• Tuberculosis and Respiratory Diseases
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• v.59 no.3
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• pp.286-297
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• 2005

Background : Non-small cell lung cancer (NSCLC) is a common cause of cancer-related death in North America and Korea, with an overall 5-year survival rate of between 4 and 14%. The TNM staging system is the best prognostic index for operable NSCLC . However, epidermal growth factor receptor (EGFR), matrix metalloproteinase-9(MMP-9), and C-erbB-2 have all been implicated in the pathogenesis of NSCLC and might provide prognostic information. Methods : Immunohistochemical staining of 81 specimens from a resected primary non-small cell lung cancer was evaluated in order to determine the role of the biological markers on NSCLC . Immunohistochemical staining for EGFR, MMP-9, and C-erbB-2 was performed on paraffin-embedded tissue sections to observe the expression pattern according to the pathologic type and surgical staging. The correlations between the expression of each biological marker and the survival time was determined. Results : When positive immunohistochemical staining was defined as the extent area>20%(more than Grade 2), the positive rates for EGFR, MMP-9, and C-erbB-2 staining were 71.6%, 44.3%, and 24.1% of the 81 patients, respectively. The positive rates of EGFR and MMP-9 stain for NSCLC according to the surgical stages I, II, and IIIa were 75.0% and 41.7%, 66.7% and 47.6%, and 76.9% and 46.2%, respectively. The median survival time of the EGFR(-) group, 71.8 months, was significantly longer than that of the EGFR(+) group, 33.5 months.(p=0.018, Kaplan-Meier Method, log-rank test).. The MMP-9(+) group had a shorter median survival time than the MMP-9(-) group, 35.0 and 65.3 months, respectively (p=0.2). The co-expression of EGFR and MMP-9 was associated with a worse prognosis with a median survival time of 26.9 months, when compared with the 77 months for both negative-expression groups (p=0.0023). There were no significant differences between the C-erbB-2(+) and C-erbB-2 (-) groups. Conclusion : In NSCLC, the expression of EGFR might be a prognostic factor, and the co-expression of EGFR and MMP-9 was found to be associated with a poor prognosis. However, C-erbB-2 expression had no prognostic significance.

• Radiation Oncology Journal
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• v.20 no.2
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• pp.116-122
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• 2002

Purpose : A randomized prospective study was conducted to compare the efficacy of early or late alternating schedules of radiotherapy, and carboplatin and ifosfamide chemotherapy in patients with limited-disease small cell lung cancer. Materials and Methods: From August 1993 to August 1996, a total of 44 patients with newly diagnosed, limited-disease small cell lung cancer, PS $H0\~2$, wt $loss<10\%$ were enrolled in a randomized trial which compared early alternating radiotherapy (RT)/chemotherapy (CT) and late alternating RT/CT. The CT regimen included ifosfamide $1.5\;g/m^2$ IV, d1-5 and carboplatin AUC 5/d IV, d2 peformed at 4 week intervals for a total of 6 cycles. RT (54 Gy/30 fr) was started after the first cycle of CT (early arm, N=22) or after the third cycle of CT (late arm, N=22) with a split course of treatment. Results : The pretreatment characteristics between the two arms were well balanced. The response rates in the early $(86\%)$ and late $(85\%)$ arm were similar. The median survival durations and 2-year survival rates were 15 months and $22.7\%$ in the early arm, and 17 months and $14.9\%$ in the late arm (p=0.47 by the log-rank test). The two-year progression free survival rates were $19.1\%$ in the early arm and $19.6\%$ in the late arm (p=0.52 by the log-rank test). Acute grade 3 or 4 hematologic and nonhematologic toxicities were similar between the two arms. Eighteen patients $(82\%)$ completed 6 cycles of CT in the early arm and 17 $(77\%)$ in the late arm. Four patients received less than 45 Gy of RT in the early arm and two in the late arm. There was no significant difference in the failure patterns. The local failure rate was $43\%$ in the early arm and $45\%$ in the late arm. The first site of failure was the brain in $24\%$ of the early arm patients compared to $35\%$ in the late arm (p=0.51). Conclusion : There were no statistical differences in the overall survival rate and the pattern of failure between the early and late alternating RT/CT in patients with limited-disease small cell lung cancer.

• Tuberculosis and Respiratory Diseases
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• v.49 no.3
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• pp.323-331
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• 2000

Purpose: Brain metastases are present in approximately 10-16% of small cell lung cancer patients at diagnosis. Brain metastasis is an important clinical problem associated with increasing the survival rate, with a cumulative incidence of up to 80% in patients surviving 2 years. Prophylactic cranial irradiation(PCI) reduces the incidence of brain matastasis and may prolong survival in patients with limited small-cell lung cancer who achieved complete remission. This study was performed to analyze the incidence of brain metastasis, survival and clinical aspects after PCI in patients with limited small-cell lung cancer who achieved complete remission. Methods : Between 1989 and 1999, forty-two patients with limited small-cell lung cancer who achived achieved complete remission after therapy were enrolled into this study retrospectively. All patients received etoposide and cisplatin(VPP) alternating with cytoxan, adriamycin, and vincristine(CAV) every 3 weeks for at least 6 cycles initially. All patients received thoracic radiotherapy: concurrent(38.1%) and sequential(61.9%). All patients received late PCI. Results : Most patients(88.1%) were men, and the median age was 58 years. The median follow-up duration was 18.1 months. During the follow-up period, 57.1% of the patients developed relapse. The most frequent site of relapse was chest(35.7%), followed by brain(14.3%), liver(11.9%), adrenal gland(44%), and bone(2.2%). With the Kaplan-Meier method, the average disease-free interval was 1,090 days(median 305 days). The average time to development of brain relapse after PCI and other sites relapse(except brain) were 2,548 days and 1,395 days(median 460 days), respectively. The average overall survival was 1,233 days(median 634 days, 21.1 months), and 2-year survival rates was 41.7%. The average overall survival in the relapse group was 642 days(median 489 days) and in the no relapse group was 2,622 days(p<0.001). The average overall survival in the brain relapse group was 928 days(median 822 days) and in the no brain relapse group was 1,308 days(median 634 days)(p=0.772). In most patients(85.7%), relapse(except brain) or systemic disease was the usual cause of death. Brain matastasis was the cause of death in 14.3% of the cases. Conclusions : We may conclude that PCI reduces and delays brain metastasis in patients with limited small cell lung cancer who achieved complete remission. We found decreased survival in relapse group but, no significant survival difference was noted according to brain matastasis. And relapse(except brain) or systemic disease was the usual cause of death. In order to increase survival, new treatment strategies for control methods for relapse and systemic disease are required.

• Radiation Oncology Journal
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• v.17 no.2
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• pp.91-99
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• 1999

Propose : This study was performed to find out the prognostic factors affecting local control, survival and disease free survival rate in nasopharyngeal carcinomas treated with chemotherapy and radiation therapy. Materials and Methods : We analysed 47 patients of nasopharyngeal carcinomas, histologically confirmed and treated at Chonnam University Hospital between July 1986 and June 1996, retrospectively. Range of patients' age were from 16 to 80 years (median; 52 years). Thirty three (70$\%$) patients was male. Histological types were composed of 3 (6$\%$) keratinizing, 30 (64$\%$) nonkeratinizing squamous cell carcinoma and 13 (28$\%$) undifferentiated carcinoma. Histoiogicai type was not known in 1 patient (2$\%$). We restaged according to the staging system of 1997 American Joint Committee on Cancer Forty seven patients were recorded as follows: 71: 11 (23$\%$), T2a; 6 (13$\%$), T2b; 9 (19$\%$), 73; 7 (15$\%$), 74: 14 (30$\%$), and NO; 7 (15$\%$), Nl: 14 (30$\%$), N2; 21 (45%), N3: 5 (10%). Clinical staging was grouped as follows: Stage 1; 2 (4$\%$), IIA: 2 (4$\%$), IIB; 10 (21$\%$), III; 14 (30$\%$), IVA; 14 (30$\%$) and IVB; 5 (11$\%$). Radiation therapy was done using 6 MV and 10 MV X- ray of linear accelerator. Electron beam was used for the Iymph nodes of posterior neck after 4500 cGy. The range of total radiation dose delivered to the primary tumor was from 6120 to 7920 cGy (median; 7020 cGy). Neoadjuvant chemotherapy was performed with cisplatin +5-fluorouracil (25 patients) or cisplatin+pepleomycin (17 patients) with one to three cycles. Five patients did not received chemotherapy. Local control rate, survival and disease free suwival rate were calculated by Kaplan-Meier method. Generalized Wilcoxon test was used to evaluate the difference of survival rates between groups. multivariate analysis using Cox proportional hazard model was done for finding prognostic factors. Results: Local control rate was 81$\%$ in 5 year. Five year survival rate was 60$\%$ (median survival; 100 months). We included age, sex, cranial nerve deflicit, histologic type, stage group, chemotherapy, elapsed days between chemotherapy and radiotherapy, total radiation dose, period of radiotherapy as potential prognostic factors in multivariate analysis. As a result, cranial none deficit (P=0.004) had statistical significance in local control rate. Stage group and total radiation dose were significant prognostic factors in survival (P=0.000, P=0.012), and in disease free survival rates (P=0.003, P=0.008), respectively. Common complications were xerostomia, tooth and ear problems. Hypothyroidism was developed in 2 patients. Conclusion : In our study, cranial none deficit was a significant prognostic factor in local control rate, and stage group and total radiation dose were significant factors in both survival and disease free survival of nasopharyngeal carcinoma. We have concluded that chemotherapy and radiotherapy used in our patients were effective without any serious complication.

• Radiation Oncology Journal
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• v.27 no.4
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• pp.181-188
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• 2009

Purpose: The aim of this study was to evaluate the results of postoperative radiotherapy in a case of perihilar cholagiocarcinoma by analyzing overall survival rate, patterns of failure, prognostic factors for overall survival, and toxicity. Materials and Methods: Between January 1998 and March 2008, 38 patients with perihilar cholangiocarcinoma underwent a surgical resection and adjuvant radiotherapy. The median patient age was 59 years (range, 28 to 72 years), which included 23 men and 15 women. The extent of surgery was complete resection in 9 patients, microscopically positive margins in 25 patients, and a subtotal resection in 4 patients. The tumor bed and regional lymphatics initially received 45 Gy or 50 Gy, but was subsequently boosted to a total dose of 59.4 Gy or 60 Gy in incompletely resected patients. The median radiotherapy dose was 59.4 Gy. Concurrent chemotherapy was administered in 30 patients. The median follow-up period was 14 months (range, 6 to 45 months). Results: The 3-year overall survival and 3-year progression free survival rates were 30% and 8%, respectively. The median survival time was 28 months. A multivariate analysis showed that differentiation was the only significant factor for overall survival. The 3-year overall survival was 34% in R0 patients and 20% in R1 patients. No statistically significant differences in survival were found between the 2 groups (p=0.3067). The first site of failure was local in 18 patients (47%). No patient experienced grade 3 or higher acute toxicity and duodenal bleeding developed in 2 patients. Conclusion: Our results suggest that adjuvant RT might be a significant factor in patients with a positive margin following a radical resection. However, there was still a high locoregional recurrence rate following surgery and postoperative radiotherapy. Further study is necessary to enhance the effect of the adjuvant radiotherapy.

• Radiation Oncology Journal
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• v.13 no.4
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• pp.359-368
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• 1995

Purpose : This is a retrospective analysis for pattern of failure, survival rate and prognostic factors of 114 patients with histologically proven invasive cancer of the uterine cervix treated with definitive irradiation. Materials and Methods : One hundred fourteen patients with invasive carcinoma of the cervix were treated with a combination of intracavitary irradiation using Fletcher-Suit applicator and external beam irradiation by 6MV X-ray at the Ewha Womans University Hospital between March 1982 and Mar 1990. The median age was 53 years(range:30-77 years). FIGO stage distribution was 19 for IB, 23 for IIA, 42 for IIB, 12 for IIIA and 18 for IIIB. Summation dose of external beam and intracavitary irradiation to point A was 80-90 Gy(median:8580 cGy) in early stage(IB-IIA) and 85-100 Gy(median:8850 cGy) in advanced stage(IIB-IIIB). Kaplan-Meier method was used to estimate the survival rate and multivariate analysis for progrostic factors was performed using the Log likelihood for Weibull Results : The pelvic failure rates by stage were $10.5{\%}$ for IB. $8.7{\%}$ for IIA, $23.8{\%}$ for IIB, $50.0{\%}$ for IIIA and $38.9{\%}$ for IIIB. The rate of distant metastasis by stage were $0{\%}$ for IB, $8.7{\%}$ for IIA, $4.8{\%}$ for IIB. $0{\%}$ for IIIA and $11.1{\%}$ for IIIB. The time of failure was from 3 to 50 months and with median of 15 months after completion of radiation therapy. There was no significant coorelation between dose to point A($\leq$90 Gy vs >90 Gy) and pelvic tumor control(P>0.05). Incidence rates of grade 2 rectal and bladder complications were $3.5{\%}$(4/114) and $7{\%}$(8/114), respectively and 1 patient had sigmoid colon obstruction and 1 patient had severe cystitis. Overall 5-year survival rate was $70.5{\%}$ and disease-free survival rate was $53.6{\%}$. Overall 5-year survival rate by stage was $100{\%}$ for IB, $76.9{\%}$ for IIA, $77.6{\%}$ for IIB $87.5{\%}$ for IIIA and $69.1{\%}$ for IIIB. Five-rear disease-free survival rate by stage was $81.3{\%}$ for IB, $67.9{\%}$ for IIA, $46.8{\%}$ for IIB, $45.4{\%}$ for IIIA and $34.4{\%}$ for IIIB. The prognostic factors for disease-free survival rate by multivariate analysis was performance status(p= 0.0063) and response rate after completion of radiation therapy(p= 0.0026) but stage, age and radiation dose to point A were not siginificant. Conclusion : The result of radiation therapy for early stage of the uterine cervix cancer was relatively good but local control rate and survival rate in advanced stage were poor inspite of high dose irradiation to point A above 90 Gy. Prospective randomized studies are recommended to establish optimal tumor doses for various stages and volume of carcinoma of uterine cervix, And ajuvant chemotherapy or radiation-sensitizing agents must be considered to increase the pelvic control and survival rate in advanced cancer of uterine cervix.

• Radiation Oncology Journal
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• v.15 no.4
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• pp.349-356
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• 1997

Purpose : To evaluate the efficacy of hyperfractionated radiation therapy in carcinoma of the cervix, especially on huge exophytic and endophytic stage Ib, IIa and IIb Materials and Materials : Fourty one patients with carcinoma of the cervix treated with hyperfractionated radiation therapy at the Department of Therapeutic Radiology, Dongsan Hospital, Keimyung University. School of Medicine from Jul, 1991 to Apr, 1994. According to FIGO s1aging system, therewere stage Ib (3 patients) IIa (6 patients) with exophytic ($\geq$5cm in dinmeter) and huge endophytic mass. and IIb (32 patients) with median age of 55 yeavs old. Radiation therapy consisted of hyperfractionated external irradition to the whole pelvis (120cGy/fraction, 2 fraction/day (minimum interval of 6 hours), 3600-5520cGy) and boost parametrial doses (for a total of 4480-6480cGy) with midline shield $(4\times10cm)$, and combined with intracavitary irradiation (up to 7480-8520cGy in Ib, IIa and 8480-9980cGy in IIb to point A). The maximum and mean follow up durations were 70 and 47 months respectively . Results : Five year local control rate was $78\%$ and the actuarial overall five year survival rate was $66.1\%$ for all patients, $44.4\%$ for stage Ib, IIa and $71.4\%$ for stage IIb. In bulky IIb (above 5cm in tumor size, 11 patients) five year local control rate and five rear survival rate was $88.9\%,\;73\%$ respectively Pelvic lymph node status (negative : $74\%,\;positive:25\%$, p=0.0015) was significant Prognostic factor affecting to five rear survival rate. There was marginally significant survival difference by total dose to A point ($>84Gy\;:\;70\%,\;>84Gy\;:\;42.8\%$, p=0.1). We consider that the difference of total dose to A point by stage (mean Ib,IIa : 79Gy. IIb 89Gy P=0.001) is one of the causes in worse local control and survival of Ib,IIa than IIb The overall recurrence rate was $39\%$ (16/41). The rates of local failure alone. distant failure alone. and combined local and distant failure were $9.7\%,\;19.5\%,\;and\;9.7\%$, respectively. Two Patients developed leukopenia ($\geq$ grade 3) and Three patients develoued grade 3 gastrointestinal complication. Above grade 3 complication was not noted. There was no treatment related death noted. Conclusion : We thought that it may be necessary to increase A point dose to more than 85Gy in hyperfractionated radiotherapy of huge exophytic and endophvtic stage Ib,IIa. We considered that hyperfractionated radiation therapy may be tolerable in huge exophytic and endophytic stage IIb cervical carcinoma with acceptable morbidity and possible survival gain but this was results in small patient group and will be confirmed by long term follow up in many patients.

• Radiation Oncology Journal
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• v.16 no.2
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• pp.147-157
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• 1998

Purpose : The aim of this retrospective study is to assess the necessity of s1aging laparotomy in the management of supradiaphragmatic CS I-II Hodgkin's disease. Prognostic factors and the usefulness of prognostic factor groups were also analyzed. Materials and Methods : From 1985 to 1995, fifty one Patients who were diagnosed as supradiaphragmatic CS I-II Hodgkin's disease at Yonsei Cancer Center in Seoul, Korea were enrolled in this study Age range was 4 to 67 with median age of 30. The number of patients with each CS IA, II A, and IIB were 16, 25, and 10, respectively. Radiotherapy(RT) was delivered using 4 or 6 MV photon beam to a total dose of 19.5 to 55.6Gy (median dose : 45Gy) with a 1.5 to 1.BGy per fraction. Chemotherapy(CT) was given in 2-12 cycles(median : 6 cycles). Thirty one Patients were treated with RT alone, 4 patients with CT alone and 16 patients with combined chemoradiotherapy. RT volumes varied from involved fields(3), subtotal nodal fields(18) or mantle fields(26). Results : Five-year disease-free survival rate(DFS) was $78.0\%$ and overall survival rate(05) was $87.6\%$. Fifty Patients achieved a complete remission after initial treatment and 8 patients were relapsed. Salvage therapy was given to 7 patients, 1 with RT alone, 4 with CT alone, 2 with RT+CT. Only two patients were successfully salvaged. Feminine gender and large media-stinal adenopathy were significant adverse prognostic factors in the univariate analysis for DFS. The significant adverse prognostic factors of OS were B symptom and clinical stage. When patients were analyzed according to European Organization for Research and Treatment of Cancer(EORTC) prognostic factor groups, the DFS in Patients with very favorable, favorable and unfavorable group was 100, 100 and $55.8\%$(p<0.05), and the 05 in each patients' group was 100, 100 and $75.1\%$(p<0.05), respectively. In very favorable and favorable groups, the DFS and 05 were all $100\%$ by RT alone, but in unfavorable group, RT with CT had a lesser relapse rate than RT alone. The subtotal nodal irradiation had better OFS than mantle RT in patients treated with RT. Conclusion : In present study, the DFS and OS in patients who did not undergo s1aging laparotomy were similar with the results in the literatures of which patients were surgically staged. Therefore, we may suggest that staging laparotomy would not influence the outcome of treatments. In univariate analysis, gender, large mediastinal adenopathy. B symptoms and clinical stage were significant prognostic factors for the survival rate. We confirm the usefulness of EORTC prognostic factor groups which may be a good.

• Journal of Chest Surgery
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• v.41 no.1
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• pp.1-11
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• 2008

Background: The Damus-Kaye-Stansel (DKS) procedure is a proximal MPA-ascending aorta anastomosis used to relieve systemic ventricular outflow tract obstructions (SVOTO) and pulmonary hypertension. The purpose of this study was to review the indications and outcomes of the DKS procedure, including the DKS pathway and semilunar valve function. Material and Method: A retrospective review of 28 patients who underwent a DKS procedure between May 1994 and April 2006 was performed. The median age at operation was 5.3 months ($13\;days{\sim}38.1\;months$) and body weight was 5.0 kg ($2.9{\sim}13.5\;kg$). Preoperative pressure gradients were $25.3{\pm}15.7\;mmHg$ ($10{\sim}60\;mmHg$). Eighteen patients underwent a preliminary pulmonary artery banding as an initial palliation. Preoperative main diagnoses were double outlet right ventricle in 9 patients, double inlet left ventricle with ventriculoarterial discordance in 6,. another functional univentricular heart in 5, Criss-cross heart in 4, complete atrioventricular septal defect in 3, and hypoplastic left heart variant in 1. DKS techniques included end-to-side anastomosis with patch augmentation in 14 patients, classical end-to-side anastomosis in 6, Lamberti method (double-barrel) in 3, and others in 5. The bidirectional cavopulmonary shunt and Fontan procedure were concomitantly performed in 6 and 2 patients, respectively. Result: There were 4 hospital deaths (14.3%), and 3 late deaths (12.5%) with a follow-up duration of $62.7{\pm}38.9$ months ($3.3{\sim}128.1$ months). Kaplan-Meier estimated actuarial survival was $71.9%{\pm}9.3%$ at 10 years. Multivariate analysis showed right ventricle type single ventricle (hazard ratio=13.960, p=0.004) and the DKS procedure as initial operation (hazard ratio=6.767, p=0.042) as significant mortality risk factors. Four patients underwent staged biventricular repair and 13 received Fontan completion. No SVOTO was detected after the procedure by either cardiac catheterization or echocardiography except in one patient. There was no semiulnar valve regurgitation (>Gr II) or semilunar valve-related reoperation, but one patient (3.6%) who underwent classical end-to-side anastomosis needed reoperation for pulmonary artery stenosis caused by compression of the enlarged DKS pathway. The freedom from reoperation for the DKS pathway and semilunar valve was 87.5% at 10 years after operation. Conclusion: The DKS procedure can improve the management of SVOTO, and facilitate the selected patients who are high risk for biventricular repair just after birth to undergo successful staged biventricular repair. Preliminary pulmonary artery banding is a safe and effective procedure that improves the likelihood of successful DKS by decreasing pulmonary vascular resistance. The long-term outcome of the DKS procedure for semilunar valve function, DKS pathway, and relief of SVOTO is satisfactory.

• Tuberculosis and Respiratory Diseases
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• v.45 no.2
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• pp.322-332
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• 1998

Background: Accurate staging is important to determine treatment modalities and to predict prognosis for the patients with lung cancer. The simple two-stage system of the Veteran's Administration Lung Cancer study Group has been used for staging of small cell lung cancer(SCLC) because treatment usually consists of chemotherapy with or without radiotherapy. However, this system does not accurately reflect segregation of patients into homogenous prognostic groups. Therefore, a variety of new staging system have been proposed as more intensive treatments including either intensive radiotherapy or surgery enter clinical trials. We evaluate the prognostic importance of TNM staging, which has the advantage of providing a uniform detailed classification of tumor spread, in patients with SCLC. Methods: The medical records of 166 patients diagnosed with SCLC between January 1989 and December 1996 were reviewed retrospectively. The influence of TNM stage on survival was analyzed in 147 patients, among 166 patients, who had complete TNM staging data. Results: Three patients were classified in stage I / II, 15 in stage III a, 78 in stage IIIb and 48 in stage IV. Survival rate at 1 and 2 years for these patients were as follows: stage I / II, 75% and 37.5% ; stage IIIa, 46.7% and 25.0% ; stage III b, 34.3% and 11.3% ; and stage IV, 2.6% and 0%. The 2-year survival rates for 84 patients who received chemotherapy(more than 2 cycles) with or without radiotherapy were as follows: stage I / II, 37.5% ; stage rna, 31.3% ; stage IIIb 13.5% ; and stage IV 0%. Overall outcome according to TNM staging was significantly different whether or not received treatment. However, there was no significant difference between stage IIIa and stage IIIb though median survival and 2-year survival rate were higher in stage IIIa than stage IIIb. Conclusion: These results suggest that the TNM staging system may be helpful for predicting the prognosis of patients with SCLC.