• Tuberculosis and Respiratory Diseases
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• 제47권3호
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• pp.339-346
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• 1999

배경: 비소세포폐암에서 비슷한 병기의 환자들도 생존 가망성은 상당한 차이를 보이는데 이러한 상황에서 보다 환자에게 효율적인 치료를 제공할 수 있게 도울 수 있는 새로운 예측인자의 필요성이 대두되었는데 보다 정확하고 재현성이 있는 폐암 병기 판정이 환자의 치료와 예후에 가장 큰 영향을 보인다고 생각된다. 비소세포폐암의 병기 판정은 1986년 Mountain 이 표명한 T(primary tumor), N(regional lymph nodes), M(distant metastasis) 시스템과 이에 각각의 병기를 따르고 있는데 이후 같은 병기내에서도 서로 다른 예후를 보이고 보다 세분화된 병기의 구분점이 있어야겠다는 공론속에서 1996년 American Joint Committee on Cancer과 Union Internationale Contre le Cancer에 의해 새로 개정된 비소세포 폐암의 병기 판정 시스템이 천명되었다. 본 연구에서는 비소세포폐암 환자에서 새로운 병기판정에 따른 생존율을 알아보고 이에 따라 술전, 술후 환자의 예후에 대한 의의를 알아 보기 위해 이 연구를 진행하였다. 방법: 연구 방법은 1981년부터 1995년까지 한양대학교 부속병원에서 비소세포폐암으로 진단된 환자중 술전에 방사선 또는 항암화학요법 치료를 받은 적이 없는 환자로서 치료적 목적으로 광범위 폐절제 및 림프절제술을 받은 환자중 사망여부의 추적이 가능한 총 84예의 환자를 대상으로 술후 얻어진 조직학적 병기를 과거의 병기판정과 새로운 TNM 병기를 기준으로 이의 생존의 관찰치와 더불어 병리조직학적 특정과 임상적 특징을 알아보았다. 결과: 환자의 median survival은 과거의 병기에 따른 결과는 stage I ; 79.1개월, stage II ; 47.3 개월, stage IIIa;22.77개월, stage IIIb; 16.1개월, stage IV;15.2개월이었고 새로운 병기에 따른 결과는 stage Ia;58.5개월, stage IIb;76.0개월, stage IIa;적용불능, stage IIIb;43.0개월, stage IIIa;22.5개월, stage IIIb;16.1개월, stage IV;15.2개월이었고 술후 36개월 뒤의 누적 백분율 생존율은 stage Ia;100%, stage Ib;80%, stage IIa; 적용불능, stage IIb;26%, stage IIIa;21%을 보였고 과거의 병기와 새로운 병기 판정에 따른 생존율에 따른 차이는 보이지 않았다. 결론: 폐암은 전세계적으로 암으로 인한 사망률 원인의 1위를 보이는 암종으로 비소세포폐암에서 비슷한 병기의 환자들도 생존 가망성은 상당한 차이를 보이는데 이러한 상황에서 보다 정확한 생존 가망성을 예측하고 각각의 환자에게 보다 효율적인 치료를 제공할 수 있게 도울 수 있는 새로운 예측 측도가 필요하게 되었다. 본 연구에서 결과는 통계학적으로 확연한 차이를 보이지 않았지만 새로 개정된 폐암 병기 판정 체계는 폐암 환자의 생존율을 높이고 비소세포폐암 환자의 예후를 보다 세분하여 정확하게 판정하는데 도움이 될 수 있으리라 사료되며 앞으로 보다 많은 추가적인 연구가 필요하다고 본다.

• Tuberculosis and Respiratory Diseases
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• 제70권4호
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• pp.301-306
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• 2011

Background: It is well-known that cell-free nucleic acids rise in patients with many types of malignancies. Several recent experimental studies using cancer cell lines have shown that changes in cell-free RNA are predictive of the response to chemotherapy. The objective of this study was to determine whether quantification of free RNA can be used as a biomarker for clinical responses to chemotherapy in patients with lung cancer. Methods: Thirty-two patients with lung cancer (non-small cell lung cancer, n=24; small cell lung cancer, n=8) were divided into 2 groups according to their responses to chemotherapy (response group, n=19; non-response group, n=13). Blood samples were collected before and after two cycles of chemotherapy. Real-time quantitative RT-PCR was used for transcript quantification of the glyceraldehyde-3-phosphate dehydrogenase gene. Results: The pre chemotherapy values (Response group $41.36{\pm}1.72$ vs. Non-response group $41.33{\pm}1.54$, p=0.78) and post chemotherapy values (Response group $39.92{\pm}1.81$ vs. Non-response group $40.41{\pm}1.47$, p=0.40) for cell free RNA concentrations, expressed as Ct GAPDH (threshold cycle glyceraldehyde-3-phosphate dehydrogenase gene) levels, was not different between the two groups. There was no significant relationship between changes in the cell free RNA level clinical responses after chemotherapy (p=0.43). Conclusion: We did not find a correlation between quantification of serum cell free RNA levels and clinical responses to chemotherapy in patients with lung cancer. Further investigations are needed to determine whether the cell free RNA level is a useful predictor of responses to chemotherapy in patients with lung cancer.

• Journal of Chest Surgery
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• 제52권4호
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• pp.221-226
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• 2019

Background: Accurate mediastinal lymph node staging is vital for the optimal therapy and prognostication of patients with lung cancer. This study aimed to determine the preoperative risk factors for pN2 disease, as well as its incidence and long-term outcomes, in patients with clinical N0-1 non-small cell lung cancer. Methods: We retrospectively analyzed patients who were treated surgically for primary non-small cell lung cancer from November 2005 to December 2014. Patients staged as clinical N0-1 via chest computed tomography (CT) and positron emission tomography (PET)-CT were divided into two groups (pN0-1 and pN2) and compared. Results: In a univariate analysis, the significant preoperative risk factors for pN2 included a large tumor size (p=0.083), high maximum standard uptake value on PET (p<0.001), and central location of the tumor (p<0.001). In a multivariate analysis, central location of the tumor (p<0.001) remained a significant preoperative risk factor for pN2 status. The 5-year overall survival rates were 75% and 22.9% in the pN0-1 and pN2 groups, respectively, and 50% and 78.2% in the patients with centrally located and peripherally located tumors, respectively. In a Cox proportional hazard model, central location of the tumor increased the risk of death by 3.4-fold (p<0.001). Conclusion: More invasive procedures should be considered when preoperative risk factors are identified in order to improve the efficacy of diagnostic and therapeutic plans and, consequently, the patient's prognosis.

• Radiation Oncology Journal
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• 제35권1호
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• pp.16-24
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• 2017

Locally advanced non-small cell lung cancer (LA-NSCLC) is composed of heterogeneous subgroups that require a multidisciplinary team approach in order to ensure optimal therapy for each patient. Since 2010, the National Comprehensive Cancer Network has recommended chemoradiation therapy (CRT) for bulky mediastinal disease and surgical combination for those patients with single-station N2 involvement who respond to neoadjuvant therapy. According to lung cancer tumor boards, thoracic surgeons make a decision on the resectability of the tumor, if it is determined to be unresectable, concurrent CRT (CCRT) is considered the next choice. However, the survival benefit of CCRT over sequential CRT or radiotherapy alone carries the risk of additional toxicity. Considering severe adverse events that may lead to death, fit patients who are able to tolerate CCRT must be identified by multidisciplinary tumor board. Decelerated approaches, such as sequential CRT or high-dose radiation alone may be a valuable alternative for patients who are not eligible for CCRT. As a new treatment strategy, investigators are interested in the application of the innovative radiation techniques, trimodality therapy combining surgery after high-dose definitive CCRT, and the combination of radiation with targeted or immunotherapy agents. The updated results and on-going studies are thoroughly reviewed in this article.

• 대한암한의학회지
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• 제17권1호
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• pp.9-16
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• 2012

Objective : The aim of this study is to evaluate the synergistic effects of Traditional Korean Medicine with Gefitinib chemotherapy on a non small cell lung cancer. Methods : A 61 year-old male patient diagnosed with left non small cell lung cancer stage IIIb (T2aN0M1a) was admitted to East-West Cancer Center (EWCC) on Apr. 2012. He received Gefitinib chemotherapy since 20th June. 2011. He suffered from many complication like as skin toxicities, peripheral neuropathy, lassitude, diarrhea and so on. He was treated with Traditional Korean Medicine consisted of herbal medicine, acupuncture, and moxibustion. The symptoms were measured by Common Terminology Criteria for Adverse Events (CTCAE version 3.0) and visual analogue scale (VAS). Performance status was measured by Eastern Cooperative Oncology Group (ECOG). Results : TKM consisting of acupuncture, moxibusion, herbal medicine significantly alleviated Gefitinib induced complication. Quality of life was also significantly improved. Conclusion : This case study suggests that TKM would beneficial to adverse effects such as skin toxicities, peripheral neuropathy, lassitude from gefitinib.

• Journal of Chest Surgery
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• 제27권11호
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• pp.922-929
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• 1994

This research represents an attempt to study the postoperative results among 32 patients who underwent complete resections of primary lung and involved mediastinal lymph nodes between January 1988 and June 1993. Ages ranged from 34 to 73 years with a mean age of 51.31 $\pm$ 8.17 years. There were 29 male patients[90.6%]. Left lung cancers were more frequent than right lung cancers. There were 19 cases of left lung cancers accounting for 59.4% of the total lung cancers. The difference, however, was insignificant. There was no T1 lesion. T2 and T3 lesions were 21[65.6%] and 11 cases[34.4%], respectively. As for cell type, squamous cell carcinomas were reported in 25 cases making up 78.1% of the cell types. Pneumonectomy was conducted on 20[62.5%] cases. Lobectomy and sleeve lobectomy were conducted on 12[37.5%] cases respectively. Mediastinal lymph node involvemednts were most frequent in subcarinal lymph node[9/13] among right lung cancers, while subaortic lymph noce[12/19] was most frequent among left lung cancers. Postoperative complications were reported in 18.9% of the total cases, including 2 cases each of paralysis of the recurrent laryngeal nerve and 1 case each of chylothorax and pyothorax. They were more frequent among patients who underwent pneumonectomy. The operative mortality stood at 3.1% with 1 patient who underwent pneumonectomy dying of pulmonary edema. The 1-year and 5-year survival rates were 50.8% and 30.1%, respectively. Patients treated with squamous cell carcinoma, involvement of single level mediastinal lymph node and lobectomy showed a higher level of survival. These fidings suggest that a long-term survival can be expected of a considerable number of N2 non-small cell lung cancer patients with a selective complete surgical resection of primary lung cancers involved mediastinal lymph nodes.

• Asian Pacific Journal of Cancer Prevention
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• 제15권2호
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• pp.731-736
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• 2014

Objective: To observe the short-term efficacy, long-term survival time and adverse responses with nedaplatin (NDP) or cisplatin (DDP) concomitant with other chemotherapy in treating non-small cell lung cancer. Materials and Methods: A retrospective, randomized, control study was conducted, in which 619 NSCLC patients in phases III and IV who were initially treated and re-treated were randomly divided into an NDP group (n=294) and a DDP group (n=325), the latter being regarded as controls. Chemotherapeutic protocols (CP/DP/GP/NP/TP) containing NDP or DDP were given to both groups. Patients in both groups were further divided to evaluate the clinical efficacies according to initial and re-treatment stage, pathological pattern, type of combined chemotherapeutic protocols, tumor stage and surgery. Results: The overall response rate (ORR) and disease control rate (DCR) in the NDP group were 48.6% and 95.2%, significantly higher than in the DDP group at 35.1% and 89.2%, respectively (P<0.01). In NSCLC patients with initial treatment, squamous carcinoma and phase III, there were significant differences in ORR and DCR between the groups (P<0.05), while ORR was significant in patients with adenocarcinoma, GP/TP and in phase IIIa (P<0.05). There was also a significant difference in DCR in patients in phase IIIb (P<0.05). According to the statistical analysis of survival time of all patients and of those in clinical phase III, the NDP group survived significantly longer than the DDP group (P<0.01). The rates of decreased hemoglobin and increased creatinine, nausea and vomiting in the NDP group were evidently lower than in DDP group (P<0.05). Conclusion: NDP concomitant with other chemotherapy is effective for treating NSCLC, with higher clinical efficacy than DDP concomitant with chemotherapy, with advantages in prolonging survival time and reducing toxic and adverse responses.

• Journal of Chest Surgery
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• 제47권1호
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• pp.13-19
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• 2014

Background: The aim of this study is to evaluate prognostic factors for survival in pathologic stage IIIA/N2 non-small-cell lung cancer (NSCLC), to identify the prognostic significance of the metastatic patterns of mediastinal lymph nodes (MLNs) relating to survival and to recurrence and metastasis. Methods: A total of 129 patients who underwent radical resection for pathologic stage IIIA-N2 NSCLC from July 1998 to April 2011 were retrospectively reviewed. The end points of this study were rates of loco-regional recurrence and distant metastasis, and survival. Results: The overall 5-year survival rate was 47.4%. A univariate analysis showed that age, pathologic T stage, and adjuvant chemotherapy were significant prognostic factors, while in multivariate analysis, pathologic T stage and adjuvant chemotherapy were significant prognostic factors. The metastasis rate was higher in patients with multi-station N2 involvement and with more than 3 positive MLNs. Further, non-regional MLN metastasis was associated with a higher loco-regional recurrence rate. Conclusion: Pathologic T stage and adjuvant chemotherapy were independent prognostic factors for long-term survival in pathologic stage IIIA/N2 NSCLC. The recurrence and the metastasis rate were affected by the metastatic patterns of MLNs. These results may be helpful for planning postoperative therapeutic strategies and predicting outcomes.

• Journal of Chest Surgery
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• 제38권6호
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• pp.421-427
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• 2005

완전절제는 pT1/2N1 비소세포폐암의 가장 효과적인 치료 방법이지만 수술 후 5년 생존율은$40\%$정도이며 많은 환자가 암의 재발로 사망하게 된다. 완전 절제된 pT1/2Nl 비소세포폐암에서 재발에 영향을 주는 인자를 규명하고자 하였다. 대상 및 방법: 1990년 1월부터 2003년 7월까지 연세대학교 의과대학 세브란스병원 흉부외과에서 pT1/2N1 비소세포폐암으로 수술받은 환자 117명을 대상으로 환자의 특성, 조직병리학적 소견, 수술방법, 림프절 전이 양상, 술 후 보조요법 등과 재발과의 관계를 후향적으로 연구하였다. 결과: 전체 환자의 평균 연령은 $59.3\pm9.1$세였으며 T1N1이 14명, T2N1이 103명이었다. 추적관찰기간은 27.5개월이었으며 5년 생존율은 $41.3\%$였다. 수술 후 재발은 44명$(37.6\%)$에서 관찰되었으며 원격전이가 40명이었다. 재발한 환자의 5년 생존율은 $3.3\%$로 재발이 없는 환자$(61.3\%)$에 비해 유의하게 낮았으며(p=0.000), 전체 환자의 5년 무재발률(freedom-from recurrence rate)은 $54.1\%$였다. 무재발률에 영향을 미치는 요인에 대한 다변량 분석 결과 다림프절군 N1 (multi-station N1)이 단일림프절군 N1 (single station N1)에 비해 재발의 위험도가 1.997배 높았다(p=0.047). 걸론: 완전 절제된 pT1/2N1 비소세포폐암 환자들에서 다림프절군 N1이 수술 후 재발의 위험인자였다.

• Tuberculosis and Respiratory Diseases
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• 제86권4호
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• pp.304-318
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• 2023

Background: Cancer-associated fibroblasts (CAFs) are key components of the tumor microenvironment and significantly contribute to immune evasion. We investigated the effects of CAFs on the immune function of CD4+ and CD8+ T cells in non-small cell lung cancer (NSCLC). Methods: We isolated CAFs and normal fibroblasts (NFs) from tumors and normal lung tissues of NSCLC patients, respectively. CAFs were co-cultured with activated T cells to evaluate their immune regulatory function. We investigated the effect of CAF conditioned medium (CAF-CM) on the cytotoxicity of T cells. CAFs were also co-cultured with activated peripheral blood mononuclear cells and further incubated with cyclooxygenase-2 (COX2) inhibitors to investigate the potential role of COX2 in immune evasion. Results: CAFs and NFs were isolated from the lung tissues (n=8) and lymph nodes (n=3) of NSCLC patients. Immune suppressive markers, such as COX2 and programmed death-ligand 1 (PD-L1), were increased in CAFs after co-culture with activated T cells. Interestingly, CAFs promoted the expression of programmed death-1 in CD4+ and CD8+ T cells, and strongly inhibited T cell proliferation in allogenic and autologous pairs of CAFs and T cells. CAF-CM decreased the cytotoxicity of T cells. COX2 inhibitors partially restored the proliferation of CD4+ and CD8+ T cells, and downregulated the expression of COX2, prostaglandin E synthase, prostaglandin E2, and PD-L1 in CAFs. Conclusion: CAFs promote immune evasion by suppressing the function of CD4+ and CD8+ T cells via their effects on COX2 and PD-L1 in NSCLC. The immunosuppressive function of CAFs could be alleviated by COX2 inhibitors.