Endobronchial brachytherapy with curative intent: the impact of reference points setting according to the bronchial diameter.

Endobronchial brachytherapy (EBB) is an effective treatment for endobronchial tumors. However, bronchial toxicity caused by over-irradiation remains problematic. To decrease bronchial toxicity, we developed a source-centralizing applicator for EBB. The purpose of the present study was to assess the efficacy and safety of EBB with varying reference dose points according to the bronchial diameter, using a source-centralizing applicator. We reviewed 15 patients with endobronchial carcinoma who were treated with curative intent using a combination of external beam radiotherapy (EBRT) and high-dose-rate EBB between 2005 and 2014. During each EBB session, we used a source-centralizing applicator that maintained the source-delivering catheter in the center of the bronchial lumen. Reference dose points were 5-7 mm from the source axis, depending on the bronchial diameter. The median radiation doses of EBRT and EBB were 40 Gy in 20 fractions and 18 Gy in 3 fractions, respectively. The median observation period was 36 months. The 3-year overall survival, progression-free survival and local control rates were 79%, 77% and 100%, respectively. Grade 2 radiation pneumonitis was observed in two cases. Bronchial toxicities, such as hemoptysis or the symptoms of chronic bronchitis, were not observed. EBB with varying reference dose points according to bronchial diameter, using a source-centralizing applicator, is a promising procedure that may be effective for tumor elimination and reducing toxicity to the bronchial wall.

The impact of epidermal growth factor receptor mutations on patterns of disease recurrence after chemoradiotherapy for locally advanced non-small cell lung cancer: a literature review and pooled analysis.

The purpose of this review was to evaluate the impact of epidermal growth factor receptor (EGFR) mutation status on disease recurrence in patients treated with chemoradiotherapy (CRT) for locally advanced non-small cell lung cancer (NSCLC). A literature search was conducted and a total of three studies were analyzed. There was no significant difference in the objective response rate between the EGFR mutation group and the EGFR wild-type group (odds ratios [OR] 1.46, 95% CI, 0.79-2.70, P = 0.228), and there was no significant difference in the incidence of disease recurrence (OR 1.37, 95% CI, 0.68-2.75, P = 0.379) between the two groups. There were significant difference in the incidence of local/locoregional progression (LP) (OR 0.35, 95% CI, 0.18-0.71, P = 0.003) and distant progression (DP) (OR 2.97, 95% CI, 1.59-5.54, P < 0.001). Brain metastasis (BM) was one of the main recurrence patterns of DP, and the incidence was significantly higher in the EGFR mutant group (OR 2.75, 95% CI, 1.43-5.31, P = 0.003). There were no statistically significant heterogeneities in these pooled analyses. The patterns of recurrence after CRT for locally advanced NSCLC were different according to EGFR mutation status. LP after CRT in patients with EGFR mutation was less frequent, but the high incidence of DP, especially BM, continued to be the major problem. On the other hand, LP continued to be the major problem in EGFR wild-type patients. In multimodality treatment for inoperable locally advanced NSCLC, we may need to consider different treatment strategies according to EGFR mutation status.

The impact of emphysema on dosimetric parameters for stereotactic body radiotherapy of the lung.

The purpose of this study was to evaluate the impact of emphysematous changes in lung on dosimetric parameters in stereotactic body radiation therapy (SBRT) for lung tumor. A total of 72 treatment plans were reviewed, and dosimetric factors [including homogeneity index (HI) and conformity index (CI)] were evaluated. Emphysematous changes in lung were observed in 43 patients (60%). Patients were divided into three groups according to the severity of emphysema: no emphysema (n = 29), mild emphysema (n = 22) and moderate to severe emphysema groups (n = 21). The HI (P < 0.001) and the CI (P = 0.029) were significantly different in accordance with the severity of emphysema in one-way analysis of variance (ANOVA). The HI value was significantly higher in the moderate to severe emphysema group compared with in the no emphysema (Tukey, P < 0.001) and mild emphysema groups (P = 0.002). The CI value was significantly higher in the moderate to severe emphysema group compared with in the no emphysema group (P = 0.044). In multiple linear regression analysis, the severity of emphysema (P < 0.001) and the mean material density of the lung within the PTV (P < 0.001) were significant factors for HI, and the mean density of the lung within the PTV (P = 0.005) was the only significant factor for CI. The mean density of the lung within the PTV was significantly different in accordance with the severity of emphysema (one-way ANOVA, P = 0.008) and the severity of emphysema (P < 0.001) was one of the significant factors for the density of the lung within the PTV in multiple linear regression analysis. Our results suggest that emphysematous changes in the lung significantly impact on several dosimetric parameters in SBRT, and they should be carefully evaluated before treatment planning.

Multimodality Treatment for Patients with Node-Positive Prostate Cancer: the Role of Radiation Therapy.

Prostate cancer is the secondary most frequently diagnosed cancer in the world. Although numerous prospective randomized trial have been conducted to guide the management of patients with localized or locally advanced prostate cancer, few clinical trials targeting node-positive prostate cancer have been reported. Therefore, there are still controversies in the optimal management of node-positive prostate cancer. Recently, efficacy of multimodality treatment, including radiation therapy (RT), for such patients has been reported in several articles. The results indicate potential benefit of RT both in adjuvant therapy after prostatectomy and in definitive therapy for node-positive prostate cancer. The aim in this article was to summarize the current evidence for RT and evaluate the role in multimodality treatment for patients with node-positive prostate cancer.

Roles of Valproic Acid in Improving Radiation Therapy for Glioblastoma: a Review of Literature Focusing on Clinical Evidence.

Glioblastoma (GBM) is the most common and aggressive type of primary brain neoplasm. The current standard therapy for GBM consists of maximal surgical resection within safe limits, followed by radiation therapy (RT) and chemotherapy with temozolomide. Despite advances in treatment, the prognosis of GBM remains poor. Epileptic seizure is one of the most common symptoms in patients with GBM. Valproic acid (VPA), a histone deacetylase inhibitor, is often used as an anti-epileptic drug in patients with brain neoplasms due to its effectiveness and low toxicity profile. Several in vivo and in vitro studies have indicated that VPA has radiosensitizing effects for gliomas and radioprotective influence on normal brain tissue or hippocampal neurons. The results of several retrospective studies have also indicated potential benefit to improve survival of patients with GBM. Moreover, the promising treatment results of a phase 2 trial of concurrent radiation therapy, temozolomide, and VPA for patients with GBM have been recently reported. The use of VPA in patients with GBM has thus recently receiving more attention. In this article, we review the role of VPA in radiation therapy for GBM, focusing on the clinical evidence.

Radiation-induced organizing pneumonia after stereotactic body radiotherapy for lung tumor.

The aim of this retrospective study was to investigate characteristics of organizing pneumonia (OP) after stereotactic body radiotherapy (SBRT) for lung tumor. Between September 2010 and June 2014, patients who were diagnosed as Stage I lung cancer and treated with SBRT at our institution were included in this study. A total of 78 patients (47 males with a median age of 80 years) were analyzed. The median follow-up period was 23 months. Five patients (6.4%) developed OP at 6-18 months after SBRT. The cumulative incidence of OP was 4.3% (95% confidence interval [CI], 1.1-11.0) and 8.2% (95% CI, 2.9-17.0) at 1 and 2 years, respectively. Tumor location (superior and middle lobe vs inferior lobe) was shown to be a borderline significant factor for the occurrence of OP ( P: = 0.069). In the subgroup analysis of patients with a radiographic follow-up period at least 6 months, or who died within 6 months after SBRT, 7 of 72 patients (9.7%) developed Grade 2 or 3 radiation pneumonitis (G2/3 RP) at 2-4 months after SBRT. A statistically significant association between G2/3 RP in the subacute phase and OP was shown ( P: = 0.040). In two of the five patients who developed OP, the symptoms and radiographic change were improved rapidly by corticosteroid administration. One patient had relapsed OP after suspending the treatment and re-administration was required. Three patients with minor symptoms were managed without corticosteroid administration and OP resolved without any relapse. The radiation-induced OP should be considered as one of the late lung injuries after SBRT for lung tumors.

Multimodality therapy using brachytherapy for caval tumor of hepatocellular carcinoma.

BACKGROUND/AIMS: Hepatocellular carcinoma (HCC) invading the inferior vena cava will expose patients to a risk of sudden death. Effective therapeutic approaches have not been established for caval tumor. This pilot study was conducted to evaluate the feasibility, safety, and clinical efficacy of multimodality therapy using endovascular brachytherapy with iridium-192 for caval tumor. METHODOLOGY: Six consecutive patients underwent endovascular high-dose-rate brachytherapy. An iridium-192 source was placed adjacent to the caval tumor through a vascular sheath introduced via the femoral vein. The total dose of brachytherapy ranged from 10 to 14Gy (5-7Gy per fraction). Hepatic arterial infusion chemotherapy was used in combination in all patients and external-beam radiotherapy was performed in 5 patients. RESULTS: Endovascular brachytherapy was technically successful in all patients. There were no complications related to brachytherapy. The median period of follow-up was 14.5 months (range, 3-29 months). Complete response and partial response were achieved in 2 (33%) and 4 (67%) patients, respectively. The 1- and 2-year survival rates were 50% and 17%, respectively, with a median survival of 14 months. CONCLUSIONS: Multimodality therapy using endovascular brachytherapy was a feasible, safe, and effective treatment for patients with advanced HCC invading the inferior vena cava.

The functional interaction between CD98 and CD147 in regulation of virus-induced cell fusion and osteoclast formation.

Membrane fusion is an important event in the functioning of a living organism. Life starts as a sperm fuses with the membrane of an egg, leading to its fertilization. Membrane fusion is also required for myogenesis, osteogenesis and placenta formation. Multinucleated giant cells originating from monocytes-macrophages are associated with granulomatous lesions formed in response to foreign bodies, viruses, and bacteria. The CD4 molecule acts as a receptor for HIV. The major virus envelope glycoprotein, gp120, attaches to CD4 molecules expressed on the host cell surface. After binding to CD4 on the target cells, HIV is internalized via direct, pH-independent fusion of the viral and cell membranes. However, attachment of HIV to CD4 on the target cells is not sufficient for fusion. Interaction of gp160-expressing cells with neighboring cells bearing surface CD4 molecules is also required for syncytium formation. Syncytium formation and subsequent generalized cell fusion have been reported as potentially important mechanisms of virus-induced cytotoxic effects. Some antibodies against CD98/FRP-1 suppressed virus-induced cell fusion and CD98-mediated cell fusion of monocytes, indicating that CD98/FRP-1 molecules are able to regulate cell fusion. In this study, the functional interaction between CD98 and CD147 was investigated. Three kinds (Ab1, 2, and 3) of anti-CD147 and three kinds of anti-CD98 antibodies were used. Ab1 suppressed CD98-mediated cell fusion, but showed no effect on cell aggregation of Cd(+)U2ME-7 cells, U937-2 cells expressing HIV gp160. On the other hand, Ab2 enhanced the CD98-mediated cell fusion. Ab1 showed suppressive effect at early stage and Ab2 showed enhancing effect at later stage. Ab2 and 3 suppressed the spontaneous cell agglutination and cell fusion of Cd(+)JME-2 cells, Jurkat cells expressing HIV gp160. Ab2 suppressed CD98-mediated cell fusion, but showed no effect on cell aggregation of Cd(+)JME-2 cells. Ab2 cancelled suppression of cell fusion induced by suppressive antibody against CD98. Ab2 and 3 also suppressed CD98-mediated cell fusion of monocytes. This study indicates the functional interaction between CD98 and CD147 in the regulation of cell fusion.

Identification of amino acids essential for the human parainfluenza type 2 virus V protein to lower the intracellular levels of the STAT2.

The V protein of SV41 targets STAT1, while a specific loss of STAT2 is induced by the hPIV2 V protein. We established HeLa cells constitutively expressing various chimeric proteins between the hPIV2 and SV41 V proteins, and which STAT (STAT1 or 2) was expressed in these cells was analyzed. Both the P-V common domain and the V specific domain of hPIV2 V protein are necessary for STAT2 lowering. The internal domain (aa145-173) containing a large number of nonidentical amino acids between hPIV2 and SV41 does not direct STAT tropism, and the regions necessary for STAT2 lowering are discontinuous. The N-terminal domain (aa1-104) and the internal domain (aa126-196) of the hPIV2 V protein do not determine STAT tropism. HeLa cells expressing A105E or H108P show distinct expression of STAT2, but do show low expression or a loss of STAT1, indicating that the amino acid residues 105 and 108 of the hPIV2 V protein are essential for STAT2 lowering. Interestingly, there is an important amino acid(s) in the region (aa121-125) for STAT2 lowering, and the presence of either amino acid residue 123 or 125 of the hPIV2 V protein is necessary for lowering of STAT2. In addition, HeLa cells expressing S216D or 1217R expressed STAT2, but no STAT1, indicating that the amino acid residues 216 and 217 of the hPIV2 V protein are indispensable for STAT2 lowering. HeLa/hPIV2V cells and HeLa/S104/P are resistant to IFN-beta, while they are sensitive to IFN-gamma. On the other hand, HeLa/SV41V, HeLa/S216D, and HeLa1217R cells are resistant to both IFNs. Intriguingly, HeLa/A105E and HeLa/H108P cells were found to be sensitive to IFN-gamma.