• 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.

• 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.

• 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.

• Nuclear Medicine and Molecular Imaging
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• v.41 no.6
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• pp.538-545
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• 2007

Purpose: We evaluated correlation of $^{18}F$-FDG uptakes, therapeutic response and relapse in pre-treatment $^{18}F$-FDG PET/CT in patients with SCLC. Materials and methods: We included 26 patients with pathologically proven small cell lung cancer. Total 102 lesions (26 lungs, 69 lymph nodes and 8 metastatic lesions) were evaluated. All patients underwent $^{18}F$-FDG PET/CT for staging. The maxSUV was used as a parameter of $^{18}F$-FDG uptake. The patients were divided into responders and non-responders according to response criteria on chest CT scan after 3 cycles of chemotherapy. We compared maxSUV between two groups by using independent t-test. To access correlation with $^{18}F$-FDG uptake and relapse, maxSUV and interval time to relapse was analyzed by correlation analysis. The cutoff value of maxSUV was evaluated by ROC curve. Results: Twelve-one patients (81%) were responders and five patients were non-responders on follow-up chest CT scan. The mean maxSUV of main lung lesions in responders and non-responders were $14.15{\pm}3.72$ and $9.17{\pm}2.15$, respectively. The maxSUV in the responders was significantly lower than that in non-responders (p<0.05). According to ROC curve, point of cut that predicts therapeutic response was 8.98 with 100% sensitivity and 57% specificity. The correlation analysis between $^{18}F$-FDG uptakes and interval time to relapse showed a significant negative correlation (p<0.05, r=-0.757). Conclusion: The pre-treatment $^{18}F$-FDG uptake of responders was significantly lower than that of non-responders. Patients with high $^{18}F$-FDG uptake in pre-treatment $^{18}F$-FDG PET/CT relapse earlier.

• Tuberculosis and Respiratory Diseases
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• v.42 no.6
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• pp.934-940
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• 1995

Small cell lung cancer(SCLC) is frequently associated with paraneoplastic syndromes, which occur in approximately 20% of patients at presentation. Clinical Cushing's syndrome secondary to ectopic ACTH production is uncommon, occurring in approximately 5% of all SCLC patients. However, biochemical evidence of hypercortisolism can be detected in up to 50% of patients. Patients with Cushing's syndrome from ectopic ACTH production show hypertension, weakness, hyperglycemia, and hypokalemic metabolic alkalosis, but differ from patients with classic Cushing's disease in that symptoms develop more rapidly. Ectopic ACTH production is associated with a poor response to chemotherapy, short survival, and a high risk of treatment-related complications. We report a case of Cushing's syndrome associated with ectopic corticotropin production in 59-year-old male patient with extensive stage of SCLC.

• Tuberculosis and Respiratory Diseases
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• v.65 no.1
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• pp.37-40
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• 2008

Nephrotic syndrome is a relatively rare complication of malignancy. A few cases of nephrotic syndrome accompanying Hodgkin's disease, non-Hodgkin lymphoma, leukemia and other malignancies have been reported since the first case of the nephrotic syndrome associated with extrarenal malignancy was reported in 1922. Hodgkin's disease and solid tumors are known to be the most common malignancies accompanying nephrotic syndrome. The pathologic findings of kidney in patients with Hodgkin's disease commonly show minimal change nephropathy. Membranous glomerulonephropathy is the most common pathologic feature in patients with solid tumors. Although membranous glomerulonephropathy related to small cell lung cancer has rarely been reported in Korea, minimal change nephropathy accompanying small cell lung cancer has never been reported. We present here a case of a 70 year-old male with minimal change nephropathy that was related to small cell lung cancer. We detected small cell lung cancer during the diagnosis work-up of nephrotic syndrome. We suggest that nephrotic syndrome can be a manifestation of underlying malignancy.

• Radiation Oncology Journal
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• v.17 no.1
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• pp.9-15
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• 1999

Purpose : This is a retrospective study to evaluate the response rate, acute toxicity, and survival rate of a combined chemotherapy and radiation therapy in limited disease small cell lung cancer, Materials and Methods : Firty-six patients with limited disease small-cell lung cancer who underwent combined chemotherapy and radiation therapy between October 1994 and April 1998 were evaluated. Six cycles of chemotherapy were planned either using a VIP regimen etoposide, ifosfamide, and cis-platin) or a EP regimen (etoposide and cis-platin). Thoracic radiation therapy was planned to deli- ver 44 Gy using 1 OMV X-ray, starting concurrently with chemotherapy. Response was evaluated 4 weeks after the completion of the planned chemotherapy and radiation therapy, and the prophylaetic cranial irradiation was planned only for the patients with complete responses. Acute toxicity was evaluated using the SWOG toxicity criteria, and the overall survival and disease-free survival were calculated using the Kaplan-Meier Method. Results : The median follow-up period was 16 months (range:2 to 41 months). Complete response was achieved En 30 (65$\%$) patients, of which 22 patients received prophylactic cranial irradiations. Acute toxicities over grade III were granulocytopenia in 23 (50$\%$), anemia in 17 (37$\%$), thrombo- cytopenia in nine (20$\%$), alopecia in nine (20$\%$), nausea/vomiting in five (11$\%$), and peripheral neuropathy in one (2$\%$). Chemotherapy was delayed in one patient, and the chemotherapy doses were reduced in 58 (24$\%$) out of the total 246 cycles. No radiation esophagitis over grade 111 was observed, while interruption during radiation therapy for a mean of 8.3 days occurred in 21 patients. The local recurrences were observed in 8 patients and local progressions were in 6 patients, and the distant metastases in 17 patients. Among these, four patients had both the local relapse and the distant metastasis. Brain was the most common metastatic site (10 patients), followed by the liver as the next common site (4 patients). The overall and progression-free survival rates were 79$\%$ and 55$\%$ in 1 year, and 45'/) and 32% in 2 years, respectively, and the median survival was 23 months. Conclusion : Relatively satisfactory local control and suwival rates were achieved after the combined chemotherapy and radiation therapy with mild to moderate acute morbidities in limited disease small cell lung cancer.

• Tuberculosis and Respiratory Diseases
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• v.66 no.6
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• pp.444-450
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• 2009

Background: Biomarkers for cancer have several potential clinical uses, including the following: early cancer detection, monitoring for recurrence prognostication, and risk stratification. However, no biomarker has been shown to have adequate sensitivity and specificity. Many investigators have tried to validate biomarkers for the early detection and recurrence of lung cancer. To evaluate plasma G-CSF as such a biomarker, protein levels were measured and were found to correlate with the clinicopathological features of primary lung tumors. Methods: Between December 2006 and May 2008, 100 patients with histologically-validated primary lung cancer were enrolled into this study. To serve as controls, 127 healthy volunteers were enrolled into this study. Plasma G-CSF levels were measured in lung cancer patients using the sandwich ELISA system (R & D inc.) prior to treatment. Results: The mean plasma G-CSF levels were 12.2$\pm$0.3 pg/mL and 46.0$\pm$3.8 pg/mL (mean$\pm$SE) in the normal and in the cancer groups, respectively. In addition, plasma G-CSF levels were higher in patients with early lung cancer than in healthy volunteers (p<.001). Plasma G-CSF levels were higher in patients who were under 65 years old or smokers. Within the cancer group, plasma G-CSF levels were higher in patients with non small cell lung cancer than in patients with small cell lung cancer (p<.05). Overall, plasma G-CSF levels were shown to increase dependent upon the type of lung cancer diagnsosed. In the order from highest to lowest, the levels of plasma G-CSF tended to decrease in the following order: large cell carcinoma, squamous cell carcinoma, adenocarcinoma, and bronchioloalveolar carcinoma. Plasma G-CSF levels tended to be higher in patients with advanced TNM stage than in localized TNM stage (I, II

• Radiation Oncology Journal
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• v.16 no.3
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• pp.291-301
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• 1998

Purpose : A retrospective study was conducted comparing single daily fraction (SDF) thoracic radiotherapy (TRT) with twice daily (BID) TRT to determine the potential benefit of BID TRT in limited-stage small cell lung cancer (SCLC). Endpoints of the study were response. survival, pattern of failure, and acute toxicity. Materials and Methods : Between November 1989 to December 1996, 78 patients with histologically proven limited-stage SCLC were treated at the Department of Therapeutic Radiology, Chungnam National University Hospital. Of these, 9 were irradiated for palliative intent, and 1 had recurrent disease. Remaining 68 patients were enrolled in this study. There were 26 patients with a median age of 58 years, and 22 (85$\%$) ECOG performance score of less than 1 in SDF TRT. There were 42 patients with a median age of 57 years, and 36 (86$\%$) ECOG performance score of less than 1 in BID TRT By radiation fractionation regimen, there were 26 in SDF TRT and 42 in BID TRT. SDF TRT consisted of 180 cGy, 5 days a week. BID TRT consisted of 150 cGy BID, 5 days a week in 13 of 42 and 120 cGy BID, in 29 of 42. And the twice daily fractions were separated by at least 4 hours. Total radiotherapy doses were between 5040 and 6940 cGy (median, 5040 cGy) in SDF TRT and was between 4320 and 5100 cGy (median, 4560 cGy) in BID TRT. Prophylactic cranial irradiation (PCI) was recommended for patients who achieved a CR. The recommended PCI dose was 2500 cGy/10 fractions. Chemotherapy consisted of CAV (cytoxan 1000 mg/$m^2$, adriamycin 40 mg/$m^2$, vincristine 1 mg/$m^2$) alternating with VPP (cisplatin 60 mg/$m^2$, etoposide 100 mg/$m^2$) every 3 weeks in 25 (96$\%$) of SDF TRT and in 40 (95$\%$) of BID TRT. Median cycle of chemotherapy was six in both group. Timing for chemotherapy was sequential in 23 of SDF TRT and in 3 BID TRT, and concurrent in 3 of SDF TRT and in 39 of BID TRT Follow-up ranged from 2 to 99 months (median, 14 months) in both groups. Results : Of the 26 SDF TRT, 9 (35$\%$) achieved a complete response (CR) and 14 (54$\%$) experienced a partial response (PR). Of the 42 BID TRT, 18 (43$\%$) achieved a CR and 23 (55$\%$) experienced a PR. There was no significant response difference between the two arms (p=0.119). Overall median and 2-year survival were 15 months and 26.8$\%$, respectively. The 2-year survivals were 26.9$\%$ and 28$\%$ in both arm, respectively (p=0.51). The 2-rear survivals were 35$\%$ in CR and 24.2$\%$ in PR, respectively. The grade 2 to 3 esophageal toxicities and grade 2 to 4 neutropenias were more common in BID TRT (p=0.028 0.003). There was no difference in locoregional and distant metastasis between the two arms (p=0 125 and 0.335, respectively). The most common site of distant metastasis was the brain. Conclusion : The median survival and 2-year survival were 17 months and 20.9$\%$ in SDF TRT with sequential chemotherapy, and 15 months and 28$\%$ in BID TRT with concurrent chemotherapy, respectively. We did not observe a substantial improvement of long-term survival in the BID TRT with concurrent chemotherapy compared with standard schedules of SDF TRT with sequential chemotherapy. The grade 2 to 3 esophageal toxicities and glade 2 to 4 neutropenias were more common in BID TRT with concurrent chemotherapy. Although the acute toxicities were more common in BID TRT with concurrent chemotherapy than SDF TRT with sequential chemotherapy, a concurrent chemotherapy and twice daily TRT was feasible. However further patient accrual and long-term follow up are needed to determine the potential benefits of BID TRT in limited-stage SCLC.

• Journal of Yeungnam Medical Science
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• v.6 no.1
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• pp.171-178
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• 1989

Eaton Lambert Syndrome(ELS)is a disorder of neuromuscular transmission. The defect of neuromuscular transmission is due to decrease in the release of acetylcholine guanta from nerve terminal. This syndrome is frequently associated with bronchogenic carcinoma. The diagnosis is established by electromyography, which characteristically shows 1) low amplitude of evoked compound muscle potential to a single supramaximal stimulus on nerve, 2) significant decremental response at low rates of stimulation 3) marked incremental response at high rates of stimulation. Our patient is 52year old man with dyspnea, coughing and muscle weakness of proximal lower limbs. He has small cell lung cancer and associated with ELS, Superior venacava syndrome and has metastatic lesion on right supraclavicular lymphnode confirmed by pathology. Metastatic mass and SVC syndrome are marked improved following chemotherapy and radiotherapy, however follow up EMG finding does not improved. We are here reporting one case which considered compatible for ELS, with a few elementary reviewed literatures.