• Journal of Chest Surgery
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• v.55 no.3
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• pp.214-224
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• 2022

Background: Studies of the prognostic role of circulating tumor cells (CTCs) in early-stage non-small cell lung cancer (NSCLC) are still limited. This study investigated the prognostic power of CTCs from the pulmonary vein (PV), peripheral blood (PB), and bone marrow (BM) for postoperative recurrence in patients who underwent curative resection for NSCLC. Methods: Forty patients who underwent curative resection for NSCLC were enrolled. Before resection, 10-mL samples were obtained of PB from the radial artery, blood from the PV of the lobe containing the tumor, and BM aspirates from the rib. A microfabricated filter was used for CTC enrichment, and immunofluorescence staining was used to identify CTCs. Results: The pathologic stage was stage I in 8 patients (20%), II in 15 (38%), III in 14 (35%), and IV in 3 (8%). The median number of PB-, PV-, and BM-CTCs was 4, 4, and 5, respectively. A time-dependent receiver operating characteristic curve analysis showed that PB-CTCs had excellent predictive value for recurrence-free survival (RFS), with the highest area under the curve at each time point (first, second, and third quartiles of RFS). In a multivariate Cox proportional hazard regression model, PB-CTCs were an independent risk factor for recurrence (hazard ratio, 10.580; 95% confidence interval, 1.637-68.388; p<0.013). Conclusion: The presence of ≥4 PB-CTCs was an independent poor prognostic factor for RFS, and PV-CTCs and PB-CTCs had a positive linear correlation in patients with recurrence.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.6
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• pp.2909-2912
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• 2012

Aim: To evaluate efficacy and tolerability of topotecan treatment for recurrent small cell lung carcinoma. Patients and Methods: A total of 62 patients were evaluated retrospectively. Statistical analysis was performed using GraphPad Instat (version 3.05). Results: DFifty five of patients (89%) were male and 7 (11%) were female. Median age was $56.7{\pm}9.3$ (34-75). Forty eight of patients (80%) were extensive stage (ES) at the time of diagnosis. Fifty of the patients (80.6 Medical Oncology Clinic) were given median 5.36 cycles of cisplatin-etoposide (2-8 cycles). Time to recurrence was $15.6{\pm}6.13$ weeks in patients with limited stage (LS) and $6.3{\pm}3.82$ weeks in extensive stage (ES) (p<0.0001). Overall survival was $14.0{\pm}6.08$ months in ES and $17.9{\pm}6.88$ months in LS. The difference between two groups was statistically meaningful (p=0.0447). The overall survival of the patients was $14.8{\pm}6.43$ months (4.5-40 months). In terms of survival, there was no difference between males and females (p=0.1171). In 17 (27%) patients who were refractory to topotecan or in whom progression occurred other chemotherapies were used. Conclusion: Small cell lung cancer is chemosensitive, but recurrences occur in short time. Other chemotherapy regimens are used in progression. Topotecan is one of them. Patients who were young and in whom recurrences occur late had given better response to topotecan. Because of the retrospective nature of the study, we couldn't reach the records exactly and consequently, rate and duration of response couldn't be calculated. In recurrent SCLC topotecan is one of the treatment choices. But both hematological and non hematological side effects should be taken into consideration.

• Journal of Yeungnam Medical Science
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• v.31 no.2
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• pp.82-88
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• 2014

Background: Lung cancer is the most common cause of cancer-related death worldwide and in Korea, and small cell lung cancer (SCLC) is the most deadly tumor type in the different lung cancer histology. Chemotherapy is the main strategy of the treatment for SCLC, and etoposide and platinum regimen has been the only standard chemotherapy for about 30 years. To test feasibility of weekly divided dose irinotecan and carboplatin for Korean patients is the aim of this study. Methods: Patients with histologically or cytologically confirmed extensive stage SCLC were included. Patients with limited stage (LD), who could not tolerate concurrent chemoradiotherapy were also included. All the patients received irinotecan $60mg/m^2$, carboplatin 2 area under the curve at day 1, 8, and 15 every 4 weeks. Study regimen was discontinued when the disease progressed or intolerable side effects occurred. No more than 6 cycles of chemotherapy were given. Results: Total 47 patients were enrolled, among them 9 patients were LD. Overall response rate was 74.5% (complete response, 14.9%; partial response, 59.6%). Side effects greater than grade 3 were neutropenia (25.5%), fatigue (12.8%), thrombocytopenia (8.5%), sepsis (4.3%), and pancytopenia (2.1%). There was no treatment related death. Conclusion: Weekly divided irinotecan and carboplatin regimen is effective, and safe as a first line therapy for both stage of SCLC. Large scaled, controlled study is feasible.

• Tuberculosis and Respiratory Diseases
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• v.50 no.1
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• pp.84-93
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• 2001

Backgrounds : In the absence of distant metastasis, small cell lung cancer (SCLC) patients presenting with supraclavicular lymph node (SCLN) involvement and pleural effusion can benefit from thoracic radiotherapy. But there are some debate as to the prognostic significance of both SCLN involvement and pleural effusion. The purpose of this study was to determine the prognostic significance of SCLN involvement and pleural effusion in SCLC. Methods : Two Hundred and fifteen patients with histologically confirmed small cell lung cancer, who were treated either at the Keimyung university Dongsan hospital and Kyungpook national university hospital from January 1994 to June 1998, were evaluated retrospectively. The patients were classified as having either limited or extensive stage using the Veterans Administration staging system. Results : SCLN was presented in 10.5% of patients(n=21). The median survival was 247 days for patients with SCLN(n=21) and 264 days for patients without(n=194) (p=0.52). After treatment, the median survival was 298 days for patients with SCLN(n=13) and 348 days for patients without(n=115) (p=0.52). SCLN involvement was not correlated with the presence of distant metastases. Median survival was 459 days for patients with a limited stage without SCLN(n=66), 650 days for those with a limited stage with SCLN (n=7) (p=0.96). Pleural effusion was presented in 24.7% of patients(n=52). The median survival was 198 days for patients with pleural effusion(n=52) and 275 days for patients without(n=163) (p<0.05). After treatment, the median survival was 294 days for patients with a pleural effusion(n=25) and 286 days for patients without(n=103) (p=0.39). The presence of pleural effusion was not correlated with that of distant metastases. The median survival was 395 days for patients with a limited stage without a pleural effusion(n=63), 451 days for those with a limited stage with pleural effusion(n=10) (p=0.92). Conclusionsa : In this study, SCLN involvement does not explain the poor survival rate and the relevance to extensive staged disease. Furthermore, the existence of a pleural effusion did not correlated with the presence of distant metastases. However, the presence of a pleural effusion appears to be a minor prognostic factor in our study. Therefore supraclavicular lymph node involvement and the presence of a pleural effusion in SCLC are not poor prognostic factors, which does not justify any amendment to the staging system currently used.

• Tuberculosis and Respiratory Diseases
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• v.63 no.2
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• pp.154-164
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• 2007

Background: Irinotecan hydrochloride, a topoisomerase I inhibitor, is effective against small-cell lung cancer. Irinotecan also can act as a potential radiation sensitizer along with cisplatin. To evaluate efficacy and toxicity of irinotecan plus cisplatin (IP) with concurrent thoracic radiotherapy, we conducted a phase II study of IP followed by concurrent IP plus hyperfractionated thoracic radiotherapy in patients with previously untreated limited-stage small-cell lung cancer. Methods: Twenty-four patients with previously untreated small-cell lung cancer were enrolled onto the study since November 2004. Irinotecan $60mg/m^2$ was administered intravenously on days 1 and 8 in combination with cisplatin $60mg/m^2$ on day1 every 21 days. From the first day of third cycle, twice-daily thoracic irradiation (total 45 Gy) was given. Prophylactic cranial irradiation was given to the patients who showed complete remission after concurrent chemoradiotherapy. Restaging was done after second and sixth cycle with chest CT and/or bronchosocpy. Results: Up to November 2004, 19 patients were assessable. The median follow-up time was 12.5 months. A total of 99 cycles (median 5.2 cycles per patient) were administered. The actual dose intensity values were cisplatin $19.6mg/m^2$/week and irinotecan $38.2mg/m^2$/week. Among the 19 patients, the objective response rate was 95% (19 patients), with 9 patients (47%) having a complete response (CR). The major grade 3/4 hematological toxicities were neutropenia (35% of cycles), anemia (7% of cycles), thrombocytopenia (7% of cycles). Febrile neutropenia was 4% of cycles. The predominant grade 3/4 non-hematological toxicities was diarrhea (5% of cycles). Toxicities was not significantly different with concurrent administration of irinotecan and cisplatin with radiotherapy, except grade 3/4 radiation esophagitis (10% of patients). No treatment-related deaths were observed. The 1-year and 2-year survival rate of eligible patients was 89% (16/18) and 47% (9/18), respectively. Conclusion: Three-week schedule of irinotecan plus cisplatin followed by concurrent IP plus hyperfractionated thoracic radiotherapy is an effective treatment for limited disease small-cell lung cancer, with acceptable toxicity.

• Radiation Oncology Journal
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• v.7 no.2
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• pp.213-225
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• 1989

An analysis has been made of two hundred seven patients who were treated at the department of Radiation Oncology of Korea University Hospital for lung cancer from January 1981 through December 1986. There were 137 patients of nonsmall cell carcinoma (137/207, 66%), 26 patients of small cell carcinoma (26/207, 12.5%) and 44 patients of unproven histology. By aims of treatment, there were 104 patients (104/207, 50%) treated for cure, 89 patients (89/207, 42.9%) for palliation and 14 patients treated postoperatively. In 22 out of 207 patients, chemotherapy was done with radiotherapy, 12 of which were patients with small cell carcinoma. Stage II patients were 49 (49/207, 23.6%), stage III patients were 157 (157/207, 75.8%) and one patient had an occult cancer The tumor was initial Iy measured by CAT scan and chest X-rays in the 165 (165/207, 79.7%) patients, among which 117 patients had tumor diameter more than 5cm and 48 patients less than 5cm. Radiation therapy was given with Cobalt 60 teletherapy unit and the treatment volume encompassed primary tumor and the mediastinum. For curative aim, daily tumor dose of 180 cGy was given up to the range of 5,400~6,120cGy/30~34F/6~7 week period and for palliative aim, daily tumor dose of 300 cGy was given up to the range of 3,600~4,500 cGy/12~15F/2~3 week period. Postoperatively, mediastinum was treated for total dose of 5,040 cGy/28F/5.5 week period. 123 patients (123/207, 59%) were followed up after completion of radiotherapy for 14 months to 7 years. Local tumor response to the irradiation was measured by chest X-ray taken at one month follow up and was evaluated for response rate, if they were regressed more than 50% or less than 50% of the initial tumor size. The treatment results were as follows; 1. The median survival time was 8.5 months and survival rates for 1 year, 2 year and 5 year was 25%, 3.5% and 1% of nonsmall cell lung ca of 74 evaluable patients. 2. More than 50% of local tumor response rate was obtained in about half of overall cases; 90.5% for small cell ca, 50% for squamous cell ca, 25% for adenoca and 57% for large cell ca. 3. Response rate more than 50% was seen in the 50% of the patient group with tumor diameter more than 5cm and in the 55% of those with tumor diameter less than 5cm. 4. By total raidation dose given, patient group which was given 5,400~6,120 cGy equivalent dose or higher showed tumor response rate more than 50% in 53% of the patients, whereas the group with dose less than 5,400cGy equivalent, in 25% of the patients. 5. Survival rate for 6 month, 1 year and 2 year was compared between the group of local tumor response rate more than 50% vs. group with response rate less than 50%; 74% vs. 43%, 33% vs, 23%, 10% vs. 1%, respectively. 6. Local failure was seen in 21%(44/207) of the patients, which occured mostly within 15 months after completion of radiation therapy. Distant metastases were seen in 49.7%(103/207) of the patients, of which 43 cases were found before initiation of radiotherapy. The most common metastatic sites were bone and brain. In this sutdy, 1 year,2 year and S year survival rates were somewhat poor compared to the other studies. It mainly seems to be due to the poor general status of the patients and the far-advanced stage of the disease. In nonsmall cell cancer patients who had limited local disease and had small primary tumor size, we observed better local response. In addition, dose higher than 6,000 cGy group showed better tumor control than lower dose group. Survival rate was better for the local control group. For imporvement of local control of the lung cancer and hence, the survival of the patients with lung cancer, proper radical radiotherapy with high dose for localized disease is needed. New modality of treatment such as high LET beam in radiation therapy or drugs for the advanced disease as well as early diagnosis is also needed.

• Radiation Oncology Journal
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• v.24 no.2
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• pp.96-102
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• 2006

Purpose: A retrospective study was performed to evaluate the efficiency and feasibility of twice daily radiation therapy plus concurrent chemotherapy for limited-stage small cell lung cancer in terms of treatment response, survival, patterns of failure, and acute toxicities. Materials and Methods: Between February 1993 and October 2002, 76 patients of histologically proven limited-stage small cell lung cancer (LS-SCLC) were treated with twice daily radiation therapy and concurrent chemotherapy. Male was in 84% (64/76), and median age was 57 years (range, 32-75 years). Thoracic radiation therapy consisted of 120 or 150 cGy per fraction, twice a day at least 6 hours apart, 5 days a week. Median total dose was 50.4 Gy (range, 45-51 Gy). Concurrent chemotherapy consisted of CAV ($cytoxan\;1000mg/m^2,\;adriamycin\;40mg/m^2,\;vincristine\;1mg/m^2$) alternating with PE ($cisplatin\;60mg/m^2,\;etoposide\;100mg/m^2$) or PE alone, every 3 weeks. The median cycle of chemotherapy was six (range, 1-9 cycle). Prophylactic cranial irradiation (PCI) was recommended to the patients who achieved a complete response (CR). PCI scheme was 25 Gy/10 fractions. Median follow up was 18 months (range, 1-136 months). Results: Overall response rate was 86%; complete response in 39 (52%) and partial response in 26 (34%) patients. The median overall survival was 23 months. One, two, and three year overall survival rate was 72%, 50% and 30%, respectively. In univariate analysis, the treatment response was revealed as a significant favorable prognostic factor for survival (p<0.001). Grade 3 or worse acute toxicities were leukopenia in 46 (61%), anemia in 5 (6%), thrombocytopenia in 10 (13%), esophagitis in 5 (6%), and pulmonary toxicity in 2 (2%) patients. Of 73 evaluable patients, 40 (55%) patients subsequently had disease progression. The most frequent first site of distant metastasis was brain. Conclusion: Twice daily radiation therapy plus concurrent chemotherapy produced favorable response and survival for LS-SCLC patients with tolerable toxicities. To improve the treatment response, which proved as a significant prognostic factor for survival, there should be further investigations about fractionation scheme, chemotherapy regimens and compatible chemoradiotherapy schedule.

• Journal of Chest Surgery
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• v.53 no.3
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• pp.93-103
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• 2020

Background: Risk assessment for pulmonary resection in patients with early-stage non-small-cell lung cancer (NSCLC) is important for minimizing postoperative morbidity. Depletion of skeletal muscle mass is closely associated with impaired nutritional status and limited physical ability. We evaluated the relationship between skeletal muscle depletion and early postoperative complications in patients with early-stage NSCLC. Methods: Patients who underwent curative lung resection between 2016 and 2018 and who were diagnosed with pathological stage I/II NSCLC were included, and their records were retrospectively analyzed. The psoas volume index (PVI, ㎤/㎥) was calculated based on computed tomography images from routine preoperative positron emission tomography-computed tomography. Early postoperative complications, defined as those occurring within 90 days of surgery, were compared between the lowest sex-specific quartile for PVI and the remaining quartiles. Results: A strong correlation was found between the volume and the cross-sectional area of the psoas muscle (R²=0.816). The overall rate of complications was 57.6% among patients with a low PVI and 32.8% among those with a normal-to-high PVI. The most common complication was prolonged air leak (low PVI, 16.9%; normal-to-high PVI, 9.6%), followed by pneumonia (low PVI, 13.6%; normal-to-high PVI, 7.9%) and recurrent pleural effusion (low PVI, 11.9%; normal-to-high PVI, 6.8%). The predictors of overall complications were low PVI (odds ratio [OR], 2.18; 95% confidence interval [CI], 1.07-4.09; p=0.03), low hemoglobin level (OR, 0.686; 95% CI, 0.54-0.87; p=0.002), and smoking history (OR, 3.93; 95% CI, 2.03-7.58; p<0.001). Conclusion: Low PVI was associated with a higher rate of early postoperative complications in patients with early-stage NSCLC.

• Tuberculosis and Respiratory Diseases
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• v.54 no.1
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• pp.57-70
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• 2003

Background : Small cell lung cancer represents approximately 20% of all carcinomas of the lung, and is recognized as having a poor long term outcome compared to non-small cell lung cancer. Therefore, this study investigated the prognostic factors in small cell lung cancer patients in order to improved the survival rate by using the proper therapeutic methods. Material and method : The clinical data from 394 patients who diagnosed with small cell lung cancer and treated from 1993 to 2001 at the Kosin University Gospel Hospital, were analyzed. Result : There were 314 male patients (79.7%), and 80 female patients (20.3%). The number of those with limited disease was 177 (44.9%), and the number of those with extensive disease was 217 (55.1%). Overall, 366 out of 394 enrolled patients had died. The median survival time was 215 days (95% CI : 192-237days). The disease stage, Karnofsky performance state, 5% body weight loss for the recent 3 months, chemotherapy regimens, and the additive chest radiotherapy were identified as being statistically significant factors for the survival time. The median survival times of the supportive care group, one anticancer therapy, and two or more treatment groups were 17 days, 211 days, and 419 day, respectively (p<0.001). These data emphasize the importance of anticancer treatment to improve survival time for patients. The group of concurrent chemoradiotherapy (30 patients) showed significantly longer survival time than the group given sequential chemoradiotherapy (55 patients) (528 days versus 373 days, p=0.0237). The favorable prognostic factors of laboratory study were groups of leukocyte =8,000/mm3, ALP=200 U/L, LDH=450 IU/L, NSE=15 ng/mL, s-GOT=40 IU/L. In extensive disease, there was no difference according to the number of metastatic site. However, the median survival time of patients with ipsilateral pleural effusion had longer than patients having other metastatic sites. According to the survey periods, three groups were divided into 1993-1995, 1996-1998, and 1999-2001. The median survival time was significantly prolonged after 1999 in comparison to previous groups (177 days, 194 days, 289 days, p=0.001, 0.002, respectively). Conclusion: Disease stage and 5% body weight loss for recent 3 months at diagnostic state were significant prognostic factors. In addition, the performance status, serum ALP, LDH, NSE, CEA levels also appear to be prognostic factors. The survival time of those patients with small cell lung cancer has been prologned in recent years. It was suggested that the used of the EP (etoposied and cisplatin) chemotherapy method and concurrent chemoradiotherapy for patients with a limited stage contributed to the improved survival time.

• Radiation Oncology Journal
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• v.31 no.4
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• pp.185-190
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• 2013

Purpose: We evaluated the effect of early chemoradiotherapy on the treatment of patients with limited stage small cell lung cancer (LS-SCLC). Materials and Methods: Between January 2006 and December 2011, thirty-one patients with histologically proven LS-SCLC who were treated with two cycles of chemotherapy followed by concurrent chemoradiotherapy and consolidation chemotherapy were retrospectively analyzed. The chemotherapy regimen was composed of etoposide and cisplatin. Thoracic radiotherapy consisted of 50 to 60 Gy (median, 54 Gy) given in 5 to 6.5 weeks. Results: The follow-up period ranged from 5 to 53 months (median, 22 months). After chemoradiotherapy, 35.5% of the patients (11 patients) showed complete response, 61.3% (19 patients) showed partial response, 3.2% (one patient) showed progressive disease, resulting in an overall response rate of 96.8% (30 patients). The 1-, 2-, and 3-year overall survival (OS) rates were 66.5%, 41.0%, and 28.1%, respectively, with a median OS of 21.3 months. The 1-, 2-, and 3-year progression free survival (PFS) rates were 49.8%, 22.8%, and 13.7%, respectively, with median PFS of 12 months. The patterns of failure were: locoregional recurrences in 29.0% (nine patients), distant metastasis in 9.7% (three patients), and both locoregional and distant metastasis in 9.7% (three patients). Grade 3 or 4 toxicities of leukopenia, anemia, and thrombocytopenia were observed in 32.2%, 29.0%, and 25.8%, respectively. Grade 3 radiation esophagitis and radiation pneumonitis were shown in 12.9% and 6.4%, respectively. Conclusion: We conclude that early chemoradiotherapy for LS-SCLC provides feasible and acceptable local control and safety.