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Nasopharyngeal carcinoma is one of the most common malignant head and neck tumors, and radiotherapy is the main treatment. However, radio-resistance is a key cause of local recurrence of nasopharyngeal carcinoma. Therefore, overcoming the radio-resistance of nasopharyngeal carcinoma and enhancing the radiosensitivity have become urgent problems in the treatment of nasopharyngeal carcinoma, which also play a key role in improving the overall survival rate of patients. In this article, recent studies on DNA, non-coding RNA (ncRNA), protein and cell behaviors related to radio-resistance of nasopharyngeal carcinoma were reviewed, aiming to provide valuable ideas for clinical treatment of nasopharyngeal carcinoma.
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Objective:To investigate the role of subventricular zone (SVZ) irradiation in the prognosis of patients with glioblastoma (GBM), and to analyze the factors affecting the prognosis of patients with GBM.Methods:Clinical data of 52 patients with GBM treated in the Affiliated Cancer Hospital of Nanjing Medical University from 2017 to 2020 were analyzed retrospectively. According to the median dose of ipsilateral or contralateral SVZ, the patients were divided into the high-dose group and low-dose group. The prognostic differences between two groups were compared and the prognostic factors were analyzed.Results:The median progression-free survival (PFS) was 17.1 months (95% CI:12.4-30.7)and the median overall survival (OS) was 38.3 months (95% CI:20.4-44.5). Univariate analysis showed that whether the tumor invading SVZ ( P = 0.039), the degree of resection ( P = 0.009) and MGMT promoter methylation status ( P = 0.039) were the influencing factors of PFS. Age ( P = 0.018), Kanofsky performance score ( P = 0.043), whether the tumor invading SVZ ( P = 0.038), degree of resection ( P = 0.020) and MGMT promoter methylation status ( P = 0.019) were the influencing factors of OS. The analysis of SVZ dose as a continuous variable showed that SVZ dose was the influencing factor of PFS ( P < 0.05) rather than OS ( P ≥ 0.05). Whether the tumor invading SVZ or not, there was no significant difference in survival between the high-dose and low-dose groups. Multivariate analysis showed that whether the tumor invading SVZ and MGMT promoter methylation were the independent prognostic factor for PFS (both P < 0.05), and OS (both P < 0.05). The SVZ dose related variables were not statistically significant in multivariate analysis. Conclusions:Patients with tumors directly invading SVZ achieve worse survival. Increasing the ipsilateral or contralateral SVZ dose does not improve patient survival. Whether SVZ irradiation affects the survival of patients still needs to be further confirmed by prospective randomized clinical studies.
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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.
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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.
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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.
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PURPOSE: The purpose of this study was to investigate the function of Zinc finger protein 488 (ZNF488) in nasopharyngeal carcinoma (NPC). MATERIALS AND METHODS: The endogenous expression of ZNF488 in NPC tissues, normal nasopharyngeal epithelium tissues and NPC cell lines were detected by quantitative reverse transcription polymerase chain reaction. ZNF488 over-expressing and knock-down NPC cell line models were established through retroviral vector pMSCV mediated over-expression and small interfering RNA (siRNA) mediated knock-down. The invasion and migration capacities were evaluated by wound healing and transwell invasion assays in ZNF488 over-expressing and control cell lines. Soft-agar colony formation and a xenograft experiment were performed to study tumorigenic ability in vitro and in vivo. Immunofluorescence and western blotting analysis were used to examine protein changes followed by ZNF488 over-expression. Microarray analysis was performed to explore gene expression profilings, while luciferase reporter assay to evaluate the transcriptive activity of Tcf/Lef. RESULTS: ZNF488 was over-expressed in NPC tissues compared with normal tissues, especially higher in 5-8F and S18, which are well-established high metastatic NPC clones. Functional studies indicate that over-expression of ZNF488 provokes invasion, whereas knock-down of ZNF488 alleviates invasive capability. Moreover, over-expression of ZNF488 promotes NPC tumor growth both in vitro and in vivo. Our data further show that over-expression of ZNF488 induces epithelial mesenchymal transition (EMT) by activating the WNT/beta-catenin signaling pathway. CONCLUSION: Our data strongly suggest that ZNF488 acts as an oncogene, promoting invasion and tumorigenesis by activating the Wnt/beta-catenin pathway to induce EMT in NPC.