Impact of Offline Adaptive Radiotherapy on Survival and Quality of Life in Locally Advanced Nasopharyngeal Carcinoma: A Propensity-Matched Retrospective Study

Impact of Offline Adaptive Radiotherapy on Survival and Quality of Life in Locally Advanced Nasopharyngeal Carcinoma: A Propensity-Matched Retrospective Study | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Impact of Offline Adaptive Radiotherapy on Survival and Quality of Life in Locally Advanced Nasopharyngeal Carcinoma: A Propensity-Matched Retrospective Study LIU Dongmei, Hongyuan HU, Tong LIU, XIE Siyu, ZHOU Jie, WANG Shuo, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6346006/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract OBJECTIVE The clinical benefits of offline adaptive radiotherapy(ART) in volumetric modulated arc therapy(VMAT) for locally advanced nasopharyngeal carcinoma (LA-NPC), particularly regarding long-term quality of life, are not well-established due to conflicting evidence.This study aims to clarify the clinical value of offline ART in LA-NPC, particularly its effects on long-term patient survival quality. MATERIALS AND METHODS Retrospectively, 355 patients with LA-NPC treated with VMAT between January 2020 and December 2021 were included to optimize between-group comparability by propensity score matching (PSM) and to systematically assess the difference in efficacy and quality of life between ART and VMAT. The primary study endpoints were overall survival (OS) and progression-free survival (PFS), distant metastasis-free survival (DMFS), and local-regional recurrence-free survival (LRFS), and the survival curves were plotted by the Kaplan-Meier method and compared with between-groups differences by the Log-rank test, and the Cox proportional risk model was used to calculate the corrected risk ratio. At the final follow-up, quality of life was assessed using the Chinese version of the European Organization for Research and Treatment of Cancer (EORTC) core quality of life questionnaire QLQ-C30 (v3.0) and the head and neck cancer-specific module QLQ-H&N35 (v1.0). RESULTS After PSM, a total of 254 patients (127 each in the ART and VMAT groups) were included in the final analysis. Survival analysis showed that no statistically significant differences were observed between the two groups in the 3-year primary survival endpoints: 96.7% vs 95.9% (P = 0.764) for OS, 88.2% vs 86.6% (P = 0.835) for PFS, 92.1% vs 92.8% (P = 0.647) for LRFS, and 91.2% vs 88.9% for DMFS (P = 0.540). The ART group exhibited significantly lower xerostomia incidence (19.1 ± 20.7 vs. 31.6 ± 23.0, P < 0.001) and reduced sticky saliva scores (8.83 ± 16.0 vs. 15.5 ± 18.4, P = 0.004) compared to the non-adaptive VMAT group,Moreover, the ART group demonstrated better cognitive function (86.8 ± 13 vs. 82.7 ± 14.7, P = 0.030) and physical function (96.2 ± 9.84 vs. 93 ± 11.8, P = 0.026). Additionally, multifactorial Cox regression analysis identified EBV and prognostic nutritional index as independent predictors of clinical outcomes. CONCLUSION This long-term follow-up study suggests that offline adaptive radiotherapy can reduce toxicity without affecting the survival of patients with LANPC. Further prospective clinical studies are necessary to validate these findings. Biological sciences/Cancer/Cancer therapy/Radiotherapy Biological sciences/Cancer/Head and neck cancer Adaptive radiotherapy Nasopharyngeal carcinoma Volumetric modulated arc therapy Prognostic analysis Propensity-matched analysis Figures Figure 1 Figure 2 Figure 3 Introduction Radiation therapy is a cornerstone treatment for locally advanced nasopharyngeal carcinoma (LA-NPC). The therapeutic efficacy and toxicity profile are critically dependent on the accuracy of radiation dose delivery to target volumes while sparing organs at risk (OARs). Intensity-Modulated Radiation Therapy (IMRT) represents a significant advancement over traditional two-dimensional radiation therapy (2D-RT) and three-dimensional conformal radiation therapy (3D-CRT) [ 1 ] . IMRT provides superior dose conformity and steeper dose fall-off gradients, which allow for more accurate targeting of the tumor while minimizing radiation exposure to surrounding normal tissues and organs. This enhanced precision not only improves tumor coverage rates but also significantly reduces the radiation dose delivered to nearby critical structures. Numerous studies have confirmed that these dosimetric advantages translate into better tumor control rates and lower rates of late toxicity, making IMRT a preferred option for the treatment of advanced NPC [ 2 – 4 ] . However, the highly conformal nature of IMRT makes it highly sensitive to dynamic anatomical changes during treatment..Barker et al. [ 5 ] demonstrated that the nasopharyngeal primary showed an asymmetric pattern of regression (median volume regression rate of 1.8%/day) accompanied by progressive parotid volume atrophy (0.6%/day) and lateral displacement (median 3.1 mm).Marzi et al. [ 6 ] also reported similar results, and since this study gave a single higher dose to the target, the GTV and parotid volume decrease was greater and showed that parotid-associated NTCP correlates with changes in GTV volume, an anatomical and spatial heterogeneity alteration that can lead to significant dosimetric bias [ 7 , 8 ] . In addition, it has been noted that weight loss in patients is also the most commonly observed anatomical change in tumor patients, and studies have shown that the median weight change in patients during treatment decreased by about 8% or so, which correlates with body contour, parotid volume, and dosimetric changes [ 9 – 11 ] . Therefore, image feedback-based replanning during IMRT can improve target area coverage and dose homogeneity, ensuring tumor control rates while reducing the risk of retention to surrounding normal tissues, especially for the parotid gland to limit xerostomia [ 12 – 16 ] . Volumetric modulated arc therapy (VMAT) represents a sophisticated form of IMRT, which is advantageous in clinical practice. A comparative analysis of IMRT and VMAT head and neck cancer plans conducted by multiple institutions has demonstrated that VMAT can enhance target coverage rates and improve the preservation of the oral and parotid glands, with a reduction in the average dose of 2.2 Gy and 2.7 Gy, respectively. Furthermore, treatment time can be reduced by 50% [ 17 ] . Adaptive Radiotherapy (ART) can effectively improve the consistency between planned and actual doses by dynamically correcting anatomical deformations during treatment [ 18 ] . However, the clinical implementation of ART faces multiple challenges: first, multimodal image acquisition (e.g., repeat CT/MRI), manual target correction, and dose optimization processes significantly increase the clinical workload and economic costs; second, there is no consensus on the trigger threshold of ART based on evidence-based medicine, and its clinical benefits, such as improvement in quality of life and local control, are controversial [ 10 , 19 , 20 ] .In particular, there is a lack of studies on quality of life (QoL) in larger samples of patients with LA-NPC treated with VMAT, and the present study was based on a single-center retrospective cohort study of the effect of offline ART on long-term survival outcomes in patients with LA-NPC. We also assessed patients' long-term quality of life after treatment using the Chinese version of the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 and QLQ-H&N35 scales. Materials and methods Patients This retrospective study was approved by the Ethics Committee of Sichuan Cancer Hospital (Approval No. SCCHEC-02-2024-192GIA) with a waiver of informed consent due to its observational nature. Patient data were anonymized and analyzed in accordance with the Declaration of Helsinki. Pre-treatment Examination All patients underwent a comprehensive baseline evaluation before treatment. This included detailed history taking, physical examination, and laboratory tests. Laboratory investigations covered routine hematologic parameters and quantitative EBV-DNA testing. Imaging evaluation included electron nasopharyngoscopy, magnetic resonance imaging (MRI) of the nasopharynx and neck, chest computed tomography(CT), abdominal ultrasound, and whole-body bone scan. In cases with suspected distant metastasis or unclear staging, 18F-deoxyglucose positron emission tomography/computed tomography (PET/CT) was further performed to clarify the extent of disease. Radiotherapy The patient was placed in the supine position with a thermoplastic head, neck and shoulder membrane immobilization position. Simulated localization was performed using 3 mm layer-thickness localization CT, and the target area and organs at risk were outlined on the Eclipse treatment planning system (v.15.6,Varian Medical Systems, Palo Alto, USA) for VMAT planning. The nasopharyngeal tumor target volume (GTV) included the main body of the nasopharyngeal primary tumor and the retropharyngeal lymph nodes, which had a short diameter of ≥ 5 mm.The metastatic lymph node volume (GTVLN), included all positive lymph nodes visualized by imaging (e.g., MRI, CT, PET-CT), which either had a short diameter of ≥ 10 mm or had the presence of central necrosis, circumferential enhancement, and extraperitoneal invasion (irrespective of the size). The high-risk clinical target volume (CTV1) was expanded 5 mm outside the GTV in three dimensions (avoiding the bone cortex and brain parenchyma) to encompass subclinical foci and nasopharyngeal target zones. The intermediate-risk clinical target zone (CTV2), is 3D-expanded 5 mm from CTV1 (circumventing the eyeballs/crystals) to appropriately cover the posterior part of the nasal cavity, the posterior part of the maxillary sinus, the pterygopalatine fossa, part of the posterior group of sieve sinuses, the parapharyngeal space, the base of the skull, and part of the cervical vertebrae and slope for the different T-stages. Cervical lymph node prophylactic zone (CTVln): selectively outline along the natural barrier of the fascial space according to N staging, ensuring that all potentially involved lymph nodes are covered. The prescribed doses of radiotherapy were GTV/GTVln 68.1-69.96 Gy/2.12-2.27Gy/30–33 sessions, CTV1 66Gy/2-2.2 Gy/30–33 sessions, CTV2 60Gy/1.8-2Gy/30–33 sessions, and CTVln 50.4-54Gy/1.8Gy/28–30 sessions. Normal organ dose limits were referred to the RTOG 0225 protocol [ 21 , 22 ] . All patients were treated once daily, 5 days per week for a total duration of 6–7 weeks. In the ART group, patients underwent enhanced CT and MRI repositioning over a median of 15 radiotherapy sessions (9–25) when significant weight loss, fixed membrane orthosis mismatch, or anatomic deviation suggested by cone-beam CT (CBCT) per fraction occurred. The new protocol design continued to utilize MRI-CT fusion to ensure consistency in the target area through rigid alignment and manual adjustments, with protocol adjustments completed within 3 days. Patient weight changes were recorded periodically during treatment. Systemic Therapy All patients received concurrent chemoradiotherapy (CCRT) with a regimen of cisplatin 75 mg/m^2 (days 1–3, once every 3 weeks). One hundred and ninety patients received 2–3 cycles of induction chemotherapy (IC) with the following regimens: the TP regimen [paclitaxel (135 mg/m^2, day 1) or docetaxel (75 mg/m^2, day 1) or albumin-conjugated paclitaxel (260 mg/m^2, day 1) + cisplatin (75 mg/m^2, days 1–3, 1 time every 3 weeks)], or the GP regimen [ gemcitabine (1000 mg/m^2, days 1 and 8) + cisplatin (75 mg/m^2, days 1–3, once every 3 weeks)]. During synchronized radiotherapy, 160 patients (81 in the ART group and 79 in the VMAT group) were treated with a combination of epidermal growth factor receptor (EGFR)-targeted therapy: nitolizumab 200 mg intravenous infusion (once weekly), which was continued until the end of radiotherapy. Follow-up and Data Collection The post-treatment follow-up protocol was as follows: every 3 months for the first 2 years and every 6 months for years 3–5. Follow-up included routine hematology (calculation of prognostic nutritional index [PNI]: PNI = serum albumin [g/L] + 5 × total number of peripheral blood lymphocytes [× 10^9/L]), quantification of EBV-DNA, nasopharyngeal and cervical MRIs, electronic nasopharyngoscopy, chest CT, and abdominal ultrasound, with additional tests added when necessary according to clinical indications. The primary endpoints were overall survival (OS, from the start of treatment to death or final follow-up), progression-free survival (PFS, from the start of treatment to disease progression or death or final follow-up), distant metastasis-free survival (DMFS, from the start of treatment to distant metastasis or death or final follow-up), and local recurrence-free survival (LRFS, from the start of treatment to nasopharyngeal or neck recurrence or death or final follow-up). After written informed consent was obtained, quality of life of surviving patients was assessed using the Chinese versions of the EORTC QLQ-C30 and QLQ-H&N35 scales. Statistical analysis To reduce the influence of baseline confounders on the results, 1:1 propensity score matching (PSM) was used to balance the baseline characteristics of the ART group and the VMAT group, and the matching variables included age, gender, T-stage, N-stage, clinical stage, treatment regimen, and EBV infection status, and the matching method was the nearest-neighbor method with no substitution, and the matching tolerance was set at 0.05, and categorical variable comparisons were made by chi-square test or the Fisher exact test, and survival analysis was performed by Kaplan-Meier method and Log-rank test. Continuous variables (e.g., age, hemoglobin [HGB], PNI, and serum lactate dehydrogenase [LDH]) were converted to categorical variables by subject work characteristics (ROC) curves. Multifactorial analyses were performed using the Cox proportional risk model, and P < 0.05 was considered statistically significant. Subgroup analyses were used to assess differences in efficacy between the two treatment modalities in different subgroups. All statistical analyses were completed using R 4.4.0 software(R Project, http://www.R-project.org/ ). Results We consecutively enrolled patients with locally advanced non-keratinizing nasopharyngeal carcinoma (WHO type II-III) who received complete volumetric modulated arc therapy (VMAT) at our institution between January 2020 and December 2021. From an initial screening of 395 treatment-naïve cases, we included patients clinically staged as III-IVA (AJCC 8th edition) and excluded those with distant metastasis, prior head/neck radiotherapy, or concurrent malignancies.Detailed inclusion/exclusion criteria are presented in Figure 1. In this study, 1:1 PSM was finally successfully completed, and a total of 254 patients were enrolled (127 patients each in the ART group and VMAT group), and the baseline characteristics of the two groups were well-balanced after the matching (all P values > 0.05, see Table 1 for details). The initial cohort analysis showed that there was a significant difference in the distribution of T stage in the ART group compared with the VMAT group (P=0.008), suggesting that the baseline tumor load was unbalanced, and this confounding factor was effectively corrected after PSM. In the matched cohort, the median follow-up time was 42 months (IQR 33.5-50.5) for the ART group and 44 months (IQR 33-49) for the VMAT group. The overall median age was 50 years (IQR 18-73) for the ART group and 49 years (IQR 21-73) for the VMAT group. According to the AJCC 8th edition staging criteria, stage III accounted for 46.9% (119/254) and stage IVA accounted for 53.1% (135/254). By the cutoff of follow-up, a cumulative total of 6 deaths, 10 local-regional recurrences, and 15 distant metastases occurred in the ART group, while 7 deaths, 6 local-regional recurrences, and 13 distant metastases were recorded in the VMAT group.Kaplan-Meier survival analysis showed that the two groups did not reach a statistically significant difference in the primary clinical endpoints (Figure 2). Univariate analysis (Table 2) showed no significant differences in overall prognosis between the ART and VMAT groups. Specifically, the risk ratios (HR) for OS, PFS, and DMFS were slightly lower in the ART group than in the VMAT group. Notably, the HR for LRFS was slightly elevated in the ART group compared with the VMAT group, suggesting that the risk of local recurrence in patients treated with ART was approximately 1.206 times higher than that in the VMAT group. Although an HR value greater than 1 suggested that patients in the ART group had a 20.6% increased risk of local recurrence compared with the VMAT group, this difference was not statistically significant (P=0.647). Other prognostic univariate analyses showed that clinical stage IVA (HR=4.874, 95% CI:1.080-21.994, P=0.039), N3 lymph node stage (HR=5.851, 95%CI:1.610-21.264, P=0.007), EBV-DNA positivity (HR=5.480, 95% CI:1.687-17.798, P=0.005), and low PNI ( HR=0.174, 95% CI:0.048-0.635, P=0.008) were significantly correlated with patients' overall survival (OS). Notably, when the low PNI group was used as a reference, it was shown that high PNI significantly improved survival outcomes (82.6% risk reduction), suggesting that good nutritional status is an important protective factor for survival benefit. Table2.A Univariable Cox analysis of the prognostic factors in the matched cohort Variable 0S PFS DMFS LRFS HR(95%CI) P HR(95%CI) P HR(95%CI) P HR(95%CI) P Age(year) >44 vs ≤44 6.442 [0.837, 49.613] 0.074 5.938 [0.772, 45.695] 0.087 6. 165 [0.801, 47.470] 0.081 6. 184 [0.803, 47.590] 0.08 Sex Male vs Female 1.395 [0.384, 5.070] 0.613 1.418 [0.390, 5. 154] 0.596 1.387 [0.382, 5.039] 0.619 1.420 [0.391, 5. 160] 0.595 T stage T4vs T1～T3 1.996 [0.653, 6. 109] 0.226 1.944 [0.636, 5.946] 0.244 2.019 [0.660, 6. 177] 0.218 1.918 [0.627, 5.867] 0.254 N stage N3 vs N0-2 5.851 [1.610, 21.264] 0.007 5.869 [1.615, 21.328] 0.007 5.722 [1.574, 20.794] 0.008 6.045 [1.663, 21.968] 0.006 Clinical Stage IVA vs III 4.874 [1.080, 21.994] 0.039 4.857 [1.077, 21.915] 0.04 4.839 [1.073, 21.833] 0.04 4.919 [1.090, 22. 194] 0.038 EBV Positive vs Negative 5.480 [1.687, 17.798] 0.005 5.539 [1.706, 17.989] 0.004 5.451 [1.678, 17.701] 0.005 5.579 [1.718, 18. 118] 0.004 Therapeutic regimen Table2(Continued).A Univariable Cox analysis of the prognostic factors in the matched cohort Variable 0S PFS DMFS LRFS HR(95%CI) P HR(95%CI) P HR(95%CI) P HR(95%CI) P ART vs VMAT 0.846 [0.284, 2.518] 0.764 0.934 [0.498, 1.75] 0.831 0.811 [0.409, 1.61] 0.55 1. 206 [0.54, 2.695] 0.647 PNI >46. 15 vs ≤46. 15 0. 174 [0.048, 0.635] 0.008 0. 190 [0.052, 0.689] 0.012 0. 181 [0.050, 0.659] 0.01 0. 185[0.051, 0.674] 0.01 LDH(U/L) >174.5vs ≤174.5 2.746 [0.922, 8. 176] 0.07 2.862 [0.962, 8.519] 0.059 2.777 [0.932, 8.268] 0.067 2.824 [0.949, 8.403] 0.062 HGB（g/L） >124.5vs ≤124.5 3.785 [0.492, 29. 115] 0.201 3.728 [0.485, 28.674] 0.206 3.717 [0.483, 28.590] 0.207 3.828 [0.498, 29.441] 0. 197 Abbreviations: CI, confidence interval; EBV, Epstein-Barr virus; PNI,Prognostic nutritional index; LDH, serum lactate dehydrogenase; HGB,Hemoglobin;HR, hazard ratio; NPC, nasopharyngeal carcinoma; OS, Overall survival; PFS, progression-free survival; DMFS, distant metastasis-free survival; LRFS, local relapse-free survival; ART,adaptive radiotherapy;VMAT,Intensity-modulated radiotherapy Incorporation of the P < 0.05 characteristics into multifactorial Cox regression analysis showed that EBV-positive status and serum PNI level were identified as independent prognostic factors for overall survival. Among them, EBV-positive patients had a significantly higher risk of death (HR=3.711, 95%CI:1.117-12.37 P=0.032); high PNI levels (>46.15) reduced the risk of OS events by 85.4% (HR=0.146, 95%CI:0.039-0.538, P=0.004) and the risk of distant metastasis by 84.9% (HR=0.151, 95%CI:0.041-0.557, P=0.005)(Table 3). Table3.A Multivariable Cox analysis of the prognostic factors in the matched cohort Variable OS PFS DMFS LRFS HR(95%CI) P HR(95%CI) P HR(95%CI) P HR(95%CI) P N stage N3 vs N0-2 5.964 [0.795, 4.752] 0.082 5.522 [0.736, 1.422] 0.096 5.649 [0.753, 2.371] 0.092 5.591 [0.745, 1.962] 0.094 Stage IVA vs III 0.955 [0.091, 10.059] 0.97 0.938 [0.089, 9.903] 0.958 0.993 [0.094, 10.451] 0.995 0.939 [0.089, 9.902] 0.958 Table3.A Multivariable Cox analysis of the prognostic factors in the matched cohort Variable OS PFS DMFS LRFS HR(95%CI) P HR(95%CI) P HR(95%CI) P HR(95%CI) P EBV-DNA Positive vs Negative 3.711 [1. 117, 12.337] 0.032 3.604 [1.077, 12.062] 0.038 3.705 [1. 115, 12.312] 0.033 3.584 [1.069, 12.014] 0.039 PNI >46. 15 vs ≤46. 15 0. 146 [0.039, 0.538] 0.004 0. 171 [0.047, 0.628] 0.008 0. 151 [0.041, 0.557] 0.005 0. 169 [0.046, 0.621] 0.007 Note: All variables were transformed into categorical variables.We selected variables using the enter approach. The P value threshold was 0.05 (P <0.05) for the removal of insignificant variables from the model. Only variables significantly associated with survival were included in the further analysis. The analysis of the final follow-up of 231 patients based on the EORTC QLQ-C30 (Table 4) and QLQ-H&N35 scales (Table 5) showed that the ART group demonstrated a significant advantage in the key indicators of quality of life. Among the functional dimensions, the physical function scores of the ART group were significantly higher than those of the VMAT group (P=0.026), and the cognitive function scores were also statistically superior (P=0.030). Regarding symptom burden, patients in the ART group had significantly fewer oral-related symptoms: dry mouth (19.1±20.7 vs. 31.6±23.0, P<0.001), salivary viscosity (8.83±16.0 vs. 15.5±18.4, P=0.004), and dysphagia scores (2.42±5.90 vs. 5.70±10.10, P= 0.003) were significantly lower than in the VMAT group. Table 4. Comparison of EORTC QLQ-C30 scores between ART and VMAT patients EORTC QLQ-C30 ART(N= 117) VMAT(N= 114) P-value Global QoL 80. 1 (12.8) 78.8 (12.9) 0.458 Physical functioning 96.2(9.84) 93.0(11.8) 0.026 Role functioning 95.3(16. 1) 94.9(14.9) 0.838 Emotional functioning 92.2(14.8) 92.6(14.7) 0.845 Cognitive functioning 86.8 (13.0) 82.7 (14.7) 0.03 Social functioning 93.7(17.7) 93.0(14.0) 0.721 Fatigue 12.8 (16.7) 9.65 (13.8) 0. 117 Nausea and vomiting 0.997(5.03) 0.292(2.20) 0. 168 Pain 2.42(8.55) 3.07(8.46) 0.563 Dyspnoea 5. 13(14.3) 3.51(11.2) 0.337 Table 4 （ Continued ） . Comparison of EORTC QLQ-C30 scores between ART and VMAT patients EORTC QLQ-C30 ART(N= 117) VMAT(N= 114) P-value Appetite loss 2.56(11.7) 2.92(12.2) 0.819 Insomnia 21.4(24.6) 21.3(29.8) 0.995 Constipation 4.56(14.5) 2,34(8.55) 0. 156 Diarrhoea 2.28(8.45) 2.34(8.55) 0.957 Financial difficulties 36.2(34.6) 37. 1(37.3) 0.841 Abbreviations: EORTC=European Organization for Research and Treatment of Cancer. LQC30=Quality of Life Questionnaire C30..QoL=Quality of life. Table 5 .Comparison of EORTC QLQ-H&N35 scores between ART and VMAT patients EORTC QLQ-H&N35 ART (N= 117） VMAT (N= 114) P-value Pain 1.07(3.87) 1.46(4.74) 0.491 Swallowing 2.42(5.90) 5.70(10.0) 0.003 Senses 14.7(24.0) 18.6(25. 1) 0.229 Speech 3.04(10.8) 2.34(7.31) 0.564 Social eating 1.92(6.78) 1.83(6.35) 0.912 Social contact 0.342(2.29) 0.702(2.99) 0.307 Teeth 16.5(26. 1) 21.6(28.0) 0. 153 Opening Mouth 3.42(11.9) 4.97(14.2) 0.369 Dry mouth 19. 1(20.7) 31.6(23.0) <0.001 Sticky saliva 8.83(16.0) 15.5(18.4) 0.004 Felt ill 2.56(11.7) 4.97(14.2) 0. 162 Pain killers 2.56(15.9) 5.26(22.4) 0.293 Nutritional supplements 19.7(39.9) 18.4(38.9) 0.812 Feeding tube 0(0) 0.018(0. 187) 0.319 Weight loss 5. 13(22.2) 7.89(27. 1) 0.397 Weight gain 14.5(35.4) 7.02(25.7) 0.066 Abbreviations: EORTC=European Organization for Research and Treatment of Cancer. QLQH&N35=Head and Neck Quality of Life Questionnaire 35. Discussion Evidence-based research on the impact of offline ART on clinical prognosis and quality of life in head and neck tumors remains limited, with significant heterogeneity in findings. a cohort study by Schwartz's team [10] showed that the 2-year local-regional control rates in the ART group and the IMRT group were 100% versus 95%, respectively, at a median follow-up of 31 months, and a statistically significant advantage of ART in terms of local control rates was confirmed in a study by Chen et al. [23] and Yang et al [24] study also confirmed the statistical superiority of ART in terms of local control rate. However, a phase III randomized controlled trial conducted by Castelli et al. [25] demonstrated that a weekly image-guided ART-based strategy did not significantly improve 2-year overall survival. No statistically significant difference in overall survival was observed between the ART and VMAT groups. Potential explanations for the null survival difference include: first, the shorter median follow-up period (42 vs. 44 months) may not have adequately captured distant recurrent events, and the 8-year follow-up study by Zhou et al [26] demonstrated that the LRFS of the ART group was significantly better than that of the control group in the long-term observation (87.4% vs. 75.6%, P<0.05), suggesting that prolonged follow-up period is crucial for assessing the clinical value of ART. Secondly, the 3-year overall survival rate of this cohort (96.7%) was significantly higher than the historical data [27, 28] , which may stem from the multidimensional treatment optimization: the VMAT technology enhanced local control by improving target coverage; In terms of treatment modality, 100% of patients received synchronous cisplatin chemotherapy combined with concurrent anti-EGFR-targeted therapy , a multimodal strategy that may have compensated for local control differences through synergistic effects of systemic therapy. On the other hand, the sample size limitation may (n=254) lead to insufficient statistical efficacy, and future multicenter randomized controlled trials with large samples need to be designed and conducted. In terms of functional retention, data from the EORTC Quality of Life Core Scale showed that the ART group demonstrated statistical superiority in the swallowing function (P=0.0028), somatic function (P=0.0261), and cognitive function dimensions (P=0.030). It is important to emphasize that quality of life assessment is susceptible to interference by multidimensional confounding factors, including but not limited to socioeconomic status, somatic health status at follow-up, and psychosomatic factors. In addition, patients' symptom adaptation mechanisms may lead to blunted subjective symptom perception, which challenges the interpretation of results in cross-sectional study designs. It is recommended that a prospective cohort study design be used in the future to establish a standardized dynamic follow-up system to more accurately assess the long-term benefit-risk ratio of radiation therapy strategies through longitudinal data collection and multifactorial regression analysis. Consistent with the findings of related studies on weight changes during adaptive radiotherapy for head and neck tumors [10, 11, 29-31] , the present cohort study showed that all enrolled patients experienced treatment-related weight loss, with a median rate of weight loss of 4.7% of baseline body weight (range: -35.2% to 17.2%). Stratified analysis showed that the median weight loss in the intensity-modulated radiation therapy (VMAT) group and adaptive radiation therapy (ART) group was 4.2% and 5.9%, respectively, but the difference between the groups did not reach statistical significance (P=0.08), and the overall weight change was consistent with the results of Beltran et al.'s [32] weight dynamics monitoring based on the CT15 time node. Notably, Langius team [31] confirmed that overall survival (OS) and disease-specific survival (DSS) were significantly lower in patients with >10% weight loss (HR=1.7, 95% CI 1.2-2.4) by a stratified model with a 5% cut-off value, suggesting that excessive weight loss during radiotherapy is an independent risk factor for prognosis. In this study, we systematically evaluated prognostic-related clinical parameters in patients with LA-NPC. Based on the validation of known prognostic markers (including advanced lymph node staging [N3], clinical IVA stage, elevated LDH, and EBV), a multifactorial Cox proportional risk model further revealed that PNI was an independent prognostic factor affecting local control rate (0.169 [0.046,0.621], P=0.007) and overall survival (0.146 [0.039,0.538],. P=0.003) independent prognostic factors( Figure 3). Prognostic heterogeneity in patients with head and neck tumors is co-regulated by tumor biology and host immunotrophic status.Available evidence suggests that PNI is not only significantly associated with treatment-associated weight fluctuation and radiotoxic side effects (acute mucositis), but also an independent predictor of survival prognosis [33, 34] . A meta-analysis including 10 studies with a total of 3,858 patients confirmed that head and neck cancer patients with lower pretreatment PNI were more likely to face significantly worse OS, DMFS, and PFS [35] .The clinical value of PNI was further validated in this study: the optimal cut-off value for PNI was determined to be 46.15 by ROC curve analysis, and the patients in the high PNI group (>46.15) showed a significantly better 5-year overall survival (98.6% vs 83.2%, 95%CI: 96.7%-100%, P=0.006) and locoregional recurrence-free survival (95.9% vs 80.4%, 95%CI: 92.7%-99.2%, P=0.021) 。 Multifactorial Cox regression modeling showed that PNI was an independent prognostic factor for VMAT treatment of nasopharyngeal cancer (OS: HR=0.32, 95%CI 0.14-0.71; LRFS: HR=0.41, 95%CI 0.19-0.89). Based on this, we suggest implementing individualized intervention strategies for patients with low PNI (≤46.15), such as pre-radiotherapy nutritional risk screening and early enteral nutritional support, which may enhance therapeutic efficacy through multiple mechanisms, such as improving the nutrient metabolism microenvironment and enhancing radiosensitivity. This study has several limitations: first, as a retrospective study, there may be selection bias in the patient enrollment criteria. second, the relatively insufficient sample size and short follow-up time may affect the statistical validity. further, the plan revision decision mainly relies on clinical experience rather than a standardized assessment system. Therefore, there is an urgent need to construct an intelligent decision-making system for ART based on multimodal imaging histology features and machine learning models to achieve dynamic and accurate optimization of treatment plans. The core elements of such systems should include: a real-time dose accumulation assessment module; a deep learning-based anatomical deformation prediction algorithm; and an automated decision support tool for quantitative risk-benefit ratio analysis. Through the integration of the above technologies, it is expected to ensure radiobiological effects while minimizing treatment-related toxic reactions. Conclusion This study confirmed that adaptive radiotherapy significantly reduces the incidence of distant radiotoxic side effects (e.g., dry mouth, swallowing dysfunction) in nasopharyngeal cancer patients. It also maintains comparable survival outcomes, thereby improving patients' long-term quality of life scores. Notably, individualized treatment strategies constructed on the basis of patients' baseline nutritional status (as assessed by the Prognostic Nutritional Index) and tumor load characteristics (volume of primary tumor, number and size of lymph node metastases, etc.) may further optimize prognosis. Declarations Funding: None Conflict of Interest: None declared. Ethics Statement: This retrospective study was approved by the Ethics Committee of Sichuan Cancer Hospital (Approval No. SCCHEC-02-2024-192GIA), and its methodology was conducted in accordance with the approved guidelines, with all patients signing an informed consent form prior to the questionnaire survey Data availability: The datasets generated and/or analyzed in this study are available upon request from the first author References Kam M K, Chau R M, Suen J, et al. Intensity-modulated radiotherapy in nasopharyngeal carcinoma: dosimetric advantage over conventional plans and feasibility of dose escalation. Int J Radiat Oncol, 2003,56(1):145-157.https://doi.org/10.1016/s0360-3016(03)00075-0 Mendenhall W M, Amdur R J, Palta J R. Intensity-modulated radiotherapy in the standard management of head and neck cancer: promises and pitfalls. J Clin Oncol, 2006,24(17):2618-2623.https://doi.org/10.1200/JCO.2005.04.7225 Marta G N, Silva V, de Andrade C H, et al. Intensity-modulated radiation therapy for head and neck cancer: systematic review and meta-analysis. Radiother Oncol, 2014,110(1):9-15.https://doi.org/10.1016/j.radonc.2013.11.010 Pow E H, Kwong D L, McMillan A S, et al. Xerostomia and quality of life after intensity-modulated radiotherapy vs. conventional radiotherapy for early-stage nasopharyngeal carcinoma: initial report on a randomized controlled clinical trial. Int J Radiat Oncol, 2006,66(4):981-991.https://doi.org/10.1016/j.ijrobp.2006.06.013 Barker J L, Garden A S, Ang K K, et al. Quantification of volumetric and geometric changes occurring during fractionated radiotherapy for head-and-neck cancer using an integrated CT/linear accelerator system. International Journal of Radiation Oncology*Biology*Physics, 2004,59(4):960-970.https://doi.org/10.1016/j.ijrobp.2003.12.024 Marzi S, Pinnarò P, D'Alessio D, et al. Anatomical and dose changes of gross tumour volume and parotid glands for head and neck cancer patients during intensity-modulated radiotherapy: effect on the probability of xerostomia incidence. Clin Oncol-Uk, 2012,24(3):e54-e62.https://doi.org/10.1016/j.clon.2011.11.006 Hansen E K, Bucci M K, Quivey J M, et al. Repeat CT imaging and replanning during the course of IMRT for head-and-neck cancer. Int J Radiat Oncol, 2006,64(2):355-362.https://doi.org/10.1016/j.ijrobp.2005.07.957 Ahn P H, Chen C C, Ahn A I, et al. Adaptive planning in intensity-modulated radiation therapy for head and neck cancers: single-institution experience and clinical implications. Int J Radiat Oncol, 2011,80(3):677-685.https://doi.org/10.1016/j.ijrobp.2010.03.014 Wang X, Lu J, Xiong X, et al. Anatomic and dosimetric changes during the treatment course of intensity-modulated radiotherapy for locally advanced nasopharyngeal carcinoma. Med Dosim, 2010,35(2):151-157.https://doi.org/10.1016/j.meddos.2009.06.007 Schwartz D L, Garden A S, Thomas J, et al. Adaptive Radiotherapy for Head-and-Neck Cancer: Initial Clinical Outcomes From a Prospective Trial. International Journal of Radiation Oncology*Biology*Physics, 2012,83(3):986-993.https://doi.org/10.1016/j.ijrobp.2011.08.017 Dewan A, Sharma S, Dewan A, et al. Impact of Adaptive Radiotherapy on Locally Advanced Head and Neck Cancer - A Dosimetric and Volumetric Study. Asian Pac J Cancer Prev, 2016,17(3):985-992.https://doi.org/10.7314/apjcp.2016.17.3.985 Bhandari V, Patel P, Gurjar O P, et al. Impact of repeat computerized tomography replans in the radiation therapy of head and neck cancers. J Med Phys , 2014,39(3):164-168.https://doi.org/10.4103/0971-6203.139005 Castelli J, Simon A, Louvel G, et al. Impact of head and neck cancer adaptive radiotherapy to spare the parotid glands and decrease the risk of xerostomia. Radiat Oncol, 2015,10:6.https://doi.org/10.1186/s13014-014-0318-z Wu Q, Chi Y, Chen P Y, et al. Adaptive replanning strategies accounting for shrinkage in head and neck IMRT. Int J Radiat Oncol, 2009,75(3):924-932.https://doi.org/10.1016/j.ijrobp.2009.04.047 Maheshwari G, Dhanawat A, Kumar H S, et al. Clinical and dosimetric impact of adaptive intensity-modulated radiotherapy in locally advanced head-and-neck cancer. J Cancer Res Ther , 2020,16(3):600-604.https://doi.org/10.4103/jcrt.JCRT_928_19 Wu Q, Chi Y, Chen P Y, et al. Adaptive replanning strategies accounting for shrinkage in head and neck IMRT. Int J Radiat Oncol, 2009,75(3):924-932.https://doi.org/10.1016/j.ijrobp.2009.04.047 Holt A, Van Gestel D, Arends M P, et al. Multi-institutional comparison of volumetric modulated arc therapy vs. intensity-modulated radiation therapy for head-and-neck cancer: a planning study. Radiat Oncol, 2013,8:26.https://doi.org/10.1186/1748-717X-8-26 Olteanu L A, Berwouts D, Madani I, et al. Comparative dosimetry of three-phase adaptive and non-adaptive dose-painting IMRT for head-and-neck cancer. Radiother Oncol, 2014,111(3):348-353.https://doi.org/10.1016/j.radonc.2014.02.017 Castelli J, Thariat J, Benezery K, et al. Weekly Adaptive Radiotherapy vs Standard Intensity-Modulated Radiotherapy for Improving Salivary Function in Patients With Head and Neck Cancer: A Phase 3 Randomized Clinical Trial. Jama Oncol , 2023,9(8):1056-1064.https://doi.org/10.1001/jamaoncol.2023.1352 Beadle B M, Chan A W. The Potential of Adaptive Radiotherapy for Patients With Head and Neck Cancer—Too Much or Not Enough? Jama Oncol , 2023,9(8):1064-1065.https://doi.org/10.1001/jamaoncol.2023.1306 Lee N, Harris J, Garden A S, 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.https://doi.org/10.1200/JCO.2008.19.9109 Su S F, Han F, Zhao C, et al. LONG-TERM OUTCOMES OF EARLY-STAGE NASOPHARYNGEAL CARCINOMA PATIENTS TREATED WITH INTENSITY-MODULATED RADIOTHERAPY ALONE. Int J Radiat Oncol, 2012,82(1):327-333.https://doi.org/10.1016/j.ijrobp.2010.09.011 Chen A M, Daly M E, Cui J, et al. Clinical outcomes among patients with head and neck cancer treated by intensity-modulated radiotherapy with and without adaptive replanning. Head Neck-J Sci Spec, 2014,36(11):1541-1546.https://doi.org/10.1002/hed.23477 Yang H, Hu W, Wang W, et al. Replanning during intensity modulated radiation therapy improved quality of life in patients with nasopharyngeal carcinoma. Int J Radiat Oncol, 2013,85(1):e47-e54.https://doi.org/10.1016/j.ijrobp.2012.09.033 Castelli J, Thariat J, Benezery K, et al. Weekly Adaptive Radiotherapy vs Standard Intensity-Modulated Radiotherapy for Improving Salivary Function in Patients With Head and Neck Cancer: A Phase 3 Randomized Clinical Trial. Jama Oncol , 2023,9(8):1056-1064.https://doi.org/10.1001/jamaoncol.2023.1352 Zhou X, Wang W, Zhou C, et al. Long-term outcomes of replanning during intensity-modulated radiation therapy in patients with nasopharyngeal carcinoma: An updated and expanded retrospective analysis. Radiother Oncol, 2022,170:136-142.https://doi.org/10.1016/j.radonc.2022.03.007 Chen A M, Daly M E, Cui J, et al. Clinical outcomes among patients with head and neck cancer treated by intensity-modulated radiotherapy with and without adaptive replanning. Head Neck-J Sci Spec, 2014,36(11):1541-1546.https://doi.org/10.1002/hed.23477 Zhao L, Wan Q, Zhou Y, et al. The role of replanning in fractionated intensity modulated radiotherapy for nasopharyngeal carcinoma. Radiother Oncol, 2011,98(1):23-27.https://doi.org/10.1016/j.radonc.2010.10.009 Ahn P H, Chen C, Ahn A I, et al. Adaptive Planning in Intensity-Modulated Radiation Therapy for Head and Neck Cancers: Single-Institution Experience and Clinical Implications. International Journal of Radiation Oncology*Biology*Physics, 2011,80(3):677-685.https://doi.org/10.1016/j.ijrobp.2010.03.014 Gul O V, Buyukcizmeci N, Basaran H. Dosimetric evaluation of three-phase adaptive radiation therapy in head and neck cancer. Radiat Phys Chem , 2023,202:110588.https://doi.org/10.1016/j.radphyschem.2022.110588 Langius J A, Bakker S, Rietveld D H, et al. Critical weight loss is a major prognostic indicator for disease-specific survival in patients with head and neck cancer receiving radiotherapy. Brit J Cancer , 2013,109(5):1093-1099.https://doi.org/10.1038/bjc.2013.458 Beltran M, Ramos M, Rovira J J, et al. Dose variations in tumor volumes and organs at risk during IMRT for head-and-neck cancer. J Appl Clin Med Phys , 2012,13(6):3723.https://doi.org/10.1120/jacmp.v13i6.3723 Fanetti G, Polesel J, Fratta E, et al. Prognostic Nutritional Index Predicts Toxicity in Head and Neck Cancer Patients Treated with Definitive Radiotherapy in Association with Chemotherapy. Nutrients , 2021,13(4).https://doi.org/10.3390/nu13041277 Miao J, Xiao W, Wang L, et al. The value of the Prognostic Nutritional Index (PNI) in predicting outcomes and guiding the treatment strategy of nasopharyngeal carcinoma (NPC) patients receiving intensity-modulated radiotherapy (IMRT) with or without chemotherapy. J Cancer Res Clin , 2017,143(7):1263-1273.https://doi.org/10.1007/s00432-017-2360-3 Shi Y, Zhang Y, Niu Y, et al. Prognostic role of the prognostic nutritional index (PNI) in patients with head and neck neoplasms undergoing radiotherapy: A meta-analysis. Plos One , 2021,16(9):e257425.https://doi.org/10.1371/journal.pone.0257425 Table 1 Table 1 is available in the Supplementary Files section. Additional Declarations No competing interests reported. Supplementary Files Table1.docx Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. 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15:08:17","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6346006/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6346006/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":82134322,"identity":"410c414b-b6f8-49c0-be17-6e802135d1fb","added_by":"auto","created_at":"2025-05-07 06:02:49","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":87460,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003ePatient inclusion and exclusion criteria\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-6346006/v1/a5d39b0e0b007c63eb1f0c87.png"},{"id":82134307,"identity":"03acaaca-9189-43c5-a1b2-98ca50860ccb","added_by":"auto","created_at":"2025-05-07 06:02:45","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":90484,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eSurvival analysis of patients with locally advanced nasopharyngeal carcinoma in ART and VMAT groups\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-6346006/v1/8cb781f177a884a379cc6b07.png"},{"id":82134323,"identity":"c4d6802b-3595-4108-91d0-b00bfa0d6417","added_by":"auto","created_at":"2025-05-07 06:02:50","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":94571,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eSurvival analysis of patients with locally advanced nasopharyngeal carcinoma by different PNI values\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-6346006/v1/5ff9fda51723dd963a3e197e.png"},{"id":82857427,"identity":"4493700f-2fac-4a4a-bfe8-e3022acfd90a","added_by":"auto","created_at":"2025-05-16 05:40:12","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1416186,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6346006/v1/ccd454d5-ffef-4c22-aa0a-c02316034c5c.pdf"},{"id":82137617,"identity":"b98f6697-3884-4a75-b8fd-ca9ea442a418","added_by":"auto","created_at":"2025-05-07 06:18:45","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":20073,"visible":true,"origin":"","legend":"","description":"","filename":"Table1.docx","url":"https://assets-eu.researchsquare.com/files/rs-6346006/v1/a3f3ba6bf279b10d08e47a05.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Impact of Offline Adaptive Radiotherapy on Survival and Quality of Life in Locally Advanced Nasopharyngeal Carcinoma: A Propensity-Matched Retrospective Study","fulltext":[{"header":"Introduction","content":"\u003cp\u003eRadiation therapy is a cornerstone treatment for locally advanced nasopharyngeal carcinoma (LA-NPC). The therapeutic efficacy and toxicity profile are critically dependent on the accuracy of radiation dose delivery to target volumes while sparing organs at risk (OARs). Intensity-Modulated Radiation Therapy (IMRT) represents a significant advancement over traditional two-dimensional radiation therapy (2D-RT) and three-dimensional conformal radiation therapy (3D-CRT)\u003csup\u003e[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]\u003c/sup\u003e. IMRT provides superior dose conformity and steeper dose fall-off gradients, which allow for more accurate targeting of the tumor while minimizing radiation exposure to surrounding normal tissues and organs. This enhanced precision not only improves tumor coverage rates but also significantly reduces the radiation dose delivered to nearby critical structures. Numerous studies have confirmed that these dosimetric advantages translate into better tumor control rates and lower rates of late toxicity, making IMRT a preferred option for the treatment of advanced NPC\u003csup\u003e[\u003cspan additionalcitationids=\"CR3\" citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eHowever, the highly conformal nature of IMRT makes it highly sensitive to dynamic anatomical changes during treatment..Barker et al.\u003csup\u003e[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]\u003c/sup\u003e demonstrated that the nasopharyngeal primary showed an asymmetric pattern of regression (median volume regression rate of 1.8%/day) accompanied by progressive parotid volume atrophy (0.6%/day) and lateral displacement (median 3.1 mm).Marzi et al.\u003csup\u003e[\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]\u003c/sup\u003ealso reported similar results, and since this study gave a single higher dose to the target, the GTV and parotid volume decrease was greater and showed that parotid-associated NTCP correlates with changes in GTV volume, an anatomical and spatial heterogeneity alteration that can lead to significant dosimetric bias \u003csup\u003e[\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]\u003c/sup\u003e. In addition, it has been noted that weight loss in patients is also the most commonly observed anatomical change in tumor patients, and studies have shown that the median weight change in patients during treatment decreased by about 8% or so, which correlates with body contour, parotid volume, and dosimetric changes \u003csup\u003e[\u003cspan additionalcitationids=\"CR10\" citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]\u003c/sup\u003e. Therefore, image feedback-based replanning during IMRT can improve target area coverage and dose homogeneity, ensuring tumor control rates while reducing the risk of retention to surrounding normal tissues, especially for the parotid gland to limit xerostomia \u003csup\u003e[\u003cspan additionalcitationids=\"CR13 CR14 CR15\" citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eVolumetric modulated arc therapy (VMAT) represents a sophisticated form of IMRT, which is advantageous in clinical practice. A comparative analysis of IMRT and VMAT head and neck cancer plans conducted by multiple institutions has demonstrated that VMAT can enhance target coverage rates and improve the preservation of the oral and parotid glands, with a reduction in the average dose of 2.2 Gy and 2.7 Gy, respectively. Furthermore, treatment time can be reduced by 50%\u003csup\u003e[\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eAdaptive Radiotherapy (ART) can effectively improve the consistency between planned and actual doses by dynamically correcting anatomical deformations during treatment\u003csup\u003e[\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]\u003c/sup\u003e. However, the clinical implementation of ART faces multiple challenges: first, multimodal image acquisition (e.g., repeat CT/MRI), manual target correction, and dose optimization processes significantly increase the clinical workload and economic costs; second, there is no consensus on the trigger threshold of ART based on evidence-based medicine, and its clinical benefits, such as improvement in quality of life and local control, are controversial\u003csup\u003e[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]\u003c/sup\u003e.In particular, there is a lack of studies on quality of life (QoL) in larger samples of patients with LA-NPC treated with VMAT, and the present study was based on a single-center retrospective cohort study of the effect of offline ART on long-term survival outcomes in patients with LA-NPC. We also assessed patients' long-term quality of life after treatment using the Chinese version of the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 and QLQ-H\u0026amp;N35 scales.\u003c/p\u003e"},{"header":"Materials and methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003ePatients\u003c/h2\u003e \u003cp\u003eThis retrospective study was approved by the Ethics Committee of Sichuan Cancer Hospital (Approval No. SCCHEC-02-2024-192GIA) with a waiver of informed consent due to its observational nature. Patient data were anonymized and analyzed in accordance with the Declaration of Helsinki.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003ePre-treatment Examination\u003c/h3\u003e\n\u003cp\u003eAll patients underwent a comprehensive baseline evaluation before treatment. This included detailed history taking, physical examination, and laboratory tests. Laboratory investigations covered routine hematologic parameters and quantitative EBV-DNA testing. Imaging evaluation included electron nasopharyngoscopy, magnetic resonance imaging (MRI) of the nasopharynx and neck, chest computed tomography(CT), abdominal ultrasound, and whole-body bone scan. In cases with suspected distant metastasis or unclear staging, 18F-deoxyglucose positron emission tomography/computed tomography (PET/CT) was further performed to clarify the extent of disease.\u003c/p\u003e\n\u003ch3\u003eRadiotherapy\u003c/h3\u003e\n\u003cp\u003eThe patient was placed in the supine position with a thermoplastic head, neck and shoulder membrane immobilization position. Simulated localization was performed using 3 mm layer-thickness localization CT, and the target area and organs at risk were outlined on the Eclipse treatment planning system (v.15.6,Varian Medical Systems, Palo Alto, USA) for VMAT planning. The nasopharyngeal tumor target volume (GTV) included the main body of the nasopharyngeal primary tumor and the retropharyngeal lymph nodes, which had a short diameter of \u0026ge;\u0026thinsp;5 mm.The metastatic lymph node volume (GTVLN), included all positive lymph nodes visualized by imaging (e.g., MRI, CT, PET-CT), which either had a short diameter of \u0026ge;\u0026thinsp;10 mm or had the presence of central necrosis, circumferential enhancement, and extraperitoneal invasion (irrespective of the size). The high-risk clinical target volume (CTV1) was expanded 5 mm outside the GTV in three dimensions (avoiding the bone cortex and brain parenchyma) to encompass subclinical foci and nasopharyngeal target zones. The intermediate-risk clinical target zone (CTV2), is 3D-expanded 5 mm from CTV1 (circumventing the eyeballs/crystals) to appropriately cover the posterior part of the nasal cavity, the posterior part of the maxillary sinus, the pterygopalatine fossa, part of the posterior group of sieve sinuses, the parapharyngeal space, the base of the skull, and part of the cervical vertebrae and slope for the different T-stages. Cervical lymph node prophylactic zone (CTVln): selectively outline along the natural barrier of the fascial space according to N staging, ensuring that all potentially involved lymph nodes are covered.\u003c/p\u003e \u003cp\u003eThe prescribed doses of radiotherapy were GTV/GTVln 68.1-69.96 Gy/2.12-2.27Gy/30\u0026ndash;33 sessions, CTV1 66Gy/2-2.2 Gy/30\u0026ndash;33 sessions, CTV2 60Gy/1.8-2Gy/30\u0026ndash;33 sessions, and CTVln 50.4-54Gy/1.8Gy/28\u0026ndash;30 sessions. Normal organ dose limits were referred to the RTOG 0225 protocol\u003csup\u003e[\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]\u003c/sup\u003e. All patients were treated once daily, 5 days per week for a total duration of 6\u0026ndash;7 weeks.\u003c/p\u003e \u003cp\u003eIn the ART group, patients underwent enhanced CT and MRI repositioning over a median of 15 radiotherapy sessions (9\u0026ndash;25) when significant weight loss, fixed membrane orthosis mismatch, or anatomic deviation suggested by cone-beam CT (CBCT) per fraction occurred. The new protocol design continued to utilize MRI-CT fusion to ensure consistency in the target area through rigid alignment and manual adjustments, with protocol adjustments completed within 3 days. Patient weight changes were recorded periodically during treatment.\u003c/p\u003e\n\u003ch3\u003eSystemic Therapy\u003c/h3\u003e\n\u003cp\u003eAll patients received concurrent chemoradiotherapy (CCRT) with a regimen of cisplatin 75 mg/m^2 (days 1\u0026ndash;3, once every 3 weeks). One hundred and ninety patients received 2\u0026ndash;3 cycles of induction chemotherapy (IC) with the following regimens: the TP regimen [paclitaxel (135 mg/m^2, day 1) or docetaxel (75 mg/m^2, day 1) or albumin-conjugated paclitaxel (260 mg/m^2, day 1)\u0026thinsp;+\u0026thinsp;cisplatin (75 mg/m^2, days 1\u0026ndash;3, 1 time every 3 weeks)], or the GP regimen [ gemcitabine (1000 mg/m^2, days 1 and 8)\u0026thinsp;+\u0026thinsp;cisplatin (75 mg/m^2, days 1\u0026ndash;3, once every 3 weeks)]. During synchronized radiotherapy, 160 patients (81 in the ART group and 79 in the VMAT group) were treated with a combination of epidermal growth factor receptor (EGFR)-targeted therapy: nitolizumab 200 mg intravenous infusion (once weekly), which was continued until the end of radiotherapy.\u003c/p\u003e\n\u003ch3\u003eFollow-up and Data Collection\u003c/h3\u003e\n\u003cp\u003eThe post-treatment follow-up protocol was as follows: every 3 months for the first 2 years and every 6 months for years 3\u0026ndash;5. Follow-up included routine hematology (calculation of prognostic nutritional index [PNI]: PNI\u0026thinsp;=\u0026thinsp;serum albumin [g/L]\u0026thinsp;+\u0026thinsp;5 \u0026times; total number of peripheral blood lymphocytes [\u0026times; 10^9/L]), quantification of EBV-DNA, nasopharyngeal and cervical MRIs, electronic nasopharyngoscopy, chest CT, and abdominal ultrasound, with additional tests added when necessary according to clinical indications. The primary endpoints were overall survival (OS, from the start of treatment to death or final follow-up), progression-free survival (PFS, from the start of treatment to disease progression or death or final follow-up), distant metastasis-free survival (DMFS, from the start of treatment to distant metastasis or death or final follow-up), and local recurrence-free survival (LRFS, from the start of treatment to nasopharyngeal or neck recurrence or death or final follow-up). After written informed consent was obtained, quality of life of surviving patients was assessed using the Chinese versions of the EORTC QLQ-C30 and QLQ-H\u0026amp;N35 scales.\u003c/p\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis\u003c/h2\u003e \u003cp\u003eTo reduce the influence of baseline confounders on the results, 1:1 propensity score matching (PSM) was used to balance the baseline characteristics of the ART group and the VMAT group, and the matching variables included age, gender, T-stage, N-stage, clinical stage, treatment regimen, and EBV infection status, and the matching method was the nearest-neighbor method with no substitution, and the matching tolerance was set at 0.05, and categorical variable comparisons were made by chi-square test or the Fisher exact test, and survival analysis was performed by Kaplan-Meier method and Log-rank test. Continuous variables (e.g., age, hemoglobin [HGB], PNI, and serum lactate dehydrogenase [LDH]) were converted to categorical variables by subject work characteristics (ROC) curves. Multifactorial analyses were performed using the Cox proportional risk model, and \u003cem\u003eP\u0026thinsp;\u0026lt;\u0026thinsp;0.05\u003c/em\u003e was considered statistically significant. Subgroup analyses were used to assess differences in efficacy between the two treatment modalities in different subgroups. All statistical analyses were completed using R 4.4.0 software(R Project, \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttp://www.R-project.org/\u003c/span\u003e\u003cspan address=\"http://www.R-project.org/\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e).\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003eWe consecutively enrolled patients with locally advanced non-keratinizing nasopharyngeal carcinoma (WHO type II-III) who received complete volumetric modulated arc therapy (VMAT) at our institution between January 2020 and December 2021. From an initial screening of 395 treatment-na\u0026iuml;ve cases, we included patients clinically staged as III-IVA (AJCC 8th edition) and excluded those with distant metastasis, prior head/neck radiotherapy, or concurrent malignancies.Detailed inclusion/exclusion criteria are presented in Figure 1.\u003c/p\u003e\n\u003cp\u003eIn this study, 1:1 PSM was finally successfully completed, and a total of 254 patients were enrolled (127 patients each in the ART group and VMAT group), and the baseline characteristics of the two groups were well-balanced after the matching (all P values \u0026gt; 0.05, see \u003cstrong\u003eTable 1\u0026nbsp;\u003c/strong\u003efor details). The initial cohort analysis showed that there was a significant difference in the distribution of T stage in the ART group compared with the VMAT group (P=0.008), suggesting that the baseline tumor load was unbalanced, and this confounding factor was effectively corrected after PSM.\u003c/p\u003e\n\u003cp\u003eIn the matched cohort, the median follow-up time was 42 months (IQR 33.5-50.5) for the ART group and 44 months (IQR 33-49) for the VMAT group. The overall median age was 50 years (IQR 18-73) for the ART group and 49 years (IQR 21-73) for the VMAT group. According to the AJCC 8th edition staging criteria, stage III accounted for 46.9% (119/254) and stage IVA accounted for 53.1% (135/254). By the cutoff of follow-up, a cumulative total of 6 deaths, 10 local-regional recurrences, and 15 distant metastases occurred in the ART group, while 7 deaths, 6 local-regional recurrences, and 13 distant metastases were recorded in the VMAT group.Kaplan-Meier survival analysis showed that the two groups did not reach a statistically significant difference in the primary clinical endpoints (Figure 2).\u003c/p\u003e\n\u003cp\u003eUnivariate analysis (Table 2) showed no significant differences in overall prognosis between the ART and VMAT groups. Specifically, the risk ratios (HR) for OS, PFS, and DMFS were slightly lower in the ART group than in the VMAT group. Notably, the HR for LRFS was slightly elevated in the ART group compared with the VMAT group, suggesting that the risk of local recurrence in patients treated with ART was approximately 1.206 times higher than that in the VMAT group. Although an HR value greater than 1 suggested that patients in the ART group had a 20.6% increased risk of local recurrence compared with the VMAT group, this difference was not statistically significant (P=0.647).\u003c/p\u003e\n\u003cp\u003eOther prognostic univariate analyses showed that clinical stage IVA (HR=4.874, 95% CI:1.080-21.994, P=0.039), N3 lymph node stage (HR=5.851, 95%CI:1.610-21.264, P=0.007), EBV-DNA positivity (HR=5.480, 95% CI:1.687-17.798, P=0.005), and low PNI ( HR=0.174, 95% CI:0.048-0.635, P=0.008) were significantly correlated with patients\u0026apos; overall survival (OS). Notably, when the low PNI group was used as a reference, it was shown that high PNI significantly improved survival outcomes (82.6% risk reduction), suggesting that good nutritional status is an important protective factor for survival benefit.\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"633\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"9\" style=\"width: 633px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTable2.A Univariable Cox analysis of the prognostic factors in the matched cohort\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 118px;\"\u003e\n \u003cp\u003eVariable\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e0S\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 45px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003ePFS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 45px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003eDMFS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 45px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003eLRFS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 46px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 118px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003eHR(95%CI)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 45px;\"\u003e\n \u003cp\u003eP\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003eHR(95%CI)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 45px;\"\u003e\n \u003cp\u003eP\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003eHR(95%CI)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 45px;\"\u003e\n \u003cp\u003eP\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003eHR(95%CI)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 46px;\"\u003e\n \u003cp\u003eP\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 118px;\"\u003e\n \u003cp\u003eAge(year)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 45px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 45px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 45px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 46px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 118px;\"\u003e\n \u003cp\u003e\u0026gt;44 vs \u0026le;44\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e6.442 [0.837, 49.613]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 45px;\"\u003e\n \u003cp\u003e0.074\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e5.938 [0.772, 45.695]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 45px;\"\u003e\n \u003cp\u003e0.087\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e6. 165 [0.801, 47.470]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 45px;\"\u003e\n \u003cp\u003e0.081\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e6. 184 [0.803, 47.590]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 46px;\"\u003e\n \u003cp\u003e0.08\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 118px;\"\u003e\n \u003cp\u003eSex\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 45px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 45px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 45px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 46px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 118px;\"\u003e\n \u003cp\u003eMale vs Female\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e1.395 [0.384, 5.070]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 45px;\"\u003e\n \u003cp\u003e0.613\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e1.418 [0.390, 5. 154]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 45px;\"\u003e\n \u003cp\u003e0.596\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e1.387 [0.382, 5.039]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 45px;\"\u003e\n \u003cp\u003e0.619\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e1.420 [0.391, 5. 160]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 46px;\"\u003e\n \u003cp\u003e0.595\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 118px;\"\u003e\n \u003cp\u003eT stage\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 45px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 45px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 45px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 46px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 118px;\"\u003e\n \u003cp\u003eT4vs T1～T3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e1.996 [0.653, 6. 109]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 45px;\"\u003e\n \u003cp\u003e0.226\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e1.944 [0.636, 5.946]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 45px;\"\u003e\n \u003cp\u003e0.244\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e2.019 [0.660, 6. 177]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 45px;\"\u003e\n \u003cp\u003e0.218\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e1.918 [0.627, 5.867]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 46px;\"\u003e\n \u003cp\u003e0.254\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 118px;\"\u003e\n \u003cp\u003eN stage\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 45px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 45px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 45px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 46px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 118px;\"\u003e\n \u003cp\u003eN3 vs N0-2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e5.851 [1.610, 21.264]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 45px;\"\u003e\n \u003cp\u003e0.007\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e5.869 [1.615, 21.328]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 45px;\"\u003e\n \u003cp\u003e0.007\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e5.722 [1.574, 20.794]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 45px;\"\u003e\n \u003cp\u003e0.008\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e6.045 [1.663, 21.968]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 46px;\"\u003e\n \u003cp\u003e0.006\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 118px;\"\u003e\n \u003cp\u003eClinical Stage\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 45px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 45px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 45px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 46px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 118px;\"\u003e\n \u003cp\u003eIVA vs III\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e4.874 [1.080, 21.994]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 45px;\"\u003e\n \u003cp\u003e0.039\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e4.857 [1.077, 21.915]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 45px;\"\u003e\n \u003cp\u003e0.04\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e4.839 [1.073, 21.833]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 45px;\"\u003e\n \u003cp\u003e0.04\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e4.919 [1.090, 22. 194]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 46px;\"\u003e\n \u003cp\u003e0.038\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 118px;\"\u003e\n \u003cp\u003eEBV\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 45px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 45px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 45px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 46px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 118px;\"\u003e\n \u003cp\u003ePositive vs Negative\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e5.480 [1.687, 17.798]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 45px;\"\u003e\n \u003cp\u003e0.005\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e5.539 [1.706, 17.989]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 45px;\"\u003e\n \u003cp\u003e0.004\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e5.451 [1.678, 17.701]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 45px;\"\u003e\n \u003cp\u003e0.005\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e5.579 [1.718, 18. 118]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 46px;\"\u003e\n \u003cp\u003e0.004\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 118px;\"\u003e\n \u003cp\u003eTherapeutic regimen\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 45px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 45px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 45px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 46px;\"\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\u003eTable2(Continued).A Univariable Cox analysis of the prognostic factors in the matched cohort\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"634\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 118px;\"\u003e\n \u003cp\u003eVariable\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 84px;\"\u003e\n \u003cp\u003e0S\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 45px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 84px;\"\u003e\n \u003cp\u003ePFS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 45px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 84px;\"\u003e\n \u003cp\u003eDMFS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 45px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 84px;\"\u003e\n \u003cp\u003eLRFS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 45px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 118px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 84px;\"\u003e\n \u003cp\u003eHR(95%CI)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 45px;\"\u003e\n \u003cp\u003eP\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 84px;\"\u003e\n \u003cp\u003eHR(95%CI)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 45px;\"\u003e\n \u003cp\u003eP\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 84px;\"\u003e\n \u003cp\u003eHR(95%CI)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 45px;\"\u003e\n \u003cp\u003eP\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 84px;\"\u003e\n \u003cp\u003eHR(95%CI)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 45px;\"\u003e\n \u003cp\u003eP\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 118px;\"\u003e\n \u003cp\u003eART vs VMAT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 84px;\"\u003e\n \u003cp\u003e0.846 [0.284, 2.518]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 45px;\"\u003e\n \u003cp\u003e0.764\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 84px;\"\u003e\n \u003cp\u003e0.934 [0.498, 1.75]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 45px;\"\u003e\n \u003cp\u003e0.831\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 84px;\"\u003e\n \u003cp\u003e0.811 [0.409, 1.61]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 45px;\"\u003e\n \u003cp\u003e0.55\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 84px;\"\u003e\n \u003cp\u003e1. 206 [0.54, 2.695]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 45px;\"\u003e\n \u003cp\u003e0.647\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 118px;\"\u003e\n \u003cp\u003ePNI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 84px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 45px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 84px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 45px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 84px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 45px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 84px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 45px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 118px;\"\u003e\n \u003cp\u003e\u0026gt;46. 15 vs \u0026le;46. 15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 84px;\"\u003e\n \u003cp\u003e0. 174 [0.048, 0.635]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 45px;\"\u003e\n \u003cp\u003e0.008\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 84px;\"\u003e\n \u003cp\u003e0. 190 [0.052, 0.689]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 45px;\"\u003e\n \u003cp\u003e0.012\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 84px;\"\u003e\n \u003cp\u003e0. 181 [0.050, 0.659]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 45px;\"\u003e\n \u003cp\u003e0.01\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 84px;\"\u003e\n \u003cp\u003e0. 185[0.051, 0.674]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 45px;\"\u003e\n \u003cp\u003e0.01\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 118px;\"\u003e\n \u003cp\u003eLDH(U/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 84px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 45px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 84px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 45px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 84px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 45px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 84px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 45px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 118px;\"\u003e\n \u003cp\u003e\u0026gt;174.5vs \u0026le;174.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 84px;\"\u003e\n \u003cp\u003e2.746 [0.922, 8. 176]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 45px;\"\u003e\n \u003cp\u003e0.07\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 84px;\"\u003e\n \u003cp\u003e2.862 [0.962, 8.519]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 45px;\"\u003e\n \u003cp\u003e0.059\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 84px;\"\u003e\n \u003cp\u003e2.777 [0.932, 8.268]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 45px;\"\u003e\n \u003cp\u003e0.067\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 84px;\"\u003e\n \u003cp\u003e2.824 [0.949, 8.403]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 45px;\"\u003e\n \u003cp\u003e0.062\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 118px;\"\u003e\n \u003cp\u003eHGB（g/L）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 84px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 45px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 84px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 45px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 84px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 45px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 84px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 45px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 118px;\"\u003e\n \u003cp\u003e\u0026gt;124.5vs \u0026le;124.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 84px;\"\u003e\n \u003cp\u003e3.785 [0.492, 29. 115]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 45px;\"\u003e\n \u003cp\u003e0.201\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 84px;\"\u003e\n \u003cp\u003e3.728 [0.485, 28.674]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 45px;\"\u003e\n \u003cp\u003e0.206\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 84px;\"\u003e\n \u003cp\u003e3.717 [0.483, 28.590]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 45px;\"\u003e\n \u003cp\u003e0.207\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 84px;\"\u003e\n \u003cp\u003e3.828 [0.498, 29.441]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 45px;\"\u003e\n \u003cp\u003e0. 197\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eAbbreviations: CI, confidence interval; EBV, Epstein-Barr virus; PNI,Prognostic nutritional index; LDH, serum lactate dehydrogenase; HGB,Hemoglobin;HR, hazard ratio; NPC, nasopharyngeal carcinoma; OS, Overall survival; PFS, progression-free survival; DMFS, distant metastasis-free survival; \u0026nbsp;LRFS, local relapse-free survival; ART,adaptive radiotherapy;VMAT,Intensity-modulated radiotherapy\u003c/p\u003e\n\u003cp\u003eIncorporation of the P \u0026lt; 0.05 characteristics into multifactorial Cox regression analysis showed that EBV-positive status and serum PNI level were identified as independent prognostic factors for overall survival. Among them, EBV-positive patients had a significantly higher risk of death (HR=3.711, 95%CI:1.117-12.37 P=0.032); high PNI levels (\u0026gt;46.15) reduced the risk of OS events by 85.4% (HR=0.146, 95%CI:0.039-0.538, P=0.004) and the risk of distant metastasis by 84.9% (HR=0.151, 95%CI:0.041-0.557, P=0.005)(Table 3).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable3.A Multivariable Cox analysis of the prognostic factors in the matched cohort\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"610\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" style=\"width: 93px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eVariable\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eOS\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 47px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePFS\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 47px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eDMFS\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 47px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eLRFS\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 47px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eHR(95%CI)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 47px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eP\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eHR(95%CI)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 47px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eP\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eHR(95%CI)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 47px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eP\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eHR(95%CI)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 47px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eP\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 93px;\"\u003e\n \u003cp\u003eN stage\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 47px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 47px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 47px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 47px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 93px;\"\u003e\n \u003cp\u003eN3 vs N0-2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003e5.964 [0.795, 4.752]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 47px;\"\u003e\n \u003cp\u003e0.082\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003e5.522 [0.736, 1.422]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 47px;\"\u003e\n \u003cp\u003e0.096\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003e5.649 [0.753, 2.371]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 47px;\"\u003e\n \u003cp\u003e0.092\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003e5.591 [0.745, 1.962]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 47px;\"\u003e\n \u003cp\u003e0.094\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 93px;\"\u003e\n \u003cp\u003eStage\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 47px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 47px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 47px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 47px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 93px;\"\u003e\n \u003cp\u003eIVA vs III\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003e0.955 [0.091, 10.059]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 47px;\"\u003e\n \u003cp\u003e0.97\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003e0.938 [0.089, 9.903]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 47px;\"\u003e\n \u003cp\u003e0.958\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003e0.993 [0.094, 10.451]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 47px;\"\u003e\n \u003cp\u003e0.995\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003e0.939 [0.089, 9.902]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 47px;\"\u003e\n \u003cp\u003e0.958\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cstrong\u003eTable3.A Multivariable Cox analysis of the prognostic factors in the matched cohort\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"610\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" style=\"width: 93px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eVariable\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eOS\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 47px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePFS\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 47px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eDMFS\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 47px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eLRFS\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 47px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eHR(95%CI)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 47px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eP\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eHR(95%CI)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 47px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eP\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eHR(95%CI)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 47px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eP\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eHR(95%CI)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 47px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eP\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 93px;\"\u003e\n \u003cp\u003eEBV-DNA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 47px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 47px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 47px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 47px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 93px;\"\u003e\n \u003cp\u003ePositive vs Negative\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 82px;\"\u003e\n \u003cp\u003e3.711 [1. 117, 12.337]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 47px;\"\u003e\n \u003cp\u003e0.032\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003e3.604 [1.077, 12.062]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 47px;\"\u003e\n \u003cp\u003e0.038\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 82px;\"\u003e\n \u003cp\u003e3.705 [1. 115, 12.312]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 47px;\"\u003e\n \u003cp\u003e0.033\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 82px;\"\u003e\n \u003cp\u003e3.584 [1.069, 12.014]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 47px;\"\u003e\n \u003cp\u003e0.039\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 93px;\"\u003e\n \u003cp\u003ePNI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 47px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 93px;\"\u003e\n \u003cp\u003e\u0026gt;46. 15 vs \u0026le;46. 15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003e0. 146 [0.039, 0.538]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 47px;\"\u003e\n \u003cp\u003e0.004\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003e0. 171 [0.047, 0.628]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 47px;\"\u003e\n \u003cp\u003e0.008\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003e0. 151 [0.041, 0.557]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 47px;\"\u003e\n \u003cp\u003e0.005\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003e0. 169 [0.046, 0.621]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 47px;\"\u003e\n \u003cp\u003e0.007\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eNote: All variables were transformed into categorical variables.We selected variables using the\u0026nbsp;enter\u0026nbsp;approach.\u0026nbsp;The P value\u0026nbsp;threshold\u0026nbsp;was\u0026nbsp;0.05\u0026nbsp;(P \u0026lt;0.05)\u0026nbsp;for\u0026nbsp;the\u0026nbsp;removal\u0026nbsp;of\u0026nbsp;insignificant\u0026nbsp;variables\u0026nbsp;from\u0026nbsp;the\u0026nbsp;model.\u0026nbsp;Only\u0026nbsp;variables\u0026nbsp;significantly\u0026nbsp;associated\u0026nbsp;with\u0026nbsp;survival\u0026nbsp;were\u0026nbsp;included\u0026nbsp;in\u0026nbsp;the\u0026nbsp;further analysis.\u003c/p\u003e\n\u003cp\u003eThe analysis of the final follow-up of 231 patients based on the EORTC QLQ-C30 (Table 4) and QLQ-H\u0026amp;N35 scales (Table 5) showed that the ART group demonstrated a significant advantage in the key indicators of quality of life. Among the functional dimensions, the physical function scores of the ART group were significantly higher than those of the VMAT group (P=0.026), and the cognitive function scores were also statistically superior (P=0.030). Regarding symptom burden, patients in the ART group had significantly fewer oral-related symptoms: dry mouth (19.1\u0026plusmn;20.7 vs. 31.6\u0026plusmn;23.0, P\u0026lt;0.001), salivary viscosity (8.83\u0026plusmn;16.0 vs. 15.5\u0026plusmn;18.4, P=0.004), and dysphagia scores (2.42\u0026plusmn;5.90 vs. 5.70\u0026plusmn;10.10, P= 0.003) were significantly lower than in the VMAT group.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003e4.\u003c/strong\u003e\u003cstrong\u003eComparison of EORTC QLQ-C30 scores between ART and\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003eVMAT\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;patients\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"609\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 152px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eEORTC QLQ-C30\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 152px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eART(N= 117)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 152px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eVMAT(N= 114)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 152px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eP-value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 152px;\"\u003e\n \u003cp\u003eGlobal QoL\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 152px;\"\u003e\n \u003cp\u003e80. 1 (12.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 152px;\"\u003e\n \u003cp\u003e78.8 (12.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 152px;\"\u003e\n \u003cp\u003e0.458\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 152px;\"\u003e\n \u003cp\u003ePhysical functioning\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 152px;\"\u003e\n \u003cp\u003e96.2(9.84)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 152px;\"\u003e\n \u003cp\u003e93.0(11.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 152px;\"\u003e\n \u003cp\u003e0.026\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 152px;\"\u003e\n \u003cp\u003eRole functioning\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 152px;\"\u003e\n \u003cp\u003e95.3(16. 1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 152px;\"\u003e\n \u003cp\u003e94.9(14.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 152px;\"\u003e\n \u003cp\u003e0.838\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 152px;\"\u003e\n \u003cp\u003eEmotional functioning\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 152px;\"\u003e\n \u003cp\u003e92.2(14.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 152px;\"\u003e\n \u003cp\u003e92.6(14.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 152px;\"\u003e\n \u003cp\u003e0.845\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 152px;\"\u003e\n \u003cp\u003eCognitive functioning\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 152px;\"\u003e\n \u003cp\u003e86.8 (13.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 152px;\"\u003e\n \u003cp\u003e82.7 (14.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 152px;\"\u003e\n \u003cp\u003e0.03\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 152px;\"\u003e\n \u003cp\u003eSocial functioning\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 152px;\"\u003e\n \u003cp\u003e93.7(17.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 152px;\"\u003e\n \u003cp\u003e93.0(14.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 152px;\"\u003e\n \u003cp\u003e0.721\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 152px;\"\u003e\n \u003cp\u003eFatigue\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 152px;\"\u003e\n \u003cp\u003e12.8 (16.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 152px;\"\u003e\n \u003cp\u003e9.65 (13.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 152px;\"\u003e\n \u003cp\u003e0. 117\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 152px;\"\u003e\n \u003cp\u003eNausea and vomiting\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 152px;\"\u003e\n \u003cp\u003e0.997(5.03)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 152px;\"\u003e\n \u003cp\u003e0.292(2.20)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 152px;\"\u003e\n \u003cp\u003e0. 168\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 152px;\"\u003e\n \u003cp\u003ePain\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 152px;\"\u003e\n \u003cp\u003e2.42(8.55)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 152px;\"\u003e\n \u003cp\u003e3.07(8.46)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 152px;\"\u003e\n \u003cp\u003e0.563\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 152px;\"\u003e\n \u003cp\u003eDyspnoea\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 152px;\"\u003e\n \u003cp\u003e5. 13(14.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 152px;\"\u003e\n \u003cp\u003e3.51(11.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 152px;\"\u003e\n \u003cp\u003e0.337\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cstrong\u003eTable\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003e4\u003c/strong\u003e\u003cstrong\u003e（\u003c/strong\u003e\u003cstrong\u003eContinued\u003c/strong\u003e\u003cstrong\u003e）\u003c/strong\u003e\u003cstrong\u003e.\u003c/strong\u003e\u003cstrong\u003eComparison of EORTC QLQ-C30 scores between ART and\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003eVMAT\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;patients\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"609\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 152px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eEORTC QLQ-C30\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 152px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eART(N= 117)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 152px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eVMAT(N= 114)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 152px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eP-value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 152px;\"\u003e\n \u003cp\u003eAppetite loss\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 152px;\"\u003e\n \u003cp\u003e2.56(11.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 152px;\"\u003e\n \u003cp\u003e2.92(12.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 152px;\"\u003e\n \u003cp\u003e0.819\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 152px;\"\u003e\n \u003cp\u003eInsomnia\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 152px;\"\u003e\n \u003cp\u003e21.4(24.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 152px;\"\u003e\n \u003cp\u003e21.3(29.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 152px;\"\u003e\n \u003cp\u003e0.995\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 152px;\"\u003e\n \u003cp\u003eConstipation\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 152px;\"\u003e\n \u003cp\u003e4.56(14.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 152px;\"\u003e\n \u003cp\u003e2,34(8.55)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 152px;\"\u003e\n \u003cp\u003e0. 156\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 152px;\"\u003e\n \u003cp\u003eDiarrhoea\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 152px;\"\u003e\n \u003cp\u003e2.28(8.45)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 152px;\"\u003e\n \u003cp\u003e2.34(8.55)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 152px;\"\u003e\n \u003cp\u003e0.957\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 152px;\"\u003e\n \u003cp\u003eFinancial difficulties\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 152px;\"\u003e\n \u003cp\u003e36.2(34.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 152px;\"\u003e\n \u003cp\u003e37. 1(37.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 152px;\"\u003e\n \u003cp\u003e0.841\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eAbbreviations: EORTC=European Organization for Research and Treatment of Cancer. LQC30=Quality of Life Questionnaire C30..QoL=Quality of life.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003e5\u003c/strong\u003e\u003cstrong\u003e.Comparison of EORTC QLQ-H\u0026amp;N35 scores between ART and\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003eVMAT\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;patients\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"612\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 153px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eEORTC QLQ-H\u0026amp;N35\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 153px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eART \u0026nbsp; (N= 117）\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 153px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eVMAT (N= 114)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 153px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eP-value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 153px;\"\u003e\n \u003cp\u003ePain\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 153px;\"\u003e\n \u003cp\u003e1.07(3.87)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 153px;\"\u003e\n \u003cp\u003e1.46(4.74)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 153px;\"\u003e\n \u003cp\u003e0.491\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 153px;\"\u003e\n \u003cp\u003eSwallowing\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 153px;\"\u003e\n \u003cp\u003e2.42(5.90)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 153px;\"\u003e\n \u003cp\u003e5.70(10.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 153px;\"\u003e\n \u003cp\u003e0.003\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 153px;\"\u003e\n \u003cp\u003eSenses\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 153px;\"\u003e\n \u003cp\u003e14.7(24.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 153px;\"\u003e\n \u003cp\u003e18.6(25. 1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 153px;\"\u003e\n \u003cp\u003e0.229\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 153px;\"\u003e\n \u003cp\u003eSpeech\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 153px;\"\u003e\n \u003cp\u003e3.04(10.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 153px;\"\u003e\n \u003cp\u003e2.34(7.31)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 153px;\"\u003e\n \u003cp\u003e0.564\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 153px;\"\u003e\n \u003cp\u003eSocial eating\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 153px;\"\u003e\n \u003cp\u003e1.92(6.78)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 153px;\"\u003e\n \u003cp\u003e1.83(6.35)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 153px;\"\u003e\n \u003cp\u003e0.912\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 153px;\"\u003e\n \u003cp\u003eSocial contact\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 153px;\"\u003e\n \u003cp\u003e0.342(2.29)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 153px;\"\u003e\n \u003cp\u003e0.702(2.99)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 153px;\"\u003e\n \u003cp\u003e0.307\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 153px;\"\u003e\n \u003cp\u003eTeeth\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 153px;\"\u003e\n \u003cp\u003e16.5(26. 1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 153px;\"\u003e\n \u003cp\u003e21.6(28.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 153px;\"\u003e\n \u003cp\u003e0. 153\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 153px;\"\u003e\n \u003cp\u003eOpening\u0026nbsp;Mouth\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 153px;\"\u003e\n \u003cp\u003e3.42(11.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 153px;\"\u003e\n \u003cp\u003e4.97(14.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 153px;\"\u003e\n \u003cp\u003e0.369\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 153px;\"\u003e\n \u003cp\u003eDry mouth\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 153px;\"\u003e\n \u003cp\u003e19. 1(20.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 153px;\"\u003e\n \u003cp\u003e31.6(23.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 153px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 153px;\"\u003e\n \u003cp\u003eSticky saliva\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 153px;\"\u003e\n \u003cp\u003e8.83(16.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 153px;\"\u003e\n \u003cp\u003e15.5(18.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 153px;\"\u003e\n \u003cp\u003e0.004\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 153px;\"\u003e\n \u003cp\u003eFelt ill\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 153px;\"\u003e\n \u003cp\u003e2.56(11.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 153px;\"\u003e\n \u003cp\u003e4.97(14.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 153px;\"\u003e\n \u003cp\u003e0. 162\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 153px;\"\u003e\n \u003cp\u003ePain killers\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 153px;\"\u003e\n \u003cp\u003e2.56(15.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 153px;\"\u003e\n \u003cp\u003e5.26(22.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 153px;\"\u003e\n \u003cp\u003e0.293\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 153px;\"\u003e\n \u003cp\u003eNutritional supplements\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 153px;\"\u003e\n \u003cp\u003e19.7(39.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 153px;\"\u003e\n \u003cp\u003e18.4(38.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 153px;\"\u003e\n \u003cp\u003e0.812\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 153px;\"\u003e\n \u003cp\u003eFeeding tube\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 153px;\"\u003e\n \u003cp\u003e0(0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 153px;\"\u003e\n \u003cp\u003e0.018(0. 187)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 153px;\"\u003e\n \u003cp\u003e0.319\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 153px;\"\u003e\n \u003cp\u003eWeight loss\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 153px;\"\u003e\n \u003cp\u003e5. 13(22.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 153px;\"\u003e\n \u003cp\u003e7.89(27. 1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 153px;\"\u003e\n \u003cp\u003e0.397\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 153px;\"\u003e\n \u003cp\u003eWeight gain\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 153px;\"\u003e\n \u003cp\u003e14.5(35.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 153px;\"\u003e\n \u003cp\u003e7.02(25.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 153px;\"\u003e\n \u003cp\u003e0.066\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eAbbreviations: EORTC=European Organization for Research and Treatment of Cancer. QLQH\u0026amp;N35=Head and Neck Quality of Life Questionnaire 35.\u0026nbsp;\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eEvidence-based research on the impact of offline ART on clinical prognosis and quality of life in head and neck tumors remains limited, with significant heterogeneity in findings. a cohort study by Schwartz\u0026apos;s team \u003csup\u003e[10]\u003c/sup\u003eshowed that the 2-year local-regional control rates in the ART group and the IMRT group were 100% versus 95%, respectively, at a median follow-up of 31 months, and a statistically significant advantage of ART in terms of local control rates was confirmed in a study by Chen et al.\u003csup\u003e[23]\u003c/sup\u003eand Yang et al\u003csup\u003e[24]\u003c/sup\u003estudy also confirmed the statistical superiority of ART in terms of local control rate. However, a phase III randomized controlled trial conducted by Castelli et al.\u003csup\u003e[25]\u003c/sup\u003e demonstrated that a weekly image-guided ART-based strategy did not significantly improve 2-year overall survival.\u003c/p\u003e\n\u003cp\u003eNo statistically significant difference in overall survival was observed between the ART and VMAT groups. Potential explanations for the null survival difference include:\u0026nbsp;first, the shorter median follow-up period (42 vs. 44 months) may not have adequately captured distant recurrent events, and the 8-year follow-up study by Zhou et al\u003csup\u003e[26]\u003c/sup\u003e demonstrated that the LRFS of the ART group was significantly better than that of the control group in the long-term observation (87.4% vs. 75.6%, P\u0026lt;0.05), suggesting that prolonged follow-up period is crucial for assessing the clinical value of ART. Secondly, the 3-year overall survival rate of this cohort (96.7%) was significantly higher than the historical data\u003csup\u003e[27, 28]\u003c/sup\u003e, which may stem from the multidimensional treatment optimization: the VMAT technology enhanced local control by improving target coverage; In terms of treatment modality, 100% of patients received synchronous cisplatin chemotherapy combined with concurrent anti-EGFR-targeted therapy , a multimodal strategy that may have compensated for local control differences through synergistic effects of systemic therapy. On the other hand, the sample size limitation may (n=254) lead to insufficient statistical efficacy, and future multicenter randomized controlled trials with large samples need to be designed and conducted.\u003c/p\u003e\n\u003cp\u003eIn terms of functional retention, data from the EORTC Quality of Life Core Scale showed that the ART group demonstrated statistical superiority in the swallowing function (P=0.0028), somatic function (P=0.0261), and cognitive function dimensions (P=0.030). It is important to emphasize that quality of life assessment is susceptible to interference by multidimensional confounding factors, including but not limited to socioeconomic status, somatic health status at follow-up, and psychosomatic factors. In addition, patients\u0026apos; symptom adaptation mechanisms may lead to blunted subjective symptom perception, which challenges the interpretation of results in cross-sectional study designs. It is recommended that a prospective cohort study design be used in the future to establish a standardized dynamic follow-up system to more accurately assess the long-term benefit-risk ratio of radiation therapy strategies through longitudinal data collection and multifactorial regression analysis.\u003c/p\u003e\n\u003cp\u003eConsistent with the findings of related studies on weight changes during adaptive radiotherapy for head and neck tumors \u003csup\u003e[10, 11, 29-31]\u003c/sup\u003e, the present cohort study showed that all enrolled patients experienced treatment-related weight loss, with a median rate of weight loss of 4.7% of baseline body weight (range: -35.2% to 17.2%). Stratified analysis showed that the median weight loss in the intensity-modulated radiation therapy (VMAT) group and adaptive radiation therapy (ART) group was 4.2% and 5.9%, respectively, but the difference between the groups did not reach statistical significance (P=0.08), and the overall weight change was consistent with the results of Beltran et al.\u0026apos;s\u003csup\u003e[32]\u003c/sup\u003eweight dynamics monitoring based on the CT15 time node. Notably, Langius team\u003csup\u003e[31]\u003c/sup\u003econfirmed that overall survival (OS) and disease-specific survival (DSS) were significantly lower in patients with \u0026gt;10% weight loss (HR=1.7, 95% CI 1.2-2.4) by a stratified model with a 5% cut-off value, suggesting that excessive weight loss during radiotherapy is an independent risk factor for prognosis.\u003c/p\u003e\n\u003cp\u003eIn this study, we systematically evaluated prognostic-related clinical parameters in patients with LA-NPC. Based on the validation of known prognostic markers (including advanced lymph node staging [N3], clinical IVA stage, elevated LDH, and EBV), a multifactorial Cox proportional risk model further revealed that PNI was an independent prognostic factor affecting local control rate (0.169 [0.046,0.621], P=0.007) and overall survival (0.146 [0.039,0.538],. P=0.003) independent prognostic factors( Figure 3). Prognostic heterogeneity in patients with head and neck tumors is co-regulated by tumor biology and host immunotrophic status.Available evidence suggests that PNI is not only significantly associated with treatment-associated weight fluctuation and radiotoxic side effects (acute mucositis), but also an independent predictor of survival prognosis\u003csup\u003e[33, 34]\u003c/sup\u003e. A meta-analysis including 10 studies with a total of 3,858 patients confirmed that head and neck cancer patients with lower pretreatment PNI were more likely to face significantly worse OS, DMFS, and PFS\u003csup\u003e[35]\u003c/sup\u003e.The clinical value of PNI was further validated in this study: the optimal cut-off value for PNI was determined to be 46.15 by ROC curve analysis, and the patients in the high PNI group (\u0026gt;46.15) showed a significantly better 5-year overall survival (98.6% vs 83.2%, 95%CI: 96.7%-100%, P=0.006) and locoregional recurrence-free survival (95.9% vs 80.4%, 95%CI: 92.7%-99.2%, P=0.021) 。 Multifactorial Cox regression modeling showed that PNI was an independent prognostic factor for VMAT treatment of nasopharyngeal cancer (OS: HR=0.32, 95%CI 0.14-0.71; LRFS: HR=0.41, 95%CI 0.19-0.89). Based on this, we suggest implementing individualized intervention strategies for patients with low PNI (\u0026le;46.15), such as pre-radiotherapy nutritional risk screening and early enteral nutritional support, which may enhance therapeutic efficacy through multiple mechanisms, such as improving the nutrient metabolism microenvironment and enhancing radiosensitivity.\u003c/p\u003e\n\u003cp\u003eThis study has several limitations: first, as a retrospective study, there may be selection bias in the patient enrollment criteria. second, the relatively insufficient sample size and short follow-up time may affect the statistical validity. further, the plan revision decision mainly relies on clinical experience rather than a standardized assessment system. Therefore, there is an urgent need to construct an intelligent decision-making system for ART based on multimodal imaging histology features and machine learning models to achieve dynamic and accurate optimization of treatment plans. The core elements of such systems should include: a real-time dose accumulation assessment module; a deep learning-based anatomical deformation prediction algorithm; and an automated decision support tool for quantitative risk-benefit ratio analysis. Through the integration of the above technologies, it is expected to ensure radiobiological effects while minimizing treatment-related toxic reactions.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThis study confirmed that adaptive radiotherapy significantly reduces the incidence of distant radiotoxic side effects (e.g., dry mouth, swallowing dysfunction) in nasopharyngeal cancer patients. It also maintains comparable survival outcomes, thereby improving patients\u0026apos; long-term quality of life scores. Notably, individualized treatment strategies constructed on the basis of patients\u0026apos; baseline nutritional status (as assessed by the Prognostic Nutritional Index) and tumor load characteristics (volume of primary tumor, number and size of lymph node metastases, etc.) may further optimize prognosis.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eFunding:\u0026nbsp;\u003c/strong\u003eNone\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflict of Interest:\u003c/strong\u003e None declared.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics Statement:\u0026nbsp;\u003c/strong\u003eThis retrospective study was approved by the Ethics Committee of Sichuan Cancer Hospital (Approval No. SCCHEC-02-2024-192GIA), and its methodology was conducted in accordance with the approved guidelines, with all patients signing an informed consent form prior to the questionnaire survey\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData availability:\u0026nbsp;\u003c/strong\u003eThe datasets generated and/or analyzed in this study are available upon request from the first author\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eKam M K, Chau R M, Suen J, et al. Intensity-modulated radiotherapy in nasopharyngeal carcinoma: dosimetric advantage over conventional plans and feasibility of dose escalation. Int J Radiat Oncol, 2003,56(1):145-157.https://doi.org/10.1016/s0360-3016(03)00075-0\u003c/li\u003e\n\u003cli\u003eMendenhall W M, Amdur R J, Palta J R. Intensity-modulated radiotherapy in the standard management of head and neck cancer: promises and pitfalls. J Clin Oncol, 2006,24(17):2618-2623.https://doi.org/10.1200/JCO.2005.04.7225\u003c/li\u003e\n\u003cli\u003eMarta G N, Silva V, de Andrade C H, et al. Intensity-modulated radiation therapy for head and neck cancer: systematic review and meta-analysis. Radiother Oncol, 2014,110(1):9-15.https://doi.org/10.1016/j.radonc.2013.11.010\u003c/li\u003e\n\u003cli\u003ePow E H, Kwong D L, McMillan A S, et al. 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Radiat Oncol, 2015,10:6.https://doi.org/10.1186/s13014-014-0318-z\u003c/li\u003e\n\u003cli\u003eWu Q, Chi Y, Chen P Y, et al. Adaptive replanning strategies accounting for shrinkage in head and neck IMRT. Int J Radiat Oncol, 2009,75(3):924-932.https://doi.org/10.1016/j.ijrobp.2009.04.047\u003c/li\u003e\n\u003cli\u003eMaheshwari G, Dhanawat A, Kumar H S, et al. Clinical and dosimetric impact of adaptive intensity-modulated radiotherapy in locally advanced head-and-neck cancer. \u003cem\u003eJ Cancer Res Ther\u003c/em\u003e, 2020,16(3):600-604.https://doi.org/10.4103/jcrt.JCRT_928_19\u003c/li\u003e\n\u003cli\u003eWu Q, Chi Y, Chen P Y, et al. Adaptive replanning strategies accounting for shrinkage in head and neck IMRT. Int J Radiat Oncol, 2009,75(3):924-932.https://doi.org/10.1016/j.ijrobp.2009.04.047\u003c/li\u003e\n\u003cli\u003eHolt A, Van Gestel D, Arends M P, et al. Multi-institutional comparison of volumetric modulated arc therapy vs. intensity-modulated radiation therapy for head-and-neck cancer: a planning study. Radiat Oncol, 2013,8:26.https://doi.org/10.1186/1748-717X-8-26\u003c/li\u003e\n\u003cli\u003eOlteanu L A, Berwouts D, Madani I, et al. Comparative dosimetry of three-phase adaptive and non-adaptive dose-painting IMRT for head-and-neck cancer. Radiother Oncol, 2014,111(3):348-353.https://doi.org/10.1016/j.radonc.2014.02.017\u003c/li\u003e\n\u003cli\u003eCastelli J, Thariat J, Benezery K, et al. Weekly Adaptive Radiotherapy vs Standard Intensity-Modulated Radiotherapy for Improving Salivary Function in Patients With Head and Neck Cancer: A Phase 3 Randomized Clinical Trial. \u003cem\u003eJama Oncol\u003c/em\u003e, 2023,9(8):1056-1064.https://doi.org/10.1001/jamaoncol.2023.1352\u003c/li\u003e\n\u003cli\u003eBeadle B M, Chan A W. The Potential of Adaptive Radiotherapy for Patients With Head and Neck Cancer\u0026mdash;Too Much or Not Enough? \u003cem\u003eJama Oncol\u003c/em\u003e, 2023,9(8):1064-1065.https://doi.org/10.1001/jamaoncol.2023.1306\u003c/li\u003e\n\u003cli\u003eLee N, Harris J, Garden A S, 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.https://doi.org/10.1200/JCO.2008.19.9109\u003c/li\u003e\n\u003cli\u003eSu S F, Han F, Zhao C, et al. LONG-TERM OUTCOMES OF EARLY-STAGE NASOPHARYNGEAL CARCINOMA PATIENTS TREATED WITH INTENSITY-MODULATED RADIOTHERAPY ALONE. Int J Radiat Oncol, 2012,82(1):327-333.https://doi.org/10.1016/j.ijrobp.2010.09.011\u003c/li\u003e\n\u003cli\u003eChen A M, Daly M E, Cui J, et al. Clinical outcomes among patients with head and neck cancer treated by intensity-modulated radiotherapy with and without adaptive replanning. Head Neck-J Sci Spec, 2014,36(11):1541-1546.https://doi.org/10.1002/hed.23477\u003c/li\u003e\n\u003cli\u003eYang H, Hu W, Wang W, et al. Replanning during intensity modulated radiation therapy improved quality of life in patients with nasopharyngeal carcinoma. Int J Radiat Oncol, 2013,85(1):e47-e54.https://doi.org/10.1016/j.ijrobp.2012.09.033\u003c/li\u003e\n\u003cli\u003eCastelli J, Thariat J, Benezery K, et al. Weekly Adaptive Radiotherapy vs Standard Intensity-Modulated Radiotherapy for Improving Salivary Function in Patients With Head and Neck Cancer: A Phase 3 Randomized Clinical Trial. \u003cem\u003eJama Oncol\u003c/em\u003e, 2023,9(8):1056-1064.https://doi.org/10.1001/jamaoncol.2023.1352\u003c/li\u003e\n\u003cli\u003eZhou X, Wang W, Zhou C, et al. Long-term outcomes of replanning during intensity-modulated radiation therapy in patients with nasopharyngeal carcinoma: An updated and expanded retrospective analysis. Radiother Oncol, 2022,170:136-142.https://doi.org/10.1016/j.radonc.2022.03.007\u003c/li\u003e\n\u003cli\u003eChen A M, Daly M E, Cui J, et al. Clinical outcomes among patients with head and neck cancer treated by intensity-modulated radiotherapy with and without adaptive replanning. Head Neck-J Sci Spec, 2014,36(11):1541-1546.https://doi.org/10.1002/hed.23477\u003c/li\u003e\n\u003cli\u003eZhao L, Wan Q, Zhou Y, et al. The role of replanning in fractionated intensity modulated radiotherapy for nasopharyngeal carcinoma. Radiother Oncol, 2011,98(1):23-27.https://doi.org/10.1016/j.radonc.2010.10.009\u003c/li\u003e\n\u003cli\u003eAhn P H, Chen C, Ahn A I, et al. Adaptive Planning in Intensity-Modulated Radiation Therapy for Head and Neck Cancers: Single-Institution Experience and Clinical Implications. International Journal of Radiation Oncology*Biology*Physics, 2011,80(3):677-685.https://doi.org/10.1016/j.ijrobp.2010.03.014\u003c/li\u003e\n\u003cli\u003eGul O V, Buyukcizmeci N, Basaran H. Dosimetric evaluation of three-phase adaptive radiation therapy in head and neck cancer. \u003cem\u003eRadiat Phys Chem\u003c/em\u003e, 2023,202:110588.https://doi.org/10.1016/j.radphyschem.2022.110588\u003c/li\u003e\n\u003cli\u003eLangius J A, Bakker S, Rietveld D H, et al. Critical weight loss is a major prognostic indicator for disease-specific survival in patients with head and neck cancer receiving radiotherapy. \u003cem\u003eBrit J Cancer\u003c/em\u003e, 2013,109(5):1093-1099.https://doi.org/10.1038/bjc.2013.458\u003c/li\u003e\n\u003cli\u003eBeltran M, Ramos M, Rovira J J, et al. Dose variations in tumor volumes and organs at risk during IMRT for head-and-neck cancer. \u003cem\u003eJ Appl Clin Med Phys\u003c/em\u003e, 2012,13(6):3723.https://doi.org/10.1120/jacmp.v13i6.3723\u003c/li\u003e\n\u003cli\u003eFanetti G, Polesel J, Fratta E, et al. Prognostic Nutritional Index Predicts Toxicity in Head and Neck Cancer Patients Treated with Definitive Radiotherapy in Association with Chemotherapy. \u003cem\u003eNutrients\u003c/em\u003e, 2021,13(4).https://doi.org/10.3390/nu13041277\u003c/li\u003e\n\u003cli\u003eMiao J, Xiao W, Wang L, et al. The value of the Prognostic Nutritional Index (PNI) in predicting outcomes and guiding the treatment strategy of nasopharyngeal carcinoma (NPC) patients receiving intensity-modulated radiotherapy (IMRT) with or without chemotherapy. \u003cem\u003eJ Cancer Res Clin\u003c/em\u003e, 2017,143(7):1263-1273.https://doi.org/10.1007/s00432-017-2360-3\u003c/li\u003e\n\u003cli\u003eShi Y, Zhang Y, Niu Y, et al. Prognostic role of the prognostic nutritional index (PNI) in patients with head and neck neoplasms undergoing radiotherapy: A meta-analysis. \u003cem\u003ePlos One\u003c/em\u003e, 2021,16(9):e257425.https://doi.org/10.1371/journal.pone.0257425\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Table 1","content":"\u003cp\u003eTable 1 is available in the Supplementary Files section.\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Adaptive radiotherapy, Nasopharyngeal carcinoma, Volumetric modulated arc therapy, Prognostic analysis, Propensity-matched analysis","lastPublishedDoi":"10.21203/rs.3.rs-6346006/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6346006/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eOBJECTIVE\u003c/h2\u003e \u003cp\u003eThe clinical benefits of offline adaptive radiotherapy(ART) in volumetric modulated arc therapy(VMAT) for locally advanced nasopharyngeal carcinoma (LA-NPC), particularly regarding long-term quality of life, are not well-established due to conflicting evidence.This study aims to clarify the clinical value of offline ART in LA-NPC, particularly its effects on long-term patient survival quality.\u003c/p\u003e\u003ch2\u003eMATERIALS AND METHODS\u003c/h2\u003e \u003cp\u003eRetrospectively, 355 patients with LA-NPC treated with VMAT between January 2020 and December 2021 were included to optimize between-group comparability by propensity score matching (PSM) and to systematically assess the difference in efficacy and quality of life between ART and VMAT. The primary study endpoints were overall survival (OS) and progression-free survival (PFS), distant metastasis-free survival (DMFS), and local-regional recurrence-free survival (LRFS), and the survival curves were plotted by the Kaplan-Meier method and compared with between-groups differences by the Log-rank test, and the Cox proportional risk model was used to calculate the corrected risk ratio. At the final follow-up, quality of life was assessed using the Chinese version of the European Organization for Research and Treatment of Cancer (EORTC) core quality of life questionnaire QLQ-C30 (v3.0) and the head and neck cancer-specific module QLQ-H\u0026amp;N35 (v1.0).\u003c/p\u003e\u003ch2\u003eRESULTS\u003c/h2\u003e \u003cp\u003eAfter PSM, a total of 254 patients (127 each in the ART and VMAT groups) were included in the final analysis. Survival analysis showed that no statistically significant differences were observed between the two groups in the 3-year primary survival endpoints: 96.7% vs 95.9% (P\u0026thinsp;=\u0026thinsp;0.764) for OS, 88.2% vs 86.6% (P\u0026thinsp;=\u0026thinsp;0.835) for PFS, 92.1% vs 92.8% (P\u0026thinsp;=\u0026thinsp;0.647) for LRFS, and 91.2% vs 88.9% for DMFS (P\u0026thinsp;=\u0026thinsp;0.540). The ART group exhibited significantly lower xerostomia incidence (19.1\u0026thinsp;\u0026plusmn;\u0026thinsp;20.7 vs. 31.6\u0026thinsp;\u0026plusmn;\u0026thinsp;23.0, P\u0026thinsp;\u0026lt;\u0026thinsp;0.001) and reduced sticky saliva scores (8.83\u0026thinsp;\u0026plusmn;\u0026thinsp;16.0 vs. 15.5\u0026thinsp;\u0026plusmn;\u0026thinsp;18.4, P\u0026thinsp;=\u0026thinsp;0.004) compared to the non-adaptive VMAT group,Moreover, the ART group demonstrated better cognitive function (86.8\u0026thinsp;\u0026plusmn;\u0026thinsp;13 vs. 82.7\u0026thinsp;\u0026plusmn;\u0026thinsp;14.7, P\u0026thinsp;=\u0026thinsp;0.030) and physical function (96.2\u0026thinsp;\u0026plusmn;\u0026thinsp;9.84 vs. 93\u0026thinsp;\u0026plusmn;\u0026thinsp;11.8, P\u0026thinsp;=\u0026thinsp;0.026). Additionally, multifactorial Cox regression analysis identified EBV and prognostic nutritional index as independent predictors of clinical outcomes.\u003c/p\u003e\u003ch2\u003eCONCLUSION\u003c/h2\u003e \u003cp\u003eThis long-term follow-up study suggests that offline adaptive radiotherapy can reduce toxicity without affecting the survival of patients with LANPC. Further prospective clinical studies are necessary to validate these findings.\u003c/p\u003e","manuscriptTitle":"Impact of Offline Adaptive Radiotherapy on Survival and Quality of Life in Locally Advanced Nasopharyngeal Carcinoma: A Propensity-Matched Retrospective Study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-05-07 06:02:40","doi":"10.21203/rs.3.rs-6346006/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"7c3baf1f-6e9e-4395-afe1-2721ffe9ae53","owner":[],"postedDate":"May 7th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":47564447,"name":"Biological sciences/Cancer/Cancer therapy/Radiotherapy"},{"id":47564448,"name":"Biological sciences/Cancer/Head and neck cancer"}],"tags":[],"updatedAt":"2025-05-16T05:24:01+00:00","versionOfRecord":[],"versionCreatedAt":"2025-05-07 06:02:40","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-6346006","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6346006","identity":"rs-6346006","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}