• Radiation Oncology Journal
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• v.27 no.3
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• pp.163-168
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• 2009

Purpose: This study was a retrospective evaluation of the efficacy of stereotactic radiosurgery (SRS) in patients with >4 metastases to the brain. Materials and Methods: Between January 2004 and December 2006, 68 patients with $\geq$4 multiple brain metastases were included and reviewed retrospectively. Twenty-nine patients received SRS and 39 patients received whole brain radiotherapy (WBRT). Patients with small cell lung cancers and melanomas were excluded. The primary lesions were non-small cell lung cancer (69.0%) and breast cancer (13.8%) in the SRS group and non-small cell lung cancer (64.1%), breast cancer (15.4%), colorectal cancer (12.8%), esophageal cancer (5.1%) in the WBRT group. SRS involved gamma-knife radiosurgery and delivered 10~20 Gy (median, 16 Gy) in a single fraction with a 50% marginal dose. WBRT was delivered daily in 3 Gy fractions, for a total of 30 Gy. After completion of treatment, a follow-up brain MRI or a contrast-enhanced brain CT was reviewed. The overall survival and intracranial progression-free survival were compared in each group. Results: The median follow-up period was 5 months (range, 2~19 months) in the SRS group and 6 months (range, 4~23 months) in the WBRT group. The mean number of metastatic lesions in the SRS and WBRT groups was 6 and 5, respectively. The intracranial progression-free survival and overall survival in the SRS group was 5.1 and 5.6 months, respectively, in comparison to 6.1 and 7.2 months, respectively, in the WBRT group. Conclusion: SRS was less effective than WBRT in the treatment of patients with >4 metastases to the brain.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.11
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• pp.4623-4627
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• 2014

Background: The epidermal growth factor receptor (EGFR) plays a vital role in the activation and inactivation of receptor tyrosine kinases. Mutations in exons 19 and 21 of EGFR are commonly found to be associated with non small cell lung carcinoma and triple negative breast cancer, enhancing sensitivity to EGFR targeting chemotherapeutic agents. Since amplification and prolonged activation of EGFR molecules have been identified in oral squamous cell carcinomas (OSCC), we investigated whether OSCCs carried mutations in exons 19 and 21 of EGFR to their incidence. Materials and Methods: Tumor chromosomal DNA isolated from forty surgically excised oral squamous cell carcinoma tissues was subjected to PCR amplification with intronic primers flanking exons 19 and 21 of the EGFR gene. The PCR amplicons were subsequently subjected to direct sequencing to elucidate the mutation status. Results: Data analysis of the EGFR exon 19 and 21 coding sequences did not show any mutations in the forty OSCC samples that were analyzed. Conclusions: To the best of our knowledge, this is the first study to have investigated the genetic status of exons 19 and 21 of EGFR in Indian OSCCs and identified that mutation in EGFR exon 19 and 21 may not contribute towards their genesis. The absence of mutations also indicates that oral cancerous lesions may not be as sensitive as other cancers to chemotherapeutic agents targeting EGFR.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.15
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• pp.6445-6449
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• 2015

Background: NSCLC is a disease involving uncontrolled cell growth, which could result in metastases into nearby tissues beyond the lungs. Materials and Methods: The aim of the present study was to analyze the influence of epidermal growth factor receptor (EGFR) gene expression on metastasis and survival in NSCLC patients. The present case-control study included 100 cases of NSCLC patients and 100 age and sex matched controls. EGFR gene expression was analyzed by quantitative real time PCR using serum RNA. Association with NSCLC patient survival was analyzed by the Kaplan-Meier method. Results: We analyzed EGFR gene expression and observed mean increased gene expression of 13.5 fold in NSCLC patients. Values reflected overall survival of patients with a median of 15.8 months in the cases of <13 fold increased gene expression vs 6.7 months with >13 fold increased EGFR gene expression (p=0.005). Distant metastatic patients with <13 fold increased EGFR gene expression had 7.9 months of median survival time while>13 fold increased EGFR gene expression had only 5 months of median survival time (p=0.03). Non metastatic patients with <13 fold increased EGFR gene expression had 18 months of median survival time as compared to only 7.1 months with >13 fold increased expression. Conclusions: Higher cell free EGFR mRNA expression may play an important role in causing distant metastases and reducing overall survival of NSCLC patients in the Indian population.

• Journal of Chest Surgery
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• v.38 no.9 s.254
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• pp.616-621
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• 2005

Background: In the resection of lung cancer, pneumonectomy occupied $20 {\~}35\%$ of all resections, and significantly high operative mortality is reported in right pneumonectomy ($10{\~}25\%$). The aim of this study is to identify the characteristics of morbidity, operative mortality and factors affecting operative mortality after pneumonectomy. Material and Method: This study recruited the database which performed pneumonectomy for lung cancer in Korea Cancer Center Hospital from Aug 1987 to Apr 2002. Result: Total of 386 pneumonectomies were peformed in that period. Sidedness were left in 238, right in 148; and the procedures were standard resection in 207, and extended resection in 179. Morbidity occurred in 115 cases ($29.8\%$, 115/386). Mortality occurred in 12 cases ($3.1\%$, 12 in 386). This mortality rate was similar to that of lobectomy ($2.1\%$, 13 in 613) during the same period. Morbidity consisted of 42 hoarseness, 17 (9) pneumonia and ARDS, 8 empyema, 5 (1) broncho-pleural fistula, 5 reoperation for bleeding, 5 (1) arrhythmia, 1 (1) pulmonary edema, and 25 others (The number in the parenthesis is the number of mortality case for that morbidity). Several factors affecting the operative mortality were evaluated. At first, extended procedure ($3.3\%$, 6 in 179) affected the operative mortality similar to the standard procedure ($2.9\%$, 6 in 207)(p=0.812). Second, the rate of operative mortality in an elderly group over 60 years ($5.5\%$, 10 in 182) was significantly higher than the younger group under 60 years ($1\%$, 2 in 204)(p=0.016). Third, sidedness of resection affects to operative mortality. Right pneumonectomy ($6.8\%$, 10 in 148) showed higher operative mortality than that of left pneumonectomy ($0.8\%$, 2 in 238)(p=0.002). The group over 60 years showed higher incidence of respiratory morbidity ($11.0\%$, 20 in 182) than that of the group under 60 years ($3.4\%$, 7 in 204)(p=0.005). Right pneumonectomy also showed significantly higher incidence ($11.5\%$, 17 in 148) than that of left pneumonectomy ($4.2\%$, 10 in 238)(p=0.008). Conclusion: Age and sidedness of pneumonectomy were the risk factors of operative mortality and respiratory complications, Therefore, careful selection of patients and more attention perioperatively were demanded in right pneumonectomy. However, because the operative mortality is acceptable, pneumonectomy could be done safely if the pneumonectomy is necessary for curative resection of lung cancer.

• Tuberculosis and Respiratory Diseases
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• v.58 no.2
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• pp.135-141
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• 2005

배경 및 목적 : Multidrug Resistance-1 (MDR1) 유전자는 다약제내성에 관여하는 P-glycoprotein을 암호화한다. MDR1 유전자의 다형성은 P-glycoprotein의 발현과 기능의 차이를 일으켜 항암화학요법 반응에 영향을 미칠 수 있을 것이다. 저자들은 소세포폐암 환자에서 MDR1 유전자의 다형성과 일배체형에 따른 항암화학요법에 대한 반응을 조사하였다. 대상 및 방법 : 경북대학병원에서 병리적으로 소세포폐암으로 진단받고 etoposide-cisplatin 항암화학요법을 받은 54명을 대상으로 하였다. 전혈 5cc에서 DNA를 추출하고 PCR-RFLP법을 통해 MDR1 유전자 엑손 21의 2677G>T 다형성과, 엑손 26의 3435C>T 다형성을 조사하고 다형성과 일배체형에 따른 항암화학요법의 반응을 조사하였다. 결 과 : 2677G>T 유전자형에 따른 항암화학요법의 반응은 유의한 차이가 없었다. 3435 CC 유전자형은 3435 CT+TT 형에 비해 치료 반응율이 유의하게 높았다 (P = 0.025). 유전자형 분석 결과와 일치되게 2677G/3435C 일배체형은 다른 일배체형에 비해 치료반응을 보이는 경우가 유의하게 많았다 (P = 0.015). 결 론 : 소세포폐암에서 MDR1 유전자의 2677G>T와 3435C>T 다형성 및 이들 다형성의 일배체형은 etoposide-cisplatin 항암화학요법의 반응을 예측할 수 있는 지표로 사용될 수 있을 것으로 생각된다.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.20
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• pp.8911-8916
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• 2014

Background: The aim of the present study was to determine the predictive/prognostic value of the secreted protein, acidic and rich in cysteine (SPARC) in cases of unresectable, locally advanced, non-small cell lung cancer. Materials and Methods: The study included 84 patients with Stage IIIA-B non-small cell lung cancer, undergoing simultaneous chemoradiotherapy including radiotherapy at a dose of 66 Gy and weekly docataxel ($20mg/m^2$) and cisplatin ($20mg/m^2$). SPARC expression was studied in biopsy material by immunohistochemical methods and correlations with treatment responses or survival were evaluated. Results: Median overall survival was $16{\pm}2.73$ (11.55-20.46) months for low expression vs $7{\pm}1.79$ months (7.92-16.08) months for high expression (p=0.039), while median local control was $13{\pm}2.31$ (8.48-17.5) months for low expression vs $6{\pm}0.85$ (4.34-7.66) months for high expression (p=0.045) and median progression-free survival was $10{\pm}2.31$ (5.48-14.5) months for low expression vs $6{\pm}1.10$ (3.85-8.15) months for high expression (p=0.022). In both univariate and multivariate analyses, high SPARC expression was associated with significantly shorter overall survival (p=0.003, p=0.007, respectively), local control (p=0.008, p=0.036) and progression-free survival (p=0.004, p=0.029) when compared to low SPARC expression. No significant difference was detected between high and low SPARC expression groups regarding age, sex, T stage, N stage, histopathology and stage-related patient characteristics. Conclusions: High SPARC expression was identified as a poor prognostic factor in cases with locally advanced NSCLC treated with concurrent chemoradiotherapy.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.14
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• pp.5691-5696
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• 2014

Background: Many clinical trials have been conducted to evaluate sorafenib for the treatment of advanced NSCLC, but the results for efficacy have been inconsistent. The aim of this study was to evaluate the efficacy and safety of sorafenib in patients with advanced NSCLC in more detail by meta-analysis. Methods: This meta-analysis of randomized controlled trials (RCTs) was performed after searching PubMed, EMBASE, ASCO Abstracts, ESMO Abstracts, and the proceedings of major conferences for relevant clinical trials. Two reviewers independently assessed the quality of the trials. Outcomes analysis were disease control rate (DCR), progression- free survival (PFS), overall survival (OS) with 95% confidence intervals (CI) and major toxicity. Subgroup analysis was conducted according to sorafenib monotherapy, in combination with chemotherapy or EGFR-TKI to investigate the preferred therapy strategy. Results: Results reported from 6 RCTs involving 2, 748 patients were included in the analysis. Compared to sorafenib-free group, SBT was not associated with higher DCR (RR 1.31 (0.96- 1.79), p=0.09), PFS (HR 0.82 (0.66-1.02), p=0.07) and OS (HR 1.01 (0.92-1.12), p=0.77). In terms of subgroup results, sorafenib monotherapy was associated with significant superior DCR and longer PFS, but failed to show advantage with regard to OS. Grade 3 or greater sorafenib-related adverse events included fatigue, hypertension, diarrhea, oral mucositis, rash and HFSR. Conclusions: SBT was revealed to yield no improvement in DCR, PFS and OS. However, sorafenib as monotherapy showed some activity in NSCLC. Further evaluation may be considered in subsets of patients who may benefit from this treatment. Sorafenib combined inhibition therapy should be limited unless the choice of platinum-doublet regimen, administration sequence or identification of predictive biomarkers are considered to receive better anti-tumor activity and prevention of resistance mechanisms.

• Journal of Chest Surgery
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• v.40 no.11
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• pp.745-751
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• 2007

Background: Mediastinoscopy is generally performed to confirm mediastinal lymph node metastasis in lung cancer patients. It still remains controversial whether mediastinoscopy should be performed in all patients with resectable non-small cell lung cancer (NSCLC). We studied the clinical value of mediastinoscopy in preoperative staging in NSCLC. Material and Method: We retrospectively studied 90 NSCLC patients who underwent radiological evaluation and mediastinoscopy followed by surgical resection from March 2002 to December 2004. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of each evaluation method were assessed and compared. Result: Specificity, PPV, NPV, and accuracy of mediastinoscopy were superior to those of radiological evaluation, but there was no significant difference in sensitivity. The sensitivity of mediastinoscopy was 28.6% in 62 patients with radiological N0/1 disease and 72.7% in 28 patients with radiological N2/3 disease. Seven of eight patients in whom positive nodes were not detected by the mediastinoscopy had subcarinal lymph node metastasis. Conclusion: Considering its invasiveness, the difficulty to reach certain node stations, and its low sensitivity in radiological N0/1 disease, mediastinoscopy should be selectively performed in radiological N2/3 disease rather than in all radiological cancer stages.

• Journal of Chest Surgery
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• v.40 no.2 s.271
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• pp.114-121
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• 2007

Background: Apoptosis plays a crucial role in carcinogenesis, as well as in development and tissue homeostasis. Terminal deoxyribonucleotidyl transferase mediated neck end labelling (TUNEL) and in situ nick end labelling (ISEL) have been used to investigate the apoptosis in tissues. Since the introduction of the M30 monoclonal antibody to overcome drawbacks of TUNEL and ISEL, the apoptosis in various tumors, with the exception of pulmonary carcinomas, has been studied. In this study, attempts were made to examine the correlation of apoptosis in non-small cell carcinomas, using both M30 and the expression of p53 protein, with the clinicopathological factors. Material and Method: Forty five patients with surgically resected non-small cell carcinomas were included. Immunohistochemical staining with M30 and p53 monoclonal antibody were peformed, and their expressions compared with the clinicopathological features. The overall survival time and recurrence-free survival time were calculated, and the factors influencing the survival time analyzed using a univariate analysis. The effects of the expression stati of M30 and p53 on the risks of cancer related to both death and recurrence were evaluated using a multivariate analysis. Result: The p53 positive group had many more M30 positive cells than the p53 negative group (p53 positive group; $61.7{\pm}26.8$ cells vs. p53 negative group; $45.6{\pm}29.6$ cells, p=0.005) and significantly more p53 positive patients showing at least 10 positive cells (apoptotic index, $Al{\ge}1$) on M30 staining (p53 positive group; 52.4% (11/21) vs. p53 negative group 16,7% (4/24), p=0.025). In the univariate analysis, the survival times in relation to smoking (pack-year), performance status (PS) and Al showed significant differences. The multivariate analysis demonstrated the relative risk (R.R) of cancer death increased almost 7.5-fold (R.R 7.482; 95% Cl $1.886{\sim}29.678$; p=0.004) and the risk of recurrence almost 3,8-fold (R.R 3.795; 95% Cl: $1.184{\sim}12.158$; p=0.025) in the high Al (${\ge}1$) compared to the low Al (<1) group. There was no prognostic effect of p53 expression on the survival time or risk of cancer death and recurrence. Conclusion: In non-small cell lung carcinomas, M30 immunohistochemistry was an excellent method for analyzing apoptosis; the high apoptotic index could be an adverse prognostic predictive factor.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.2
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• pp.629-635
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• 2014

Background: Acute myeloid leukemia (AML) is a fatal hematological malignancy which is resistant to a variety of chemotherapy drugs. Myeloid cell leukemia-1 (Mcl-1), a death-inhibiting protein that regulates apoptosis, has been shown to be overexpressed in numerous malignancies. In addition, it has been demonstrated that the expression level of the Mcl-1 gene increases at the time of leukemic relapse following chemotherapy. The aim of this study was to target Mcl-1 by small interference RNA (siRNA) and analyze its effects on survival and chemosensitivity of acute myeloid leukemia cell line HL-60. Materials and Methods: siRNA transfection was performed with a liposome approach. The expression levels of mRNA and protein were measured by real-time quantitative PCR and Western blot analysis, respectively. Trypan blue assays were performed to evaluate tumor cell growth after siRNA transfection. The cytotoxic effects of Mcl-1 siRNA (siMcl-1) and etoposide were determined using MTT assay on their own and in combination. Apoptosis was quantified using a DNA-histone ELISA assay. Results: Transfection with siMcl-1 significantly suppressed the expression of Mcl-1 mRNA and protein in a time-dependent manner, resulting in strong growth inhibition and spontaneous apoptosis. Surprisingly, pretreatment with siMcl-1 synergistically enhanced the cytotoxic effect of etoposide. Furthermore, Mcl-1 down-regulation significantly increased apoptosis sensitivity to etoposide. No significant biological effects were observed with negative control siRNA treatment. Conclusions: Our results suggest that specific suppression of Mcl-1 by siRNA can effectively induce apoptosis and overcome chemoresistance of leukemic cells. Therefore, siMcl-1 may be a potent adjuvant in leukemia chemotherapy.