Efficacy and Safety of Chemotherapy Combined with Stereotactic Radiotherapy in the Treatment of Nasopharyngeal Carcinoma.

BACKGROUND The aim of this study was to investigate the efficacy and safety of chemotherapy (CT) combined with stereotactic radiotherapy (SRT) in the treatment of nasopharyngeal carcinoma (NPC). MATERIAL AND METHODS A total of 329 NPC patients without any previous treatment were included in this study between January 2009 and November 2013. These patients were divided into three groups: CT group (n=114), SRT group (n=109), and CT + SRT group (n=106). Contrast-enhanced nasopharyngeal computed tomography (CT)/magnetic resonance (MR) scan was performed on the third month after treatment. Short-term efficacy was evaluated according to the Response Evaluation Criteria in Solid Tumors (RECIST). Toxicity was graded according to the Acute Radiation Morbidity Scoring Criteria (RTOG) and the World Health Organization (WHO) toxicity grading scale. Overall survival (OS), progression free survival (PFS), and incidence rate of acute toxicity (grade ≥3) were calculated after a 24 month follow-up. RESULTS Total response rate of all patients was 85.41%. Compared with the CT group and the SRT group, the CT + SRT group showed a substantially improved efficacy in NPC treatment. The incidence rate of the acute toxicity in the CT + SRT group was slightly higher than in the CT group and the SRT group, but the difference was not statistically significant. No treatment-related deaths were observed. The CT + SRT group had the highest two-year OS and PFS, followed by the CT group and the SRT group. CONCLUSIONS It was shown that NPC patients treated with CT + SRT had better short- and long-term efficacy than those treated with CT or SRT alone.

In Vivo and In Vitro Effects of ATM/ATR Signaling Pathway on Proliferation, Apoptosis, and Radiosensitivity of Nasopharyngeal Carcinoma Cells.

AIM: The study investigated the ability of ataxia-telangiectasia mutated (ATM)/Rad3-related (ATR) signaling pathway to influence the proliferation, apoptosis, and radiosensitivity of nasopharyngeal carcinoma (NPC) cells. MATERIALS AND METHODS: NPC tissues and corresponding adjacent normal tissues were collected from 143 NPC patients. The NPC CNE2 cells were assigned into a control group, X-ray group, CGK-733 group, and X-ray+CGK-733 group. The mRNA levels of ATM and ATR were evaluated using quantitative real-time polymerase chain reaction (qRT-PCR) and the protein levels of ATM and ATR using western blotting. The positive expression of ATM and ATR in tissues and nude mouse tumor tissues was determined by immunohistochemistry. Cell proliferation, migration, invasion, and apoptosis rates were analyzed by the 3-(4,5)-dimethylthiahiazo (-z-y1)-3,5-di- phenytetrazoliumromide (MTT) assay, scratch test, transwell assay, and flow cytometry, respectively. A nude mouse model of NPC was established to observe tumor volume and growth. RESULTS: The mRNA levels of ATR and ATM and the expression of ATR and ATM protein in NPC tissues were significantly higher than those in adjacent normal tissues. The colony formation assay showed that the colony-forming rate decreased, showing radiation dose-dependent and CGK-733 concentration-dependent manners. Expression of ATM, ATR, Chk1, and Chk2 was evidently increased in the X-ray, CGK-733, and X-ray+CGK-733groups compared with the control group, and the aforementioned expression was highest in the X-ray+CGK-733 group among the four groups. The cell proliferation, invasion, and migration were decreased, tumor volume decreased and cell apoptosis increased in the X-ray, CGK-733, and X-ray+CGK-733 groups compared with the control group; the X-ray+CGK-733 group exhibited lowest cell proliferation, invasion and migration, smallest tumor volume, and highest cell apoptosis among the four groups. CONCLUSIONS: Inhibition of ATM/ATR signaling pathway reduces proliferation and enhances apoptosis and radiosensitivity of NPC cells.

Numb Gene Enhances Radiation Sensitivity of Nonsmall Cell Lung Cancer Stem Cells.

OBJECTIVE: To study the effects of Numb gene expression on radiation sensitivity of nonsmall cell lung cancer (NSCLC) stem cells. MATERIALS AND METHODS: The side population (SP) cells A549-SP were transfected with pcDNA3.1 (pcDNA3.1 group), pcDNA-Numb (pcDNA-Numb group) and shRNA-Numb (shRNA-Numb group). Real-time quantitative polymerase chain reaction and Western blot were performed to determine Numb expression; MTT method was used to measure the proliferation activity change of the NSCLC stem cells both before and after irradiation with different doses of 60Coγ ray; Hoechst staining and Annexin V-FITC/PI were used to detect the apoptosis of the NSCLC stem cells; and colony-forming assay was used to determine the effect of Numb expression on radiation sensitivity of the NSCLC stem cells. RESULTS: Increased mRNA and protein expressions of the A549-SP cells were found in the pcDNA-Numb group, and decreased mRNA and protein expressions were found in the shRNA-Numb group. The optical density value of the cells decreased in the pcDNA-Numb group but increased in the shRNA-Numb group. The cells with over-expressed Numb showed obvious nuclear condensation and fragmentation; the apoptosis rate increased significantly. The cells with knockdown Numb showed less nuclear damage; the apoptosis rate significantly decreased. After irradiation, the cells in the pcDNA-Numb group showed decreased survival rate, clonality, and the values of D0, Dq, N, and SF2; whereas the cells in the shRNA-Numb group showed the opposite trend. CONCLUSIONS: Radiation sensitivity of NSCLC stem cells was enhanced with the increase of Numb expression. Determination of Numb expression helped to evaluate the response of lung cancer to radiotherapy, which was important for guiding tumor treatment clinically.

Margin evaluation of translational and rotational set-up errors in intensity modulated radiotherapy for cervical cancer.

A clinical target volume (CTV) to planning target volume (PTV) margin recipes was routinely used to ensure dose was actually delivered to target for all (most) patients. Currently used margin recipes were associated with only translational set-up errors in radiotherapy. However, when set-up errors extended to six-degree (6D) scope (three translational and three rotational set-up errors), margin recipe should be re-evaluated. The purpose of this study was to investigate dosimetric changes of targets (both CTV and PTV) coverage when 6D set-up errors were introduced and testify the practicability of currently used margin recipe in radiotherapy. A total number of 105 cone beam computer tomography scans for ten patients with cervical cancer were derived prior to treatment delivery and 6D set-up errors were acquired with image registration tools. Target coverage was evaluated retrospectively for 6D set-up errors introduced plan with 6 mm CTV to PTV margin. Target coverage of PTV showed significant decreases (3.3 %) in set-up errors introduced plans compared with original plans. But CTV coverage was not susceptible to these set-up errors. A tendency of coverage decrease for PTV along with distance away from treatment was testified, from -0.2 to -6.2 %. However, CTV seems changed less, from -0.2 to -0.8 %. The result indicate that a CTV to PTV margin of 6 mm was sufficient to take into account 6D set-up errors for most patients with cervical cancer. Future research suggests a smaller margin to further improve both tumor coverage and organs at risk sparing.

The role of concurrent chemotherapy to intensity-modulated radiotherapy (IMRT) after neoadjuvant docetaxel and cisplatin treatment in locoregionally advanced nasopharyngeal carcinoma.

The goal of this study was to assess the efficacy of concurrent chemotherapy to intensity-modulated radiotherapy (IMRT) after neoadjuvant chemotherapy (NACT) in locoregionally advanced nasopharyngeal carcinoma (NPC). A total of 120 patients with stage III-IVB NPC treated with NACT followed by IMRT alone (39 patients, arm 1) or CCRT (81 patients, arm 2) between May 2009 and June 2012 were eligible for study inclusion. NACT consisted of docetaxe (DOC, 60 mg/m(2), day 1) and cisplatin (DDP, 100 mg/m(2), days 1-5, every 3 weeks). Concurrent chemotherapy was nedaplatin (NDP, 25 mg/m(2), days 1-3, every 3 weeks). The median follow-up period was 41 (range 5-52) months, and the 3-year overall survival, distant metastases-free survival, locoregional relapse-free survival, and progression-free survival rates of arm 1 and arm 2 were 83.3 and 87.4% (P = 0.516), 81.7 and 79.6% (P = 0.596), 86 and 92.3% (P = 0.920), 76.4 and 76.4% (P = 0.709), respectively. During radiotherapy, the most commonly recorded grade 3/4 adverse events were anemia (7.7 vs. 4.9%), leucopenia (10.2 vs. 3.7%), thrombocytopenia (12.8 vs. 3.7%), neutropenia (15.4 vs. 6.2%), nausea/vomiting (7.7 vs. 12.3%), stomatitis/mucositis (38.5 vs. 46.9%), xerostomia (35.9 vs. 30.8%), dermatitis (7.7 vs. 7.4%), and fatigue(15.4 vs. 17.2%) for arm 1 and arm 2. The results of this study indicated that added concurrent chemotherapy to IMRT after neoadjuvant DOC and DDP treatment for locoregionally advanced NPC was probably not be necessary.

Cerebellar, brainstem and spinal cord metastases from esophageal cancer following radiotherapy: A case report and literature review.

Cerebellar, brainstem and spinal cord metastases from esophageal cancer following radiotherapy are extremely rare. The current study presents the case of a 74-year-old male who was admitted to the Zhejiang Cancer Hospital (Hangzhou, China) with a poorly-differentiated neuroendocrine carcinoma of the esophagus. Following radiotherapy, multiple abnormal signals in the brainstem and spinal cord were found on magnetic resonance imaging (MRI). Following palliative radiochemotherapy, the clinical symptoms and abnormal MRI signals in the brainstem and spinal cord were found to improve. This case revealed that brain metastasis from esophageal carcinoma may occur simultaneously with brainstem and spinal cord metastases.

[Enoxaparin for the prevention of post surgical pulmonary embolism].

OBJECTIVE: To evaluate the efficacy and safety of the administration of enoxaparin, a low molecular weight heparin (LMWH), in the prevention of post surgical deep vein thrombosis (DVT) and pulmonary embolism (PE). METHODS: 1928 patients hospitalized for general surgery were randomly divided into: (1) test group (n = 960) to receive enoxaparin (40 mg, s.c., 12 hours before and after surgery, then once daily for 7 consecutive days); (2) control group (n = 968) without intervention. The incidence of DVT,PE and bleeding were recorded for statistical analysis during hospitalization and a 2 months follow-up after discharge. RESULTS: (1) No significant difference was found between the two groups in age, sex, average body mass index, type of surgery, and DVT / PE risk factors (obesity, varicose veins, and history of: venous thrombosis, chronic obstructive pulmonary disease, chronic heart failure, and hormone therapy). The percentage of non-malignant / malignant tumor surgery were 36.5% / 63.5% (average operation time 2.3 hours) in control group and 35.6% / 64.4% (2.2 hours) in test group (both P > 0.05). (2) During the hospitalization period, 59 cases (incidence=6.1%) of DVT and 14 cases (incidence=1.4%) of PE (among them 6 were fetal, 42.8% of all PE cases) were found in the control group, while 28 cases of DVT (2.9%) and 3 cases (0.3%) of PE (1 fetal, 33.3% of all PE cases) were found in test group. The incidence of DVT, PE (total), and PE (fetal) were significant lower in test group (P < 0.05 or P < 0.01). During the follow up, 14 more cases of DVT (1.4%) and 1 more case (0.1%) of PE (a fetal) were found in the control group, and 2 more DVT cases (0.2%) in test group, with the DVT incidence in test group significantly lower (P < 0.01). (3) During the enoxaparin administration, 30 cases (3.1%) minor bleeding and 8 cases (0.8%) major bleeding were found in the control group, while 33 cases (3.4%) minor bleeding events and 9 cases (0.9%) major bleeding events were found in the test group. THE RESULTS: in the two groups were not significantly different in either type of bleeding events (both P > 0.05). Also no significant difference was found in the bleeding events after the ending of enoxaparin administration and during the follow up. CONCLUSION: Enoxaparin may reduce the incidence of DVT and PE in patients undergoing general surgery without increased risk of bleeding.