identity":"d15e5c7d-5e3f-441f-a6ac-bdbc54a4dc86","order_by":3,"name":"Christian Betz","email":"","orcid":"","institution":"University Medical Center Hamburg-Eppendorf","correspondingAuthor":false,"prefix":"","firstName":"Christian","middleName":"","lastName":"Betz","suffix":""},{"id":435741537,"identity":"f908a82f-7488-4673-805c-90374bf2c49e","order_by":4,"name":"Waldemar Wilczak","email":"","orcid":"","institution":"University Medical Center Hamburg-Eppendorf","correspondingAuthor":false,"prefix":"","firstName":"Waldemar","middleName":"","lastName":"Wilczak","suffix":""},{"id":435741538,"identity":"9dcf5171-ef03-4f59-b67e-5ad86664a2b8","order_by":5,"name":"Martin Gosau","email":"","orcid":"","institution":"University Medical Center Hamburg-Eppendorf","correspondingAuthor":false,"prefix":"","firstName":"Martin","middleName":"","lastName":"Gosau","suffix":""}],"badges":[],"createdAt":"2025-03-28 05:08:13","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6324918/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6324918/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":79832408,"identity":"afa5453c-0a4e-4014-a0fb-506087f13c5d","added_by":"auto","created_at":"2025-04-03 10:51:50","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":175146,"visible":true,"origin":"","legend":"\u003cp\u003eComparison of 5- and 10-year-recurrence-free survival and overall survival among different treatment modalities in oral squamous cell carcinoma patients with pN1 neck\u003c/p\u003e\n\u003cp\u003e(A) \u003cstrong\u003e5-Year-Recurrence-free survival\u003c/strong\u003e: Group 3 (surgery + PORT) exhibited the highest RFS, although no statistically significant differences were found when compared to group 1 (surgery only, p = 0.092) or group 2 (surgery + RCT, p = 0.096). No significant difference in RFS was observed between group 1 and group 2 (p \u0026gt; 0.05).\u003c/p\u003e\n\u003cp\u003e(B) \u003cstrong\u003e10-Year-Recurrence-free survival\u003c/strong\u003e: A significant improvement in RFS was observed for group 3 (surgery + PORT) compared to both group 1 (surgery only, p = 0.010) and group 2 (surgery + RCT, p = 0.030). No significant difference was found between group 1 and group 2 (p = 0.855).\u003c/p\u003e\n\u003cp\u003e(C) \u003cstrong\u003e5-Year-Overall survival\u003c/strong\u003e: A significant difference in overall survival was found between group 3 (surgery + PORT) and group 1 (surgery only, p = 0.038). No significant differences were observed between group 1 (surgery only) and group 2 (surgery + RCT, p = 0.412), or between group 3 (surgery + PORT) and group 2 (p = 0.426).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e10-Year-Overall survival\u003c/strong\u003e: No significant differences were found between the groups (p \u0026gt; 0.05). However, a trend toward slightly better survival was noted in group 3 (surgery + PORT) compared to group 1 (surgery only), with a p-value of 0.175.\u003c/p\u003e","description":"","filename":"floatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-6324918/v1/4dda57d522967a29bb929e13.png"},{"id":85783984,"identity":"bb821bb0-2f30-4cc4-8214-aba1cd90edd5","added_by":"auto","created_at":"2025-07-01 15:46:43","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1762188,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6324918/v1/73ff8dd8-5693-4725-aee4-fbf4fee5a428.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Impact of Postoperative Radiotherapy and Radiochemotherapy on Survival Outcomes in Oral Squamous Cell Carcinoma Patients with pN1 Neck","fulltext":[{"header":"Introduction","content":"\u003cp\u003eOral squamous cell carcinoma (OSCC) is one of the most common malignancies worldwide, accounting for a significant proportion of head and neck cancers (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e). Approximately 30%-40% of patients with OSCC develop lymph node metastases, with the presence of cervical metastases significantly correlating with a substantial reduction in survival rates (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eCurrently, the surgical management of OSCC typically involves radical resection of the primary tumor in combination with appropriate neck dissection, which is regarded as the standard treatment approach (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e). The decision to administer postoperative radiotherapy (PORT) remains a topic of ongoing debate, particularly in cases of pN1 neck, defined by a single ipsilateral lymph node metastasis without extranodal extension (ENE), as outlined in the 8th UICC classification (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e). Although the American Society of Clinical Oncology (ASCO) guidelines recommend adjuvant radiotherapy for patients with higher-risk features, such as multiple nodal metastases or ENE, the benefits of PORT in low-risk cases, such as patients with pN1 neck, are not clearly defined (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e). However, some studies suggest that PORT could potentially improve locoregional control and survival in pN1 neck cases, while others report no clear survival advantage (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e). Nonetheless, the impact of PORT on the quality of life in these patients remains a critical consideration, as the potential side effects and long-term consequences of treatment may outweigh the benefits of improved survival outcomes (\u003cspan additionalcitationids=\"CR10 CR11\" citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThe role of chemotherapy, particularly in combination with radiotherapy, is another important factor in the management of OSCC, though its role in patients with pN1 neck remains less clear. Chemotherapy is often employed as part of adjuvant radiochemotherapy (RCT) for more advanced or high-risk cases, such as those with ENE or multiple nodal metastases (\u003cspan additionalcitationids=\"CR14 CR15 CR16\" citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e). While chemotherapy in combination with radiotherapy has demonstrated survival benefits in higher-risk OSCC patients (\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e), its potential role in patients with pN1 neck without adverse features remains uncertain.\u003c/p\u003e \u003cp\u003eThis study aims to evaluate the role of different treatment regimes in patients with OSCC and a single ipsilateral cervical lymph node metastasis without ENE (pN1) regarding survival outcomes and recurrence. By comparing patients treated with surgery alone versus those receiving PORT or adjuvant RCT, we aim to provide evidence to guide clinical decisions in this patient cohort.\u003c/p\u003e"},{"header":"Materials and Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy design and participants\u003c/h2\u003e \u003cp\u003eThis retrospective study included patients diagnosed with primary OSCC who underwent radical tumor resection and neck dissection at a high-volume tertiary center in Germany between January 1, 2011, and December 31, 2020. The treatment protocol adhered to the current German guidelines, and all procedures were performed following recommendations from multidisciplinary oncology board meetings.\u003c/p\u003e \u003cp\u003eNeck dissection was conducted according to a standardized protocol. For patients without clinically detectable neck metastases, a unilateral selective neck dissection (SND) involving levels I to IV was performed. In cases with tumors located at or near the midline, a bilateral SND was carried out. If ipsilateral lymph node metastases were identified preoperatively, intraoperatively (via frozen section), or postoperatively, a modified radical neck dissection (MRND) was performed on the affected side, along with a contralateral SND. In patients with contralateral lymph node metastases, bilateral MRND was performed. The decision for adjuvant therapy was based on individual patient risk factors, in accordance with the German treatment guidelines.\u003c/p\u003e \u003cp\u003eThe exclusion criteria included patients with recurrent OSCC, squamous cell carcinoma of the lip, those who had received neoadjuvant immunotherapy, patients who declined neck dissection, individuals who underwent sentinel lymph node biopsy, and those who had limited neck dissection due to severe comorbidities.\u003c/p\u003e \u003cp\u003eThe study protocol was approved by the Ethics Committee of the \u0026Auml;rztekammer Hamburg (ethics vote: 2024-101379-BO-ff), and written informed consent was not required per national and institutional regulations. The manuscript adhered to STROBE guidelines.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eClinicopathological characteristics\u003c/h3\u003e\n\u003cp\u003eClinicopathological data were extracted from patient medical records, including age, sex, tumor localization, TNM classification, depth of invasion, ENE, grading, resection margins, and the presence of perineural, vascular, and lymphovascular invasion. We also recorded the dates of surgery, last follow-up, recurrence, and death.\u003c/p\u003e \u003cp\u003eDuring the study period, the TNM classification was updated from the 7th to the 8th edition. Patients initially classified according to the 7th edition were reclassified according to the 8th edition to ensure consistency (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e). As ENE was not considered in the 7th TNM classification, some patients classified as pN1 under this system had to be excluded due to the presence of ENE (n\u0026thinsp;=\u0026thinsp;11).\u003c/p\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis\u003c/h2\u003e \u003cp\u003eData analysis was conducted using SPSS software, version 28.0 (SPSS, Chicago, IL, USA). Correlation analysis was performed utilizing the chi-square test. Recurrence-free survival (RFS) and overall survival (OS) were estimated using the Kaplan-Meier method, and comparisons of survival outcomes between patients undergoing different treatment modalities were analyzed using the log-rank test. RFS was defined as the interval from surgery to the occurrence of local or regional recurrence, with data censored at the last follow-up in cases without recurrence. OS was defined as the time from surgical resection to death from any cause, with data censored at the last follow-up for patients who were still alive. For identifying prognostic factors of survival, univariate Cox analysis was performed, followed by a multivariate Cox analysis that incorporated factors showing significance in the univariate analysis.\u003c/p\u003e \u003cp\u003eFigures were generated using SPSS.\u003c/p\u003e \u003cp\u003eA p-value of \u0026lt;\u0026thinsp;0.05 was considered statistically significant.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003eClinicopathological characteristics of the cohort\u003c/h2\u003e \u003cp\u003eThe study included 98 patients, with a slightly higher proportion of males (57; 58.2%) than females (41; 41.8%). The median age at surgery was evenly distributed, with 53 patients (54.1%) under 65 years and 45 (45.9%) aged 65 years or older.\u003c/p\u003e \u003cp\u003ePathological staging revealed that T2 was the most common T stage, observed in 37 patients (37.8%), followed by T4a in 28 patients (28.6%), T1 in 21 patients (21.4%), and T3 in 12 patients (12.2%). Clinically, T2 was also the most frequent stage, present in 37 cases (37.8%). Other clinical T stages included T1 in 12 cases (12.2%), T3 in 7 cases (7.1%), T4a in 22 cases (22.5%), and T4b in a single case (1.0%).\u003c/p\u003e \u003cp\u003eRegarding clinical N stage, nearly half of the patients (46; 46.9%) were node-negative (N0). Among the remaining patients, N1 was observed in 20 cases (20.4%), N2b in 9 cases (9.18%), N2c in 4 cases (4.1%), and N2a and N3b in 1 case each (1.0%). All patients in the cohort were classified as M0, indicating the absence of distant metastases at the time of diagnosis.\u003c/p\u003e \u003cp\u003eTumor grading showed that the majority of cases (67; 68.4%) were moderately differentiated (G2), while 23 (23.5%) were poorly differentiated (G3), and 3 (3.1%) were well-differentiated (G1). Lymphovascular invasion was identified in 37 patients (37.8%), while 61 patients (62.2%) showed no evidence of such invasion. Vascular invasion was rare, occurring in only 3 cases (3.1%). Perineural invasion was present in 20 patients (20.0%), whereas 78 patients (79.6%) had no signs of perineural involvement. Resection margins were negative (R0) in 96 cases (99.0%), with only 2 patients (2.0%) having positive margins (R1).\u003c/p\u003e \u003cp\u003eThe clinical outcomes demonstrated a recurrence rate of 26.5%, with 26 patients experiencing recurrence, while 72 patients (73.5%) showed no signs of recurrence during follow-up. Distant metastases during follow-up were rare, occurring in only 5 patients (5.1%).\u003c/p\u003e \u003cp\u003eRegarding treatment, 35 patients (35.7%) underwent surgery alone, 19 patients (19.4%) received surgery with RCT, and 44 patients (44.9%) underwent surgery followed by PORT.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eCorrelation between clinicopathological characteristics and pN1 neck\u003c/h2\u003e \u003cp\u003eChi-square test was performed to assess the associations between clinicopathological characteristics and therapy types. In terms of sex, females and males were evenly distributed across therapy types, with no significant association observed (p\u0026thinsp;=\u0026thinsp;0.745). Age at surgery was significantly associated with therapy type (p\u0026thinsp;=\u0026thinsp;0.046). Patients under 65 years of age were more likely to receive surgery only (34.0%) or surgery with RCT (28.3%), while those aged 65 years or older predominantly received PORT (53.3%).\u003c/p\u003e \u003cp\u003ePathological T stage showed a significant association with therapy type (p\u0026thinsp;=\u0026thinsp;0.049). Patients with T1 tumors most frequently underwent surgery only (61.9%), while those with advanced stages, such as T3 and T4a, were more likely to receive PORT (58.3% and 57.1%, respectively).\u003c/p\u003e \u003cp\u003eGrading did not show a significant relationship with therapy type (p\u0026thinsp;=\u0026thinsp;0.342), although poorly differentiated tumors (G3) tended toward PORT (65.2%). Other histopathological features, including lymphovascular invasion (p\u0026thinsp;=\u0026thinsp;0.477), vascular invasion (p\u0026thinsp;=\u0026thinsp;0.816), and perineural invasion (p\u0026thinsp;=\u0026thinsp;0.188), did not show significant associations with therapy type. However, patients with perineural invasion were slightly more likely to receive PORT (50.0%). Similarly, resection margins did not demonstrate a significant association (p\u0026thinsp;=\u0026thinsp;0.376), though patients with positive margins tended toward PORT (50.0%).\u003c/p\u003e \u003cp\u003eRecurrence was significantly associated with therapy type (p\u0026thinsp;=\u0026thinsp;0.033). Patients with no recurrence were more likely to receive PORT (52.8%), whereas those with recurrence were more likely to have undergone surgery only (50.0%). The presence of distant metastases during follow-up did not show a significant association with therapy type (p\u0026thinsp;=\u0026thinsp;0.385).\u003c/p\u003e \u003cp\u003eRegarding tumor localization, no significant association was found with therapy type (p\u0026thinsp;=\u0026thinsp;0.879). Tumors located in the floor of the mouth or lower jaw were evenly distributed across all therapy types, while those in the hard palate showed a slight preference for surgery only (50.0%) and PORT (30.0%).\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eUnivariate and multivariate analysis for recurrence-free survival\u003c/h3\u003e\n\u003cp\u003eThe univariate analysis demonstrated that the type of therapy, vascular invasion, and resection margin were significantly associated with RFS (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05).\u003c/p\u003e \u003cp\u003ePatients treated with surgery followed by PORT had a significantly lower risk of recurrence compared to those treated with surgery alone (HR\u0026thinsp;=\u0026thinsp;0.280, 95% CI: 0.106\u0026ndash;0.737, p\u0026thinsp;=\u0026thinsp;0.010). Similarly, the presence of vascular invasion was associated with a markedly increased risk of recurrence (HR\u0026thinsp;=\u0026thinsp;13.004, 95% CI: 2.727\u0026ndash;62.002, p\u0026thinsp;=\u0026thinsp;0.001). Positive resection margins also showed a strong association with recurrence, with a HR of 24.987 (95% CI: 4.175-149.567, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Other factors, including age, sex, pathological T category, tumor grading, lymphovascular invasion, and perineural invasion, did not reach statistical significance in the univariate analysis (p\u0026thinsp;\u0026gt;\u0026thinsp;0.05).\u003c/p\u003e \u003cp\u003eIn the multivariate analysis, PORT remained independently associated with improved RFS (HR\u0026thinsp;=\u0026thinsp;0.279, 95% CI: 0.098\u0026ndash;0.789, p\u0026thinsp;=\u0026thinsp;0.016), confirming its protective effect. Although vascular invasion and resection margins were significant in univariate analysis, their association with RFS was attenuated in the multivariate model, with p-values of 0.251 and 0.072, respectively.\u003c/p\u003e\n\u003ch3\u003eUnivariate and multivariate analysis for overall survival\u003c/h3\u003e\n\u003cp\u003eThe univariate analysis revealed that type of therapy and resection margins were significantly associated with OS (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05). Patients treated with surgery followed by PORT exhibited a trend toward improved survival compared to those treated with surgery alone (HR\u0026thinsp;=\u0026thinsp;0.504, 95% CI: 0.240\u0026ndash;1.058, p\u0026thinsp;=\u0026thinsp;0.050). Additionally, positive resection margins were associated with a markedly worse OS (HR\u0026thinsp;=\u0026thinsp;9.386, 95% CI: 2.042\u0026ndash;43.136, p\u0026thinsp;=\u0026thinsp;0.004). Other clinicopathological factors, including age, sex, pathological T category, tumor grading, lymphovascular invasion, vascular invasion, and perineural invasion, were not significantly associated with OS in the univariate analysis (p\u0026thinsp;\u0026gt;\u0026thinsp;0.05).\u003c/p\u003e \u003cp\u003eIn the multivariate analysis, the protective effect of PORT on OS became more pronounced and reached statistical significance (HR\u0026thinsp;=\u0026thinsp;0.361, 95% CI: 0.165\u0026ndash;0.790, p\u0026thinsp;=\u0026thinsp;0.011), confirming its independent role in improving survival outcomes. Furthermore, positive resection margins remained a significant predictor of worse survival in the adjusted model (HR\u0026thinsp;=\u0026thinsp;14.036, 95% CI: 2.886\u0026ndash;68.258, p\u0026thinsp;=\u0026thinsp;0.001).\u003c/p\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003eRecurrence-free survival\u003c/h2\u003e \u003cp\u003eThe 5-year-RFS was highest among patients who underwent surgery followed by PORT. However, this outcome only demonstrated a trend toward improved survival in the surgery plus PORT group, without reaching statistical significance when compared to the surgery-alone group (p\u0026thinsp;=\u0026thinsp;0.092) or the surgery combined with RCT group (p\u0026thinsp;=\u0026thinsp;0.096). Additionally, no significant difference in RFS at 5 years was found between the surgery-alone group and the surgery with RCT group (p\u0026thinsp;\u0026gt;\u0026thinsp;0.05).\u003c/p\u003e \u003cp\u003eAt 10 years, a significant improvement in RFS was observed in the surgery\u0026thinsp;+\u0026thinsp;PORT group compared to both the surgery-alone group (p\u0026thinsp;=\u0026thinsp;0.010) and the surgery\u0026thinsp;+\u0026thinsp;RCT group (p\u0026thinsp;=\u0026thinsp;0.030). However, no significant difference in RFS was found between the surgery-alone group and the surgery\u0026thinsp;+\u0026thinsp;RCT group (p\u0026thinsp;=\u0026thinsp;0.855).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003eOverall survival\u003c/h2\u003e \u003cp\u003eRegarding 5-year-OS, a significant difference was observed between the surgery with PORT group and the surgery-alone group (p\u0026thinsp;=\u0026thinsp;0.038). No significant differences in OS were found between the surgery-alone group and the surgery with RCT group (p\u0026thinsp;=\u0026thinsp;0.412), or between the surgery with PORT group and the surgery with RCT group (p\u0026thinsp;=\u0026thinsp;0.426).\u003c/p\u003e \u003cp\u003eAt 10 years, no significant differences in OS were observed between the treatment groups (p\u0026thinsp;\u0026gt;\u0026thinsp;0.05). However, a trend toward slightly better survival was noted in the surgery with PORT group compared to the surgery-alone group, with a p-value of 0.175.\u003c/p\u003e \u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eThe role of PORT in the management of OSCC patients with pN1 neck, particularly in the absence of other adverse pathological features, remains a subject of ongoing debate. Additionally, the potential benefits of RCT in improving survival outcomes are also under investigation. This study examines the efficacy of different treatment strategies \u0026ndash; surgery alone, surgery with PORT, and surgery with adjuvant RCT \u0026ndash; for managing the pN1 neck in OSCC patients. The results highlight significant differences in the effects of these treatment modalities on recurrence and survival, providing valuable insights for clinical decision-making in this patient population.\u003c/p\u003e \u003cp\u003eInitially, we assessed the factors influencing treatment selection. Age at surgery and pathological T stage emerged as significant predictors of treatment modality. Notably, patients under 65 years of age were more likely to undergo surgery alone or surgery with RCT, while those aged 65 or older were predominantly treated with PORT, especially in cases with advanced tumor stages such as T3 or T4a (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05). Additionally, recurrence was strongly associated with treatment choice. Patients who did not experience recurrence were more likely to have received PORT, whereas those who experienced recurrence were more likely to have been treated with surgery alone (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05).\u003c/p\u003e \u003cp\u003eIn terms of RFS, the addition of PORT to surgery demonstrated the most favorable long-term outcomes, particularly at 10 years. At this time point, patients who underwent surgery with PORT had significantly better RFS compared to those treated with surgery alone (p\u0026thinsp;=\u0026thinsp;0.010) or surgery with RCT (p\u0026thinsp;=\u0026thinsp;0.030). These findings suggest that PORT provides a substantial long-term benefit in preventing recurrence. In contrast, at 5 years, no significant differences in RFS were observed between the treatment groups (p\u0026thinsp;\u0026gt;\u0026thinsp;0.05).\u003c/p\u003e \u003cp\u003eFurthermore, no significant difference in 5-Year-RFS was found between the surgery-only and surgery with RCT groups (p\u0026thinsp;\u0026gt;\u0026thinsp;0.05), suggesting that the addition of chemotherapy to radiotherapy does not provide a clear advantage over surgery alone in the medium term.\u003c/p\u003e \u003cp\u003eUnivariate analysis confirmed that PORT significantly reduced the risk of recurrence compared to surgery alone (HR\u0026thinsp;=\u0026thinsp;0.280, p\u0026thinsp;=\u0026thinsp;0.010). Multivariate analysis further supported this finding, with PORT remaining independently associated with improved RFS (HR\u0026thinsp;=\u0026thinsp;0.279, p\u0026thinsp;=\u0026thinsp;0.016). Additionally, while factors such as vascular invasion and positive resection margins were significant in the univariate analysis, their impact on RFS was diminished in the multivariate model, highlighting the moderating role of PORT in improving outcomes.\u003c/p\u003e \u003cp\u003eConsistent with our findings, most studies on pN1 neck in OSCC patients suggest that PORT reduces the risk of regional recurrence. Barry et al. performed a matched-pair analysis on 90 OSCC patients, including 30 with pN1, comparing those who received surgery with PORT to those treated with surgery alone. Their study demonstrated a significant improvement in locoregional tumor control in the PORT group (\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e). Similarly, Liu et al. evaluated the treatment outcomes in a cohort of 432 OSCC patients, 216 of whom received surgery alone and 216 received surgery with PORT. They observed a significantly improved RFS in patients who underwent surgery with PORT, with a higher 5-year RFS rate in this group compared to the surgery-only group (\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e). K\u0026auml;mmerer et al., in a multicenter trial involving 209 patients, found that PORT had a positive impact on progression-free survival, delaying disease progression relative to non-RT treatment. However, they also noted that patients who received PORT reported a significantly reduced quality of life up to three years post-treatment compared to the observation group (\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e). In contrast to the previously described findings and our own results, Tsai et al. found no significant differences in neck recurrence rates or RFS between patients who underwent surgery alone and those treated with surgery and PORT (7.7% vs. 15.8%, p\u0026thinsp;\u0026gt;\u0026thinsp;0.05) (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eRegarding OS, patients who received surgery followed by PORT demonstrated significantly better survival at 5 years compared to those who underwent surgery alone (p\u0026thinsp;=\u0026thinsp;0.038). However, no significant differences in OS were observed between the surgery-only and surgery with RCT groups (p\u0026thinsp;=\u0026thinsp;0.412) or between the surgery with PORT and surgery with RCT groups (p\u0026thinsp;=\u0026thinsp;0.426). These results suggest that PORT provides a survival advantage over surgery alone, but the addition of chemotherapy does not significantly enhance survival at this early time point.\u003c/p\u003e \u003cp\u003eAt 10 years, while no statistically significant differences in OS were observed (p\u0026thinsp;\u0026gt;\u0026thinsp;0.05), a trend toward improved survival in the surgery\u0026thinsp;+\u0026thinsp;PORT group compared to surgery alone persisted, though it did not reach statistical significance (p\u0026thinsp;=\u0026thinsp;0.175).\u003c/p\u003e \u003cp\u003eUnivariate analysis showed that PORT was associated with a trend toward improved survival compared to surgery alone (HR\u0026thinsp;=\u0026thinsp;0.504, p\u0026thinsp;=\u0026thinsp;0.050). In multivariate analysis, PORT significantly improved OS (HR\u0026thinsp;=\u0026thinsp;0.361, p\u0026thinsp;=\u0026thinsp;0.011), confirming its beneficial impact on survival outcomes. However, positive resection margins emerged as a strong predictor of poor survival (HR\u0026thinsp;=\u0026thinsp;14.036, p\u0026thinsp;=\u0026thinsp;0.001), underscoring the importance of achieving negative margins to improve prognosis. The addition of RCT did not demonstrate a clear survival benefit in the multivariate analysis (HR\u0026thinsp;=\u0026thinsp;0.423, p\u0026thinsp;=\u0026thinsp;0.087), suggesting that while RCT may offer some advantages, it does not provide significant improvements in OS over PORT alone.\u003c/p\u003e \u003cp\u003eIn contrast to our findings, several studies have failed to demonstrate a significant difference in OS. For instance, Liu et al. found no substantial difference in OS between patients who underwent surgery alone and those treated with surgery plus PORT, with similar 5-year OS rates in both groups (\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e). Similarly, in a multicenter trial involving 209 patients, K\u0026auml;mmerer et al. reported that PORT did not significantly affect OS in this cohort (\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e). On the contrary, Barry et al. observed that the addition of PORT suggested a survival benefit; however, this finding did not reach statistical significance (\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e). These inconsistencies may stem from variations in patient populations and treatment protocols. For example, Chen et al. analyzed a cohort of 1,467 OSCC patients and found that PORT was associated with improved OS, with a hazard ratio of 0.76 (95% CI, 0.63\u0026ndash;0.92). Notably, a survival benefit was observed in patients younger than 70 years, and those with pT2 disease also benefitted from PORT. In contrast, no significant survival advantage was noted for patients aged 70 years or older (\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e). Moreover, Shrime et al. demonstrated that PORT conferred survival benefits only in patients with T2 tongue and tumors located at the floor of the mouth, with no observed benefit in other subsites (\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e). Additionally, an analysis by Suresh and Crameri, which included 1,909 patients (898 of whom received PORT), indicated a survival benefit in the overall cohort, with an adjusted hazard ratio of 0.82 (95% CI 0.72\u0026ndash;0.94). This benefit was evident regardless of the adequacy of neck dissection, and patients with lymph node metastases larger than 10 mm experienced greater benefit from PORT compared to those with smaller metastases (\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eWhile the benefits of PORT in reducing regional recurrence are well-documented, it is essential to consider the associated implications for patients' quality of life. Several studies, including those by Bekiroglu et al. and Barry et al., have highlighted the significant short-term and long-term functional impairments that patients may experience following PORT. These impairments include pain, dysphagia, speech disturbances, xerostomia, and restricted mouth opening, all of which can substantially affect patients' daily functioning and overall well-being (\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThe benefit of adding chemotherapy to radiotherapy remains a topic of debate. In contrast to our findings, a cohort study by Lee et al., which included 1,598 patients with pT1/2 N1 HNSCC without positive margins or ENE, demonstrated that patients receiving adjuvant RCT had a 13.8% improvement in survival compared to those treated with PORT. However, no significant difference in survival was observed between patients treated with PORT and those treated with surgery alone (\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e). Similarly, Chang et al. reported that 5-year-OS rates for patients treated with surgery alone, PORT, and RCT were 62.2%, 58.7%, and 71.1%, respectively (P\u0026thinsp;=\u0026thinsp;0.03). Adjuvant RCT was associated with significantly improved survival compared to PORT in the overall group (p\u0026thinsp;=\u0026thinsp;0.008). However, this benefit was particularly evident in the pT2 group, where RCT resulted in significantly better survival rates than PORT (p\u0026thinsp;=\u0026thinsp;0.001). In contrast, no significant survival differences were observed between the two treatment approaches for patients with pT1 disease (\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e).\u003c/p\u003e \u003cdiv id=\"Sec14\" class=\"Section2\"\u003e \u003ch2\u003eLimitations of this study\u003c/h2\u003e \u003cp\u003eWhile this study offers valuable insights into the management of the pN1 neck in patients with OSCC, several limitations should be considered. The retrospective nature of the study, along with the relatively small sample size, may limit the generalizability of the findings. Additionally, the study did not account for certain patient factors, such as performance status or comorbidities, which may also influence treatment decisions and outcomes. Further studies with larger cohorts, including prospective trials, are needed to confirm these findings and better understand the role of PORT and RCT in improving long-term survival in this patient population. Nevertheless, the strengths of our study may lie in the fact that all patients were classified according to the 8th UICC staging system, and the cohort was thoroughly characterized in terms of pathological characteristics.\u003c/p\u003e \u003c/div\u003e"},{"header":"Conclusion","content":"\u003cp\u003eIn the management of OSCC patients with pN1 neck, PORT is associated with improved RFS and OS, especially in the long term. Surgery combined with PORT provides the most significant survival benefit, while the addition of RCT does not show a clear advantage over surgery alone or surgery with PORT. Our results indicate that PORT should be considered the preferred adjuvant treatment for OSCC patients with pN1 neck, while RCT may be reserved for those with specific high-risk characteristics. Nonetheless, impairments in quality of life should be taken into account.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eASCO - American Society of Clinical Oncology\u003c/p\u003e\n\u003cp\u003eCI - confidence interval\u003c/p\u003e\n\u003cp\u003eENE - extranodal extension\u003c/p\u003e\n\u003cp\u003eHR - hazard ratio\u003c/p\u003e\n\u003cp\u003eMRND - modified radical neck dissection\u003c/p\u003e\n\u003cp\u003eOS - overall survival\u003c/p\u003e\n\u003cp\u003eOSCC - oral squamous cell carcinoma\u003c/p\u003e\n\u003cp\u003ePORT - postoperative radiotherapy\u003c/p\u003e\n\u003cp\u003ePFS - progression-free survival\u003c/p\u003e\n\u003cp\u003eRFS - recurrence-free survival\u003c/p\u003e\n\u003cp\u003eRCT - radiochemotherapy\u003c/p\u003e\n\u003cp\u003eSND - selective neck dissection\u003c/p\u003e\n\u003cp\u003eSLNB - sentinel lymph node biopsy\u003c/p\u003e\n\u003cp\u003eUICC - Union for International Cancer Control\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eData availability statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe data that support the findings of this study are available from the corresponding author upon reasonable request.\u003c/p\u003e\n\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare no competing interests.\u003c/p\u003e\n\n\u003cp\u003e\u003cstrong\u003eEthics approval\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was performed in line with the principles of the 1964 Helsinki Declaration and its later amendments. The Ethics Committee of the \u0026Auml;rztekammer Hamburg approved the study\u0026rsquo;s design and methods (2024-101379-BO-ff). In accordance with national regulations and institutional regulations, written informed consent was not required from the participating patients.\u003c/p\u003e\n\n\u003cp\u003e\u003cstrong\u003eConflict of interest\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors have no financial or non-financial conflicts of interest to disclose.\u003c/p\u003e\n\n\u003cp\u003e\u003cstrong\u003eAuthor contribution\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAS: conception and design of the study, acquisition, analysis and interpretation of data, drafting the manuscript, and revising it critically for important intellectual content and scientific integrity. RS, CP, CB, WW and MG: reading and revising the manuscript critically for important intellectual content and scientific integrity. All authors read and agreed to the final version of the manuscript.\u003c/p\u003e\n"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eFerlay J, Colombet M, Soerjomataram I, Mathers C, Parkin DM, Pineros M, et al. Estimating the global cancer incidence and mortality in 2018: GLOBOCAN sources and methods. Int J Cancer. 2019;144(8):1941-53. https://doi.org/10.1002/ijc.31937\u003c/li\u003e\n\u003cli\u003eStruckmeier AK, Buchbender M, Lutz R, Kesting M. Improved recurrence rates and progression-free survival in primarily surgically treated oral squamous cell carcinoma - results from a German tertiary medical center. Clin Oral Investig. 2024;28(5):262. https://doi.org/10.1007/s00784-024-05644-z\u003c/li\u003e\n\u003cli\u003eShimura S, Ogi K, Miyazaki A, Shimizu S, Kaneko T, Sonoda T, et al. Selective Neck Dissection and Survival in Pathologically Node-Positive Oral Squamous Cell Carcinoma. 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Adjuvant radiotherapy and health-related quality of life of patients at intermediate risk of recurrence following primary surgery for oral squamous cell carcinoma. Oral Oncol. 2011;47(10):967-73. https://doi.org/10.1016/j.oraloncology.2011.07.003\u003c/li\u003e\n\u003cli\u003eBarry CP, Wong D, Clark JR, Shaw RJ, Gupta R, Magennis P, et al. Postoperative radiotherapy for patients with oral squamous cell carcinoma with intermediate risk of recurrence: A case match study. Head Neck. 2017;39(7):1399-404. https://doi.org/10.1002/hed.24780\u003c/li\u003e\n\u003cli\u003eBrown JS, Blackburn TK, Woolgar JA, Lowe D, Errington RD, Vaughan ED, et al. A comparison of outcomes for patients with oral squamous cell carcinoma at intermediate risk of recurrence treated by surgery alone or with post-operative radiotherapy. Oral Oncol. 2007;43(8):764-73. https://doi.org/10.1016/j.oraloncology.2006.09.010\u003c/li\u003e\n\u003cli\u003eCooper JS, Pajak TF, Forastiere AA, Jacobs J, Campbell BH, Saxman SB, et al. Postoperative concurrent radiotherapy and chemotherapy for high-risk squamous-cell carcinoma of the head and neck. N Engl J Med. 2004;350(19):1937-44. https://doi.org/10.1056/NEJMoa032646\u003c/li\u003e\n\u003cli\u003eBernier J, Cooper JS, Pajak TF, van Glabbeke M, Bourhis J, Forastiere A, et al. Defining risk levels in locally advanced head and neck cancers: a comparative analysis of concurrent postoperative radiation plus chemotherapy trials of the EORTC (#22931) and RTOG (# 9501). Head Neck. 2005;27(10):843-50. https://doi.org/10.1002/hed.20279\u003c/li\u003e\n\u003cli\u003eBernier J, Domenge C, Ozsahin M, Matuszewska K, Lefebvre JL, Greiner RH, et al. Postoperative irradiation with or without concomitant chemotherapy for locally advanced head and neck cancer. N Engl J Med. 2004;350(19):1945-52. https://doi.org/10.1056/NEJMoa032641\u003c/li\u003e\n\u003cli\u003eCooper JS, Zhang Q, Pajak TF, Forastiere AA, Jacobs J, Saxman SB, et al. Long-term follow-up of the RTOG 9501/intergroup phase III trial: postoperative concurrent radiation therapy and chemotherapy in high-risk squamous cell carcinoma of the head and neck. Int J Radiat Oncol Biol Phys. 2012;84(5):1198-205. https://doi.org/10.1016/j.ijrobp.2012.05.008\u003c/li\u003e\n\u003cli\u003eMohamad I, Glaun MDE, Prabhash K, Busheri A, Lai SY, Noronha V, et al. Current Treatment Strategies and Risk Stratification for Oral Carcinoma. Am Soc Clin Oncol Educ Book. 2023;43:e389810. https://doi.org/10.1200/EDBK_389810\u003c/li\u003e\n\u003cli\u003eLiu T, David M, Batstone M, Clark J, Low TH, Goldstein D, et al. The utility of postoperative radiotherapy in intermediate-risk oral squamous cell carcinoma. Int J Oral Maxillofac Surg. 2021;50(2):143-50. https://doi.org/10.1016/j.ijom.2020.06.006\u003c/li\u003e\n\u003cli\u003eKammerer PW, Tribius S, Cohrs L, Engler G, Ettl T, Freier K, et al. Adjuvant Radiotherapy in Patients with Squamous Cell Carcinoma of the Oral Cavity or Oropharynx and Solitary Ipsilateral Lymph Node Metastasis (pN1)-A Prospective Multicentric Cohort Study. Cancers (Basel). 2023;15(6). https://doi.org/10.3390/cancers15061833\u003c/li\u003e\n\u003cli\u003eChen MM, Harris JP, Hara W, Sirjani D, Divi V. Association of Postoperative Radiotherapy With Survival in Patients With N1 Oral Cavity and Oropharyngeal Squamous Cell Carcinoma. JAMA Otolaryngol Head Neck Surg. 2016;142(12):1224-30. https://doi.org/10.1001/jamaoto.2016.3519\u003c/li\u003e\n\u003cli\u003eShrime MG, Gullane PJ, Dawson L, Kim J, Gilbert RW, Irish JC, et al. The impact of adjuvant radiotherapy on survival in T1-2N1 squamous cell carcinoma of the oral cavity. Arch Otolaryngol Head Neck Surg. 2010;136(3):225-8. https://doi.org/10.1001/archoto.2010.22\u003c/li\u003e\n\u003cli\u003eSuresh K, Cramer JD. Postoperative radiation therapy vs observation for pN1 oral cavity squamous cell carcinoma. Head Neck. 2019;41(12):4136-42. https://doi.org/10.1002/hed.25958\u003c/li\u003e\n\u003cli\u003eLee A, Givi B, Roden DF, Tam MM, Wu SP, Gerber NK, et al. Utilization and Survival of Postoperative Radiation or Chemoradiation for pT1-2N1M0 Head and Neck Cancer. Otolaryngol Head Neck Surg. 2018;158(4):677-84. https://doi.org/10.1177/0194599817746391\u003c/li\u003e\n\u003cli\u003eChang CC, Wu YT, Lu HH, Cheng YJ, Tsai MH. The role of postoperative radiotherapy or chemoradiation in pT1-2N1M0 oral squamous cell carcinoma. J Formos Med Assoc. 2024. https://doi.org/10.1016/j.jfma.2024.03.005\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003e\u003cstrong\u003eTable 1.\u003c/strong\u003e Clinicopathological characteristics of the cohort\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"446\"\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eVariable\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCategory\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 162px;\"\u003e\n \u003cp\u003e\u003cstrong\u003en (%)\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eSex\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eFemale\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 162px;\"\u003e\n \u003cp\u003e41 (41.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMale\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 162px;\"\u003e\n \u003cp\u003e57 (58.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAge at surgery\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt; 65 years\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 162px;\"\u003e\n \u003cp\u003e53 (54.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026ge; 65 years\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 162px;\"\u003e\n \u003cp\u003e45 (45.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"4\" valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePathological T stage\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eT1\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 162px;\"\u003e\n \u003cp\u003e21 (21.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eT2\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 162px;\"\u003e\n \u003cp\u003e37 (37.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eT3\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 162px;\"\u003e\n \u003cp\u003e12 (12.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eT4a\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 162px;\"\u003e\n \u003cp\u003e28 (28.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"6\" valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eClinical T stage\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eT1\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 162px;\"\u003e\n \u003cp\u003e12 (12.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eT2\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 162px;\"\u003e\n \u003cp\u003e37 (37.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eT3\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 162px;\"\u003e\n \u003cp\u003e7 (7.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eT4a\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 162px;\"\u003e\n \u003cp\u003e22 (22.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eT4b\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 162px;\"\u003e\n \u003cp\u003e1 (1.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMissing\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 162px;\"\u003e\n \u003cp\u003e19 (19.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"7\" valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eClinical N stage\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eN0\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 162px;\"\u003e\n \u003cp\u003e46 (46.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eN1\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 162px;\"\u003e\n \u003cp\u003e20 (20.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eN2a\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 162px;\"\u003e\n \u003cp\u003e1 (1.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eN2b\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 162px;\"\u003e\n \u003cp\u003e9 (9.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eN2c\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 162px;\"\u003e\n \u003cp\u003e4 (4.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eN3b\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 162px;\"\u003e\n \u003cp\u003e1 (1.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMissing\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 162px;\"\u003e\n \u003cp\u003e17 (17.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eM stage\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eM0\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 162px;\"\u003e\n \u003cp\u003e98 (100.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"4\" valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eGrading\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eG1\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 162px;\"\u003e\n \u003cp\u003e3 (3.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eG2\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 162px;\"\u003e\n \u003cp\u003e67 (68.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eG3\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 162px;\"\u003e\n \u003cp\u003e23 (23.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eGx\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 162px;\"\u003e\n \u003cp\u003e5 (5.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eLymphovascular invasion\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eL0\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 162px;\"\u003e\n \u003cp\u003e61 (62.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eL1\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 162px;\"\u003e\n \u003cp\u003e37 (37.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eVascular invasion\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eV0\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 162px;\"\u003e\n \u003cp\u003e95 (96.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eV1\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 162px;\"\u003e\n \u003cp\u003e3 (3.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePerineural invasion\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePn0\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 162px;\"\u003e\n \u003cp\u003e78 (79.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePn1\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 162px;\"\u003e\n \u003cp\u003e20 (20.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eResection margin\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eR0\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 162px;\"\u003e\n \u003cp\u003e96 (99.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eR1\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 162px;\"\u003e\n \u003cp\u003e2 (2.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eRecurrence\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eNo\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 162px;\"\u003e\n \u003cp\u003e72 (73.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eYes\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 162px;\"\u003e\n \u003cp\u003e26 (26.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eOccurrence of distant metastases during observation period\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eNo\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 162px;\"\u003e\n \u003cp\u003e93 (94.9)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eYes\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 162px;\"\u003e\n \u003cp\u003e5 (5.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"3\" valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTherapy\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eSurgery only\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 162px;\"\u003e\n \u003cp\u003e35 (35.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eSurgery + RCT\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 162px;\"\u003e\n \u003cp\u003e19 (19.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eSurgery + PORT\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 162px;\"\u003e\n \u003cp\u003e44 (44.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cstrong\u003eAbbreviations\u003c/strong\u003e: T stage \u0026ndash; tumor stage, N stage \u0026ndash; node stage, M \u0026ndash; metastasis, RCT \u0026ndash; radiochemotherapy, PORT \u0026ndash; postoperative radiotherapy.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003cstrong\u003eTable 2.\u0026nbsp;\u003c/strong\u003eAssociation between clinicopathological variables and type of therapy\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"567\"\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 107px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eVariable\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCharacteristic\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"4\" valign=\"top\" style=\"width: 356px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eType of therapy\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 92px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eSurgery only\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003en (%)\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 92px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eSurgery + RCT\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003en (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eSurgery + PORT\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003en (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ep value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 107px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eSex\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eFemale\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 92px;\"\u003e\n \u003cp\u003e13 (31.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 92px;\"\u003e\n \u003cp\u003e9 (22.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e19 (46.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e0.745\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMale\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 92px;\"\u003e\n \u003cp\u003e22 (38.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 92px;\"\u003e\n \u003cp\u003e10 (17.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e25 (43.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 107px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAge at surgery\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt; 65 years\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 92px;\"\u003e\n \u003cp\u003e18 (34.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 92px;\"\u003e\n \u003cp\u003e15 (28.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e20 (37.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e0.046*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026ge; 65 years\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 92px;\"\u003e\n \u003cp\u003e17 (37.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 92px;\"\u003e\n \u003cp\u003e4 (9.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e24 (53.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"4\" valign=\"top\" style=\"width: 107px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePathological T stage\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eT1\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 92px;\"\u003e\n \u003cp\u003e13 (61.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 92px;\"\u003e\n \u003cp\u003e3 (14.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e5 (23.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"4\" valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e0.049*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eT2\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 92px;\"\u003e\n \u003cp\u003e15 (40.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 92px;\"\u003e\n \u003cp\u003e6 (16.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e16 (43.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eT3\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 92px;\"\u003e\n \u003cp\u003e2 (16.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 92px;\"\u003e\n \u003cp\u003e3 (25.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e7 (58.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eT4a\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 92px;\"\u003e\n \u003cp\u003e5 (17.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 92px;\"\u003e\n \u003cp\u003e7 (25.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e16 (57.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"3\" valign=\"top\" style=\"width: 107px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eGrading\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eG1\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 92px;\"\u003e\n \u003cp\u003e1 (33.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 92px;\"\u003e\n \u003cp\u003e1 (33.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e1 (33.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"3\" valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e0.342\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eG2\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 92px;\"\u003e\n \u003cp\u003e26 (38.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 92px;\"\u003e\n \u003cp\u003e13 (19.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e28 (41.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eG3\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 92px;\"\u003e\n \u003cp\u003e6 (26.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 92px;\"\u003e\n \u003cp\u003e2 (8.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e15 (65.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 107px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eLymphovascular invasion\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eL0\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 92px;\"\u003e\n \u003cp\u003e21 (34.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 92px;\"\u003e\n \u003cp\u003e10 (16.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e30 (49.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e0.477\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eL1\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 92px;\"\u003e\n \u003cp\u003e14 (37.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 92px;\"\u003e\n \u003cp\u003e9 (24.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e14 (37.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 107px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eVascular invasion\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eV0\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 92px;\"\u003e\n \u003cp\u003e34 (35.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 92px;\"\u003e\n \u003cp\u003e18 (19.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e43 (45.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e0.816\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eV1\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 92px;\"\u003e\n \u003cp\u003e1 (33.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 92px;\"\u003e\n \u003cp\u003e1 (33.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e1 (33.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 107px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePerineural invasion\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePn0\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 92px;\"\u003e\n \u003cp\u003e31 (39.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 92px;\"\u003e\n \u003cp\u003e13 (16.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e34 (43.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e0.188\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePn1\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 92px;\"\u003e\n \u003cp\u003e4 (20.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 92px;\"\u003e\n \u003cp\u003e6 (30.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e10 (50.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 107px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eResection margin\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eR0\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 92px;\"\u003e\n \u003cp\u003e29 (34.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 92px;\"\u003e\n \u003cp\u003e14 (16.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e42 (49.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e0.376\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eR1\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 92px;\"\u003e\n \u003cp\u003e0 (0.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 92px;\"\u003e\n \u003cp\u003e1 (50.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e1 (50.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 107px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eRecurrence\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eNo\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 92px;\"\u003e\n \u003cp\u003e22 (30.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 92px;\"\u003e\n \u003cp\u003e12 (16.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e38 (52.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e0.033*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eYes\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 92px;\"\u003e\n \u003cp\u003e13 (50.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 92px;\"\u003e\n \u003cp\u003e7 (26.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e6 (23.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 107px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eDistant metastases during follow-up\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eNo\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 92px;\"\u003e\n \u003cp\u003e33 (35.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 92px;\"\u003e\n \u003cp\u003e17 (16.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e43 (46.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e0.385\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eYes\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 92px;\"\u003e\n \u003cp\u003e2 (40.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 92px;\"\u003e\n \u003cp\u003e2 (40.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e1 (20.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"5\" valign=\"top\" style=\"width: 107px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eLocalization\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eFloor of the mouth\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 92px;\"\u003e\n \u003cp\u003e21 (37.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 92px;\"\u003e\n \u003cp\u003e11 (19.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e24 (42.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"5\" valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e0.879\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eLower jaw\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 92px;\"\u003e\n \u003cp\u003e6 (31.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 92px;\"\u003e\n \u003cp\u003e4 (21.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e9 (43.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eUpper jaw\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 92px;\"\u003e\n \u003cp\u003e1 (25.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 92px;\"\u003e\n \u003cp\u003e0 (0.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e3 (75.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eHard palate\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 92px;\"\u003e\n \u003cp\u003e5 (50.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 92px;\"\u003e\n \u003cp\u003e2 (20.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e3 (30.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eBuccal plane\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 92px;\"\u003e\n \u003cp\u003e2 (22.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 92px;\"\u003e\n \u003cp\u003e2 (22.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e5 (55.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eA p value\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was considered statistically significant. Statistically significant differences are marked with an asterisk.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAbbreviations\u003c/strong\u003e: RCT \u0026ndash; radiochemotherapy, PORT \u0026ndash; postoperative radiotherapy.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003cstrong\u003eTable 3.\u0026nbsp;\u003c/strong\u003eUnivariate and multivariate analysis of recurrence-free survival\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 150px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eClinicopathological characteristics\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" valign=\"top\" style=\"width: 236px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eUnivariate analysis\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"5\" valign=\"top\" style=\"width: 218px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMultivariate analysis\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 81px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eOR\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 77px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e95% CI\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 79px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ep value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 72px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eOR\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 73px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e95% CI\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 73px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ep value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 150px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAge \u0026lt; 65 vs. \u0026ge; 65 years\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 81px;\"\u003e\n \u003cp\u003e0.984\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 77px;\"\u003e\n \u003cp\u003e0.435-2.066\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 79px;\"\u003e\n \u003cp\u003e0.894\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"5\" rowspan=\"7\" valign=\"top\" style=\"width: 218px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 150px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eSex\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 81px;\"\u003e\n \u003cp\u003e2.189\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 77px;\"\u003e\n \u003cp\u003e0.993-4.827\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 79px;\"\u003e\n \u003cp\u003e0.052\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"4\" valign=\"top\" style=\"width: 386px;\"\u003e\n \u003cp\u003e\u003cstrong\u003epT category\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 150px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eT1\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" valign=\"top\" style=\"width: 236px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 150px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eT2\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 81px;\"\u003e\n \u003cp\u003e2.202\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 77px;\"\u003e\n \u003cp\u003e0.621-7.810\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 79px;\"\u003e\n \u003cp\u003e0.222\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 150px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eT3\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 81px;\"\u003e\n \u003cp\u003e2.146\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 77px;\"\u003e\n \u003cp\u003e0.429-10.743\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 79px;\"\u003e\n \u003cp\u003e0.353\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 150px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eT4a\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 81px;\"\u003e\n \u003cp\u003e1.848\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 77px;\"\u003e\n \u003cp\u003e0.490-6.969\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 79px;\"\u003e\n \u003cp\u003e0.364\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"9\" valign=\"top\" style=\"width: 604px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eType of therapy\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 150px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eSurgery only\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" valign=\"top\" style=\"width: 236px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"5\" valign=\"top\" style=\"width: 218px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 150px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eSurgery + adjuvant RCT\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 81px;\"\u003e\n \u003cp\u003e0.793\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 77px;\"\u003e\n \u003cp\u003e0.316-1.989\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 79px;\"\u003e\n \u003cp\u003e0.621\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 73px;\"\u003e\n \u003cp\u003e0.318\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 73px;\"\u003e\n \u003cp\u003e0.076-1.327\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 73px;\"\u003e\n \u003cp\u003e0.116\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 150px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eSurgery + PORT\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 81px;\"\u003e\n \u003cp\u003e0.280\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 77px;\"\u003e\n \u003cp\u003e0.106-0.737\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 79px;\"\u003e\n \u003cp\u003e0.010*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 73px;\"\u003e\n \u003cp\u003e0.279\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 73px;\"\u003e\n \u003cp\u003e0.098-0.789\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 73px;\"\u003e\n \u003cp\u003e0.016*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 150px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eGrading\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 81px;\"\u003e\n \u003cp\u003e0.501\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 77px;\"\u003e\n \u003cp\u003e0.172-1.461\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 79px;\"\u003e\n \u003cp\u003e0.206\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"5\" rowspan=\"2\" valign=\"top\" style=\"width: 218px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 150px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eLymphovascular invasion\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 81px;\"\u003e\n \u003cp\u003e1.458\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 77px;\"\u003e\n \u003cp\u003e0.630-3.376\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 79px;\"\u003e\n \u003cp\u003e0.379\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 150px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eVascular invasion\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 81px;\"\u003e\n \u003cp\u003e13.004\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 77px;\"\u003e\n \u003cp\u003e2.727-62.002\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 79px;\"\u003e\n \u003cp\u003e0.001*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 72px;\"\u003e\n \u003cp\u003e4.822\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 73px;\"\u003e\n \u003cp\u003e0.328-70.822\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 73px;\"\u003e\n \u003cp\u003e0.251\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 150px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePerineural invasion\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 81px;\"\u003e\n \u003cp\u003e1.189\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 77px;\"\u003e\n \u003cp\u003e0.428-3.304\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 79px;\"\u003e\n \u003cp\u003e0.739\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"5\" valign=\"top\" style=\"width: 218px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 150px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eResection margin\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 81px;\"\u003e\n \u003cp\u003e24.987\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 77px;\"\u003e\n \u003cp\u003e4.175-149.567\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 79px;\"\u003e\n \u003cp\u003e\u0026lt;0.001*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 73px;\"\u003e\n \u003cp\u003e13.514\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 73px;\"\u003e\n \u003cp\u003e0.792-230.700\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 73px;\"\u003e\n \u003cp\u003e0.072\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eA p value\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was considered statistically significant. Statistically significant differences are marked with an asterisk.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAbbreviations\u003c/strong\u003e: CI \u0026ndash; confidence interval, HR \u0026ndash; hazard ratio, PORT \u0026ndash; postoperative radiotherapy, RCT \u0026ndash; radiochemotherapy, RFS \u0026ndash; recurrence-free survival.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 4.\u003c/strong\u003e Univariate and multivariate analysis of overall survival\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 150px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eClinicopathological characteristics\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" valign=\"top\" style=\"width: 238px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eUnivariate analysis\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"5\" valign=\"top\" style=\"width: 216px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMultivariate analysis\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 80px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eHR\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e95% CI\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 82px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ep value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 71px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eHR\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 72px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e95% CI\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 73px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ep value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 150px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAge \u0026lt; 65 vs. \u0026ge; 65 years\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 80px;\"\u003e\n \u003cp\u003e1.572\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e0.823-3.003\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 82px;\"\u003e\n \u003cp\u003e0.171\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"5\" rowspan=\"7\" valign=\"top\" style=\"width: 216px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 150px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eSex\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 80px;\"\u003e\n \u003cp\u003e1.202\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e0.629-2.297\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 82px;\"\u003e\n \u003cp\u003e0.577\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"4\" valign=\"top\" style=\"width: 388px;\"\u003e\n \u003cp\u003e\u003cstrong\u003epT category\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 150px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eT1\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" valign=\"top\" style=\"width: 238px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 150px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eT2\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 80px;\"\u003e\n \u003cp\u003e0.935\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e0.403-2.171\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 82px;\"\u003e\n \u003cp\u003e0.876\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 150px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eT3\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 80px;\"\u003e\n \u003cp\u003e1.045\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e0.317-3.450\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 82px;\"\u003e\n \u003cp\u003e0.942\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 150px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eT4a\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 80px;\"\u003e\n \u003cp\u003e0.639\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e0.253-1.612\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 82px;\"\u003e\n \u003cp\u003e0.343\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"9\" valign=\"top\" style=\"width: 604px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eType of therapy\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 150px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eSurgery only\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" valign=\"top\" style=\"width: 238px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"5\" valign=\"top\" style=\"width: 216px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 150px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eSurgery + adjuvant RCT\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 80px;\"\u003e\n \u003cp\u003e0.759\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e0.327-1.763\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 82px;\"\u003e\n \u003cp\u003e0.521\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 72px;\"\u003e\n \u003cp\u003e0.423\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 72px;\"\u003e\n \u003cp\u003e0.158-1.132\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 72px;\"\u003e\n \u003cp\u003e0.087\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 150px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eSurgery + PORT\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 80px;\"\u003e\n \u003cp\u003e0.504\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e0.240-1.058\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 82px;\"\u003e\n \u003cp\u003e0.050\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 72px;\"\u003e\n \u003cp\u003e0.361\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 72px;\"\u003e\n \u003cp\u003e0.165-0.790\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 72px;\"\u003e\n \u003cp\u003e0.011*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 150px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eGrading\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 80px;\"\u003e\n \u003cp\u003e1.150\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e0.543-2.437\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 82px;\"\u003e\n \u003cp\u003e0.715\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"5\" rowspan=\"4\" valign=\"top\" style=\"width: 216px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 150px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eLymphovascular invasion\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 80px;\"\u003e\n \u003cp\u003e1.063\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e0.536-2.109\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 82px;\"\u003e\n \u003cp\u003e0.861\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 150px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eVascular invasion\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 80px;\"\u003e\n \u003cp\u003e5.542\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e0.680-45.136\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 82px;\"\u003e\n \u003cp\u003e0.110\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 150px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePerineural invasion\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 80px;\"\u003e\n \u003cp\u003e1.1355\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e0.623-2.945\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 82px;\"\u003e\n \u003cp\u003e0.443\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 150px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eResection margin\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 80px;\"\u003e\n \u003cp\u003e9.386\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e2.042-43.136\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 82px;\"\u003e\n \u003cp\u003e0.004*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 72px;\"\u003e\n \u003cp\u003e14.036\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 72px;\"\u003e\n \u003cp\u003e2.886-68.258\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 72px;\"\u003e\n \u003cp\u003e0.001*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eA p value\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was considered statistically significant. Statistically significant differences are marked with an asterisk.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAbbreviations\u003c/strong\u003e: HR \u0026ndash; hazard ratio, CI \u0026ndash; confidence interval, PORT \u0026ndash; postoperative radiotherapy, RCT \u0026ndash; radiochemotherapy, OS \u0026ndash; overall survival.\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"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, head and neck squamous cell carcinoma, neck dissection, lymph node metastases, radiotherapy, radiochemotherapy","lastPublishedDoi":"10.21203/rs.3.rs-6324918/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6324918/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eThe lymph node management of oral squamous cell carcinoma (OSCC) patients with pN1 neck remains a clinical challenge. This study investigates the impact of different treatment modalities \u0026ndash; surgery alone, surgery with postoperative radiotherapy (PORT), and surgery with radiochemotherapy (RCT) \u0026ndash; on recurrence and survival outcomes in OSCC patients with pN1 neck.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eA retrospective cohort study was conducted on 98 patients who underwent tumor resection and neck dissection, with a subset receiving adjuvant therapy, between 2011 and 2020. Clinicopathological characteristics were examined for associations with treatment modality using chi-square test. Kaplan-Meier survival curves for overall survival (OS) and recurrence-free survival (RFS), along with the log-rank test, were employed to assess survival over a 10-year period. The prognostic significance of clinicopathological factors and treatment modalities was evaluated using Cox proportional hazards models.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eThe addition of PORT following surgery significantly reduced the risk of recurrence (OR\u0026thinsp;=\u0026thinsp;0.280, p\u0026thinsp;=\u0026thinsp;0.010) and notably enhanced RFS, particularly at 10 years (p\u0026thinsp;=\u0026thinsp;0.010). PORT was also associated with a statistically significant improvement in 5-year-OS (p\u0026thinsp;=\u0026thinsp;0.031) compared to surgery alone, with a trend toward improved OS at 10 years (p\u0026thinsp;=\u0026thinsp;0.175). In contrast, surgery alone did not yield comparable 10-year survival outcomes. Additionally, the inclusion of RCT did not show a distinct survival advantage over the combination of surgery and PORT.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eOur results indicate that PORT should be considered the standard adjuvant treatment for these patients, as it improves RFS, particularly in the long term, while the addition of chemotherapy does not provide significant additional benefits over PORT alone.\u003c/p\u003e","manuscriptTitle":"Impact of Postoperative Radiotherapy and Radiochemotherapy on Survival Outcomes in Oral Squamous Cell Carcinoma Patients with pN1 Neck","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-04-03 10:51:45","doi":"10.21203/rs.3.rs-6324918/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":"46573961-5a7f-4727-8439-8048e138ddf0","owner":[],"postedDate":"April 3rd, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-07-01T15:38:31+00:00","versionOfRecord":[],"versionCreatedAt":"2025-04-03 10:51:45","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-6324918","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6324918","identity":"rs-6324918","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}