Objective:To analyze the safety of reduced clinical target volume (CTV) irradiation of suspicious positive lymph nodes in IIa region in patients with N 0-N 1 nasopharyngeal carcinoma (NPC) and the protective effect of submandibular gland and long-term resting dry mouth, and to explore the diagnostic value of multimodal imaging for suspicious cervical lymph nodes. Methods:Clinical data of T 0-4N 0-1M 0 stage NPC patients admitted to Jiangsu Cancer Hospital from July 2015 to April 2017 were retrospectively analyzed. Clinical, radiation therapy planning, multimodal imaging and other relevant data were collected. All patients were treated with an optimized regimen of IMRT with a prophylactic radiation dose of 50.4 Gy (named as CTV50) for IIa region. Imaging characteristics and treatment response of suspicious lymph nodes were monitored by MRI, MRI-DWI, PET-CT and repeated enhanced positioning CT, etc. The dosimetry of the submandibular gland between optimized and standard dose plans (CTV50 vs. CTV60) was compared by paired t-test. The long-term dry mouth degree of the patients was evaluated using advanced radiation injury from Radiation Therapy Oncology Group (RTOG), Jiangsu Cancer Hospital Multi-dimensional Dry Mouth Evaluation Scale and summated xerostomia inventory (SXI). The difference of dry mouth degree was analyzed by rank-sum test. Results:A total of 106 patients were included in this study, including 149 cervical lymph node negative sides, 73 sides of which had ≤3 recognizable lymph nodes, and 76 of which were>3 in Ⅱa region. Among patients with N 1 stage, 63 patients underwent contralateral single neck area optimization, and 43 patients (N 0 stage and N 1 stage patients with retropharyngeal lymph node metastasis) underwent double-neck area optimization. A total of 109 suspicious lymph nodes with a short diameter of >5 mm were found on the largest cross section, of which 105 had clear portal structure. The ratio of long to short diameter was ≥1.5 in 93 cases, and the maximum standardized uptake value (SUV max) in PET-CT was ≥2.5 in 76 cases. No lymph node recurrence was found in the CTV optimized area. There was no significant difference in the average dose of GTV in tumor target area after optimization ( P>0.05), and the D mean and V 39 Gy in submandibular gland were significantly lower than those in unoptimized plan (both P<0.01). There was no significant difference in long-term dry mouth and resting dry mouth between patients with unilateral and bilateral optimization of submandibular gland (both P>0.05). Conclusions:The optimal program of CTV50 reduction irradiation in Ⅱa area of N 0-N 1 NPC patients is safe and effective. The submandibular gland has obvious dosimetric advantages, and patients have a good subjective response to resting dry mouth. The multimodal imaging tools such as enhanced CT, MRI-DWI and PET-CT should be performed to deliver individual evaluation and treatment for suspicious lymph nodes.

Objective:To investigate the treatment strategy and prognostic factors of nasopharyngeal necrosis after the first radical radiotherapy for nasopharyngeal carcinoma.Methods:Clinical data of 1020 patients with nasopharyngeal carcinoma undergoing radical intensity-modulated radiotherapy in Jiangsu Cancer Hospital from January 2013 to January 2022 were retrospectively analyzed. Nasopharyngeal necrosis was confirmed by nasopharyngeal MRI, electronic nasopharyngoscopy and biopsy. Patients with nasopharyngeal necrosis were treated with electronic nasopharyngoscope irrigation debridement, combined with systemic anti-infection and nutritional support therapy. Kaplan-Meier method was used to calculate the survival, and Cox regression analysis was used to analyze the relationship between clinical factors and patients' survival.Results:Nasopharyngeal necrosis occurred in 20 cases of 1020 nasopharyngeal carcinoma patients after the first radical intensity-modulated radiotherapy, with an incidence rate of 1.96%. Odd smell and headache were common in nasopharyngeal necrosis patients. All patients had locally advanced nasopharyngeal carcinoma at initial treatment, including 2 (10%) cases of T 3 stage and 18 (90%) cases of T 4 stage. Nasopharyngeal necrosis occurred in the primary nasopharyngeal lesions. According to the stages of nasopharyngeal necrosis, there were 6 (30%) cases of stage I, 14 (70%) cases of stage II and no stage III. The occurrence time of nasopharyngeal necrosis was from 2 to 24 months after radiotherapy, and the median time was 5 months. All 16 cases of nasopharyngeal necrosis were cured clinically after debridement and irrigation under nasopharyngoscope, systemic anti-infection and symptomatic support treatment. Among them, 9 cases had no necrotic cavity and complete healing and 7 cases had residual necrotic cavity. Four patients died of massive nasopharyngeal hemorrhage or due to the inability to nasopharyngeal irrigation. The 5-year survival rates were 37.5% and 85.7% in patients with and without internal carotid artery involvement ( P=0.008), and 25.0% and 77.8% in patients with and without diabetes mellitus ( P=0.016). Univariate Cox regression analysis showed that necrotic lesions involving internal carotid artery ( HR=5.80, 95% CI=1.14-29.38, P=0.034) and diabetes mellitus ( HR=10.24, 95% CI=1.19-88.04, P=0.034) were the influencing factors of overall survival. Conclusions:Nasopharyngoscope irrigation debridement combined with anti-inflammation and nutritional support treatment are effective interventions for nasopharyngeal necrosis after the first radical intensity-modulated radiotherapy in patients with nasopharyngeal carcinoma. The necrosis involving the internal carotid artery and diabetes mellitus are important factors affecting the survival of patients. Vascular invasion caused by vascular rupture is the main cause of death.

Objective:To investigate the feasibility of individualized primary clinical target volume (CTV) delineation in intensity-modulated radiotherapy for nasopharyngeal carcinoma (NPC).Methods:Clinical data of 87 consecutive patients newly diagnosed with lateralized NPC in Jiangsu Cancer Hospital between October 2016 and February 2018 were retrospectively analyzed. Lateralized NPC is defined as tumor invasion not exceeding the contralateral wall. According to the tumor spread, the primary CTV was optimized as follows: CTV2 only covered the medial part of the contralateral pterygopalatine fossa, whereas the contralateral foramen oval was not included; on the level of parapharyngeal space, the contralateral side of CTV only covered the posterior lateral lymph nodes, whereas the contralateral internal jugular vein was not regularly covered. Failure patterns and 5-year survival [local control rate (LCR), progression-free survival (PFS) and overall survival (OS)] were evaluated by Kaplan-Meier method. Paired t-test and rank-sum test were used to analyze the dose variation in the optimized region and adverse reactions. Results:The median follow-up time was 59.5 months. The 5-year LCR, PFS, and OS were 98.9%, 86.5% and 92.1%, respectively. There was no local recurrence in the optimized area of CTV. Dosimetric comparison results showed that the doses of parotid gland, temporal lobe, cochlea and middle ear on the contralateral side were reduced by 13.45%, 9.14%, 38.83%, and 29.36%, respectively. Four cases (4.6%) developed grade 3 hearing loss, all on the ipsilateral side. The optimized scheme significantly alleviated the hearing loss on the contralateral side compared to that on the ipsilateral side ( P<0.001). Other grade 3 late adverse reactions included cranial nerve injury, subcutaneous fibrosis in the neck and visual impairment, with 1 case each. Conclusion:Individualized primary CTV for lateralized NPC is feasible and safe, with obvious dosimetric advantages and reduced adverse reaction rate, which is worthy of clinical promotion.

Objective:To explore the effect of clinical target volume (CTV) optimization on long-term survival and late xerostomia of patients with nasopharyngeal carcinoma (NPC).Methods:Clinical data of 763 patients with NPC treated with intensity-modulated radiotherapy (IMRT) in the Jiangsu Cancer Hospital from January 2015 to November 2018 were retrospectively analyzed. All patients were divided into the modified and conventional CTV groups. Propensity score matching (PSM) was applied to balance the distribution of baseline features. The degree of xerostomia was evaluated by Radiation Therapy Oncology Group (RTOG) / European Organisation for Research and Treatment of Cancer (EORTC) standard and Jiangsu Cancer Hospital Multi-dimensional Radiotherapy-Induced Xerostomia scale. Survival analysis was performed by Kaplan-Meier method. The difference of xerostomia between two groups was compared by rank-sum test. The dose parameters of salivary glands were compared by independent sample t-test. Prognostic factors of survival and xerostomia were assessed by univariate / multivariate regression analyses. Results:There were no significant differences in overall survival, local recurrence-free survival, distant metastasis-free survival and progression-free survival between conventional and modified CTV groups before and after PSM. There were no significant differences in the incidence of late xerostomia above grade 2 of RTOG/EORTC standard between two groups. Using multi-dimensional scale criteria, NPC patients in the modified CTV group developed less late xerostomia than those in the conventional CTV group ( P<0.05). D mean and V 26 Gy of bilateral parotid glands, D mean and V 39 Gy of bilateral submandibular glands, and D mean of sublingual glands and mouths were reduced after optimization of CTV (all P<0.001). Univariate analysis showed that clinical staging, T staging and N staging were the independent prognostic factors of overall survival. Multivariate analysis demonstrated that clinical staging was the independent prognostic factor of overall survival. The risk factor for xerostomia during night sleep was the D mean of sublingual glands. Conclusion:The optimization of CTV in IIb region in NPC treated with IMRT can better protect salivary glands and reduce the incidence of late radiation-induced xerostomia on the premise of ensuring long-term survival.

Objective:To determine the safety of prophylactic irradiation dose CTV 60Gy optimized to CTV 50Gy for II b region in patients with stage N 0-N 1 nasopharyngeal carcinoma (NPC) and the dose advantage and clinical value for parotid gland protection, and to understand the diagnostic value of PET-CT and diffusion-weighted imaging (DWI) for suspicious positive lymph nodes in the neck (5 mm≤maximum short diameter<10 mm). Methods:Clinical data of 157 patients with primary non-metastatic NPC (N 0-N 1) admitted to our hospital from June 2015 to March 2017 were retrospectively analyzed. 104 patients underwent II b clinical target volume optimization guided by multimodal imaging system. Survival analysis was performed by Kaplan - Meier method. Univariate/multivariate regression analysis was performed to analyze the pattern of cervical lymph node recurrence. Paired t-test was used to compare the differences in target volume and parotid gland dose parameters before and after dose optimization. Results:Sixty patients underwent single-neck optimization in stage N 1, 25 patients received double-neck optimization (only those with retropharyngeal lymph node metastasis), and 19 patients underwent double-neck optimization in stage N 0. Three patients had cervical regional recurrence, all in-field. The 5-year overall survival rate was 93.3%. The lymph node recurrence-free survival rate, local recurrence-free survival rate, distant metastasis-free survival rate and disease-free survival rate were 97.1%, 91.3%, 88.5% and 80.8%, respectively. Cervical lymph node recurrence was associated with local recurrence in the nasopharynx, regardless of retropharyngeal lymph node status. Fourteen patients had suspicious positive cervical lymph nodes in II b region, with a mean maximum short diameter of 7.1 (5~9) mm on the largest cross-sectional plane, and 11 of them were positive on PET-CT, with a mean SUV max of 2.96 (2.5~3.3). There was no significant difference in GTV after optimization ( P>0.05). D mean, D max, D 50% and V 26Gy of parotid gland were significantly lower than those of conventional plan (all P<0.01). Conclusions:It is safe to optimize CTV 60Gy to CTV 50Gy in II b region in patients with N 0-N 1 NPC, and the exposure dose to normal tissues around the parotid gland and neck is significantly reduced. For small lymph nodes that do not meet the diagnostic criteria, it needs to be individualized in combination with multimodality imaging systems, such as PET-CT and DWI.

Objective:To explore the significance of the clinical target volume (CTV) dose optimization in the upper and middle neck in protecting the laryngopharynx, anterior and posterior rings during intensity-modulated radiotherapy (IMRT) and multimodal imaging system for nasopharyngeal carcinoma.Methods:Clinical data of 298 nasopharyngeal carcinoma patients admitted to Jiangsu Cancer Hospital from 2016 to 2018 were retrospectively analyzed. According to the following five strategies of CTV dose optimization in the upper and middle neck: group A, complete optimization of bilateral cervical lymph nodes (CLNs), that is, the CTV doses of bilateral CLNs were 50.4 Gy; group B, complete optimization of unilateral CLNs, that is, the CTV dose of unilateral CLNs was 50.4 Gy and the contralateral CLNs was 60 Gy; group C, incomplete optimization of bilateral CLNs, that is, the CTV doses of bilateral CLNs were 50.4 Gy, while the suspicious positive CLNs were selectively boosted to 60 Gy; group D, incomplete optimization of unilateral CLNs, that is, the CTV dose of unilateral CLNs was 50.4 Gy and the suspicious positive CLNs were selectively boosted to 60 Gy, and the CTV dose of contralateral side was 60 Gy; group E: no optimization, that is, the CTV doses of bilateral CLNs were 60 Gy.Results:Among 298 patients, 215 patients received dose optimization and 83 cases did not receive dose optimization. In the dose optimization schemes, 114 cases were assigned in group A, 36 cases in group B, 60 cases in group C and 5 cases in group D. The median (range) follow-up time was 28.5(6.0-46.3) months. The overall survival rate was 95.6%, the progression-free survival rate was 84.2% and the locoregional control rate of CLNs was 98.0%. Local relapse of CLNs occurred in six patients, including 1 case of retropharyngeal lymph node, 4 cases of Ⅱ area and 1 case of Ⅳ area. The P values of average dose of laryngopharynx in group A, group B, group C and group D compared with that in group E were<0.001, 0.016, 0.001 and 0.572, respectively. The P values of the average dose of the anterior ring in group A, group B, group C and group D compared with that in group E were<0.001, 0.011, <0.001 and 0.805, respectively. The P values of the average dose of the posterior ring in group A, group B, group C and group D compared with that in group E were<0.001, 0.004, <0.001 and 0.252, respectively.Conclusions:Combined with the metastatic rules of CLNs and multimodal imaging system, it is safe to optimize the CTV dose of the upper and middle neck during IMRT in nasopharyngeal carcinoma patients, which can significantly reduce the doses of laryngopharynx, anterior and posterior rings, thereby providing evidence for reducing the CTV dose in the upper and middle neck.

Objective To explore the clinical value of magnetic resonance diffusion-weighted imaging ( MR-DWI ) in the early diagnosis of cervical lymph node recurrence after radiotherapy of nasopharyngeal carcinoma, aiming to provide reference for targeted diagnosis and treatment of these patients. Methods The MR-DWI features of 17 patients with recurrent cervical lymph nodes after radiotherapy from 2005 to 2016 were retrospectively analyzed. The results of diagnosis and treatment after lymph node recurrence were summarized. Results The recurrent lymph nodes of 17 patients showed a high signal or mixed signal on MR-DWI images. The sensitivity of MR-DWI and T2WI fat suppression sequence was 100% and 60%. Positron emission tomography-computed tomography ( PET-CT) or biopsy was performed to validate the diagnosis in patients with highly suspected single cervical recurrence. Besides, surgical treatment yielded better clinical prognosis. Conclusions MR-DWI is highly sensitive to recurrent cervical lymph nodes of nasopharyngeal carcinoma after radiotherapy, especially for the small lymph nodes of 5-10 mm in diameter, which are easily ignored. PET-CT examination should be performed, the nature of the lymph nodes should be confirmed by multi-modality imaging diagnosis, and timely operation has important clinical significance in improving the therapeutic effect and quality of life for patients with cervical lymphnode recurrence.

Objective: To investigate the high-risk factors for parotid lymph node (PLN) metastasis from nasopharyngeal carcinoma (NPC) and evaluate the feasibility of local intensity-modulated radiotherapy (IMRT) in patients with high-risk NPC. Methods: Clinical data of 440 NPC patients admitted to Department of Radiotherapy of Jiangsu Cancer Hospital from May, 2011 to March, 2017 were collected. The imaging features, treatment strategies and clinical prognosis of PLN metastasis were retrospectively analyzed. The whole group adopts the technique of intensity modulated radiotherapy. Total parotid or partial parotid irradiation, selective PLN irradiation, X-Ray and/or electronic line supplementation, dose 45-60 Gy. The χ² test or Fisher′s accurate probability method test and single factor analysis, Logistic regression model multi-factor analysis. Kaplan-Meier survival analysis, log-rank test differences. Results: PLN was observed in the parotid of 230 cases. At the end of follow-up, 11 patients (2.5%, 11/440) were diagnosed with PLN metastases. Among 11 cases, 9 patients (81.8%) had PLN size ≥5 mm. Multivariate analysis demonstrated that extracapsular spread of level Ⅱ was an independent risk factor for PLN metastasis. The patients with PLN size ≥5 mm or extracapsular spread of level Ⅱ were assigned into the high-risk PLN metastasis group. The patients in the high-risk group were further divided into the radiotherapy and non-radiotherapy subgroups. Survival analysis demonstrated that for 230 patients with PLN metastasis, the local recurrence-free survival (LRFS) significantly differed, whereas the overall survival (OS), disease metastasis-free survival (DMFS) and progression-free survival (PFS) did not considerably differ between the radiotherapy and non-radiotherapy subgroups in the high-risk PLN metastasis patients. Conclusions The PLN metastasis rate of NPC is low. Extracapsular spread of level Ⅱ is an independent risk factor. Radiotherapy of the parotid region is considered for patients with PLN size≥5 mm or those with PLN size<5 mm complicated with extracapsular spread of level Ⅱ.

Objective To clarify the diagnostic value of diffusion-weighed imaging ( DWI) in the medial group of retropharyngeal lymph nodes in nasopharyngeal carcinoma, understand the clinical characteristics of retropharyngeal lymph nodes and explore the feasibility of optimizing the target volume of CT V60. Methods Clinical data of 437 patients with clinical stage Ⅰ-IVa nasopharyngeal carcinoma admitted to Jiangsu Cancer Hospital from 2011 to 2017 were retrospectively analyzed. All patients underwent magnetic resonance imaging (MRI),DWI (1 000 s/mm2) and enhanced CT scans to analyze the clinical characteristics of retropharyngeal lymph nodes and investigate the dosimetric advantage and safety of CT V60 lower margin on the upper margin of C2. Results The medial lymph nodes with a transverse diameter of 2. 0-19. 0 mm were detected 13 of 437 patients,and 53. 8% of the lymph nodes were measured 2-5 mm in transverse diameter. The medial lymph nodes were distributed between the superior margin of C1and 1/3 of C3.Its occurrence was related to N stage,double cervical lymph node metastases,especially the transverse diameter of cervical lymph node＞ 3 cm.The sensitivity of DWI,T2and enhanced CT were 100%,61. 5% and 23. 1%.After the special cases were excluded,the lower margin of CT V60on the superior margin of C2was separated. The radiation dose and volume of the swallowing structures were significantly decreased. The 5-year survival rate was 80% without recurrence in the optimized region. Conclusions The incidence of the medial group of retropharyngeal lymph nodes is low with a diameter of less than 5 mm. DWI possesses advantages in displaying the medial group of retropharyngeal lymph nodes. Isolating the lower margin of CT V60from the superior margin of C2is safe and feasible and has dosimetric advantages for protecting swallowing structure.

Objective To investigate the relationship between the incidence of radiation-induced brain stem injury after intensity-modulated radiotherapy (IMRT) and the radiation dose volume in patients with nasopharyngeal carcinoma.Methods A retrospective analysis was performed on the data of 258 patients newly diagnosed with nasopharyngeal carcinoma who received IMRT in our group from 2005 to 2013.The radiation dose per unit volume of brain stem was analyzed.The relationship between the incidence of brain stem injury induced by IMRT and the radiation dose volume was studied.The survival rate was calculated using the Kaplan-Meier method.The factors influencing the radiation-induced brain stem injury were analyzed using the Cox regression model.Results Two patients with stage T3 disease and three patients with T4 disease had radiation-induced brain stem injury.The 3-and 5-year injury incidence rates were 1.6％ and 2.4％,respectively.The latency ranged between 9 and 58 months,with a median latency of 19 months.The median D1％ and Dmax for the brain stem were 54.24 and 59.22 Gy in all patients,54.31 and 59.45 Gy in patients with stage T3 disease,and 61.29 and 66.37 Gy in patients with stage T4 disease,respectively.In the five patients with brain stem injury,the D1％ and Dmax were larger than 60 and 63 Gy,respectively.The univariate analysis showed that the incidence of radiation-induced brain stem injury was correlated with D1％,Dmax,D0.1 cm3,D0.5 cm3,and D1.0 cm3 (all P=0.01).The incidence of radiation-induced brain stem injury was significantly lower in patients with D1％,Dmax,D0.1 cm3,D0.5 cm3,and D1.0 cm3 no larger than 60,63,60,58,and 56 Gy,respectively (all P =0.00).Conclusions The incidence of radiation-induced brain stem injury after IMRT is relatively low in patients with nasopharyngeal carcinoma.Strict control of the dose to the brain stem may help to reduce the incidence of brain stem injury and improve the long-term quality of life.