• Tuberculosis and Respiratory Diseases
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• v.49 no.4
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• pp.453-465
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• 2000

Background : Lung carcinogenesis is a multistage process involving alterations in multiple genes and diverse pathway. Mutational activation of oncogenes and inactivation of tumor suppressor genes, and subsequent increased genetic instability are the major genetic events. The p53 gene and FHIT gene as tumor suppressor genes contribute to the pathogenesis of lung cancer, evidenced by mutation, microsatellite instability(MI) and loss of heterozygosity(LOH). Methods : We analysed genetic mutations of p53 and FHIT gene in 29 surgical specimens of nonsmall cell lung cancer using PCR-single strand conformation polymorphism, DNA sequencing and RT-PCR. MI and LOH were analyzed in loci of D3S1285, D9S171, and TP53. Results : In 2 cases, point mutation of p53 gene was observed on exon 5. MI of 3 times and LOH of 14 times were observed in at least one locus. In terms of the location of microsatellite, D3S1285 as a marker of FH1T was observed in 5 cases out of 26 specimens; D9S171 as a marker of p16 in 5 out of 17; and TP53 as a marker of p53 in 7 out of 27. In view of histologic type, squamous cell carcinoma presented higher frequency of microsatellite alteration, compared to others. Mutation of FHIT gene was observed in 11 cases and 6 cases of those were point mutation as a silent substitution on exon 8. FHIT mRNA expression exhibited deletion on exon 6 to 9 in 4 cases among 15 specimens, presenting beta-actin normally. Conclusion : Our results show comparable frequency of genetic alteration in nonsmall cell lung cancer to previous studies of Western countries. Microsatellite analysis might have a role as a tumor marker especially in squamous cell carcinoma. Understanding molecular abnormalities involved in the pathogenesis could potentially lead to prevention, earlier diagnosis and the development of novel investigational approaches to the treatment of lung cancer.

• Tuberculosis and Respiratory Diseases
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• v.44 no.4
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• pp.776-784
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• 1997

Background : Various combinations of treatment modalities have been reported in stage III non-small cell lung cancer (NSCLC). however, the standard treatment modality has not established yet. Recently, the efficacy of concurrent chemotherapy and radiation therapy has been reported in locally advanced lung cancer. We evaluate the response rate, toxicity, and survival of concurrent chemotherapy with etoposide and cisplatin(EP) and radiation therapy for unresectable stage III NSCLC. Method : Between October 1995 and December 1996, 32 patients with histologically proven unresectable stage III NSCLC without malignant pleural effusion were entered into this study. Twenty-nine patients were eligible for the response, survival, and toxicity analysis. Induction was two cycles of chemotherapy with etoposide and cisplatin plus concurrent chest RT to 4500cGy. Resection was attempted if the clinical response offered surgical resectability. Boost radiation therapy upto 5940cGy and one cycle of EP were performed if the disease were stable or responsive but still unresectable. Results : Of 29 eligible patients, 22(75.9%) showed partial response(PR). The progression free interval was 6.3months(range 1.1 to 19.5months). Surgical resection was performed in one patient. The median survival was 12.1months and one-year survival rate was 50.6%. The major toxicity was leukopenia($\geq$ grade 3, 46%). Thrombocytopenia over grade 3 was found in 11%. Radiation pneumonitis occurred in 13 patients(46%). Conclusion : Concurrent chemotherapy(EP) plus radiotherapy was effective and tolerable in the treatment of unresectable stage III NSCLC.

• Journal of Chest Surgery
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• v.31 no.3
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• pp.271-278
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• 1998

In order to access the value of computed tomography in mediastinal LN staging of NSCLCa, 581 LN stations of 77 patients were selected from 552 patients who were diagnosed as Lung Ca and operated in Seoul National University Hospital from 1992 to 1995. The selection criteria were as follows ; the patients 1) whose preoperative chest CTs were available; 2) underwent curative resection (lobectomy or more) with complete lymph node dissection; 3) whose final pathologic diagnosis were proven to be non-small cell lung cancer. We adopted Receiver Operating Characteristic curve method to determine a proper size criterion for diagnosing malignant mediastinal adenopathy. From curve analysis, we decided the size criterion of lymph node to 1 cm in their short axis. Using this size criterion, it's sensitivity was 43.9%, specificity was 87.4%, and accuracy was 83.1%. Eventhough we couldn't determine the precise size criterion for the adenoca, it seemed that shorter than 1 cm size criterion should be applied in that particular cell type. Lymph node stations associated with the tuberculosis or bronchiectasis tend to be overestimated in nodal staging and have relatively high false positive rate. The low sensitivity of CT scan suggest that radical and complete dissection or precise mediastinal lymph node evaluation through the surgical approach is mandatory.

• Journal of the Korean Society of Radiology
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• v.10 no.4
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• pp.233-239
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• 2016

Comparison of the dose aspect that radiation therapy treatments using IMRT, tomotherapy, mArc (modulated arc therapy). The experimental subject is non-small cell lung cancer patient. The prescription dose is 58.0 Gy to the volume of PTV(planning target volume). and spinal cord, esophagus, and liver organ is the normal organ(OAR, organ at risk). Average PTV value is 57.60 Gy in mArc and 61.04 Gy in tomotherapy and 58.95 Gy in IMRT. The average dose of the Esophagus is 2.84 Gy in m-Arc, 5.14 Gy in tomotherapy, 1.84 Gy in IMRT. The average dose of the Liver is 19.44 Gy in m-Arc, 12.22 Gy in tomotherapy, 21.97 Gy in IMRT. The average dose of the Spinal cord is 5.72 Gy in m-Arc, 7.08 Gy in tomotherapy, 6.15 Gy in IMRT. Results of this study is no significant difference between mArc and tomotherapy and Linac based IMRT in dose study and also, mArc's dose coverage and dose volume histogram is better than IMRT and tomotherapy. but, This study is limited to a disease of cancer. in addition, fewer number of groups. The wide range the more research can be developed patient-specific treatment techniques and be applied to the patients

• Radiation Oncology Journal
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• v.29 no.1
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• pp.28-35
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• 2011

Purpose: Recently, the use of radiosurgery as a local therapy in patients with early stage non-small cell lung cancer has become favored over surgical resection. To evaluate the efficacy of radiosurgery, we analyzed the results of stereotactic body radiosurgery in patients with primary or recurrent non-small cell lung cancer. Materials and Methods: We reviewed medical records retrospectively of total 24 patients (28 lesions) with non-small cell lung cancer (NSCLC) who received stereotactic body radiosurgery (SBRT) at Inha University Hospital. Among the 24 patients, 19 had primary NSCLC and five exhibited recurrent disease, with three at previously treated areas. Four patients with primary NSCLC received SBRT after conventional radiation therapy as a boost treatment. The initial stages were IA in 7, IB in 3, IIA in 2, IIB in 2, IIIA in 3, IIIB in 1, and IV in 6. The T stages at SBRT were T1 lesion in 13, T2 lesion in 12, and T3 lesion in 3. 6MV X-ray treatment was used for SBRT, and the prescribed dose was 15~60 Gy (median: 50 Gy) for PTV1 in 3~5 fractions. Median follow up time was 469 days. Results: The median GTV was 22.9 mL (range, 0.7 to 108.7 mL) and median PTV1 was 65.4 mL (range, 5.3 to 184.8 mL). The response rate at 3 months was complete response (CR) in 14 lesions, partial response (PR) in 11 lesions, and stable disease (SD) in 3 lesions, whereas the response rate at the time of the last follow up was CR in 13 lesions, PR in 9 lesions, SD in 2 lesions, and progressive disease (PD) in 4 lesions. Of the 10 patients in stage 1, one patient died due to pneumonia, and local failure was identified in one patient. Of the 10 patients in stages III-IV, three patients died, local and loco-regional failure was identified in one patient, and regional failure in 2 patients. Total local control rate was 85.8% (4/28). Local recurrence was recorded in three out of the eight lesions that received below biologically equivalent dose 100 $Gy_{10}$. Among 20 lesions that received above 100 $Gy_{10}$, only one lesion failed locally. There was a higher recurrence rate in patients with centrally located tumors and T2 or above staged tumors. Conclusion: SBRT using a CyberKnife was proven to be an effective treatment modality for early stage patients with NSCLC based on high local control rate without severe complications. SBRT above total 100 $Gy_{10}$ for peripheral T1 stage patients with NSCLC is recommended.

• Tuberculosis and Respiratory Diseases
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• v.60 no.6
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• pp.645-652
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• 2006

Objective: Patients with lung cancer have a relative high risk of developing secondary primary lung cancers. This study examined the additional value of autofluorescence bronchoscopy (AFB) for diagnosing synchronous lung cancers and premalignant lesions. Methods: Patients diagnosed with lung cancer from January 2005 to December 2005 were enrolled in this study. The patients underwent a lung cancer evaluation, which included white light bronchoscopy (WLB), followed by AFB. In addition to the primary lesions, any abnormal or suspicious lesions detected during WLB and AFB were biopsied. Results: Seventy-six patients had non-small cell lung cancer (NSCLC) and 23 had small cell lung cancer (SCLC). In addition to the primary lesions, 84 endobronchial biopsies were performed in 46 patients. Five definite synchronous cancerous lesions were detected in three patients with initial unresectable NSCLC and in one with SCLC. The secondary malignant lesions found in two patients were considered metastatic because of the presence of mediastinal nodes or systemic involvement. One patient with an unresectable NSCLC, two with a resectable NSCLC, and one with SCLC had severe dysplasia. The detection rate for cancerous lesions by the clinician was 6.0% (6/99) including AFB compared with 3.0% (3/99) with WLB alone. The prevalence of definite synchronized cancer was 4.0% (4/99) after using AFB compared with 2.0% (2/99) before, and the staging-up effect was 1.0% (1/99) after AFB. Since the majority of patients were diagnosed with advanced disease, the subjects with newly detected cancerous lesions did not have their treatment plans altered, except for one patient with a stage-up IV NSCLC who did not undergo radiotherapy. Conclusions: Additional AFB is effective in detecting early secondary cancerous lesions and is a more precise tool in the staging workup of patients with primary lung cancer than with WLB alone.

• Tuberculosis and Respiratory Diseases
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• v.46 no.4
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• pp.455-465
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• 1999

Background: Even though lung cancer has become a major cancer in Korea, national survey for lung cancer has not been available except several reports from individual hospitals. Methods: Korean Academy of Tuberculosis and Respiratory Diseases retrospectively investigated the characteristics of lung cancer diagnosed from January 1997 to December 1997 at general hospitals over 400 beds. Results: Among 3,794 patients, 76.8% are smokers and 89.8% of male patients are smokers. Squamous cell carcinoma is the leading type of lung cancer(44.7%) followed by adenocarcinoma(27.9%). Smoking rate in adenocarcinoma was significantly lower than in squamous cell carcinoma and small cell cancer. Cough is the most common symptom, however, 7.2% are asymptomatic. Bronchoscopic biopsy has a main role in the diagnosis of squamous cell carcinoma and small cell cancer but percutaneous needle biopsy has more important role in adenocarcinoma. Two-thirds of NSCLC patients were found in unresectable advanced stages. Conclusion: In contrast to other countries, squamous cell carcinoma is still the most frequent type of lung cancer. High proportions of smoker and advanced, unresectable lung cancer urge us to develop the program for cessation of smoking and early detection.

• Radiation Oncology Journal
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• v.8 no.1
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• pp.73-77
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• 1990

From January 1981 to December 1989, total 42 patients with atelectasis from lung cancer were treated with radiation therapy at the Department of Therapeutic Radiology in Kyung Hee University Hospital. The reexpansion of atelectasis after radiotherapy of the lung was evaluated retrospectively, utillzing treatment records and follow-up chest radiographs. Of the patients with non-small cell carcinoma of the lung, the response rate was $62\%$ (21/34). Patient with small cell carcinoma showed a $75\%$ (6/8) response rate. There appears to be some evidence of a relationship of total tumor dose versus response of atelectasis; radiation dose over 40 Gy (1337 ret), had a favorable effect on the rate of response compared with that below 40 Gy (1297 ret), $70\%$(21/30) and $50\%$ (6/12), respectively (p<0.01). Total response rate (partial and complete responses) of all patients was $64\%$ (27/42). Franction size was not contributed to the difference of response rates between small fraction ($180\~200$ cGy) and large fraction (300 cGy), $53\%$ (14/22) and $65\%$ (13/20), respectively. The results of this study suggest that radiation therapy has a definite positive role in management of atelectasis caused by lung cancer, especially in inoperable non-small cell carcinoma.

• Tuberculosis and Respiratory Diseases
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• v.44 no.4
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• pp.756-765
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• 1997

Background : To study the prognosis of patients with lung cancer, many investigators have reported the methods to detect cell proliferation in tissues including PCNA, thymidine autoradiography, flow cytometry and Ki-67. PCNA, also known as cyclin, is a cell related nuclear protein with 36KD intranuclear polypeptide that is maximally elevated in S phase of proliferating cells. In this study, PCNA was identified by paraffin-embedding tissue using immunohistochemistry which has an advantage of simplicity and maintenance of tissue architecture. The variation of PCNA expression is known to be related with proliferating fraction, histologic type, anatomic(TNM) stage, degree of cell differentiation, S-phase fraction and survival rate. We analyzed the correlation between PCNA expression and S-phase fraction, survival. Method : To investigate expression of PCNA in primary lung cancer, we used immunohistochemical stain to paraffin-embedded sections of 57 resected primary non-small cell lung cancer specimen and the results were analyzed according to the cell type, cell differentiation, TNM stage, S-phase fraction and survival. Results : PCNA expression was divided into five group according to degree of staging(-, +, ++, +++, ++++). Squamous cell type showed high positivity than in adenocarcinoma. Nonsignificant difference related to TNM stage was noticed. Nonsignificant difference related to degree of cell differentiation was noticed. S-phase fraction was increased with advance of PCNA positivity, but it could not reach the statistic significance. The 2 year survival rate and median survival time were -50% 13 months, +75% 41.3 months, ++73% 33.6 months, +++67% 29.0 months, ++++25% 9 months with statistic significance (P<0.05, Kaplan-Meier, generalized Wilcox). Conclusion : From this study, PCNA expression was high positive in squamous cell cancer. And, there was no relationship between PCNA positivity and TNM stage, cellular differentiation or S-phase fraction. But, the patients with high positive PCNA staining showed poor survival rate than the patients with lower positive PCNA staining (p<0.05). It was concluded that PCNA immunostaining is a simple and useful method for survival prediction in paraffin embedded tissue of non-small cell lung cancer.

• Tuberculosis and Respiratory Diseases
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• v.40 no.6
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• pp.659-668
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• 1993

Background: p53 is currently considered as a tumor suppressive gene product, and its alterations are suggested to be involved in several human malignancies, including non-small cell lung cancers. p53 expression rates are variable in many reports and among cell types. Also, whether the phase of p53 expression is early or late during carcinogenesis is not certain. Thus, We have investigated to evaluate p53 expression rates of the various cell types and tissues and identify expression phase (early or late). Method: We obtained 71 tissue from 50 non-small cell lung cancer patients and performed the simple immunohistochemical staining using nonspecific monoclonal antibody(NCL-p53DO7). Results: 1) In non-small cell lung cancer patients. the expression rate of lungs(46.5%) is higher than that(25.0%) of lymph nodes. But, there is no significant difference between two groups. 2) Among the various cell types, p53 expression rates in squamous cell carcinoma and adenocarcinoma are 58.3% and 50.0% respectively without significant difference. 3) p53 expression rates in various stages are 33.3%, 60.0%, 40.0%, 60.0% and 66.7% in stage I, II, IIIa, IIIb and IV, respectively with no significant difference. 4) p53 expression rates in the various T parameters are 33.3%, 50.0%, 16.7% and 100% in T1, T2, T3 and T4, respectively and p53 expression rates in the various N parameters are 27.3%, 22.2% and 25.0% in N1, N2 and N3, respectively. There are no significant differences in the expression rates among varous T & N parameters. 5) p53 expression rates of lymph nodes in patients who have positive stains in lungs are 12.5% and 50.0% in N1 and N2. 6) p53 expression rates of all lymph nodes in patients who have negative stains in lungs are 0.0%. Conclusion: The above results show that p53 expression rate in non-small cell lung cancers is not correlated with cell type and progression of stage and it is thought to need further investigations about at what phase p53 expression influences the development and progression of lung cancers.