• Radiation Oncology Journal
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• 제36권1호
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• pp.35-44
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• 2018

Purpose: To evaluate clinical outcomes according to radiation dose in patients with limited-stage small-cell lung cancer (LS-SCLC) treated with concurrent chemoradiotherapy (CCRT). Materials and Methods: From January 2006 to December 2015, 38 patients with LS-SCLC were treated with CCRT with etoposide and cisplatin. Total radiation doses ranged from 45 Gy to 66 Gy (1.8-2 Gy/fraction) and were classified into three groups: 45-54 Gy, 60-63 Gy, and 66 Gy. The impact of radiation dose on survival outcomes were evaluated. Toxicities were evaluated according to the Common Terminology Criteria for Adverse Events version 4.03. Results: The median follow-up period was 21 months. The 2-year overall survival (OS) and local failure-free survival (LFFS) rates were 45.8% and 67.5%, respectively. The 2-year LFFS rates were 33.3% for 45-54 Gy group, 68.6% for 60-63 Gy group, and 87.1% for 66 Gy group (p = 0.014). In multivariate analysis, radiation dose was a significant factor for LFFS (p = 0.015). Although radiation dose was not a significant factor for OS and disease-free survival (DFS) in multivariate analysis, both OS and DFS of 66 Gy group tended to be better than that of 45-63 Gy group in univariate analysis. However, there were no differences in severe toxicities among three groups. Conclusion: Higher radiation dose achieved better local control in patients with LS-SCLC treated with CCRT. In addition, a total dose of 66 Gy tended to improve OS and DFS.

• Asian Pacific Journal of Cancer Prevention
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• 제16권4호
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• pp.1421-1425
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• 2015

Aims: Pleiotrophin (PTN), an angiogenic factor, is associated with various types of cancer, including lung cancer. Our aim was to investigate the possibility of using serum PTN as an early indicator regarding disease diagnosis, classification and prognosis, for patients with non-small cell lung cancer (NSCLC). Methods: Significant differences among PTN levels in patients with small cell lung cancer (SCLC, n=40), NSCLC (n=136), and control subjects with benign pulmonary lesions (n=21), as well as patients with different pathological subtypes of NSCLC were observed. Results: A serum level of PTN of 300.1 ng/ml, was determined as the cutoff value differentiating lung cancer patients and controls, with a sensitivity and specificity of 78.4% and 66.7%, respectively. Negative correlations between serum PTN level and pathological differentiation level, stage, and survival time were observed in our cohort of patients with NSCLC. In addition, specific elevation of PTN levels in pulmonary tissue in and around NSCLC lesions in comparison to normal pulmonary tissue obtained from the same subjects was also observed (n=2). Conclusion: This study suggests that the serum PTN level of patients with NSCLC could be an early indicator for diagnosis and prognosis. This conclusion should be further assessed in randomized clinical trials.

• Journal of Chest Surgery
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• 제45권1호
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• pp.40-44
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• 2012

Background: The experience of a single-institution regarding surgery for small cell lung cancer (SCLC) was reviewed to evaluate the surgical outcomes and prognoses. Materials and Methods: From July 1990 to December 2009, thirty-four patients (28 male) underwent major pulmonary resection and lymph node dissection for SCLC. Lobectomy was performed in 24 patients, pneumonectomy in eight, bilobectomy in one, and segmentectomy in one. Surgical complications, mortality, the disease-free survival (DFS) rate, and the overall survival rate were analyzed retrospectively. Results: The median follow-up period was 26 months (range, 4 to 241 months), and there was one surgical mortality (2.9%). Six patients (17.6%) experienced recurrence, all of which were systemic. Eight patients died during follow-up; four died of disease progression and the other four died of pneumonia or of another non-cancerous cause. The three-year DFS rate was $79.2{\pm}2.6%$ and the overall survival rate was $66.4{\pm}10.5%$. Recurrence or death was significantly prevalent in the patients with lymph node metastasis (p=0.001) as well as in those who did not undergo adjuvant chemotherapy (p=0.008). The three-year survival rate was significantly greater in the patients with pathologic stage I/II cancer than in those with stage III cancer (84% vs. 13%, p=0.001). Conclusion: Major pulmonary resection for small cell lung cancer is feasible in selected patients. Patients with pathologic stage I or II disease showed an excellent survival rate after surgery and adjuvant treatment. Prospective randomized studies will be needed to define the role of surgery in early-stage small cell lung cancer.

• Tuberculosis and Respiratory Diseases
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• 제61권2호
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• pp.143-149
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• 2006

연구배경: Toptisomerase I 억제제인 irinotecan 과 소세포폐암 치료의 근간인 cisplatin의 복합화학용법을 확장기 소세포폐암 환자에게 1차 치료법으로 실시하여 반응률, 생존율 및 부작용을 확인하였다. 방 법: 2002년 6월부터 2005년 2월까지 확진된 확장기 소세포폐암 환자 39명에게 irinotecan $60mg/m^2$, 제 1, 8, 15일째 cisplatin $60mg/m^2$ 제1일째에 28일 간격으로 4회 투여하였다. 결 과: 반응률은 77%(완전반응 8%), 중앙생존기간은 14.8개월, 1-및 2-년 생존율은 60.9%, 27.6%였으며, 중앙 무진행생존기간은 8.4개월, 6-및 12-개월 무진행생존율은 75.0%, 18.8%였다. WHO grade 3 이상의 부작용은 백혈구 감소증 23%, 설사 26%였으나, 심한 설사때문에 2명은 치료방법을 바꾸었고, 1명은 사망하였다. 결 론: Irinotecan과 cisplatin 복합화학요법은 확장기 소세포폐암 환자의 1차 치료법으로 유용하며, 부작용으로서 설사에 대해서는 치명적일수 있으므로 심각한 주의가 요망된다.

• Asian Pacific Journal of Cancer Prevention
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• 제15권24호
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• pp.10591-10596
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• 2015

Background: Tumor necrosis factor (TNF) receptor-associated factor 6 (TRAF6) has been reported to be associated with the development of various cancers. However, the role of TRAF6 in lung cancer remains unclear. Objective: To explore the expression and clinicopathological significance of TRAF6 protein in lung cancer tissues. Materials and Methods: Three hundred and sixty-five lung cancer samples and thirty normal lung tissues were constructed into 3 microarrays. The expression of TRAF6 protein was determined using immunohistochemistry (IHC). Furthermore, correlations between the expression of TRAF6 and clinicopathological parameters were investigated. Results: The expression of TRAF6 in total lung cancer tissues (365 cases), as well as in small cell lung cancer (SCLC, 26 cases) and non-small cell lung cancer (NSCLC, 339 cases) was significantly higher compared with that in normal lung tissues. The ROC curve showed that the area under curve of TRAF6 was 0.663 (95%CI 0.570~0.756) for lung cancer. The diagnostic sensitivity and specificity of TRAF6 were 52.6% and 80%, respectively. In addition, the expression of TRAF6 was correlated with clinical TNM stage, tumor size and lymph node metastasis in all lung cancers. Consistent correlations were also observed for NSCLCs. Conclusions: TRAF6 might be an oncogene and the expression of TRAF6 protein is related to the progression of lung cancer. Thus, TRAF6 might become a target for diagnosis and gene therapy for lung cancer patients.

• Journal of Chest Surgery
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• 제31권12호
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• pp.1195-1199
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• 1998

배경: 소세포폐암에 있어 수술의 적응은 제한적이었으며 수술의 결과에 대하여서도 논란이 많다. 대상 환자는 1992년 1월부터 1996년 12월까지 신촌세브란스 흉부외과에서 수술한 9명의 환자로서 남자가 8명, 여자가 1명이었으며 평균 연령은 57.2세(range; 35∼76세)이었다. 대상 및 방법: 수술전 소세포폐암으로 진단되었던 예는 5예이었으며 4예에서의 수술전 진단은 분화가 안된 편평상피세포암이었다. 수술은 전예에서 폐절제술 및 종격동림프절박리술을 시행하였고 폐단엽절제술이 5예, 폐단엽절제술과 분엽절제술 및 늑골을 포함한 En-block 절제 1예, 폐이엽절제술 2예, 전폐절제술 1예 등이었다. 결과: 수술사망 예는 없었으며 수술 후 합병증으로는 출혈 1예, 심부정맥 1예 등이 있었다. 수술 후 전예에서 소세포암이 확인되었고 수술 후 병기는 T1N0M0 1예, T2N0M0 4예, T3N0M0 1예, T3N1M0 1예, T2N2M0 1예, T4N0M0 1예이었다. 수술 후 5예에서는 항암화학요법을, 4예에서는 항암화학요법 및 방사선치료를 시행하였다. 전예에서 추적이 가능하여 평균 추적기간은 평균 33.0개월(1-63개월이었고 추적기간중 림프절로의 전이가 없는 경우 6예 중에서는 1예에서만 장골에 전이가 발견되었으나 생존해있고, 림프절로의 전이가 있거나 T4 병변인 3예에서는 2예는 국소 부위, 1예는 뇌에 재발이 있었으며 이중 2예는 사망하였다. 결론: 소세포폐암에서도 TNM 병기가 유용하며 종격동 또는 구역 림프절로의 전이가 없는 경우에는 수술 후 성적이 양호하여 초기 병기의 소세포폐암 환자에서는 항암화학요법과 함께 적극적인 수술 절제가 필요한 것으로 생각된다.

• Asian Pacific Journal of Cancer Prevention
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• 제14권1호
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• pp.489-494
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• 2013

Background: Lung cancer is one of the commonest and most lethal cancers throughout the world. The epidemiological and pathological profile varies among different ethnicities and geographical regions. At present adenocarcinoma is the commonest histological subtype of non-small cell lung cancer (NSCLC) in most of the Western and Asian countries. However, in India squamous cell carcinoma has been reported as the commonest histological type in most of the series. The aim of the study was to analyze the current clinico-pathological profile and survival of lung cancer at our centre. Materials and Methods: We analyzed 434 pathologically confirmed lung cancer cases registered at our centre over a period of three years. They were evaluated for their clinical and pathological profiles, treatment received and outcome. The available histology slides were reviewed by an independent reviewer. Results: Median age was 55 years with a male:female ratio of 4.6:1. Some 68% of patients were smokers. There were 85.3% NSCLC and 14.7% SCLC cases. Among NSCLCs, adenocarcinoma was the commonest histological subtype after the pathology review. Among NSCLC, 56.8% cases were of stage IV while among SCLC 71.8% cases had extensive stage disease. Some 29% of patients did not receive any anticancer treatment. The median overall and progression free survivals of the patients who received treatment were 12.8 and 7.8 months for NSCLC and 9.1 and 6.8 months for SCLC. Conclusions: This analysis suggests that adenocarcinoma may now be the commonest histological subtype also in India, provided a careful pathological review is done. Most of the patients present at advanced stage and outcome remains poor.

• Tuberculosis and Respiratory Diseases
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• 제75권3호
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• pp.95-103
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• 2013

Background: Small cell lung cancer (SCLC) transformation during epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) treatment in lung cancer has been suggested as one of possible resistance mechanisms. Methods: We evaluated whether SCLC transformation or neuroendocrine (NE) differentiation can be found in the cell line model. In addition, we also investigated its effect on responses to conventional chemotherapeutic drugs of the SCLC treatment. Results: Resistant cell lines to various kinds of EGFR-TKIs such as gefitinib, erlotinib, CL-387,785 and ZD6474 with A549, PC-9 and HCC827 lung adenocarcinoma cell lines were established. Among them, two resistant cell lines, A549/GR (resistant to gefitinib) and PC-9/ZDR (resistant to ZD6474) showed increased expressions of CD56 while increased synaptophysin, Rb, p16 and poly(ADP-ribose) polymerase were found only in A549/GR in western blotting, suggesting that NE differentiation occurred in A549/GR. A549/GR cells were more sensitive to etoposide and cisplatin, chemotherapeutic drugs for SCLC, compared to parental cells. Treatment with cAMP and IBMX induced synaptophysin and chromogranin A expression in A549 cells, which also made them more sensitive to etoposide and cisplatin than parental cells. Furthermore, we found a tissue sample from a patient which showed increased expressions of CD56 and synaptophysin after development of resistance to erlotinib. Conclusion: NE differentiation can occur during acquisition of resistance to EGFR-TKI, leading to increased chemosensitivity.

• Radiation Oncology Journal
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• 제37권3호
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• pp.156-165
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• 2019

Purpose: Prophylactic cranial irradiation (PCI) is a standard treatment for limited-stage small cell lung cancer (LS-SCLC) showing a response to initial treatment, but many patients do not receive PCI due to comorbidities or refusal. This study aims to define the patient group for whom PCI can be omitted with minimal risk. Materials and Methods: Patients with LS-SCLC who underwent radiotherapy with curative aim at our institution between January 2004 and December 2015 were retrospectively reviewed. Patients who did not receive PCI were evaluated for brain metastasis-free survival (BMFS), progression-free survival (PFS), overall survival (OS), and prognostic factors for survival, and treatment outcomes were compared with a patient cohort who received PCI. Results: A total of 350 patients achieved a response following thoracic radiotherapy, and 190 of these patients did not receive PCI. Stage I-II and a complete response (CR) to initial therapy were good prognostic factors for BMFS and OS on univariate analysis. Patients with both stage I-II and a CR who declined PCI showed comparable 2-year BMFS to those who received PCI (92% vs. 89%). In patients who achieved CR, PCI did not significantly improve OS or PFS. Conclusion: There should be less concern about omitting PCI in patients with comorbidities if they have stage I-II or a CR, with brain metastasis control being comparable to those patients who receive PCI.

• Radiation Oncology Journal
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• 제2권2호
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• pp.221-228
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• 1984

The recogition that the vast majority of patients with small cell lung cancer have distant metastatic disease at the time of diagnosis lead to the use of systemic chemotherapy and consequent major improvement in survival, but recently evaulated treatment strategies, integration of large field chest irradiation with chemotherapy lead to the improved the local control and relapse free survival in limited SCLC. Therefore, it is logical to combine the two modalities in an effort to maximize the therapeutic effect. Authors performed the combination chemotherapy of CAV (Cyclophosphamide, Adriamycin, an6 Vincristine) and radiotherapy of primary tumor and regional lymphatics with prophylatic cranial irradiation in 42 patients of limited SCLC, from Mar. 1978 to Dec. 1982 Seoul National University Hospital. The results are as follows : 1. CR and PR after 2 cycles chemotherapy is $7\%$ and $43\%$, respectively however, subsequent response to radiotherapy is $38\%$ and $43\%$ in CR and PR. 2. Overall median survival peroid is 8.6 months. 3. 1 year and 2 years survival rate is $46.3\%$ and $20.5\%$, respectively. 4. Incidence of proven brain metastasis is $5\%$.