• Asian Pacific Journal of Cancer Prevention
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• v.15 no.4
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• pp.1699-1702
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• 2014

Objective: To evaluate clinical efficacy of a dose escalating schedule of paclitaxel concurrent with radiotherapy in treating patients with locally advanced non-small cell lung (NSCLC). Methods: Patients with locally advanced NSCLC were treated with conventional fractionated radiotherapy or three dimensional conformal radiotherapy (3 DCRT), concurrently with a dose escalating schedule of paclitaxel. All patients were divided into three groups, A with paclitaxel $30mg/m^2$, B with paclitaxel $60mg/m^2$ and C with paclitaxel $90mg/m^2$. Paclitaxel was repeated every week for a total of 4 or 6 weeks. Results: Among 109 patients, response rates were 68.8%, 71.1% and 71.8% (p>0.05) for group A (n=32), B (n=38), and C (n=39) respectively. Accordingly, disease control rates were 81.3%, 81.6% and 82.1% (p>0.05). Progression-free survival time was $8.0{\pm}5.0$ months, $11.6{\pm}6.1$ months, and $14.8{\pm}7.9$ months (p<0.05), respectively. Overall survival time was $15.4{\pm}7.6$ months, $18.2{\pm}8.0$ months, and $22.0{\pm}7.6$ months (p<0.05), one-year survival rates were 62.5%, 73.1% and 90.0% (p>0.05) and two-year survival rates were 31.3%, 38.5% and 50.0% (p<0.05). Main side-effects were bone marrow suppression, radiation related esophagitis and gastrointestinal reaction. Conclusion: In treating patients with NSCLC, concurrent chemoradiotherapy with paclitaxel improves early response compared with conventional fractionated radiotherapy or 3 DCRT. The survival rate was improved with the addition of paclitaxel, but there was an increase in adverse reactions when the dose of paclitaxel was increased.

• Journal of Physiology & Pathology in Korean Medicine
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• v.23 no.3
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• pp.710-714
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• 2009

Several studies showed that the survival rate of stage IIIB disease with malignant pleural effusion is worse than stage IIIB disease without malignant effusion. But, malignant pleural effusion was considered T4. To analyze changes the survival time for malignant pleural effusion, in the seventh revision of TNM classification for lung cancer. The records of all patients had to have either a histological or cytological diagnosis of non-small cell lung cancer (NSCLC), who were admitted to Wonkwang university hospital between January 2004 and December 2006 were reviewed retrospectively. We evaluated the survival time of 187 patients with advanced lung cancer with and without malignant pleural effusion. This included the pleural effusion or nodule M1 a (pleural dissemination, currently classified as T4), nodule(s) in the other lung M1 a (contralateral lung nodule, currently classified as M1), nodule(s) with the same lobe as the primary tumor T3 (currently classified as T4), other T4 factors T4 (T4 MO anyN), and extrathoracic sites of disease M1b (distant metastasis, currently classified M1). Among the 187 patients, T4anyNMO was 57 patients in the current TNM classification. In the next edition of the TNM classification, T4MOanyN-T4 (excluding same lobe nodules) was 12 patients, pleural dissemiantion-M1a was 45 patients, contralateral lung nodule(s)-M1a was 7 patients, and metastatic disease-M1b was 55 patients. We compared the survival time for these groups. Survival time was 11 months, 8 months, 11 months, and 4 months. The survival time of malignant pleural effusion was shorter than other T4 factors without pleural effusion. But, there was no remarkable difference in statistics due to small cases (p=0.23). We strongly suggest that malignant pleural effusion in advanced NSCLC will be categorized with metastatic disease.

• Journal of Chest Surgery
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• v.37 no.4
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• pp.349-355
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• 2004

Non-small cell lung cancer (NSCLC) with invasion of mediastinal structures is classified as stage IIIB, and has been considered surgically unresectable However, in a selected group of these patients, better results after surgical resection compared to non-surgical group have been reported. The aim of this study is to evaluate the role of surgical resection in treatment of mediastinal T4 NSCLC. Material and Method: Among 1067 patients who underwent surgical intervention for non-small cell lung cancer from Aug 1987 to Dec 2001 in Korea cancer center hospital, 82 patients had an invasion of T4 mediastinal structures (7.7%). Resection was possible in 63patients (63/82 resectability 76.8%). Their medical records in Data Base were reviewed, and they were followed up completely until Jun 2002. Surgical results and prognostic factors of NSCLC invading mediastinal structures were evaluated retrospectively. Result Lung cancer was resected completely in 52 patients (63.4%, 52/82). Lung resection was lobectomy (or more) in 14, pneumonectomy in 49. The mediastinal structures invaded by primary tumor were great vessel (61.9%), heart (19%), vagus nerve (9.5%), esophagus (7.9%), and vertebral body (7.9%). Nodal status was N0 in 11, N1 in 24, and N2 in 28 (44.4%). Neoadjuvant therapy was done in 6 (9.5%, 5 chemotherapy, 1 radiotherapy), and adjuvant therapy was added in 44 (69.8%, 15 chemotherapy, 29 radiotherapy) in resection group (n=63). Complication was occurred in 23 (31.7%), and operative mortality was 9.5% in resection group. Median and 5 year overall survival including operative mortality was 18.1 months and 21.7% in resection group (n=63), 6.2months and 0% in exploration only group (n=19, p=.001), 39 months and 32.9% in N2 (-) resection group (n=35), and 8.8 months and 8.6% in N2 (+) resection group (n=28, p=.007). The difference of overall survival by mediastinal structure was not significant. Conclusion: The operative risk of NSCLC invading mediastinal structures was high but acceptable, and long-term result of resection was favorable in selected group. Aggressive resection is recommended in well selected pateints with good performace and especially N2 (-) NSCLC with mediastinal invasion.

• Tuberculosis and Respiratory Diseases
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• v.68 no.4
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• pp.231-235
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• 2010

Lymphadenopathy in the thoracic cavity is frequently caused by inflammatory diseases. In very rare cases, the node-bronchial fistula has been reported to be the cause of complications of pulmonary tuberculosis. A male patient with necrotizing pneumonia and mediastinal lymph node enlargements identified by chest computed tomography was also found to have a node-bronchial fistula caused by lung cancer. The patient was treated for tuberculosis with pneumonia for one week before a definitive diagnosis was made. A further investigation revealed him to have non-small cell lung cancer (NSCLC, adenocarcinoma) and multiple mediastinal lymphadenopathies accompanied with the node-bronchial fistula. We report this specific case that had been previously treated for tuberculosis but was later revealed to be NSCLC accompanied with a node-bronchial fistula.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.17
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• pp.7297-7301
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• 2014

Objective: To explore the radiosensitization effect of overexpression of silent information regulator 6 (SIRT6) on A549 non-small cell lung cancer (NSCLC) cells. Methods: Adenovirus vector Ad-SIRT6 causing overexpression of SIRT6 was established. Western blotting and MTT assay were adopted to detect the level of SIRT6 protein and the inhibitory rate of A549 cell proliferation after different concentrations of adenovirus transduction (0, 25, 100, 200, and 400 pfu/cell) for 24 h. Control group, Ad-null group and Ad-SIRT6 group were designed in this experiment and virus concentration of the latter two groups was 200 pfu/cell. Colony formation assays were employed to test survival fraction (SF) of the 3 groups after 0, 2, 4, 6, 8, 10 X-ray irradiation. Flow cytometry was used to detect the status of cell cycle of 3 groups after 48 h of 4Gy X-ray irradiation and Western blotting was used to determine the expression of apoptosis-related genes of 3 groups after 48 h of 4GyX-ray irradiation. Results: In the range of 25~400 pfu/cell, the inhibitory rate of A549 cell proliferation increased as adenovirus concentration raised. The inhibitory rates under the concentrations of 0, 25, 100, 200, and 400 pfu/cell were 0%, $4.23{\pm}0.34%$, $12.7{\pm}2.57%$, $22.6{\pm}3.38%$, $32.2{\pm}3.22%$, $38.7{\pm}4.09%$ and $47.8{\pm}5.58%$ and there were significantly differences among groups (P<0.05). SF in Ad-SIRT6 group was lower than Ad-null and control groups after 4~10Gy X-ray irradiation (P<0.05) and the sensitization enhancement ratio (SER) was 1.35 when compared with control group. Moreover, after 48 h of 4Gy X-ray irradiation, there appeared a significant increase in G1-phase cell proportion, upregulated expression of the level of apoptosis-promoting genes (Bax and Cleaved caspase-3), but a obvious decline in S-phase and G2-phase cell proportion and a significant decrease of the level of apoptosis-inhibiting gene (Bal-2) in the Ad-SIRT6 group (P<0.05). Conclusion: The over-expression of adenovirus-mediated SIRT6, which has radiosensitization effect on A549 cells of NSCLC, can inhibit the proliferation of A549 cells and cause G0/G1 phase retardation as well as induce apoptosis of cells.

• Journal of Integrative Natural Science
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• v.15 no.4
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• pp.171-177
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• 2022

ROS1 (c-ros oncogene) is one of the gene with mutation in NSCLC (non-small cell lung cancer). The increased expression of ROS1 is leading to the increase proliferation of cell, cell migration and survival. Crizotinib and Entrectinib are the drugs that have been approved by FDA against ROS1 protein, but recently patients started to develop resistance against Crizotinib and there is a need of new drug that could act as an effective drug against ROS1 for NSCLC. In this study, we have performed virtual screening, where compounds are taken from Zinc 15 dataset and molecular docking was performed. The top compounds were taken based upon their binding affinity and their interactions with the residues. The compounds stability and chemical reactivity was also studied through Density Functional theory and their properties. Further study of these compounds could reveal the required information of ROS1-inhibitor complex and in the discovery of potent inhibitors.

• Journal of Korean Neurosurgical Society
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• v.64 no.2
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• pp.271-281
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• 2021

Objective : Immune checkpoint inhibitors (ICIs) are approved for treating non-small-cell lung cancer (NSCLC); however, the safety and efficacy of combined ICI and Gamma Knife radiosurgery (GKS) treatment remain undefined. In this study, we retrospectively analyzed patients treated with ICIs with or without GKS at our institute to manage patients with brain metastases from NSCLC. Methods : We retrospectively reviewed medical records of patients with brain metastases from NSCLC treated with ICIs between January 2015 and December 2017. Of 134 patients, 77 were assessable for brain responses and categorized into three groups as follows : group A, ICI alone (n=26); group B, ICI with concurrent GKS within 14 days (n=24); and group C, ICI with non-concurrent GKS (n=27). Results : The median follow-up duration after brain metastasis diagnosis was 19.1 months (range, 1-77). At the last follow-up, 53 patients (68.8%) died, 20 were alive, and four were lost to follow-up. The estimated median overall survival (OS) of all patients from the date of brain metastasis diagnosis was 20.0 months (95% confidence interval, 12.5-27.7) (10.0, 22.5, and 42.1 months in groups A, B, and C, respectively). The OS was shorter in group A than in group C (p=0.001). The intracranial disease progression-free survival (p=0.569), local progression-free survival (p=0.457), and complication rates did not significantly differ among the groups. Twelve patients showed leptomeningeal seeding (LMS) during follow-up. The 1-year LMS-free rate in treated with ICI alone group (69.1%) was significantly lower than that in treated with GKS before ICI treatment or within 14 days group (93.2%) (p=0.004). Conclusion : GKS with ICI showed no favorable OS outcome in treating brain metastasis from NSCLC. However, GKS with ICI did not increase the risk of complications. Furthermore, compared with ICI alone, GKS with ICI may be associated with a reduced incidence of LMS. Further understanding of the mechanism, which remains unknown, may help improve the quality of life of patients with brain metastasis.

• Tuberculosis and Respiratory Diseases
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• v.71 no.6
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• pp.425-430
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• 2011

Background: High 2-[$^{18}F$] fluoro-2-deoxy-D-glucose (FDG) uptake on positron emission tomography-computed tomography (PET-CT) is a prognostic factor for poor survival in non-small cell lung cancer (NSCLC), especially in Stage I. We determined whether the high FDG uptake value of a primary tumor was associated with recurrence and death in patients with resected Stage I and Stage II NSCLC. Methods: We identified consecutive patients who underwent complete surgical resection for Stage I and II NSCLC between 2006 and 2009, who had preoperative PET-CT, and reviewed clinical records retrospectively. FDG uptake was measured as the maximal standardized uptake value (SUVmax) for body weight. Patients were divided into two groups based on SUVmax: (i) above or (ii) below the cut-off value (SUVmax=5.9) determined by a receiver operating characteristic (ROC) curve. Results: Of 57 patients who were enrolled consecutively, 32 (56%) had Stage I NSCLC and 25 (44%) had Stage II. The 5-year recurrence-free survival (RFS) for patients with high (${\geq}5.9$) and low (<5.9) SUVmax were 31% and 57%, respectively (p=0.014). The 5-year overall survival (OS) rates were 39% and 60%, respectively (p=0.029). In univariate analyses, SUVmax (p=0.014), T staging (p=0.025), and differentiation of tumor tissue (p=0.034) were significantly associated with RFS. But, multivariate analyses did not show that SUVmax was an independently significant factor for RFS (p=0.180). Conclusion: High FDG uptake on PET-CT is not an independent prognostic factor for poor outcomes (disease recurrence in patients with resected Stage I and II NSCLC).

• Radiation Oncology Journal
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• v.30 no.3
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• pp.140-145
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• 2012

Purpose: Combined chemoradiotherapy is standard management for locally advanced non-small cell lung cancer (LA-NSCLC), but standard treatment for elderly patients with LA-NSCLC has not been confirmed yet. We evaluated the feasibility and efficacy of concurrent chemoradiotherapy (CCRT) for elderly patients with LA-NSCLC. Materials and Methods: Among patients older than 65 years with LA-NSCLC, 36 patients, who underwent CCRT were retrospectively analyzed. Chemotherapy was administered 3-5 times with 4 weeks interval during radiotherapy. Thoracic radiotherapy was delivered to the primary mass and regional lymph nodes. Total dose of 54-59.4 Gy (median, 59.4 Gy) in daily 1.8 Gy fractions and 5 fractions per week. Results: Regarding the response to treatment, complete response, partial response, and no response were shown in 16.7%, 66.7%, and 13.9%, respectively. The 1- and 2-year overall survival (OS) rates were 58.2% and 31.2%, respectively, and the median survival was 15 months. The 1- and 2-year progression-free survivals (PFS) were 41.2% and 19.5%, respectively, and the median PFS was 10 months. Regarding to the toxicity developed after CCRT, pneumonitis and esophagitis with grade 3 or higher were observed in 13.9% (5 patients) and 11.1% (4 patients), respectively. Treatment-related death was not observed. Conclusion: The treatment-related toxicity as esophagitis and pneumonitis were noticeably lower when was compared with the previously reported results, and the survival rate was higher than radiotherapy alone. The results indicate that CCRT is an effective in terms of survival and treatment related toxicity for elderly patients over 65 years old with LA-NSCLC.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.1
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• pp.321-326
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• 2014

Background: Mutations in the tyrosine kinase domain of the epidermal growth factor receptor (EGFR) in non-small cell lung cancer (NSCLC) are predictive of response to EGFR-targeted therapy in advanced stages of disease. This study aimed to determine the frequency of EGFR mutations in NSCLCs and to correlate their presence with clinical characteristics in multiethnic Malaysian patients. Materials and Methods: In this prospective study, EGFR mutations in exons 18, 19, 20 and 21 in formalin-fixed paraffin-embedded biopsy specimens of consecutive NSCLC patients were asessed by real-time polymerase chain reaction. Results: EGFR mutations were detected in NSCLCs from 55 (36.4%) of a total of 151 patients, being significantly more common in females (62.5%) than in males (17.2%) [odds ratio (OR), 8.00; 95% confidence interval (CI), 3.77-16.98; p<0.001] and in never smokers (62.5%) than in ever smokers (12.7%) (OR, 11.50; 95%CI, 5.08-26.03; p<0.001). Mutations were more common in adenocarcinoma (39.4%) compared to non-adenocarcinoma NSCLCs (15.8%) (p=0.072). The mutation rates in patients of different ethnicities were not significantly different (p=0.08). Never smoking status was the only clinical feature that independently predicted the presence of EGFR mutations (adjusted OR, 5.94; 95%CI, 1.94-18.17; p=0.002). Conclusions: In Malaysian patients with NSCLC, the EGFR mutation rate was similar to that in other Asian populations. EGFR mutations were significantly more common in female patients and in never smokers. Never smoking status was the only independent predictor for the presence of EGFR mutations.