• Tuberculosis and Respiratory Diseases
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• v.66 no.1
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• pp.20-26
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• 2009

Background: $^{18}F$-Fluorodeoxyglucose positron emission tomography (FDG-PET) is widely used for the diagnosis and staging of non-small cell lung cancer (NSCLC). The aim of this study is to determine whether the bone marrow hypermetabolism seen on FDG-PET predicts a response to chemotherapy in patients with NSCLC. Methods: We evaluated the patients with advanced NSCLC and who were treated with combination chemotherapy. For determination of the standardized uptake value (SUV) of the bone marrow (BM SUV) on FDG-PET, regions of interest (ROIs) were manually drawn over the lumbar vertebrae (L1, 2, 3). ROIs were also drawn on a homogenous transaxial slice of the liver to obtain the bone marrow/ liver SUV ratio (BM/L SUV ratio). The response to chemotherapy was evaluated according to the Response Evaluation Criteria in Solid Tumor (RECIST) criteria after three cycles of chemotherapy. Results: Fifty-nine NSCLC patients were included in the study. Multivariate analysis was performed using a logistic regression model. The BM SUV and the BM/L SUV ratio on FDG-PET were not associated with a response to chemotherapy in NSCLC patients (p=0.142 and 0.978, respectively). Conclusion: The bone marrow hypermetabolism seen on FDG-PET can not predict a response to chemotherapy in NSCLC patients.

• Radiation Oncology Journal
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• v.11 no.1
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• pp.97-102
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• 1993

A retrospective analysis of various characteristics in 32 limited stage small cell lung cancer patients treated at the Department of Therapeutic Radiology in Kangnam St. Mary's Hospital, Catholic University Medical College from April 1983 to September 1991, was carried out to identify factors which had prognostic significance for survival from initiation of radiation therapy. There were 26 men and 6 women. Median age was 63 years (range: 24-78 years). The follow up duration was 1.5 to 44 months (median: 9 months). External radiation therapy was done with daily 160-180 cGy,5 fraction/week, total of 1000-6660 cGy (median: 4500 cGy) to the mediastinum by 6 MV linear accelerator. Of 32 Patients, 27 ($84.4{\%}$) patients were treated with combined modality (chemotherapy plus radiation therapy), and 5 ($15.6{\%}$) patients were treated with radiation therapy only. Complete responders were 12 patients ($37.5{\%}$), partial responders were 11 ($34.4{\%}$), and no responders were 9($28.1{\%}$). Karnofsky performance status over 70 (p<0.04), chemotherapy regimen (CAV, PV, and CAV+PV) (p<0.04),6 or more cycles of chemotherapy (p<0.007), radiation therapy over 4500 cGy (p<0.03), and radiation therapy responder (CR+PR) (p<0.003) showed a significantly favorable influence on 1 year survival rate. Age (p=0.545), sex (p=0.666), presence of superior vena cava syndrome (p=0.719), prophylactic cranial irradiation (p=0.217), and radiation therapy duration (p=0.491) had no effect on survival. Radiation induced side effects were transient esophagitis in 11 ($34{\%}$), general weakness in 9($28{\%}$), gastrointestinal symptoms in terms of nausea, vomiting and indigestion in 5 ($15{\%}$) and leukopenia in 1 ($3{\%}$).

• Radiation Oncology Journal
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• v.27 no.3
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• pp.133-139
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• 2009

Purpose: This study was designed to analyze the outcome and toxicity of thoracic radiation therapy (TRT) and chemotherapy for patients who suffer with limited-stage small-cell lung cancer (LS-SCLC). Materials and Methods: We retrospectively studied 35 patients with LS-SCLC. TRT was administered once daily (1.8 to 2 Gy per fraction) and it was directed to the primary tumor for a total 50 to 66 Gy in 6 to 7 weeks. The patients received four cycles of etoposide plus cisplatin. TRT was begun on day 1 of the first cycle of chemotherapy in the concurrent arm and after the fourth cycle in the sequential arm. Results: The median progression-free survival time was 16.5 months (95% confidence interval [CI], 9.0 to 24.1 months) for the sequential arm, and 26.3 months (95% CI, 16.6 to 35.9 months) for the concurrent arm. The 2-year progression-free survival rate was 16.0 percent for the sequential arm and 50.0 percent for the concurrent arm (p=0.0950 by log-rank test). Leukopenia was more severe and more frequent in the concurrent arm than in the sequential arm. However, severe esophagitis was infrequent in both arms. The radiotherapy was interrupted more frequently in the concurrent arm than in the sequential arm due to hematologic toxicities (p=0.001). Conclusion: This study suggests that concurrent TRT with etoposide plus cisplatin is more effective for the treatment of LS-SCLC than sequential TRT. However, there is a significant increase in the risk of toxicities, and radiotherapy was frequently interrupted in the concurrent arm due to hematologic toxicities.

• Nuclear Medicine and Molecular Imaging
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• v.40 no.4
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• pp.205-210
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• 2006

Purpose: FDG uptake on positron omission tomography (PET) has been considered a prognostic indicator in non-small cell lung cancer (NSCLC). The aim of this study was to assess the clinical significance of maximum value of SUV (maxSUV) in recurrence prediction in patients with surgically resected NSCLC. Materials & methods: NSCLC patients (n=42, F:M =14:28, age $62.3{\pm}12.3$ y) who underwent curative resection after FDG-PET were enrolled. Twenty-nine patients had pathologic stage 1, and 13 had pathologic stage II. Thirty-one patients were additionally treated with adjuvant oral chemotherapy. MaxSUVs of primary tumors were analyzed for correlation with tumor recurrence and compared with pathologic or clinical prognostic indicators. The median follow-up duration was 16 mo (range, 3-26 mo). Results: Ten (23.8%) of the 42 patients experienced recurrence during a median follow-up of 7.5 mo (range, 3-13 mo). Univariate analysis revealed that disease-free survival (DFS) was significantly correlated with maxSUV (<7 vs. $\geq7$, p=0.006), tumor size (<3 cm vs. $\geq3$ cm, p=0.024), and tumor tell differentiation (well/moderate vs. poor, p=0.044). However, multivariate Cox proportional analysis identified maxSUV as the single determinant for DFS (p=0.014). Patients with a maxSUV of $\geq7$(n=10) had a significantly lower 1-year DFS rate (50.0%) than those with a maxSUV of <7 (n=32, 87.5%). Conclusion: MaxSUV is a significant independent predictor for recurrence in surgically resected NSCLC. FDG uptake can be added to other well-known factors in prognosis prediction of NSCLC.

• Radiation Oncology Journal
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• v.25 no.2
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• pp.101-108
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• 2007

[ $\underline{Purpose}$ ]: To compare radiation therapy alone to combined modality therapy about survival rate and tolerance of elderly patients ($70=or{\geq}$) with non-small-cell lung cancer (NSCLC). $\underline{Materials\;and\;Methods}$: Between 1998 and 2002, 57 patients given radiation therapy due to NSCLC (Stage III) were analysed retrospectively. Radiation therapy alone (RT), concurrent chemoradiation (CRT), and sequential chemoradiation (SCRT) was done to 33, 16 and 8 patients, respectively. Patients' median age was 74 (range $70{\sim}85$). Male and female are 51 patients and 6 patients, respectively. 23 patients were stage IIIa and 34 were stage IIIb. Patients' characteristic distribution of RT and CRT was not significantly different except mass size that RT has a bigger than CRT. The fraction size of radiation therapy was 1.8 Gy in CRT and $1.8{\sim}3\;Gy$ in other groups. Total radiation dose was $51{\sim}63\;Gy$ according to the fraction size. If the prescribed total radiation dose was successfully irradiated, we stated that it was completion of radiation therapy. $\underline{Results}$: 52 patients were dead. Median period of radiation therapy was as follow: RT, 35 days, CRT, 60.5 days and SCRT, 35 days. Overall median survival time (MST) was 10.1 months. The 1 yr- and 2 yr-overall survival rate was 39.8% and 17.6%, respectively. MST of RT, CRT and SCRT was 8.9, 8.2 and 11.7 months, respectively. The 1 yr survival rate of RT, CRT and SCRT was 38.4%, 37.5% and 50% (not significant). Patients given incomplete radiation therapy were 12 (RT, 5 CRT, 6 SCRT, 1). N stage (p=0.081) and the difference of treatment methods (p=0.079) were the factors affecting incompletion of radiation therapy, but it was not significant. In case of combined-agents chemotherapy, 4 of 8 ceased radiation therapy. T stage ($T{\geq}3$), mass size (${\geq}5\;cm$), Karnofsky performance scale (${\leq}70$) and completion of radiation therapy were the prognostic factors in uni- and multi-variate analysis. $\underline{Conclusion}$: In elderly patients with NSCLC, radiation therapy alone was a treatment method with similar survival period compared with other methods. Generally, patients given radiation therapy alone was tolerable to a treatment. Before planning concurrent chemoirradiation in elderly patients with NSCLC, physicians pay attention to a selection of patients and chemotherapy agents considering general condition and toxicity.

• Tuberculosis and Respiratory Diseases
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• v.60 no.1
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• pp.57-64
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• 2006

Background : Recently, there have been several studies showing that irinotecan hydrochloride, a topoisomerase I inhibitor, is effective against extensive disease(ED) small cell lung cancer (SCLC). We conducted a phase II trial to evaluate the efficacy and toxicity of irinotecan plus cisplatin as a 1st line therapy for both limited and extensive disease SCLC. Methods : The study was conducted between January 2002 and June 2004. Patients were treated with $60mg/m^2$ irinotecan on day 1, 8, 15 and $60mg/m^2$ cisplatin on day 1, every 4 weeks. During concurrent thoracic irradiation for limited disease (LD)-SCLC patients, dose of irinotecan was reduced to $40mg/m^2$. Prophylactic cranial irradiation was given to patients with complete remission (CR) after chemotherapy. Results : Median ages of LD- and ED- SCLC were 64 years and performance status (PS) was 0-2. In patients with LD-SCLC, the response rate after concurrent chemoradiotherapy was 85% (CR, 6; Partial response [PR], 11). The median survival was 20 months (95% CIs, 15.6 to 24.4) with 1-and 2-year survival rates of 85% and 35%, respectively. Median progression free survival (PFS) was 12 months (95% CIs, 6.2 to 18.1) with 1- year PFS of 36%. In ED-SCLC, the response rate was 83.4% (CR, 1; PR, 14). The median survival was 14.5 months (95% CIs, 8.8 to 20.1) with 1-year survival rates of 75%. Median PFS was 6.3 months (95% CIs, 5.6 to 7.1) with 1- year PFS of 20%. The major toxicities (grade 3 or 4) of this regimen included leukopenia, anemia, thrombocytopenia, nausea/vomiting, and diarrhea without life threatening complication. Conclusion : Our data shows that the combination of irinotecan plus cisplatin as a first line therapy is effective and tolerable in the treatment of both LD- and ED- SCLC.

• Tuberculosis and Respiratory Diseases
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• v.42 no.4
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• pp.502-512
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• 1995

Background: One quarter to one third of patients with NSCLC present with primary tumors that although confined to the thorax are too extensive for surgical resection. Until resently standard treatment for these patients had been thoracic radiation, which produces tumor regression in most patients but few cures and dismal 5-year survival rate. The fact that death for most patients with stage III tumors is caused by distant metastases has promped a reevaluation of combined modality treatment approaches that include systemic chemotherapy. Therefore, we report the results observed in a study to evaluate the effect of multimodality treatment in locally advanced non-small cell lung cancer from 1/91 to 8/93 in CNUH. Method: We grouped the patients according to the treatment modalities and evaluated response rate, median survival and the effect of prognostic variables. Among 67 patients evaluated, twenty seven patients classified with group A, received cisplatin and etoposide containing combination chemotherapy alone, eighteen patients, classified with group B, received chemotherapy and radiotherapy, fifteen patients, group C, received neoadjuvant or adjuvant chemotherapy and surgery with/without radiation therapy, seven patients, group D, received only supportive care. Result: The major response rate for group A and B was 37% and 61% respectively. There was no statistically significant difference in response rate between A and B groups(p=0.97). The analysis of prognostic factors showed that differences of age, sex, pathology, blood type, smoking year, stage and ECOG performance did not related to improvement in survival. Median survival time was 8.6 months for group A, 13.4 months for group B, 19.2 months for group C, and 5.4 months for group D, respectively and there was statistically significant difference(p=0.003), suggesting that multimodality therapy was associated with signigicant improvement in survival. Subset survival analysis showed a significant therapeutic effect for earlier stage and good performance state(p=0.007, 0.009, respectively). A possible survival advantages were observed for major response groups. Conclusion: It was suggested that multimodality therapy for the management of patients who had stage III disease, has yielded good median survival and long survival for seleted patients. But, it is necessory to validate above result with further investigation in large scale and in prospective randomized trials.

• Radiation Oncology Journal
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• v.29 no.1
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• pp.44-52
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• 2011

Purpose: To evaluate the outcomes and prognostic factors of postoperative radiotherapy (PORT) for patients with pathological stage III non-small-cell lung cancer (NSCLC) at a single institution. Materials and Methods: From 2000 to 2007, 88 patients diagnosed as having pathologic stage III NSCLC after curative resection were treated with PORT. There were 80 patients with pathologic stage IIIA and eight patients with pathologic stage IIIB in the AJCC 6th staging system. The majority of patients (n=83) had pathologic N2 disease, and 56 patients had single station mediastinal LN metastasis. PORT was administered using conventional technique (n=76) or three-dimensional conformal technique (n=12). The median radiation dose was 54 Gy (range, 30.6 to 63 Gy). Thirty-six patients received chemotherapy. Radiation pneumonitis was graded by the Radiation Therapy Oncology Group system, and other treatment-related toxicities were assessed by CTCAE v 3.0. Results: Median survival was 54 months (range, 26 to 77 months). The 5-year overall survival (OS) and disease free survival (DFS) rates were 45% and 38%, respectively. The number of metastatic lymph nodes was associated with overall survival (hazard ratio, 1.037; p-value=0.040). The 5-year locoregional recurrence free survival (LRFS) and distant metastasis free survival (DMFS) rates were 88% and 48%, respectively. Multiple stations of mediastinal lymph node metastasis was associated with decreased DFS and DMFS rates (p-value=0.0014 and 0.0044, respectively). Fifty-one relapses occurred at the following sites: 10 loco-regional, 41 distant metastasis. Grade 2 radiation pneumonitis was seen in three patients, and symptoms were well tolerated with anti-tussive medication. Grade 2 radiation esophagitis was seen in 11 patients. There were no grade 3 or more severe complications associated with PORT. Conclusion: Our retrospective data show that PORT for pathological stage III NSCLC is a safe and feasible treatment and could improve loco-regional control. The number of metastatic lymph nodes and stations of mediastinal lymph node metastasis were analyzed as prognostic factors. Furthermore, efforts are needed to reduce distant metastasis, which is a major failure pattern of advanced stage NSCLC.

• Tuberculosis and Respiratory Diseases
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• v.64 no.4
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• pp.285-292
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• 2008

Background: A diagnosis of malignant pleural effusion is clinically important, as the prognosis of lung cancer patients with malignant pleural effusion is poor. The diagnosis will be difficult if a cytological test is negative. This study was performed to investigate whether the detection of hypermethylation of the p16 (CDKN2A) and retinoic acid receptor b2 (RARB2) genes in pleural fluid is useful for a diagnosis of malignant pleural effusion. Methods: Pleural effusion was collected from 43 patients and was investigated for the aberrant promoter methylation of the RARB2 and CDKN2A genes by use of methylation-specific PCR. Results were compared with findings from a pleural biopsy and from pleural fluid cytology. Results: Of 43 cases, 17 cases of pleural effusion were due to benign diseases, and 26 cases were from lung cancer patients with malignant pleural effusion. Hypermethylation of the RARB2 and CDKN2A genes was not detected in the case of benign diseases, independent of whether or not the patients had ever smoked. In 26 cases of malignant pleural effusion, hypermethylation of RARB2, CDKN2A or either of these genes was detected in 14, 5 and 15 cases, respectively. The sensitivities of a pleural biopsy, pleural fluid cytology, hypermethylation of RARB2, hypermethylation of CDKN2A, or hypermethylation of either of the genes were 73.1%, 53.8%, 53.8%, 19.2%, and 57.7%, respectively; negative predictive values were 70.8%, 58.6%, 58.6%, 44.7%, and 60.7%, respectively. If both genes are considered together, the sensitivity and negative predictive value was lower than that for a pleural biopsy, but higher than that for pleural fluid cytology. The sensitivity of hypermethylation of the RARB2 gene for malignant pleural effusion was lower in small cell lung cancers than in non-small cell lung cancers. Conclusion: These results demonstrate that detection of hypermethylation of the RARB2 and CDKN2A genes showed a high specificity, and sensitivity was higher than for pleural fluid cytology. With a better understanding of the pathogenesis of lung cancer according to histological types at the molecular level, and if appropriate genes are selected for hypermethylation testing, more precise results may be obtained.

• Journal of Life Science
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• v.19 no.9
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• pp.1314-1320
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• 2009

Histone deacetylase inhibitor (HDACI) is a new promising candidate as an antineoplastic agent for the treatment of solid and hematologic malignancies. In order to evaluate cell death and to elucidate the related mechanism(s) in NSCLC cells after HDACI, sodium butyrate (SB), a representative HDACI, was used to treat H460 cells for 48 hrs. SB exposure resulted in a significant reduction of cell viability at concentrations below 7.5 mM, and about 50% of cell death occurred at 20 mM. The types of cell death induced by SB were both apoptosis and necrosis, evaluated by Annexin-V staining combined with propidium iodide. SB treatment significantly evoked G2/M cell cycle arrest and subsequently induced cell death with caspase-dependent manner. While ERK protein content was not altered after SB, phosphorylated forms of ERK were markedly reduced. Taken together, SB is significantly able to induce cell death in NSCLC cell line H460, and it is suggested that the reduction of ERK phosphorylation might be closely involved in the cancer cell death mechanism initiated by HDACI.