The optimization of delineation mode of oral cavity and combined with dose limit of lip in intensity-modulated radiotherapy for nasopharyngeal carcinoma

The optimization of delineation mode of oral cavity and combined with dose limit of lip in intensity-modulated radiotherapy for nasopharyngeal carcinoma | 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 The optimization of delineation mode of oral cavity and combined with dose limit of lip in intensity-modulated radiotherapy for nasopharyngeal carcinoma Cai Xian He, Zhang rui Ye, Ji Yong Peng, Rong hui Zheng, Rui hao Wang, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-9032761/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 11 You are reading this latest preprint version Abstract Background To compare the dosimetric advantages of different oral cavity contouring methods, with and without lip dose constraint, for reducing oral toxicity in intensity-modulated radiotherapy (IMRT) for nasopharyngeal carcinoma (NPC). Methods Thirty newly diagnosed NPC patients treated with IMRT were retrospectively enrolled. For each patient, two IMRT plans were generated based on either an large oral cavity (LO) or a small oral cavity (SO) contouring approach. The plan offering superior oral protection was identified using paired sample t-tests. A third plan was created by adding lip contouring and dose constraint to the preferred oral contouring method. Oral protection was evaluated using analysis of variance. Results Compared to the SO plan, the LO plan significantly reduced the mean dose to the region of interest (ROI, defined as LO minus SO), lips, hard palate, and dentition (all P < 0.05), confirming LO as the preferred contouring method. The LO + Lip plan, based on the LO contour, further significantly reduced the mean dose to the LO, the ROI, lips, hard palate, and dentition(all P < 0.05). Among the SO, LO, and LO + Lip plans, no statistically significant differences were observed in target coverage or other organs at risk (OARs), except for a minor difference in PCTV2 V100% ( P = 0.045), which remained well above the clinical requirement of 95%. Conclusion In NPC IMRT, LO + Lip can reduce the mean dose to the oral cavity, its substructures (ROI, hard palate, dentition), and lips, thereby achieving enhanced oral protection without compromising target coverage or other OARs. Nasopharyngeal carcinoma Intensity-modulated radiotherapy Oral cavity Lips Dosimetry Figures Figure 1 Figure 2 Background Nasopharyngeal carcinoma (NPC) is a malignant tumor originating from the nasopharyngeal epithelium, exhibiting significant ethnic susceptibility and geographical aggregation, with over 60% of cases occurring in Southeast Asia[ 1 – 3 ]. Radiotherapy is the primary curative treatment for NPC. Intensity-modulated radiotherapy (IMRT), with its high conformality, precisely covers targets while effectively sparing most organs at risk (OARs), making it the mainstream technique. This technology has further evolved into more advanced modalities like volumetric modulated arc therapy (VMAT) and tomotherapy (TOMO)[ 4 ]. However, the multi-field IMRT technique for NPC, which often involves anterior, posterior, and lateral beams, may expose the entire oral cavity to radiation, leading to a series of radiation-related oral toxicities. These include mucositis, ulcers, mucosal infections, pain, sensory disturbances, and long-term effects such as xerostomia, neuropathic pain, radiation caries, and periodontal disease, which severely impact patients' quality of life[ 5 – 8 ]. Therefore, defining a reasonable oral cavity contour and applying appropriate dose constraints are crucial for reducing radiation-induced oral toxicity and improving long-term quality of life in NPC patients. While limiting the mean dose to the oral cavity OAR to 40 Gy is widely accepted[ 9 – 12 ], significant controversy remains regarding its optimal contouring boundaries. Currently, two main contouring approaches exist: the "small oral cavity" (SO) and the "large oral cavity" (LO)[ 13 , 14 ]. Compared to SO, the LO includes additional structures such as the dentition, hard palate, and soft palate. Furthermore, the lips, essential for speech, mastication, and aesthetics[ 15 , 16 ], are excluded from both standard contouring methods. Thus, the optimal strategy for delineating the oral cavity as an OAR—whether the LO or SO approach is superior, and whether separately contouring and constraining the lips provides added benefit—lacks evidence-based answers. This study compares the radiation doses to the oral cavity using LO and SO contouring methods and evaluates the additional benefit of lip contouring with dose constraint, aiming to provide a basis for determining the optimal oral protection strategy in clinical practice. Methods Patients Thirty newly diagnosed NPC patients treated at the Department of Radiation Oncology, Affiliated Cancer Hospital & Institute of Guangzhou Medical University between July 2019 and April 2023 were retrospectively enrolled. All treatment plans were designed by the same medical team using the Monaco 5.11.03 planning system. Inclusion criteria were: (1) pathologically confirmed NPC; (2) primary tumor not invading the oropharynx; (3) no submandibular lymph node metastasis; (4) receiving curative-dose radiotherapy; (5) complete and clear clinical records and simulation CT images. Exclusion criteria included: (1) distant metastasis or recurrence at initial diagnosis; (2) concurrent other primary head and neck tumors; (3) prior history of head and neck radiotherapy or surgery; (4) metallic dental prostheses affecting CT image quality or coexisting oral deformities. The median age was 47 years (range: 25–66), with 21 males and 9 females. According to the UICC/AJCC 8th edition staging system, there were 3 stage I, 9 stage II, 12 stage III, and 6 stage IVa patients. Oral Cavity and Lip OAR Contouring and Dose Constraints To evaluate different oral protection strategies, three planning scenarios were defined: small oral cavity contouring (SO), large oral cavity contouring (LO), and large oral cavity contouring combined with lip constraint (LO+Lip). The SO boundaries were defined with reference to Sun Y et al.[14] and the RTOG 0225 protocol[17], primarily including the tongue body, tongue base, and oral floor. The LO boundaries, referencing Charlotte L. Brouwer et al.[13], extended the SO to include the dentition, hard palate, and soft palate regions. The LO+Lip plan further contoured the lips as an independent OAR. Specific boundaries for all contours are detailed in Table 1 . Illustrations of LO and SO contours are shown in Figure 1 . For dose constraints, both SO and LO followed QUANTEC recommendations[18], with Dmean < 40 Gy. For the lips, not routinely constrained in NPC radiotherapy, a constraint of Dmean < 20 Gy was set based on the Danish Head and Neck Cancer Group guidelines[19]. Table 1. Contouring boundaries for the large oral cavity (LO), small oral cavity (SO), and lips. Cranial Boundary Caudal Boundary Anterior Boundary Posterior Boundary Lateral Boundary LO Mucosa of hard palate and near maxillary bone on imaging Bottom of tongue mucosa and hyoid bone; disappearance of anterior belly of digastric muscle Inner surface of mandible and maxilla; lateral margin of dental alveoli Boundary of soft palate, uvula, and inferior tongue base. Medial border of mandible and maxilla; lateral margin of dental alveoli SO Inferior border of hard palate or soft palate, when tongue mucosa appears The anterior belly of the digastric muscle disappeared Posterior border of mandible or none Palate; oropharynx; palatine tonsil; hyoid bone Medial border of dental alveoli or mandible Lips Hard palate (laterally), anterior nasal spine (midline) Inferior border of dental alveoli, superior border of mandibular body External skin surface Mandibular body, teeth, tongue, air (if present) Depressor anguli oris, buccinator, levator anguli oris muscles LO: large oral cavity contouring with constraint; SO: Small oral cavity contouring with constraint; LO+Lip: large oral cavity contouring combined with lip constraint. Radiotherapy Planning All patients were immobilized with a head-neck-shoulder thermoplastic mask in a supine position and underwent contrast-enhanced CT simulation (slice thickness 2.5–5 mm). Target volumes were contoured by senior radiation oncologists: Gross Tumor Volume of the primary nasopharynx (GTVnx) and involved lymph nodes (GTVnd) were determined based on nasopharyngoscopy, physical examination, and MRI[20]; Clinical Target Volumes (CTVs) were contoured according to the 2018 international consensus guidelines[21]. CTV1 and CTV2 were created by expanding GTV and CTV1 by 5–10 mm, respectively, with adjustments for anatomical barriers. All CTVs were expanded by 3–5 mm to form Planning Target Volumes (PTVs). Prescription doses were: PTV-GTVnx 68–70 Gy, PTV-CTV1 60–62 Gy, PTV-CTV2 50–54 Gy, PTV-GTVnd 66–70 Gy, delivered in 33 fractions. Other OARs were contoured and constrained according to the 2019 international guideline for NPC radiotherapy[22]. For each patient, three plans (SO, LO, LO+Lip) were sequentially designed by the same medical physicist in the Monaco 5.11.03 system. The three plans differed only in the oral cavity/lip contouring and constraints; all other parameters (including target and other OAR contours and constraints, dose prescription, number and direction of IMRT beams, dose calculation algorithm, etc.) were kept identical. A total of 90 plans from 30 patients were generated and reviewed by a senior physician for analysis. Statistical Analysis Data were analyzed using SPSS 27.0. Comparisons between two groups (e.g., LO vs. SO) were performed using paired sample t-tests or Wilcoxon signed-rank tests. Comparisons among the three plans (SO, LO, LO+Lip) were performed using repeated measures analysis of variance (ANOVA) or Friedman's test. A two-sided P -value ≤ 0.05 was considered statistically significant. Results 1.Impact of Different Oral Contouring Modes on Overall Oral Dose For the mean dose to the LO volume, a stepwise decreasing trend was observed across SO, LO, and LO + Lip plans, with means of 39.87 Gy, 39.45 Gy, and 38.68 Gy, respectively ( P = 0.018). Pairwise comparisons showed the LO + Lip plan mean dose was significantly lower than both the LO plan ( P = 0.008) and the SO plan ( P = 0.001), while the difference between LO and SO was not significant ( P > 0.05). Differences in mean lip dose were more pronounced. The mean lip doses for SO, LO, and LO + Lip plans were 25.70 Gy, 24.30 Gy, and 20.70 Gy, respectively ( P < 0.001). Pairwise comparisons revealed statistically significant differences between any two groups ( P < 0.05), indicating the LO + Lip plan provided the optimal lip protection. Details are shown in Table 2 and Fig. 2 . Table 2 Dosimetric parameters for the large oral cavity and lips under different contouring and constraint methods. OAR Plan (Mean ± SD) Parameter(Gy) SO LO LO + Lip Statistic (Z/F) P -value LO Dmean 39.87 ± 1.95 39.45 ± 1.54 38.68 ± 1.69 Z : 8.08 LO vs SO: -0.724 LO vs LO + Lip: 2.861 SO vs LO + Lip: -3.99 0.018 0.469 0.008 0.001 Lips Dmean 25.70 ± 2.59 24.30 ± 2.37 20.70 ± 0.81 F : (1.93,55.96) LO vs SO: LO vs LO + Lip: SO vs LO + Lip: 0.001 0.003 0.001 0.001 LO: large oral cavity contouring with constraint; SO: Small oral cavity contouring with constraint; LO + Lip: large oral cavity contouring combined with lip constraint. Dmean: Mean dose. Z: Friedman test statistic; F: Repeated measures ANOVA statistic. 2.Dose Comparison Analysis of Oral Subregions For oral subregion analysis, the area additionally contoured in LO compared to SO (defined as LO-SO region) was one of the indicators. The results showed that the mean doses to the LO-SO region, dentition, and hard palate decreased across SO, LO, and LO + Lip plans, with statistically significant differences among the three groups (all P 0.05). Details are shown in Table 3 . Table 3 Dosimetric parameters for oral subregions under different contouring and constraint methods. Oral Subregion Parameter(Gy) Plan (Mean ± SD) Statistic (Z/F) P -values SO LO LO + Lip ROI (LO-SO region) Dmean 40.54 ± 2.82 39.63 ± 1.90 37.86 ± 2.35 F : (1.93,55.83) LO vs SO: LO vs LO + Lip: SO vs LO + Lip: 0.001 0.025 0.001 0.001 Small Oral Cavity (Tongue+Base+Oral Floor) Dmean 39.39 ± 1.80 39.48 ± 2.16 39.43 ± 1.96 Z : -1.267 LO vs SO: -0.86 LO vs LO + Lip: 0.18 SO vs LO + Lip: 0.09 0.531 0.39 0.86 0.93 Dentition Dmean 32.83 ± 3.26 31.47 ± 2.33 29.11 ± 2.45 F : (1.99,57.61) LO vs SO: LO vs LO + Lip: SO vs LO + Lip: 0.001 0.009 0.001 0.001 Hard Palate Dmean 46.29 ± 5.45 44.91 ± 5.75 42.68 ± 5.80 Z : 31.20 LO vs SO: -2.49 LO vs LO + Lip: -4.28 SO vs LO + Lip: -4.43 0.001 0.013 0.001 0.001 Soft Palate Dmean 60.94 ± 3.85 61.07 ± 3.16 61.25 ± 3.40 F : (1.75,50.64) LO vs SO: LO vs LO + Lip: SO vs LO + Lip: 0.35 1.00 0.89 0.41 LO, SO, LO + Lip: large oral cavity, small oral cavity, and LO combined with lip constraint, respectively. Dmean: Mean dose. Z: Friedman test statistic; F: Repeated measures ANOVA statistic. 3.Analysis of Radiotherapy Target Dose Except for a minor but statistically significant difference in PCTV2 V100% among the three groups ( P = 0.045), all other target dosimetric parameters were met and showed no significant differences ( P > 0.05). The mean V100% for PCTV2 in all three plans exceeded 99.5%, well above the clinical requirement of > 95%. Details are shown in Table 4 . Table 4 Target coverage, conformity index (CI), and homogeneity index (HI) under different contouring/constraint methods Target Parameter Plan (Mean ± SD) Statistic (Z) P -values LO + Lip LO SO PGTVnx V 100%Dpre V 110%Dpre V D93%Dpre 98.81 ± 1.63 0 ± 0.02 100 ± 0.05 98.56 ± 1.52 0 ± 0.02 100 ± 0.09 98.68 ± 1.41 100 ± 0.01 100 ± 0.04 0.28 1.29 2.25 0.87 0.52 0.33 PGTVnd V 100%Dpre V 110%Dpre V D93%Dpre 99.68 ± 0.97 0 ± 0.01 100 ± 0.00 99.71 ± 1.04 0 ± 0.01 100 ± 0.00 99.71 ± 1.03 0 ± 0.01 100 ± 0.00 1.75 1.21 2.00 0.42 0.55 0.37 PCTV1 V 100%Dpre 98.87 ± 1.01 98.90 ± 1.04 99.08 ± 1.04 0.32 0.85 PCTV2 V 100%Dpre 99.50 ± 1.20 99.57 ± 1.25 99.57 ± 1.06 6.18 0.045 PGTVnx CI HI 0.45 ± 0.18 1.05 ± 0.01 0.45 ± 0.18 1.05 ± 0.01 0.44 ± 0.18 1.05 ± 0.01 0.76 2.38 0.25 0.30 PGTVnd CI HI 0.26 ± 0.18 1.05 ± 0.01 0.25 ± 0.18 1.05 ± 0.01 0.27 ± 0.19 1.05 ± 0.01 2.61 0.55 0.27 0.76 PCTV1 CI HI 0.29 ± 0.15 1.16 ± 0.02 0.31 ± 0.14 1.16 ± 0.02 0.30 ± 0.15 1.16 ± 0.02 0.10 1.24 0.95 0.54 PCTV2 CI HI 0.83 ± 0.25 1.26 ± 0.03 0.82 ± 0.25 1.27 ± 0.03 0.82 ± 0.24 1.26 ± 0.03 1.51 2.58 0.47 0.28 V100%Dpre: Volume percentage receiving ≥ prescription dose; V110%Dpre: Volume percentage receiving ≥ 110% prescription dose; VD93%Dpre: Volume percentage receiving ≥ 93% prescription dose. CI: Conformity Index; HI: Homogeneity Index. 4.Analysis of Dose to Other Organs at Risk No statistically significant differences were observed among the SO, LO, and LO + Lip plans for any evaluated parameter of all other OARs besides the oral cavity and lips (all P > 0.05). Details are shown in Table 5 . Table 5 Dosimetric parameters for other organs at risk. OAR Parameter Plan (Mean ± SD) Statistic (Z/F) P -value LO SO LO + Lip Brainstem + 1-3mm V 60 0 ± 0.03 0 ± 0.02 0 ± 0.07 0.56 0.77 Spinal Cord+5mm V 50 0 ± 0.18 0 ± 0.18 0 ± 0.21 1.20 0.55 Optic Chiasm Dmax 23.14 ± 20.15 26.15 ± 20.13 27.38 ± 19.67 5.4 0.07 Optic Nerves Dmax 17.95 ± 21.82 20.12 ± 22.36 20.80 ± 21.98 3.8 0.15 Temporal Lobes Dmax 57.42 ± 2.20 57.61 ± 2.85 57.65 ± 2.32 (1.71,49.51) 0.66 Eyeballs Dmax 23.72 ± 15.72 24.00 ± 15.20 23.66 ± 15.04 (1.53,44.24) 0.61 Lens Dmax 6.88 ± 4.03 7.09 ± 4.62 6.72 ± 3.83 0.20 0.90 Parotid Glands Dmean 31.24 ± 2.79 31.30 ± 2.74 31.38 ± 2.78 (1.55,44.82) 0.51 Mandible Dmax 38.20 ± 3.11 38.14 ± 3.55 38.13 ± 3.50 (1.90,54.97) 0.93 Temporomandibular Joints Dmax 34.22 ± 7.34 33.87 ± 7.22 34.90 ± 7.08 1.28 0.52 Pituitary Gland Dmax 40.79 ± 16.14 40.81 ± 16.31 43.10 ± 16.18 0.22 0.90 Larynx Dmean 44.32 ± 2.42 44.73 ± 2.45 44.82 ± 2.54 (1.85,53.58) 0.13 Esophagus Dmean 26.30 ± 8.89 26.38 ± 9.20 26.38 ± 9.17 (1.93,55.87) 0.90 Thyroid Gland Dmean 48.67 ± 2.12 49.13 ± 2.17 49.00 ± 2.31 (1.83,53.06) 0.12 Trachea Dmean 39.77 ± 7.25 40.12 ± 7.27 40.85 ± 7.53 0.87 0.65 LO, SO, LO + Lip: large oral cavity, small oral cavity, and LO combined with lip constraint, respectively. Vx: Volume receiving ≥ X Gy. Dmean: Mean dose; Dmax: Maximum dose. Z: Friedman test statistic; F: Repeated measures ANOVA statistic. Discussion This study systematically investigates, for the first time, the impact of different oral cavity OAR contouring strategies and the addition of lip dose constraint on dose distribution in NPC IMRT. The results demonstrate that the large oral cavity (LO) contouring mode offers superior dosimetric protection for extended regions like dentition and hard palate compared to the small oral cavity (SO) mode. Building upon this, combining lip constraint (LO + Lip) further significantly optimizes the dose to the overall oral cavity, lips, and these substructures, without compromising target coverage or protection of other OARs. 1.Dosimetric Advantages of the large Oral Cavity (LO) Contouring Mode Currently, controversy remains regarding the optimal contouring boundaries for the oral cavity OAR. Our findings indicate that while no significant difference was found in the mean dose to the entire LO volume between LO and SO plans ( P = 0.251), the LO plan significantly reduced the dose to the dentition and hard palate—structures included in LO but excluded from SO ( P < 0.05). This aligns with the concept advocated by Charlotte L. Brouwer et al.[ 13 ] that expanded contouring provides more comprehensive protection for functional oral structures. Furthermore, Cavallo et al.[ 23 ] found that a small oral cavity volume receiving high dose is a risk factor for acute xerostomia, indirectly supporting the potential clinical benefit of adopting the LO contour. Notably, the soft palate dose showed no difference among the three groups, likely because its proximity to high-dose targets dictates its coverage, suggesting that contouring adjustments alone have limited protective effect for subregions immediately adjacent to targets. 2.Synergistic Effect of Combining Lip Constraint The lips are not only crucial for appearance and function but their submucosa contains abundant minor salivary glands related to radiation-induced xerostomia, yet they are often not systematically protected. Currently, only the Danish Head and Neck Cancer Group has proposed a lip dose constraint standard[ 19 ]. In this study, referencing this standard, the lips were contoured as an OAR with a constraint of Dmean < 20 Gy. The results showed a clear decreasing trend in mean lip dose (Dmean) across SO, LO, and LO + Lip plans ( P < 0.001), with the LO + Lip plan significantly reducing the mean lip dose to 20.70 Gy, a reduction of approximately 20%. More importantly, the LO + Lip plan, compared to either the LO or SO plan, not only protected the lips but also further reduced the dose to the overall oral cavity, dentition, and hard palate ( P < 0.05). Additionally, the LO + Lip plan reduced the mean dentition dose to 29.11 Gy, significantly below the reported average dose threshold of 35.80 Gy associated with radiation caries risk[ 24 ], providing a dosimetric basis for reducing long-term complication risks. 3.Impact on Target Coverage and Dose to Other OARs Protecting normal tissues in radiotherapy must not compromise target coverage or significantly increase dose to other critical organs. Our results show that the SO, LO, and LO + Lip plans exhibited no statistically significant differences in coverage, homogeneity, or conformity indices for the vast majority of targets. The only observed difference was a minimal decrease in PCTV2 V100% for the LO + Lip group (mean 99.50% vs. 99.57% for LO/SO), which, while statistically significant ( P = 0.045), had an absolute reduction of only 0.07% and remained well above the 95% clinical acceptability threshold. This minor change may be related to the posterior boundary of the oral cavity (including soft palate) being close to PCTV2, but its clinical impact is negligible. Simultaneously, the doses to all other OARs showed no differences among the three groups (all P > 0.05), demonstrating that the LO + Lip dose optimization was confined to the oral region and did not shift risk to other important organs. This study has several limitations. First, it is a single-center retrospective dosimetric study with a relatively small sample size and lacks clinical toxicity correlation. Second, the study is limited to IMRT; its applicability to newer techniques like VMAT, tomotherapy, or proton therapy requires further validation. Finally, treatment plans were generated using the Monaco planning system; generalizability to other planning systems needs further investigation. Conclusion In NPC IMRT, the large oral cavity (LO) contouring mode is more reasonable than the small oral cavity (SO) mode. Combining this with lip dose constraint (LO + Lip) provides enhanced protection for the oral cavity and lips without substantially affecting target coverage or the protection of other organs at risk. Abbreviations IMRT: intensity modulated radiation therapy; NPC: Nasopharyngeal carcinoma; LO: large oral cavity contouring with constraint; SO: Small oral cavity contouring with constraint; OAR: oragn at risk; VMAT: Volume Intensity Modulated Radiotherapy; TOMO: Tomotherapy; CT: Computed Tomography; UICC: The Union for International Cancer Control ; AJCC: American Joint Committee On Cancer; RTOG: The Radiation Therapy Oncology Group; QUANTEC : quantitative analyses of normal tissue effects in the clinic; DAHANCA : Danish head and neck cancer association; GTV: gross tumour volume ; CTV1: clinical tumour volume 1; CTV2 : clinical tumour volume 2; ROI: region of interest ; DVH: Dose-Volume Histogram; Vx: Volume receiving ≥ X Gy; Dmean: Mean dose; Dmax: Maximum dose; Z: Friedman test statistic; F: Repeated measures ANOVA statistic; V100%Dpre: Volume percentage receiving ≥ prescription dose; V110%Dpre: Volume percentage receiving ≥ 110% prescription dose; VD93%Dpre: Volume percentage receiving ≥ 93% prescription dose; CI: Conformity Index; HI: Homogeneity Index. Declarations Ethics approval and consent to participate This study was performed in accordance with the Declaration of Helsinki. Ethical approval was obtained from the Ethnics Committee of the Affiliated Cancer Hospital & Institute of Guangzhou Medical University(No.GYZL-ZN-2023(047)). Written informed consent was acquired from all participants. Consent for publication All authors consent to the publication of this manuscript in BMC oral health. Availability of data and materials The data that support the findings of this study are available from the corresponding author upon reasonable request. Competing Interest Not applicable. Funding Not applicable. Authors' contributions Caixian He: Data acquisition, data analysis and interpretation, statistical analysis, manuscript preparation, manuscript editing and manuscript review; Zhangrui Ye: Data acquisition, data analysis, manuscript preparation, manuscript editing and manuscript review; Jiyong peng: Data acquisition, data analysis, manuscript preparation, manuscript editing and manuscript review; Ronghui Zheng: Study concepts, study design and manuscript review; Ruihao Wang: Study concepts, study design and manuscript review; Kai Liao: Study concepts, study design and manuscript review. Acknowledgements Not applicable. References Su ZY, Siak PY, Lwin YY, Cheah SC. Epidemiology of nasopharyngeal carcinoma: current insights and future outlook. Cancer Metastasis Rev. 2024;43(3):919-939. Bray F, Laversanne M, Sung H, et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2024;74(3):229-263. 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Yang J, Yang L, Han Q, et al. The dose limits of teeth protection for patients with nasopharyngeal carcinoma undergoing radiotherapy based on the early oral health-related quality of life. Open Med (Wars). 2023;18(1):20230673. Additional Declarations No competing interests reported. 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China","correspondingAuthor":false,"prefix":"","firstName":"Cai","middleName":"Xian","lastName":"He","suffix":""},{"id":623929510,"identity":"c32b2d75-6852-4400-b4a7-f38a962e4fd2","order_by":1,"name":"Zhang rui Ye","email":"","orcid":"","institution":"Department of Radiation Oncology, Affiliated Cancer Hospital \u0026 Institute of Guangzhou Medical University, Guangzhou, 510090, Guangdong, P. R. China","correspondingAuthor":false,"prefix":"","firstName":"Zhang","middleName":"rui","lastName":"Ye","suffix":""},{"id":623929511,"identity":"06c126fa-f146-4ec5-8075-766c0ce3aa97","order_by":2,"name":"Ji Yong Peng","email":"","orcid":"","institution":"Department of Radiation Oncology, Affiliated Cancer Hospital \u0026 Institute of Guangzhou Medical University, Guangzhou, 510090, Guangdong, P. R. China","correspondingAuthor":false,"prefix":"","firstName":"Ji","middleName":"Yong","lastName":"Peng","suffix":""},{"id":623929512,"identity":"130d6944-2a5b-4e1a-a73c-822f6b419afb","order_by":3,"name":"Rong hui Zheng","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABDElEQVRIiWNgGAWjYDACCSTGgQ8MDAlgDg+xWg7OIFkLMw8xWuRnNx97+HWPTZ58dI/hYZtfdXm6MxIYH7xtY5A3x6GFcc6xdGOZZ2nFhnfOGBzO7WMrNruRwGw4t43BcGcDdi3MEjlm0hIHDidunJED1NLDk7jtRgKbNG8bQ4LBAexa2CTyvyG0WPZIgLSw/8anhUcih03yA1DLfAmgFoYfBmBbmPFpkZBIM5NmOJCWuEEireBgb0NC4rYzD5sl55yTMNyAQ4v8jORnkj8O2CTOn5G8+cOPP3WJ244nH/zwpsxGHpct4CAAxQJYAWMbiM/YwIAUX1gB4w+QdSB1DH/wKhwFo2AUjIIRCgAIPmKtxpAvlQAAAABJRU5ErkJggg==","orcid":"","institution":"Department of Radiation Oncology, Affiliated Cancer Hospital \u0026 Institute of Guangzhou Medical University, Guangzhou, 510090, Guangdong, P. R. China","correspondingAuthor":true,"prefix":"","firstName":"Rong","middleName":"hui","lastName":"Zheng","suffix":""},{"id":623929513,"identity":"83a8ac47-8a36-432c-af91-184918cb704c","order_by":4,"name":"Rui hao Wang","email":"","orcid":"","institution":"Department of Radiation Oncology, Affiliated Cancer Hospital \u0026 Institute of Guangzhou Medical University, Guangzhou, 510090, Guangdong, P. R. China","correspondingAuthor":false,"prefix":"","firstName":"Rui","middleName":"hao","lastName":"Wang","suffix":""},{"id":623929514,"identity":"d8731340-0267-4b17-8f69-e5822964d888","order_by":5,"name":"Kai Liao","email":"","orcid":"","institution":"Department of Radiation Oncology, Affiliated Cancer Hospital \u0026 Institute of Guangzhou Medical University, Guangzhou, 510090, Guangdong, P. R. China","correspondingAuthor":false,"prefix":"","firstName":"Kai","middleName":"","lastName":"Liao","suffix":""}],"badges":[],"createdAt":"2026-03-04 17:23:16","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-9032761/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-9032761/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":107617835,"identity":"a27c9c0f-c47f-4e15-a0f3-3bc9c78c9408","added_by":"auto","created_at":"2026-04-23 09:22:49","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":545301,"visible":true,"origin":"","legend":"\u003cp\u003eSchematic diagram of different oral cavity contouring modes. (A) Green shading: large oral cavity (LO) in sagittal view; (B) Purple shading: small oral cavity (SO) in sagittal view.\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-9032761/v1/1145f25d1782271b0bcf94e1.png"},{"id":107707134,"identity":"7755189a-fe22-449f-bb8c-067daafe869e","added_by":"auto","created_at":"2026-04-24 09:19:35","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":630075,"visible":true,"origin":"","legend":"\u003cp\u003eDosimetric parameters for the three contouring/constraint plans. SO: Small oral cavity; LO: large oral cavity; LO+Lip: large oral cavity + lips.\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-9032761/v1/a8f589b19007878af1441fde.png"},{"id":107709097,"identity":"479271ef-0a01-47f0-9308-fb35bd9e0577","added_by":"auto","created_at":"2026-04-24 09:34:48","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1934576,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-9032761/v1/2a3fbb3a-1d7e-40a0-86bb-5705361217e3.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"The optimization of delineation mode of oral cavity and combined with dose limit of lip in intensity-modulated radiotherapy for nasopharyngeal carcinoma","fulltext":[{"header":"Background","content":"\u003cp\u003eNasopharyngeal carcinoma (NPC) is a malignant tumor originating from the nasopharyngeal epithelium, exhibiting significant ethnic susceptibility and geographical aggregation, with over 60% of cases occurring in Southeast Asia[\u003cspan additionalcitationids=\"CR2\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Radiotherapy is the primary curative treatment for NPC. Intensity-modulated radiotherapy (IMRT), with its high conformality, precisely covers targets while effectively sparing most organs at risk (OARs), making it the mainstream technique. This technology has further evolved into more advanced modalities like volumetric modulated arc therapy (VMAT) and tomotherapy (TOMO)[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e].\u003c/p\u003e \u003cp\u003e However, the multi-field IMRT technique for NPC, which often involves anterior, posterior, and lateral beams, may expose the entire oral cavity to radiation, leading to a series of radiation-related oral toxicities. These include mucositis, ulcers, mucosal infections, pain, sensory disturbances, and long-term effects such as xerostomia, neuropathic pain, radiation caries, and periodontal disease, which severely impact patients' quality of life[\u003cspan additionalcitationids=\"CR6 CR7\" citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. Therefore, defining a reasonable oral cavity contour and applying appropriate dose constraints are crucial for reducing radiation-induced oral toxicity and improving long-term quality of life in NPC patients. While limiting the mean dose to the oral cavity OAR to 40 Gy is widely accepted[\u003cspan additionalcitationids=\"CR10 CR11\" citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e], significant controversy remains regarding its optimal contouring boundaries. Currently, two main contouring approaches exist: the \"small oral cavity\" (SO) and the \"large oral cavity\" (LO)[\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. Compared to SO, the LO includes additional structures such as the dentition, hard palate, and soft palate. Furthermore, the lips, essential for speech, mastication, and aesthetics[\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e], are excluded from both standard contouring methods.\u003c/p\u003e \u003cp\u003e Thus, the optimal strategy for delineating the oral cavity as an OAR\u0026mdash;whether the LO or SO approach is superior, and whether separately contouring and constraining the lips provides added benefit\u0026mdash;lacks evidence-based answers. This study compares the radiation doses to the oral cavity using LO and SO contouring methods and evaluates the additional benefit of lip contouring with dose constraint, aiming to provide a basis for determining the optimal oral protection strategy in clinical practice.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003e\u003cstrong\u003ePatients\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThirty newly diagnosed NPC patients treated at the Department of Radiation Oncology, Affiliated Cancer Hospital \u0026amp; Institute of Guangzhou Medical University between July 2019 and April 2023 were retrospectively enrolled. All treatment plans were designed by the same medical team using the Monaco 5.11.03 planning system. Inclusion criteria were: (1) pathologically confirmed NPC; (2) primary tumor not invading the oropharynx; (3) no submandibular lymph node metastasis; (4) receiving curative-dose radiotherapy; (5) complete and clear clinical records and simulation CT images. Exclusion criteria included: (1) distant metastasis or recurrence at initial diagnosis; (2) concurrent other primary head and neck tumors; (3) prior history of head and neck radiotherapy or surgery; (4) metallic dental prostheses affecting CT image quality or coexisting oral deformities. The median age was 47 years (range: 25\u0026ndash;66), with 21 males and 9 females. According to the UICC/AJCC 8th edition staging system, there were 3 stage I, 9 stage II, 12 stage III, and 6 stage IVa patients.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eOral Cavity and Lip OAR Contouring and Dose Constraints\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eTo evaluate different oral protection strategies, three planning scenarios were defined: small oral cavity contouring (SO), large oral cavity contouring (LO), and large oral cavity contouring combined with lip constraint (LO+Lip). The SO boundaries were defined with reference to Sun Y et al.[14] and the RTOG 0225 protocol[17], primarily including the tongue body, tongue base, and oral floor. The LO boundaries, referencing Charlotte L. Brouwer et al.[13], extended the SO to include the dentition, hard palate, and soft palate regions. The LO+Lip plan further contoured the lips as an independent OAR. Specific boundaries for all contours are detailed in \u003cstrong\u003eTable 1\u003c/strong\u003e. Illustrations of LO and SO contours are shown in \u003cstrong\u003eFigure 1\u003c/strong\u003e.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eFor dose constraints, both SO and LO followed QUANTEC recommendations[18], with Dmean \u0026lt; 40 Gy. For the lips, not routinely constrained in NPC radiotherapy, a constraint of Dmean \u0026lt; 20 Gy was set based on the Danish Head and Neck Cancer Group guidelines[19].\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 1.\u0026nbsp;\u003c/strong\u003eContouring boundaries for the large oral cavity (LO), small oral cavity (SO), and lips.\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 45px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 128px;\"\u003e\n \u003cp\u003eCranial Boundary\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 118px;\"\u003e\n \u003cp\u003eCaudal Boundary\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 92px;\"\u003e\n \u003cp\u003eAnterior Boundary\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp\u003ePosterior Boundary\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 92px;\"\u003e\n \u003cp\u003eLateral Boundary\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 45px;\"\u003e\n \u003cp\u003eLO\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 128px;\"\u003e\n \u003cp\u003eMucosa of hard palate and near maxillary bone on imaging\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 118px;\"\u003e\n \u003cp\u003eBottom of tongue mucosa and hyoid bone; disappearance of anterior belly of digastric muscle\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 92px;\"\u003e\n \u003cp\u003eInner surface of mandible and maxilla; lateral margin of dental alveoli\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp\u003eBoundary of soft palate, uvula, and inferior tongue base.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 92px;\"\u003e\n \u003cp\u003eMedial border of mandible and maxilla; lateral margin of dental alveoli\u003c/p\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: 45px;\"\u003e\n \u003cp\u003eSO\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 128px;\"\u003e\n \u003cp\u003eInferior border of hard palate or soft palate, when tongue mucosa appears\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 118px;\"\u003e\n \u003cp\u003eThe anterior belly of the digastric muscle disappeared\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 92px;\"\u003e\n \u003cp\u003ePosterior border of mandible or none\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp\u003ePalate; oropharynx; palatine tonsil; hyoid bone\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 92px;\"\u003e\n \u003cp\u003eMedial border of dental alveoli or mandible\u003c/p\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: 45px;\"\u003e\n \u003cp\u003eLips\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 128px;\"\u003e\n \u003cp\u003eHard palate (laterally), anterior nasal spine (midline)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 118px;\"\u003e\n \u003cp\u003eInferior border of dental alveoli, superior border of mandibular body\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 92px;\"\u003e\n \u003cp\u003eExternal skin surface\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp\u003eMandibular body, teeth, tongue, air (if present)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 92px;\"\u003e\n \u003cp\u003eDepressor anguli oris, buccinator, levator anguli oris muscles\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"6\" valign=\"top\" style=\"width: 567px;\"\u003e\n \u003cp\u003eLO: large oral cavity contouring with constraint; SO: Small oral cavity contouring with constraint; LO+Lip: large oral cavity contouring combined with lip constraint.\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 1px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cstrong\u003eRadiotherapy Planning\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll patients were immobilized with a head-neck-shoulder thermoplastic mask in a supine position and underwent contrast-enhanced CT simulation (slice thickness 2.5\u0026ndash;5 mm). Target volumes were contoured by senior radiation oncologists: Gross Tumor Volume of the primary nasopharynx (GTVnx) and involved lymph nodes (GTVnd) were determined based on nasopharyngoscopy, physical examination, and MRI[20]; Clinical Target Volumes (CTVs) were contoured according to the 2018 international consensus guidelines[21]. CTV1 and CTV2 were created by expanding GTV and CTV1 by 5\u0026ndash;10 mm, respectively, with adjustments for anatomical barriers. All CTVs were expanded by 3\u0026ndash;5 mm to form Planning Target Volumes (PTVs). Prescription doses were: PTV-GTVnx 68\u0026ndash;70 Gy, PTV-CTV1 60\u0026ndash;62 Gy, PTV-CTV2 50\u0026ndash;54 Gy, PTV-GTVnd 66\u0026ndash;70 Gy, delivered in 33 fractions. Other OARs were contoured and constrained according to the 2019 international guideline for NPC radiotherapy[22].\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eFor each patient, three plans (SO, LO, LO+Lip) were sequentially designed by the same medical physicist in the Monaco 5.11.03 system. The three plans differed only in the oral cavity/lip contouring and constraints; all other parameters (including target and other OAR contours and constraints, dose prescription, number and direction of IMRT beams, dose calculation algorithm, etc.) were kept identical. A total of 90 plans from 30 patients were generated and reviewed by a senior physician for analysis.\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStatistical Analysis\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eData were analyzed using SPSS 27.0. Comparisons between two groups (e.g., LO vs. SO) were performed using paired sample t-tests or Wilcoxon signed-rank tests. Comparisons among the three plans (SO, LO, LO+Lip) were performed using repeated measures analysis of variance (ANOVA) or Friedman\u0026apos;s test. A two-sided \u003cstrong\u003e\u003cem\u003eP\u003c/em\u003e\u003c/strong\u003e-value \u0026le; 0.05 was considered statistically significant.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003e\u003cstrong\u003e1.Impact of Different Oral Contouring Modes on Overall Oral Dose\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eFor the mean dose to the LO volume, a stepwise decreasing trend was observed across SO, LO, and LO\u0026thinsp;+\u0026thinsp;Lip plans, with means of 39.87 Gy, 39.45 Gy, and 38.68 Gy, respectively (\u003cstrong\u003eP\u003c/strong\u003e\u0026thinsp;=\u0026thinsp;0.018). Pairwise comparisons showed the LO\u0026thinsp;+\u0026thinsp;Lip plan mean dose was significantly lower than both the LO plan (\u003cstrong\u003eP\u003c/strong\u003e\u0026thinsp;=\u0026thinsp;0.008) and the SO plan (\u003cstrong\u003eP\u003c/strong\u003e\u0026thinsp;=\u0026thinsp;0.001), while the difference between LO and SO was not significant (\u003cstrong\u003eP\u003c/strong\u003e\u0026thinsp;\u0026gt;\u0026thinsp;0.05).\u003c/p\u003e\n\u003cp\u003eDifferences in mean lip dose were more pronounced. The mean lip doses for SO, LO, and LO\u0026thinsp;+\u0026thinsp;Lip plans were 25.70 Gy, 24.30 Gy, and 20.70 Gy, respectively (\u003cstrong\u003eP\u003c/strong\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Pairwise comparisons revealed statistically significant differences between any two groups (\u003cstrong\u003eP\u003c/strong\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05), indicating the LO\u0026thinsp;+\u0026thinsp;Lip plan provided the optimal lip protection. Details are shown in Table \u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e\u003cstrong\u003eand\u003c/strong\u003e Fig. \u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e.\u003c/p\u003e\n\u003cp\u003e\u003c/p\u003e\u0026nbsp;\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eDosimetric parameters for the large oral cavity and lips under different contouring and constraint methods.\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003eOAR\u003cbr\u003e\u003c/th\u003e\n \u003cth align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003cbr\u003e\u003c/th\u003e\n \u003cth align=\"left\" colspan=\"4\" nameend=\"c6\" namest=\"c3\"\u003ePlan (Mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD)\u003cbr\u003e\u003c/th\u003e\n \u003cth align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003cbr\u003e\u003c/th\u003e\n \u003cth align=\"left\" colspan=\"2\" nameend=\"c9\" namest=\"c8\"\u003e\u0026nbsp;\u003cbr\u003e\u003c/th\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003cth align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003eParameter(Gy)\u003cbr\u003e\u003c/th\u003e\n \u003cth align=\"left\" colname=\"c4\"\u003eSO\u003cbr\u003e\u003c/th\u003e\n \u003cth align=\"left\" colname=\"c5\"\u003eLO\u003cbr\u003e\u003c/th\u003e\n \u003cth align=\"left\" colname=\"c6\"\u003eLO\u0026thinsp;+\u0026thinsp;Lip\u003cbr\u003e\u003c/th\u003e\n \u003cth align=\"left\" colspan=\"2\" nameend=\"c8\" namest=\"c7\"\u003eStatistic \u003cem\u003e(Z/F)\u003c/em\u003e\u003cbr\u003e\u003c/th\u003e\n \u003cth align=\"left\" colname=\"c9\"\u003e\u003cem\u003eP\u003c/em\u003e-value\u003cbr\u003e\u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colname=\"c1\"\u003eLO\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003eDmean\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c4\"\u003e39.87\u0026thinsp;\u0026plusmn;\u0026thinsp;1.95\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c5\"\u003e39.45\u0026thinsp;\u0026plusmn;\u0026thinsp;1.54\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c6\"\u003e38.68\u0026thinsp;\u0026plusmn;\u0026thinsp;1.69\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\" nameend=\"c8\" namest=\"c7\"\u003e\u003cem\u003eZ\u003c/em\u003e: 8.08\u003cbr\u003eLO vs SO: -0.724\u003cbr\u003eLO vs LO\u0026thinsp;+\u0026thinsp;Lip: 2.861\u003cbr\u003eSO vs LO\u0026thinsp;+\u0026thinsp;Lip: -3.99\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c9\"\u003e\u003cstrong\u003e0.018\u003c/strong\u003e\u003cbr\u003e0.469\u003cbr\u003e\u003cstrong\u003e0.008\u003c/strong\u003e\u003cbr\u003e\u003cstrong\u003e0.001\u003c/strong\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colname=\"c1\"\u003eLips\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003eDmean\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c4\"\u003e25.70\u0026thinsp;\u0026plusmn;\u0026thinsp;2.59\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c5\"\u003e24.30\u0026thinsp;\u0026plusmn;\u0026thinsp;2.37\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c6\"\u003e20.70\u0026thinsp;\u0026plusmn;\u0026thinsp;0.81\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\" nameend=\"c8\" namest=\"c7\"\u003e\u003cem\u003eF\u003c/em\u003e: (1.93,55.96)\u003cbr\u003eLO vs SO:\u003cbr\u003eLO vs LO\u0026thinsp;+\u0026thinsp;Lip:\u003cbr\u003eSO vs LO\u0026thinsp;+\u0026thinsp;Lip:\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c9\"\u003e\u003cstrong\u003e0.001\u003c/strong\u003e\u003cbr\u003e\u003cstrong\u003e0.003\u003c/strong\u003e\u003cbr\u003e\u003cstrong\u003e0.001\u003c/strong\u003e\u003cbr\u003e\u003cstrong\u003e0.001\u003c/strong\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003ctfoot\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"9\"\u003eLO: large oral cavity contouring with constraint; SO: Small oral cavity contouring with constraint; LO\u0026thinsp;+\u0026thinsp;Lip: large oral cavity contouring combined with lip constraint. Dmean: Mean dose. Z: Friedman test statistic; F: Repeated measures ANOVA statistic.\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tfoot\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026nbsp;2.Dose Comparison Analysis of Oral Subregions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eFor oral subregion analysis, the area additionally contoured in LO compared to SO (defined as LO-SO region) was one of the indicators. The results showed that the mean doses to the LO-SO region, dentition, and hard palate decreased across SO, LO, and LO\u0026thinsp;+\u0026thinsp;Lip plans, with statistically significant differences among the three groups (all \u003cstrong\u003eP\u003c/strong\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05). For the core small oral cavity region (tongue and oral floor) and the soft palate, no statistically significant differences in mean dose were observed among the three plans (\u003cstrong\u003eP\u003c/strong\u003e\u0026thinsp;\u0026gt;\u0026thinsp;0.05). Details are shown in Table \u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e.\u003c/p\u003e\n\u003cp\u003e\u003c/p\u003e\u0026nbsp;\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eDosimetric parameters for oral subregions under different contouring and constraint methods.\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003eOral Subregion\u003cbr\u003e\u003c/th\u003e\n \u003cth align=\"left\" colname=\"c2\" morerows=\"1\" rowspan=\"2\"\u003eParameter(Gy)\u003cbr\u003e\u003c/th\u003e\n \u003cth align=\"left\" colspan=\"3\" nameend=\"c5\" namest=\"c3\"\u003ePlan (Mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD)\u003cbr\u003e\u003c/th\u003e\n \u003cth align=\"left\" colname=\"c6\" morerows=\"1\" rowspan=\"2\"\u003eStatistic \u003cem\u003e(Z/F)\u003c/em\u003e\u003cbr\u003e\u003c/th\u003e\n \u003cth align=\"left\" colname=\"c7\" morerows=\"1\" rowspan=\"2\"\u003e\u003cem\u003eP\u003c/em\u003e-values\u003cbr\u003e\u003c/th\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003cth align=\"left\" colname=\"c3\"\u003eSO\u003cbr\u003e\u003c/th\u003e\n \u003cth align=\"left\" colname=\"c4\"\u003eLO\u003cbr\u003e\u003c/th\u003e\n \u003cth align=\"left\" colname=\"c5\"\u003eLO\u0026thinsp;+\u0026thinsp;Lip\u003cbr\u003e\u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colname=\"c1\"\u003eROI\u003cbr\u003e(LO-SO region)\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c2\"\u003eDmean\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c3\"\u003e40.54\u0026thinsp;\u0026plusmn;\u0026thinsp;2.82\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c4\"\u003e39.63\u0026thinsp;\u0026plusmn;\u0026thinsp;1.90\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c5\"\u003e37.86\u0026thinsp;\u0026plusmn;\u0026thinsp;2.35\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c6\"\u003e\u003cem\u003eF\u003c/em\u003e: (1.93,55.83)\u003cbr\u003eLO vs SO:\u003cbr\u003eLO vs LO\u0026thinsp;+\u0026thinsp;Lip:\u003cbr\u003eSO vs LO\u0026thinsp;+\u0026thinsp;Lip:\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c7\"\u003e\u003cstrong\u003e0.001\u003c/strong\u003e\u003cbr\u003e\u003cstrong\u003e0.025\u003c/strong\u003e\u003cbr\u003e\u003cstrong\u003e0.001\u003c/strong\u003e\u003cbr\u003e\u003cstrong\u003e0.001\u003c/strong\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colname=\"c1\"\u003eSmall Oral Cavity (Tongue+Base+Oral Floor)\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c2\"\u003eDmean\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c3\"\u003e39.39\u0026thinsp;\u0026plusmn;\u0026thinsp;1.80\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c4\"\u003e39.48\u0026thinsp;\u0026plusmn;\u0026thinsp;2.16\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c5\"\u003e39.43\u0026thinsp;\u0026plusmn;\u0026thinsp;1.96\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c6\"\u003e\u003cem\u003eZ\u003c/em\u003e: -1.267\u003cbr\u003eLO vs SO: -0.86\u003cbr\u003eLO vs LO\u0026thinsp;+\u0026thinsp;Lip: 0.18\u003cbr\u003eSO vs LO\u0026thinsp;+\u0026thinsp;Lip: 0.09\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c7\"\u003e0.531\u003cbr\u003e0.39\u003cbr\u003e0.86\u003cbr\u003e0.93\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colname=\"c1\"\u003eDentition\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c2\"\u003eDmean\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c3\"\u003e32.83\u0026thinsp;\u0026plusmn;\u0026thinsp;3.26\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c4\"\u003e31.47\u0026thinsp;\u0026plusmn;\u0026thinsp;2.33\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c5\"\u003e29.11\u0026thinsp;\u0026plusmn;\u0026thinsp;2.45\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c6\"\u003e\u003cem\u003eF\u003c/em\u003e: (1.99,57.61)\u003cbr\u003eLO vs SO:\u003cbr\u003eLO vs LO\u0026thinsp;+\u0026thinsp;Lip:\u003cbr\u003eSO vs LO\u0026thinsp;+\u0026thinsp;Lip:\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c7\"\u003e\u003cstrong\u003e0.001\u003c/strong\u003e\u003cbr\u003e\u003cstrong\u003e0.009\u003c/strong\u003e\u003cbr\u003e\u003cstrong\u003e0.001\u003c/strong\u003e\u003cbr\u003e\u003cstrong\u003e0.001\u003c/strong\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colname=\"c1\"\u003eHard Palate\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c2\"\u003eDmean\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c3\"\u003e46.29\u0026thinsp;\u0026plusmn;\u0026thinsp;5.45\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c4\"\u003e44.91\u0026thinsp;\u0026plusmn;\u0026thinsp;5.75\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c5\"\u003e42.68\u0026thinsp;\u0026plusmn;\u0026thinsp;5.80\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c6\"\u003e\u003cem\u003eZ\u003c/em\u003e: 31.20\u003cbr\u003eLO vs SO: -2.49\u003cbr\u003eLO vs LO\u0026thinsp;+\u0026thinsp;Lip: -4.28\u003cbr\u003eSO vs LO\u0026thinsp;+\u0026thinsp;Lip: -4.43\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c7\"\u003e\u003cstrong\u003e0.001\u003c/strong\u003e\u003cbr\u003e\u003cstrong\u003e0.013\u003c/strong\u003e\u003cbr\u003e\u003cstrong\u003e0.001\u003c/strong\u003e\u003cbr\u003e\u003cstrong\u003e0.001\u003c/strong\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colname=\"c1\"\u003eSoft Palate\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c2\"\u003eDmean\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c3\"\u003e60.94\u0026thinsp;\u0026plusmn;\u0026thinsp;3.85\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c4\"\u003e61.07\u0026thinsp;\u0026plusmn;\u0026thinsp;3.16\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c5\"\u003e61.25\u0026thinsp;\u0026plusmn;\u0026thinsp;3.40\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c6\"\u003e\u003cem\u003eF\u003c/em\u003e: (1.75,50.64)\u003cbr\u003eLO vs SO:\u003cbr\u003eLO vs LO\u0026thinsp;+\u0026thinsp;Lip:\u003cbr\u003eSO vs LO\u0026thinsp;+\u0026thinsp;Lip:\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c7\"\u003e0.35\u003cbr\u003e1.00\u003cbr\u003e0.89\u003cbr\u003e0.41\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003c/p\u003e\n\u003cp\u003eLO, SO, LO\u0026thinsp;+\u0026thinsp;Lip: large oral cavity, small oral cavity, and LO combined with lip constraint, respectively. Dmean: Mean dose. Z: Friedman test statistic; F: Repeated measures ANOVA statistic.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e3.Analysis of Radiotherapy Target Dose\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eExcept for a minor but statistically significant difference in PCTV2 V100% among the three groups (\u003cstrong\u003eP\u003c/strong\u003e\u0026thinsp;=\u0026thinsp;0.045), all other target dosimetric parameters were met and showed no significant differences (\u003cstrong\u003eP\u003c/strong\u003e\u0026thinsp;\u0026gt;\u0026thinsp;0.05). The mean V100% for PCTV2 in all three plans exceeded 99.5%, well above the clinical requirement of \u0026gt;\u0026thinsp;95%. Details are shown in Table \u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e.\u003c/p\u003e\n\u003cp\u003e\u003c/p\u003e\u0026nbsp;\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eTarget coverage, conformity index (CI), and homogeneity index (HI) under different contouring/constraint methods\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003eTarget\u003cbr\u003e\u003c/th\u003e\n \u003cth align=\"left\" colname=\"c2\" morerows=\"1\" rowspan=\"2\"\u003eParameter\u003cbr\u003e\u003c/th\u003e\n \u003cth align=\"left\" colspan=\"3\" nameend=\"c5\" namest=\"c3\"\u003ePlan (Mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD)\u003cbr\u003e\u003c/th\u003e\n \u003cth align=\"left\" colname=\"c6\" morerows=\"1\" rowspan=\"2\"\u003eStatistic \u003cem\u003e(Z)\u003c/em\u003e\u003cbr\u003e\u003c/th\u003e\n \u003cth align=\"left\" colname=\"c7\" morerows=\"1\" rowspan=\"2\"\u003e\u003cem\u003eP\u003c/em\u003e-values\u003cbr\u003e\u003c/th\u003e\n \u003cth align=\"left\" colspan=\"1\" nameend=\"c8\" namest=\"c8\"\u003e\u0026nbsp;\u003cbr\u003e\u003c/th\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003cth align=\"left\" colname=\"c3\"\u003eLO\u0026thinsp;+\u0026thinsp;Lip\u003cbr\u003e\u003c/th\u003e\n \u003cth align=\"left\" colname=\"c4\"\u003eLO\u003cbr\u003e\u003c/th\u003e\n \u003cth align=\"left\" colname=\"c5\"\u003eSO\u003cbr\u003e\u003c/th\u003e\n \u003cth align=\"left\" colspan=\"1\" nameend=\"c8\" namest=\"c8\"\u003e\u0026nbsp;\u003cbr\u003e\u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colname=\"c1\"\u003ePGTVnx\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c2\"\u003eV\u003csub\u003e100%Dpre\u003c/sub\u003e\u003cbr\u003eV\u003csub\u003e110%Dpre\u003c/sub\u003e\u003cbr\u003eV\u003csub\u003eD93%Dpre\u003c/sub\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c3\"\u003e98.81\u0026thinsp;\u0026plusmn;\u0026thinsp;1.63\u003cbr\u003e0\u0026thinsp;\u0026plusmn;\u0026thinsp;0.02\u003cbr\u003e100\u0026thinsp;\u0026plusmn;\u0026thinsp;0.05\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c4\"\u003e98.56\u0026thinsp;\u0026plusmn;\u0026thinsp;1.52\u003cbr\u003e0\u0026thinsp;\u0026plusmn;\u0026thinsp;0.02\u003cbr\u003e100\u0026thinsp;\u0026plusmn;\u0026thinsp;0.09\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c5\"\u003e98.68\u0026thinsp;\u0026plusmn;\u0026thinsp;1.41\u003cbr\u003e100\u0026thinsp;\u0026plusmn;\u0026thinsp;0.01\u003cbr\u003e100\u0026thinsp;\u0026plusmn;\u0026thinsp;0.04\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c6\"\u003e0.28\u003cbr\u003e1.29\u003cbr\u003e2.25\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c7\"\u003e0.87\u003cbr\u003e0.52\u003cbr\u003e0.33\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"1\" nameend=\"c8\" namest=\"c8\"\u003e\u0026nbsp;\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colname=\"c1\"\u003ePGTVnd\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c2\"\u003eV\u003csub\u003e100%Dpre\u003c/sub\u003e\u003cbr\u003eV\u003csub\u003e110%Dpre\u003c/sub\u003e\u003cbr\u003eV\u003csub\u003eD93%Dpre\u003c/sub\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c3\"\u003e99.68\u0026thinsp;\u0026plusmn;\u0026thinsp;0.97\u003cbr\u003e0\u0026thinsp;\u0026plusmn;\u0026thinsp;0.01\u003cbr\u003e100\u0026thinsp;\u0026plusmn;\u0026thinsp;0.00\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c4\"\u003e99.71\u0026thinsp;\u0026plusmn;\u0026thinsp;1.04\u003cbr\u003e0\u0026thinsp;\u0026plusmn;\u0026thinsp;0.01\u003cbr\u003e100\u0026thinsp;\u0026plusmn;\u0026thinsp;0.00\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c5\"\u003e99.71\u0026thinsp;\u0026plusmn;\u0026thinsp;1.03\u003cbr\u003e0\u0026thinsp;\u0026plusmn;\u0026thinsp;0.01\u003cbr\u003e100\u0026thinsp;\u0026plusmn;\u0026thinsp;0.00\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c6\"\u003e1.75\u003cbr\u003e1.21\u003cbr\u003e2.00\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c7\"\u003e0.42\u003cbr\u003e0.55\u003cbr\u003e0.37\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"1\" nameend=\"c8\" namest=\"c8\"\u003e\u0026nbsp;\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colname=\"c1\"\u003ePCTV1\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c2\"\u003eV\u003csub\u003e100%Dpre\u003c/sub\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c3\"\u003e98.87\u0026thinsp;\u0026plusmn;\u0026thinsp;1.01\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c4\"\u003e98.90\u0026thinsp;\u0026plusmn;\u0026thinsp;1.04\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c5\"\u003e99.08\u0026thinsp;\u0026plusmn;\u0026thinsp;1.04\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c6\"\u003e0.32\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c7\"\u003e0.85\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"1\" nameend=\"c8\" namest=\"c8\"\u003e\u0026nbsp;\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colname=\"c1\"\u003ePCTV2\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c2\"\u003eV\u003csub\u003e100%Dpre\u003c/sub\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c3\"\u003e99.50\u0026thinsp;\u0026plusmn;\u0026thinsp;1.20\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c4\"\u003e99.57\u0026thinsp;\u0026plusmn;\u0026thinsp;1.25\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c5\"\u003e99.57\u0026thinsp;\u0026plusmn;\u0026thinsp;1.06\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c6\"\u003e6.18\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c7\"\u003e\u003cstrong\u003e0.045\u003c/strong\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"1\" nameend=\"c8\" namest=\"c8\"\u003e\u0026nbsp;\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colname=\"c1\"\u003ePGTVnx\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c2\"\u003eCI\u003cbr\u003eHI\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c3\"\u003e0.45\u0026thinsp;\u0026plusmn;\u0026thinsp;0.18\u003cbr\u003e1.05\u0026thinsp;\u0026plusmn;\u0026thinsp;0.01\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c4\"\u003e0.45\u0026thinsp;\u0026plusmn;\u0026thinsp;0.18\u003cbr\u003e1.05\u0026thinsp;\u0026plusmn;\u0026thinsp;0.01\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c5\"\u003e0.44\u0026thinsp;\u0026plusmn;\u0026thinsp;0.18\u003cbr\u003e1.05\u0026thinsp;\u0026plusmn;\u0026thinsp;0.01\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c6\"\u003e0.76\u003cbr\u003e2.38\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c7\"\u003e0.25\u003cbr\u003e0.30\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"1\" nameend=\"c8\" namest=\"c8\"\u003e\u0026nbsp;\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colname=\"c1\"\u003ePGTVnd\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c2\"\u003eCI\u003cbr\u003eHI\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c3\"\u003e0.26\u0026thinsp;\u0026plusmn;\u0026thinsp;0.18\u003cbr\u003e1.05\u0026thinsp;\u0026plusmn;\u0026thinsp;0.01\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c4\"\u003e0.25\u0026thinsp;\u0026plusmn;\u0026thinsp;0.18\u003cbr\u003e1.05\u0026thinsp;\u0026plusmn;\u0026thinsp;0.01\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c5\"\u003e0.27\u0026thinsp;\u0026plusmn;\u0026thinsp;0.19\u003cbr\u003e1.05\u0026thinsp;\u0026plusmn;\u0026thinsp;0.01\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c6\"\u003e2.61\u003cbr\u003e0.55\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c7\"\u003e0.27\u003cbr\u003e0.76\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"1\" nameend=\"c8\" namest=\"c8\"\u003e\u0026nbsp;\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colname=\"c1\"\u003ePCTV1\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c2\"\u003eCI\u003cbr\u003eHI\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c3\"\u003e0.29\u0026thinsp;\u0026plusmn;\u0026thinsp;0.15\u003cbr\u003e1.16\u0026thinsp;\u0026plusmn;\u0026thinsp;0.02\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c4\"\u003e0.31\u0026thinsp;\u0026plusmn;\u0026thinsp;0.14\u003cbr\u003e1.16\u0026thinsp;\u0026plusmn;\u0026thinsp;0.02\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c5\"\u003e0.30\u0026thinsp;\u0026plusmn;\u0026thinsp;0.15\u003cbr\u003e1.16\u0026thinsp;\u0026plusmn;\u0026thinsp;0.02\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c6\"\u003e0.10\u003cbr\u003e1.24\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c7\"\u003e0.95\u003cbr\u003e0.54\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"1\" nameend=\"c8\" namest=\"c8\"\u003e\u0026nbsp;\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colname=\"c1\"\u003ePCTV2\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c2\"\u003eCI\u003cbr\u003eHI\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c3\"\u003e0.83\u0026thinsp;\u0026plusmn;\u0026thinsp;0.25\u003cbr\u003e1.26\u0026thinsp;\u0026plusmn;\u0026thinsp;0.03\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c4\"\u003e0.82\u0026thinsp;\u0026plusmn;\u0026thinsp;0.25\u003cbr\u003e1.27\u0026thinsp;\u0026plusmn;\u0026thinsp;0.03\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c5\"\u003e0.82\u0026thinsp;\u0026plusmn;\u0026thinsp;0.24\u003cbr\u003e1.26\u0026thinsp;\u0026plusmn;\u0026thinsp;0.03\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c6\"\u003e1.51\u003cbr\u003e2.58\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c7\"\u003e0.47\u003cbr\u003e0.28\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"1\" nameend=\"c8\" namest=\"c8\"\u003e\u0026nbsp;\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003ctfoot\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"8\"\u003eV100%Dpre: Volume percentage receiving\u0026thinsp;\u0026ge;\u0026thinsp;prescription dose; V110%Dpre: Volume percentage receiving\u0026thinsp;\u0026ge;\u0026thinsp;110% prescription dose; VD93%Dpre: Volume percentage receiving\u0026thinsp;\u0026ge;\u0026thinsp;93% prescription dose. CI: Conformity Index; HI: Homogeneity Index.\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tfoot\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e4.Analysis of Dose to Other Organs at Risk\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNo statistically significant differences were observed among the SO, LO, and LO\u0026thinsp;+\u0026thinsp;Lip plans for any evaluated parameter of all other OARs besides the oral cavity and lips (all \u003cstrong\u003eP\u003c/strong\u003e\u0026thinsp;\u0026gt;\u0026thinsp;0.05). Details are shown in Table \u003cspan refid=\"Tab5\" class=\"InternalRef\"\u003e5\u003c/span\u003e.\u003c/p\u003e\n\u003cp\u003e\u003c/p\u003e\u0026nbsp;\u003ctable float=\"Yes\" id=\"Tab5\" border=\"1\" class=\"fr-table-selection-hover\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 5\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eDosimetric parameters for other organs at risk.\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003eOAR\u003cbr\u003e\u003c/th\u003e\n \u003cth align=\"left\" colname=\"c2\" morerows=\"1\" rowspan=\"2\"\u003eParameter\u003cbr\u003e\u003c/th\u003e\n \u003cth align=\"left\" colspan=\"3\" nameend=\"c5\" namest=\"c3\"\u003ePlan (Mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD)\u003cbr\u003e\u003c/th\u003e\n \u003cth align=\"left\" colname=\"c6\" morerows=\"1\" rowspan=\"2\"\u003eStatistic \u003cem\u003e(Z/F)\u003c/em\u003e\u003cbr\u003e\u003c/th\u003e\n \u003cth align=\"left\" colname=\"c7\" morerows=\"1\" rowspan=\"2\"\u003e\u003cem\u003eP\u003c/em\u003e-value\u003cbr\u003e\u003c/th\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003cth align=\"left\" colname=\"c3\"\u003eLO\u003cbr\u003e\u003c/th\u003e\n \u003cth align=\"left\" colname=\"c4\"\u003eSO\u003cbr\u003e\u003c/th\u003e\n \u003cth align=\"left\" colname=\"c5\"\u003eLO\u0026thinsp;+\u0026thinsp;Lip\u003cbr\u003e\u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colname=\"c1\"\u003eBrainstem\u0026thinsp;+\u0026thinsp;1-3mm\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c2\"\u003eV\u003csub\u003e60\u003c/sub\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c3\"\u003e0\u0026thinsp;\u0026plusmn;\u0026thinsp;0.03\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c4\"\u003e0\u0026thinsp;\u0026plusmn;\u0026thinsp;0.02\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c5\"\u003e0\u0026thinsp;\u0026plusmn;\u0026thinsp;0.07\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c6\"\u003e0.56\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c7\"\u003e0.77\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colname=\"c1\"\u003eSpinal Cord+5mm\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c2\"\u003eV\u003csub\u003e50\u003c/sub\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c3\"\u003e0\u0026thinsp;\u0026plusmn;\u0026thinsp;0.18\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c4\"\u003e0\u0026thinsp;\u0026plusmn;\u0026thinsp;0.18\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c5\"\u003e0\u0026thinsp;\u0026plusmn;\u0026thinsp;0.21\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c6\"\u003e1.20\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c7\"\u003e0.55\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colname=\"c1\"\u003eOptic Chiasm\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c2\"\u003eDmax\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c3\"\u003e23.14\u0026thinsp;\u0026plusmn;\u0026thinsp;20.15\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c4\"\u003e26.15\u0026thinsp;\u0026plusmn;\u0026thinsp;20.13\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c5\"\u003e27.38\u0026thinsp;\u0026plusmn;\u0026thinsp;19.67\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c6\"\u003e5.4\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c7\"\u003e0.07\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colname=\"c1\"\u003eOptic Nerves\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c2\"\u003eDmax\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c3\"\u003e17.95\u0026thinsp;\u0026plusmn;\u0026thinsp;21.82\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c4\"\u003e20.12\u0026thinsp;\u0026plusmn;\u0026thinsp;22.36\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c5\"\u003e20.80\u0026thinsp;\u0026plusmn;\u0026thinsp;21.98\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c6\"\u003e3.8\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c7\"\u003e0.15\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colname=\"c1\"\u003eTemporal Lobes\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c2\"\u003eDmax\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c3\"\u003e57.42\u0026thinsp;\u0026plusmn;\u0026thinsp;2.20\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c4\"\u003e57.61\u0026thinsp;\u0026plusmn;\u0026thinsp;2.85\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c5\"\u003e57.65\u0026thinsp;\u0026plusmn;\u0026thinsp;2.32\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c6\"\u003e(1.71,49.51)\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c7\"\u003e0.66\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colname=\"c1\"\u003eEyeballs\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c2\"\u003eDmax\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c3\"\u003e23.72\u0026thinsp;\u0026plusmn;\u0026thinsp;15.72\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c4\"\u003e24.00\u0026thinsp;\u0026plusmn;\u0026thinsp;15.20\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c5\"\u003e23.66\u0026thinsp;\u0026plusmn;\u0026thinsp;15.04\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c6\"\u003e(1.53,44.24)\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c7\"\u003e0.61\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colname=\"c1\"\u003eLens\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c2\"\u003eDmax\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c3\"\u003e6.88\u0026thinsp;\u0026plusmn;\u0026thinsp;4.03\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c4\"\u003e7.09\u0026thinsp;\u0026plusmn;\u0026thinsp;4.62\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c5\"\u003e6.72\u0026thinsp;\u0026plusmn;\u0026thinsp;3.83\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c6\"\u003e0.20\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c7\"\u003e0.90\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colname=\"c1\"\u003eParotid Glands\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c2\"\u003eDmean\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c3\"\u003e31.24\u0026thinsp;\u0026plusmn;\u0026thinsp;2.79\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c4\"\u003e31.30\u0026thinsp;\u0026plusmn;\u0026thinsp;2.74\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c5\"\u003e31.38\u0026thinsp;\u0026plusmn;\u0026thinsp;2.78\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c6\"\u003e(1.55,44.82)\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c7\"\u003e0.51\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colname=\"c1\"\u003eMandible\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c2\"\u003eDmax\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c3\"\u003e38.20\u0026thinsp;\u0026plusmn;\u0026thinsp;3.11\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c4\"\u003e38.14\u0026thinsp;\u0026plusmn;\u0026thinsp;3.55\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c5\"\u003e38.13\u0026thinsp;\u0026plusmn;\u0026thinsp;3.50\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c6\"\u003e(1.90,54.97)\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c7\"\u003e0.93\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colname=\"c1\"\u003eTemporomandibular Joints\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c2\"\u003eDmax\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c3\"\u003e34.22\u0026thinsp;\u0026plusmn;\u0026thinsp;7.34\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c4\"\u003e33.87\u0026thinsp;\u0026plusmn;\u0026thinsp;7.22\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c5\"\u003e34.90\u0026thinsp;\u0026plusmn;\u0026thinsp;7.08\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c6\"\u003e1.28\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c7\"\u003e0.52\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colname=\"c1\"\u003ePituitary Gland\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c2\"\u003eDmax\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c3\"\u003e40.79\u0026thinsp;\u0026plusmn;\u0026thinsp;16.14\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c4\"\u003e40.81\u0026thinsp;\u0026plusmn;\u0026thinsp;16.31\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c5\"\u003e43.10\u0026thinsp;\u0026plusmn;\u0026thinsp;16.18\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c6\"\u003e0.22\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c7\"\u003e0.90\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colname=\"c1\"\u003eLarynx\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c2\"\u003eDmean\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c3\"\u003e44.32\u0026thinsp;\u0026plusmn;\u0026thinsp;2.42\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c4\"\u003e44.73\u0026thinsp;\u0026plusmn;\u0026thinsp;2.45\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c5\"\u003e44.82\u0026thinsp;\u0026plusmn;\u0026thinsp;2.54\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c6\"\u003e(1.85,53.58)\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c7\"\u003e0.13\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colname=\"c1\"\u003eEsophagus\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c2\"\u003eDmean\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c3\"\u003e26.30\u0026thinsp;\u0026plusmn;\u0026thinsp;8.89\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c4\"\u003e26.38\u0026thinsp;\u0026plusmn;\u0026thinsp;9.20\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c5\"\u003e26.38\u0026thinsp;\u0026plusmn;\u0026thinsp;9.17\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c6\"\u003e(1.93,55.87)\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c7\"\u003e0.90\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colname=\"c1\"\u003eThyroid Gland\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c2\"\u003eDmean\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c3\"\u003e48.67\u0026thinsp;\u0026plusmn;\u0026thinsp;2.12\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c4\"\u003e49.13\u0026thinsp;\u0026plusmn;\u0026thinsp;2.17\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c5\"\u003e49.00\u0026thinsp;\u0026plusmn;\u0026thinsp;2.31\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c6\"\u003e(1.83,53.06)\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c7\"\u003e0.12\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colname=\"c1\"\u003eTrachea\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c2\"\u003eDmean\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c3\"\u003e39.77\u0026thinsp;\u0026plusmn;\u0026thinsp;7.25\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c4\"\u003e40.12\u0026thinsp;\u0026plusmn;\u0026thinsp;7.27\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c5\"\u003e40.85\u0026thinsp;\u0026plusmn;\u0026thinsp;7.53\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c6\"\u003e0.87\u003cbr\u003e\u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c7\"\u003e0.65\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003ctfoot\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"7\"\u003eLO, SO, LO\u0026thinsp;+\u0026thinsp;Lip: large oral cavity, small oral cavity, and LO combined with lip constraint, respectively. Vx: Volume receiving\u0026thinsp;\u0026ge;\u0026thinsp;X Gy. Dmean: Mean dose; Dmax: Maximum dose. Z: Friedman test statistic; F: Repeated measures ANOVA statistic.\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tfoot\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis study systematically investigates, for the first time, the impact of different oral cavity OAR contouring strategies and the addition of lip dose constraint on dose distribution in NPC IMRT. The results demonstrate that the large oral cavity (LO) contouring mode offers superior dosimetric protection for extended regions like dentition and hard palate compared to the small oral cavity (SO) mode. Building upon this, combining lip constraint (LO\u0026thinsp;+\u0026thinsp;Lip) further significantly optimizes the dose to the overall oral cavity, lips, and these substructures, without compromising target coverage or protection of other OARs.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026nbsp;1.Dosimetric Advantages of the large Oral Cavity (LO) Contouring Mode Currently, controversy remains regarding the optimal contouring boundaries for the oral cavity OAR.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eOur findings indicate that while no significant difference was found in the mean dose to the entire LO volume between LO and SO plans (\u003cstrong\u003eP\u003c/strong\u003e\u0026thinsp;=\u0026thinsp;0.251), the LO plan significantly reduced the dose to the dentition and hard palate\u0026mdash;structures included in LO but excluded from SO (\u003cstrong\u003eP\u003c/strong\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05). This aligns with the concept advocated by Charlotte L. Brouwer et al.[\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e] that expanded contouring provides more comprehensive protection for functional oral structures. Furthermore, Cavallo et al.[\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e] found that a small oral cavity volume receiving high dose is a risk factor for acute xerostomia, indirectly supporting the potential clinical benefit of adopting the LO contour. Notably, the soft palate dose showed no difference among the three groups, likely because its proximity to high-dose targets dictates its coverage, suggesting that contouring adjustments alone have limited protective effect for subregions immediately adjacent to targets.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e2.Synergistic Effect of Combining Lip Constraint\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe lips are not only crucial for appearance and function but their submucosa contains abundant minor salivary glands related to radiation-induced xerostomia, yet they are often not systematically protected. Currently, only the Danish Head and Neck Cancer Group has proposed a lip dose constraint standard[\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. In this study, referencing this standard, the lips were contoured as an OAR with a constraint of Dmean\u0026thinsp;\u0026lt;\u0026thinsp;20 Gy. The results showed a clear decreasing trend in mean lip dose (Dmean) across SO, LO, and LO\u0026thinsp;+\u0026thinsp;Lip plans (\u003cstrong\u003eP\u003c/strong\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001), with the LO\u0026thinsp;+\u0026thinsp;Lip plan significantly reducing the mean lip dose to 20.70 Gy, a reduction of approximately 20%. More importantly, the LO\u0026thinsp;+\u0026thinsp;Lip plan, compared to either the LO or SO plan, not only protected the lips but also further reduced the dose to the overall oral cavity, dentition, and hard palate (\u003cstrong\u003eP\u003c/strong\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05). Additionally, the LO\u0026thinsp;+\u0026thinsp;Lip plan reduced the mean dentition dose to 29.11 Gy, significantly below the reported average dose threshold of 35.80 Gy associated with radiation caries risk[\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e], providing a dosimetric basis for reducing long-term complication risks.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e3.Impact on Target Coverage and Dose to Other OARs\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eProtecting normal tissues in radiotherapy must not compromise target coverage or significantly increase dose to other critical organs. Our results show that the SO, LO, and LO\u0026thinsp;+\u0026thinsp;Lip plans exhibited no statistically significant differences in coverage, homogeneity, or conformity indices for the vast majority of targets. The only observed difference was a minimal decrease in PCTV2 V100% for the LO\u0026thinsp;+\u0026thinsp;Lip group (mean 99.50% vs. 99.57% for LO/SO), which, while statistically significant (\u003cstrong\u003eP\u003c/strong\u003e\u0026thinsp;=\u0026thinsp;0.045), had an absolute reduction of only 0.07% and remained well above the 95% clinical acceptability threshold. This minor change may be related to the posterior boundary of the oral cavity (including soft palate) being close to PCTV2, but its clinical impact is negligible. Simultaneously, the doses to all other OARs showed no differences among the three groups (all \u003cstrong\u003eP\u003c/strong\u003e\u0026thinsp;\u0026gt;\u0026thinsp;0.05), demonstrating that the LO\u0026thinsp;+\u0026thinsp;Lip dose optimization was confined to the oral region and did not shift risk to other important organs.\u003c/p\u003e\n\u003cp\u003eThis study has several limitations. First, it is a single-center retrospective dosimetric study with a relatively small sample size and lacks clinical toxicity correlation. Second, the study is limited to IMRT; its applicability to newer techniques like VMAT, tomotherapy, or proton therapy requires further validation. Finally, treatment plans were generated using the Monaco planning system; generalizability to other planning systems needs further investigation.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003e In NPC IMRT, the large oral cavity (LO) contouring mode is more reasonable than the small oral cavity (SO) mode. Combining this with lip dose constraint (LO\u0026thinsp;+\u0026thinsp;Lip) provides enhanced protection for the oral cavity and lips without substantially affecting target coverage or the protection of other organs at risk.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eIMRT: intensity modulated radiation therapy; NPC: Nasopharyngeal carcinoma; LO: large oral cavity contouring with constraint; SO: Small oral cavity contouring with constraint; OAR: oragn at risk; VMAT: Volume Intensity Modulated Radiotherapy; TOMO: Tomotherapy; CT: Computed Tomography; UICC: The Union for International Cancer Control ; AJCC: American Joint Committee On Cancer; RTOG: The Radiation Therapy Oncology Group; QUANTEC : quantitative analyses of normal tissue effects in the clinic; DAHANCA : Danish head and neck cancer association; GTV: gross tumour volume ; CTV1: clinical tumour volume 1; CTV2 : clinical tumour volume 2; ROI: region of interest ; DVH: Dose-Volume Histogram; Vx: Volume receiving \u0026ge; X Gy; Dmean: Mean dose; Dmax: Maximum dose; Z: Friedman test statistic; F: Repeated measures ANOVA statistic; V100%Dpre: Volume percentage receiving \u0026ge; prescription dose; V110%Dpre: Volume percentage receiving \u0026ge; 110% prescription dose; VD93%Dpre: Volume percentage receiving \u0026ge; 93% prescription dose; CI: Conformity Index; HI: Homogeneity Index.\u003c/p\u003e\n\u003cp\u003e\u003cbr\u003e\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was performed in accordance with the Declaration of Helsinki. Ethical approval was obtained from the Ethnics Committee of the Affiliated Cancer Hospital \u0026amp; Institute of Guangzhou Medical University(No.GYZL-ZN-2023(047)). Written informed consent was acquired from all participants.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll authors consent to the publication of this manuscript in BMC oral health.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\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\u003cp\u003e\u003cstrong\u003eCompeting Interest\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026apos; contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eCaixian He: Data acquisition, data analysis and interpretation, statistical analysis, manuscript preparation, manuscript editing and manuscript review; Zhangrui Ye: Data acquisition, data analysis, manuscript preparation, manuscript editing and manuscript review; Jiyong peng: Data acquisition, data analysis, manuscript preparation, manuscript editing and manuscript review; Ronghui Zheng: Study concepts, study design and manuscript review; Ruihao Wang: Study concepts, study design and manuscript review; Kai Liao: Study concepts, study design and manuscript review.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n \u003cli\u003eSu ZY, Siak PY, Lwin YY, Cheah SC. Epidemiology of nasopharyngeal carcinoma: current insights and future outlook. Cancer Metastasis Rev. 2024;43(3):919-939.\u003c/li\u003e\n \u003cli\u003eBray F, Laversanne M, Sung H, et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2024;74(3):229-263.\u003c/li\u003e\n \u003cli\u003eChang ET, Ye W, Zeng YX, Adami HO. The Evolving Epidemiology of Nasopharyngeal Carcinoma. Cancer Epidemiol Biomarkers Prev. 2021;30(6):1035-1047.\u003c/li\u003e\n \u003cli\u003eNg WT, Chow JCH, Beitler JJ, et al. Current Radiotherapy Considerations for Nasopharyngeal Carcinoma. Cancers (Basel). 2022;14(23):5773. Published 2022 Nov 24.\u003c/li\u003e\n \u003cli\u003ePan XB, Liu Y, Huang ST, Pei S, Chen KH, Qu S, Li L, Zhu XD. Dosimetry of Submandibular Glands on Xerostomia for Nasopharyngeal Carcinoma. Front Oncol.2021 Jan 11;10:601403.\u003c/li\u003e\n \u003cli\u003ePalmier NR, Migliorati CA, Prado-Ribeiro AC, et al. Radiation-related caries: current diagnostic, prognostic, and management paradigms. Oral Surg Oral Med Oral Pathol Oral Radiol. 2020;130(1):52-62.\u003c/li\u003e\n \u003cli\u003eGomes-Silva W, Morais-Faria K, Rivera C, et al. Impact of radiation on tooth loss in patients with head and neck cancer: a retrospective dosimetric-based study. Oral Surg Oral Med Oral Pathol Oral Radiol. 2021;132(4):409-417.\u003c/li\u003e\n \u003cli\u003eBergamaschi L, Vincini MG, Zaffaroni M, et al. Management of radiation-induced oral mucositis in head and neck cancer patients: a real-life survey among 25 Italian radiation oncology centers. Support Care Cancer. 2023;32(1):38.\u003c/li\u003e\n \u003cli\u003eWalker MP, Wichman B, Cheng AL, Coster J, Williams KB. Impact of radiotherapy dose on dentition breakdown in head and neck cancer patients. Pract Radiat Oncol. 2011;1(3):142\u0026ndash;8.\u003c/li\u003e\n \u003cli\u003eLee NY, Zhang Q, Pfister DG, et al. Addition of bevacizumab to standard chemoradiation for locoregionally advanced nasopharyngeal carcinoma (RTOG 0615): A phase 2 multi-institutional trial. Lancet Oncol 2012; 13:172-180.\u003c/li\u003e\n \u003cli\u003eNRG-HN001: Randomized phase II and phase III studies of individualized treatment for nasopharyngeal carcinoma based on biomarker Epstein Barr virus (EBV) deoxyribonucleic acid (DNA). Accessed October 20, 2018.\u003c/li\u003e\n \u003cli\u003eNg WT, Ngan RK, Chan SH, et al. Management of nasopharyngeal carcinoma. Bernier J, editor. Head and Neck Cancer - Multimodality Management. 2nd ed. Switzerland: Springer; 2016.\u003c/li\u003e\n \u003cli\u003eCharlotte L. Brouwer et al. CT-based delineation of organs at risk in the head and neck region: DAHANCA, EORTC, GORTEC, HKNPCSG, NCIC CTG, NCRI, NRG Oncology and TROG consensus guidelines. Radiotherapy and Oncology, 2015;117: 83-90.\u003c/li\u003e\n \u003cli\u003eSun Y, Yu XL, Luo W, et al. Recommendation for a contouring method and atlas of organs at risk in nasopharyngeal carcinoma patients receiving intensity-modulated radiotherapy. Radiother Oncol. 2014;110(3):390-397.\u003c/li\u003e\n \u003cli\u003eSumi M, Yamada T, Takagi Y, et al. MR imaging of labial glands. AJNR Am J Neuroradiol 2007; 28:1552\u0026ndash;6.\u003c/li\u003e\n \u003cli\u003eVan de Water TA, Bijl HP, Westerlaan HE, Langendijk JA. Delineation guidelines for organs at risk involved in radiation-induced salivary dysfunction and xerostomia. Radiother Oncol. 2009 Dec;93(3):545-52.\u003c/li\u003e\n \u003cli\u003eLee N, Harris J, Garden AS, et al. Intensity-modulated radiation therapy with or without chemotherapy for nasopharyngeal carcinoma: radiation therapy oncology group phase II trial 0225. J Clin Oncol. 2009;27(22):3684-3690.\u003c/li\u003e\n \u003cli\u003eBentzen SM, Constine LS, Deasy JO, et al. Quantitative Analyses of Normal Tissue Effects in the Clinic (QUANTEC): an introduction to the scientific issues. Int J Radiat Oncol Biol Phys. 2010;76(3 Suppl):S3-S9.\u003c/li\u003e\n \u003cli\u003eDAHANCA radiotherapy guidelines 2013.Accessed October 20, 2018.\u003c/li\u003e\n \u003cli\u003eGr\u0026eacute;goire V, Eisbruch A, Hamoir M, et al. Proposal for the delineation of the nodal CTV in the node-positive and the post-operative neck[J]. Radiother Oncol, 2006,79(1):15-20.\u003c/li\u003e\n \u003cli\u003eLee AW, Ng WT, Pan JJ, et al. International guideline for the delineation of the clinical target volumes (CTV) for nasopharyngeal carcinoma. Radiother Oncol. 2018;126(1):25-36.\u003c/li\u003e\n \u003cli\u003eLee AW, Ng WT, Pan JJ, et al. International Guideline on Dose Prioritization and Acceptance Criteria in Radiation Therapy Planning for Nasopharyngeal Carcinoma. Int J Radiat Oncol Biol Phys. 2019;105(3):567-580.\u003c/li\u003e\n \u003cli\u003eCavallo A, Iacovelli NA, Facchinetti N, et al. Modelling Radiation-Induced Salivary Dysfunction during IMRT and Chemotherapy for Nasopharyngeal Cancer Patients. Cancers (Basel). 2021;13(16):3983.\u003c/li\u003e\n \u003cli\u003eYang J, Yang L, Han Q, et al. The dose limits of teeth protection for patients with nasopharyngeal carcinoma undergoing radiotherapy based on the early oral health-related quality of life. Open Med (Wars). 2023;18(1):20230673.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"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":"bmc-oral-health","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"ohea","sideBox":"Learn more about [BMC Oral Health](http://bmcoralhealth.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/ohea/default.aspx","title":"BMC Oral Health","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Nasopharyngeal carcinoma, Intensity-modulated radiotherapy, Oral cavity, Lips, Dosimetry","lastPublishedDoi":"10.21203/rs.3.rs-9032761/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-9032761/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003e To compare the dosimetric advantages of different oral cavity contouring methods, with and without lip dose constraint, for reducing oral toxicity in intensity-modulated radiotherapy (IMRT) for nasopharyngeal carcinoma (NPC).\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eThirty newly diagnosed NPC patients treated with IMRT were retrospectively enrolled. For each patient, two IMRT plans were generated based on either an large oral cavity (LO) or a small oral cavity (SO) contouring approach. The plan offering superior oral protection was identified using paired sample t-tests. A third plan was created by adding lip contouring and dose constraint to the preferred oral contouring method. Oral protection was evaluated using analysis of variance.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eCompared to the SO plan, the LO plan significantly reduced the mean dose to the region of interest (ROI, defined as LO minus SO), lips, hard palate, and dentition (all \u003cb\u003eP\u003c/b\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05), confirming LO as the preferred contouring method. The LO\u0026thinsp;+\u0026thinsp;Lip plan, based on the LO contour, further significantly reduced the mean dose to the LO, the ROI, lips, hard palate, and dentition(all \u003cb\u003eP\u003c/b\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05). Among the SO, LO, and LO\u0026thinsp;+\u0026thinsp;Lip plans, no statistically significant differences were observed in target coverage or other organs at risk (OARs), except for a minor difference in PCTV2 V100% (\u003cb\u003eP\u003c/b\u003e\u0026thinsp;=\u0026thinsp;0.045), which remained well above the clinical requirement of 95%.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003e In NPC IMRT, LO\u0026thinsp;+\u0026thinsp;Lip can reduce the mean dose to the oral cavity, its substructures (ROI, hard palate, dentition), and lips, thereby achieving enhanced oral protection without compromising target coverage or other OARs.\u003c/p\u003e","manuscriptTitle":"The optimization of delineation mode of oral cavity and combined with dose limit of lip in intensity-modulated radiotherapy for nasopharyngeal carcinoma","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-04-23 09:22:43","doi":"10.21203/rs.3.rs-9032761/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"reviewerAgreed","content":"238771556534465669505974620614115093491","date":"2026-05-15T01:28:34+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-05-14T09:27:58+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"271945866461362784225745910862821924934","date":"2026-05-12T03:50:28+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"265620890155116684707038086648552275347","date":"2026-05-11T23:25:07+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-04-15T13:13:48+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"100040239818018991967180243445714359479","date":"2026-04-15T09:55:55+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-04-15T08:20:36+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-03-26T17:32:54+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2026-03-16T10:08:42+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-03-12T00:43:25+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Oral Health","date":"2026-03-11T16:48:42+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-oral-health","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"ohea","sideBox":"Learn more about [BMC Oral Health](http://bmcoralhealth.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/ohea/default.aspx","title":"BMC Oral Health","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"c971ee1a-9b40-48d9-9a5b-8eb62062ba99","owner":[],"postedDate":"April 23rd, 2026","published":true,"recentEditorialEvents":[{"type":"reviewerAgreed","content":"238771556534465669505974620614115093491","date":"2026-05-15T01:28:34+00:00","index":59,"fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-05-14T09:27:58+00:00","index":58,"fulltext":""},{"type":"reviewerAgreed","content":"271945866461362784225745910862821924934","date":"2026-05-12T03:50:28+00:00","index":57,"fulltext":""},{"type":"reviewerAgreed","content":"265620890155116684707038086648552275347","date":"2026-05-11T23:25:07+00:00","index":56,"fulltext":""}],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-04-23T09:22:43+00:00","versionOfRecord":[],"versionCreatedAt":"2026-04-23 09:22:43","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-9032761","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-9032761","identity":"rs-9032761","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}