Distribution pattern of medial group retropharyngeal lymph nodes and its implication in optimizing clinical target volume in nasopharyngeal carcinoma.

Purpose: This study aimed to determine the diagnostic value of diffusion-weighted imaging (DWI) and to elucidate the clinical characteristics of medial group retropharyngeal lymph nodes (RLNs) based on multi-modal imaging. Also, we intended to explore the feasibility of optimizing the CTV60 boundary based on the characteristics of medial group RLNs. Methods: A total of 549 patients with nasopharyngeal carcinoma received magnetic resonance imaging (MRI), DWI, and contrast-enhanced computed tomography (CT) to detect and evaluate clinical characteristics of medial group RLNs. [18F]Fluorodeoxyglucose positron emission tomography/computed tomography was utilized to identify fluorodeoxyglucose uptaking and contrast-enhanced CT to ensure the reliability of CTV optimization during radiotherapy. The DESdC (Drinking, Eating, Swallowing Difficulties, and Coughing while Eating or Drinking) score was utilized to evaluate swallowing disability. Results: Fourteen of 549 patients had medial group RLNs with a transverse diameter of 2.0-19.0 mm, which distributed between the upper margin of 1st cervical vertebra (C1) and the upper one-third of C3. Lasso regression and Pearson chi-square test suggested that its occurrence was associated with stage N, bilateral cervical lymph node metastases, especially when the transverse diameter of cervical lymph nodes was > 3 cm. The sensitivity of DWI, T2 STIR, and contrast-enhanced CT was 100%, 57.1%, and 21.4%, respectively. We optimized CTV60 of medial group RLNs from the base of skull to the upper edge of C2 excluding specific cases. For patients with CTV60 optimization, radiation dose and volume of swallowing structures decreased obviously. Based on our radiotherapy strategy on CTV60, acute toxicities of enrolled patients were well tolerated. Ninety-six of 549 patients had scores with DESdC score. Eighty-three patients scored 1, seven patients scored 2, one patient scored 3, and three patients scored 4. The median interval from the onset of symptoms was 72 (4-114) months. The 5-year overall survival, progression-free survival, local recurrence-free survival, and distant metastasis-free survival were 87%, 80%, 93%, and 85%, respectively. None of the patients with regional recurrence happened in the optimized region. Conclusion: DWI possesses superiorities in displaying lymph nodes. Based on the low incidence of the medial RLNs, CTV60 of medial group RLNs from the base of skull to the upper edge of C2 is feasible and has dosimetric advantages for protecting swallowing structures.

Isoliquiritigenin suppresses the proliferation and induced apoptosis via miR-32/LATS2/Wnt in nasopharyngeal carcinoma.

Nasopharyngeal Carcinoma is limited by the various severe side-effects and surgery is rarely performed. Iosliquiritigenin has a series of biological activities, such as antiviral, anti-free radical and antitumor. However, the role and underlying mechanism of isoliquiritigenin in nasopharyngeal carcinoma have not been understood yet. Herein, the results revealed that isoliquiritigenin could inhibit cell proliferation in nasopharyngeal carcinoma cell lines, including C666-1 and CNE2, in both Cell Counting Kit-8 (CCK-8) and 5-Ethynyl-2'-deoxyuridine (EdU) assay. In addition, isoliquiritigenin promoted nasopharyngeal carcinoma cell apoptosis, with the up-regulations of Bax, Caspase-3 and Caspase-9 and the down-regulation of Bcl-2. Meanwhile, isoliquiritigenin suppressed nasopharyngeal carcinoma cells migration and invasion with the down-regulation of matrix metalloproteinases (MMP)-2 and MMP-9. Furthermore, the expression of miR-32 was up-regulated in the nasopharyngeal carcinoma tissues, while isoliquiritigenin could significantly down-regulate the expression of miR-32. And over-expression of miR-32 promoted the nasopharyngeal carcinoma cells growth, migration and invasion, and suppressed apoptosis. However, isoliquiritigenin treatment dramatically inhibited the effect of miR-32. Besides, luciferase reporter assay confirmed that large tumor suppressor 2 (LATS2) was a direct target of miR-32. And isoliquiritigenin increased the expression of LATS2, while silencing of LATS2 promoted the nasopharyngeal carcinoma cells growth. Moreover, western blotting discovered that isoliquiritigenin inhibited nasopharyngeal carcinoma cells growth via Wnt signaling pathway. Finally, CNE2 cells transplanted xenografts tumor model in nude mice were performed and it suggested that isoliquiritigenin could inhibit the development of xenografts nude mice, along with the decrease of tumor volume and the expression of miR-32 and LATS2. Overall, isoliquiritigenin was confirmed to be a potent anti-nasopharyngeal carcinoma compound both in vitro and in vivo, and accomplished by regulation of miR-32/LATS2/Wnt.

A retrospective dosimetry study of intensity-modulated radiotherapy for nasopharyngeal carcinoma: radiation-induced brainstem injury and dose-volume analysis.

BACKGROUND: Radiation therapy is the standard radical treatment for nasopharyngeal carcinoma (NPC) but also causes transient as well as long-term complications. Patients who develop severe radiation-induced brainstem injuries have a poor prognosis due to the lack of effective medical therapies. However, the relationship between brainstem injury and radiation volume dose is unknown. In this study, we found that radiation-induced brainstem injury was significantly associated with brainstem dose per unit volume. METHODS: A retrospective analysis was performed on a consecutive cohort of 327 patients with NPC receiving IMRT from May 2005 to December 2014. Dose-volume data and long-term outcome were analyzed. RESULTS: The median follow-up duration was 56 months (range, 3-141 months), and six with T4 and two with T3 patients had radiation-induced brainstem injuries. The 3-year and 5-year incidences were 2.2% and 2.8%, respectively. The latency period of brainstem injury ranged from 9 to 58 months, with a median period of 21 months. The Cox regression analysis showed that brainstem radiation toxicity was associated with the T4 stage, D2% of gross tumor volume of nasopharyngeal primary lesions and their direct extensions (GTVnx), Dmax (the maximum point dose), D1%, D0.1cc (the top dose delivered to a 0.1-ml volume), and D1cc (the top dose delivered to a 1-ml volume) of the brainstem (p < 0.05). Receiver operating characteristic (ROC) curves showed that GTVnx D2% and the Dmax, D1%, D0.1cc, and D1cc of the brainstem were significant predictors of brainstem injury. The area under the ROC curve for these five parameters was 0.724, 0.813, 0.818, 0.818, and 0.798, respectively (p < 0.001), and the cutoff points 77.26 Gy, 67.85 Gy, 60.13 Gy, 60.75 Gy, and 54.58 Gy, respectively, were deemed as the radiation dose limit. CONCLUSIONS: Radiotherapy-induced brainstem injury was uncommon in patients with NPC who received definitive IMRT. Multiple dose-volume data may be the dose tolerance of radiation-induced brainstem injury.

MicroRNA-125b inhibits cell proliferation and induces cell apoptosis in esophageal squamous cell carcinoma by targeting BMF.

MicroRNAs (miRNAs) have been reported to regulate the expression of genes by suppressing translation or facilitating mRNA decay. Their expression regulates a wide variety of cellular processes, including the development and progression of cancer. Esophageal squamous cell carcinoma (ESCC) is a malignant cancer with high morbidity and recurrence in Asia. In the present study, the biological function of miR-125b and its underlying mechanism in ESCC were explored. The results revealed that miR-125b expression was significantly decreased in ESCC tissues and cell lines. A decrease in miR-125b was markedly related to lymphatic metastasis in patients. Functional analysis revealed that the overexpression of miR-125b using miR-125b mimics significantly inhibited cell growth and induced cell apoptosis, and increased the G1 phase of the cell cycle in EC109 and EC9706 cells. Notably, the miR-125b inhibitors revealed the opposite effect. Additionally, overexpression of miR-125b significantly inhibited tumor growth in vivo. Furthermore, BCL-2-modifying factor (BMF) was considered to be a potential candidate target of miR-125b based on miRNA target databases. miR-125b negatively regulated BMF expression by directly binding to its 3'-untranslated region. BMF was a functional target of miR-125b in the regulation of cell proliferation, cell apoptosis and the cell cycle in EC109 and EC9706 cells. In clinical ESCC specimens, BMF expression was upregulated, and negatively correlated with that of miR-125b. In conclusion, miR-125b had an antitumor role in ESCC cells mediated by targeting BMF, which can be potentially useful for tumorigenesis in ESCC.

Prognostic factors of radiotherapy in patients with node-positive thoracic esophageal squamous cell carcinoma after radical surgery.

The aim of this study was to retrospectively analyze and assess the outcomes and prognostic factors of radiotherapy in patients with node-positive thoracic esophageal squamous cell carcinoma after radical surgery. One hundred twenty-six patients with node-positive thoracic esophageal squamous cell carcinoma who had undergone adjuvant therapy (postoperative radiotherapy alone or postoperative sequential chemoradiotherapy without receiving postoperative concurrent chemoradiotherapy) after radical surgery, were retrospectively reviewed from January 1996 to December 2003. Univariate and multivariate analyses were performed using log-rank and Cox proportional hazard models, and survival curves were estimated using the Kaplan-Meier method. The 1-, 3- and 5-year overall survival rates of all 126 patients were 71.4, 39.1, and 22.0%, and disease-free survival rates were 64.3, 36.4, and 21.5%, respectively. Lymph node ratio (the ratio of the number of metastatic lymph nodes to the number of lymph nodes removed, LNR) > or = 0.2 (P= 0.006), pT3 + pT4 (P= 0.06) and sequential chemoradiotherapy (P= 0.08) were associated with a poorer survival by univariate analysis. In multivariate analysis, LNR (P= 0.01, hazard ratio = 0.57, 95% confidence interval, 0.37-0.87) and tumor depth of invasion (P= 0.03, hazard ratio = 0.62, 95% confidence interval, 0.41-0.96) were the independent predictors of survival. Sequential chemoradiotherapy receded survival tendency without significant difference (P= 0.09, hazard ratio = 0.64, 95% confidence interval, 0.37-1.08). Therefore, LNR and tumor depth of invasion were the independent prognostic factors of radiotherapy in patients with node-positive thoracic esophageal squamous cell carcinoma after radical surgery. The addition of chemotherapy does not seem to confer a survival benefit.