• Journal of Chest Surgery
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• v.41 no.5
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• pp.659-662
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• 2008

Video-assisted pulmonary lobectomy was introduced in the early 1990's by several authors, and the frequency of video-assisted thoracic surgery (VATS) lobectomy for lung cancer has been slowly increasing because of its safety and oncologic acceptability in patients with early stage lung cancer However, VATS is limited by 2D imaging, an unsteady camera platform, and limited maneuverability of its instruments. The da Vinci Surgical System was recently introduced to overcome these limitations. It has a 3D endoscopic system with high resolution and magnified binocular views and EndoWrist instruments. We report three cases of da Vinci robot system-assisted pulmonary lobectomy in patients with early stage lung cancer.

• Radiation Oncology Journal
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• v.21 no.4
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• pp.253-260
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• 2003

Purpose: No general consensus has been reached regarding the necessity of postoperative radiation therapy (PORT) and the optimal techniques of its application for patients with chest wall invasion (pT3cw) and node negative (NO) non-small cell lung cancer (NSCLC). We retrospectively analyzed the PT3cwN0 NSCLC patients who received PORT because of presumed inadequate resection margin on surgical findings. Materials and Methods: From Aug. 1994 till June 2000, 21 pT3cwN0 NSCLC patients received PORT at Samsung Medical Center; all of whom underwent curative on-bloc resection of the primary tumor plus the chest wall and regional lymph node dissection. PORT was typically stalled 3 to 4 weeks after operation using 6 or 10 MV X-rays from a linear accelerator. The radiation target volume was confined to the tumor bed plus the immediate adjacent tissue, and no regional lymphatics were included. The planned radiation dose was 54 Gy by conventional fractionation schedule. The survival rates were calculated and the failure patterns analyzed. Results: Overall survival, disease-free survival, loco-regional recurrence-free survival, and distant metastases-free survival rates at 5 years were 38.8$\%$, 45.5$\%$, 90.2$\%$, and 48.1$\%$, respectively. Eleven patients experienced treatment failure: six with distant metastases, three with intra-thoracic failures, and two with combined distant and intra-thoracic failures. Among the five patients with intra-thoracic failures, two had pleural seeding, two had in-field local failures, and only one had regional lymphatic failure in the mediastinum. No patients suffered from acute and late radiation side effects of RTOG grade 3 or higher. Conclusion: The strategy of adding PORT to surgery to improve the probability, not only of local control but also of survival, was justified, considering that local control was the most important component in the successful treatment of pT3cw NSCLC patients, especially when the resection margin was not adequate. The incidence and the severity of the acute and late side effects of PORT were markedly reduced, which contributed to improving the patients' qualify of life both during and after PORT, without increasing the risk of regional failures by eliminating the regional lymphatics from the radiation target volume.

• Journal of the Korean Society of Radiology
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• v.9 no.6
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• pp.393-401
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• 2015

Radiation therapy for lung cancer is an effective treatment during monotherapy or combination therapy. Studies have reported that the optimum utilization rate of radiation therapy is estimated at 61% to 74%. Radiation therapy in Korea has been investigated to be low; further studies are needed. This study was intended to assess the appropriateness of the use of radiation and to reveal the use of radiation therapy-related factors by examining radiation therapy in lung cancer patients of Busan and South Gyeongnam Province. This study was aimed at the population diagnosed with lung cancer in Busan and South Gyeongnam Province. To conduct the study, 1036 patients enrolled in two hospitals were collected and 897 appropriate as subjects were selected. We compared the optimum utilization rate and actual rate of radiation therapy, and revealed the adequacy and related factors for use of radiotherapy. Of 897 patients, 503 (56%) were treated with medical therapy and 394 (44%) were given radiotherapy. The radiotherapy utilization rate of all lung cancer patients was 42%. The proportion of non-small cell lung cancer by histologic type was 33% and that of small cell lung cancer was 90%. Factors related to radiation therapy used in cancer were age, histological type, clinical stage, doctor refereed to, and clinical examination. Compared to radiation utilization by region (site), curative chest therapy was 42%; palliative treatment was 26%. In the comparison of histologic types, utilization of small-cell lung cancer is lower; the lowest especially in the stage III. Utilization of radiation therapy in Busan and South Gyeongnam Province was lower than the reasonable one. Utilization difference could be explained by patient factors, tumor factors, and health service factors. To improve utilization,development ofoutreach service programs and activation of the multidisciplinary team are required.

• Radiation Oncology Journal
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• v.24 no.4
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• pp.230-236
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• 2006

$\underline{Purpose}$: To analyze the response, toxicity, patterns of failure and survival rate of patients with locally advanced non-small cell lung cancer who were treated with concurrent chemoradiotherapy with weekly paclitaxel. $\underline{Materials\;and\;Methods}$: Twenty-three patients with locally advanced non-small cell lung cancer patients who received radical chemoradiotherapy from October 1999 to September 2004 were included in this retrospective study. Patients received total $55.4{\sim}64.8$ (median 64.8) Gy (daily 1.8 Gy per fraction, 5 days per weeks) over $7{\sim}8$ weeks. 50 or $60\;mg/m^2$ of paclitaxel was administered on day 1, 8, 15, 22, 29 and 36 of radiotherapy. Four weeks after the concurrent chemoradiotherapy, three cycles of consolidation chemotherapy consisted of paclitaxel $135\;mg/m^2$ and cisplatin $75\;mg/m^2$ was administered every 3 weeks. $\underline{Results}$: Of the 23 patients, 3 patients refused to receive the treatment during the concurrent chemoradiotherapy. One patient died of bacterial pneumonia during the concurrent chemoradiotherapy. Grade 2 radiation esophagitis was observed in 4 patients (17%). Sixteen patients received consolidation chemotherapy. During the consolidation chemotherapy, 8 patients (50%) experienced grade 3 or 4 neutropenia and one of those patients died of neutropenic sepsis. Overall response rate for 20 evaluable patients was 90% including 4 complete responses (20%) and 14 partial responses (70%). Among 18 responders, 9 had local failure, 3 had local and distant failure and 2 had distant failure only. Median progression-free survival time was 9.5 months and 2-year progression-free survival rate was 19%. Eleven patients received second-line or third-line chemotherapy after the treatment failure. The median overall survival time was 21 months. 2-year and 5-year survival rate were 43% and 33%, respectively. Age, performance status, tumor size were significant prognostic factors for progression-free survival. $\underline{Conclusion}$: Concurrent chemoradiotherapy with weekly paclitaxel revealed high response rate and low toxicity rate. But local failure occurred frequently after the remission and large tumor size was a poor prognostic factor. Further investigations are needed to improve the local control.

• Radiation Oncology Journal
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• v.27 no.3
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• pp.126-132
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• 2009

Purpose: We wanted to evaluate the prognostic factors for the pathologic N2 non-small cell lung cancer (NSCLC) patients who were treated by postoperative radiotherapy. Materials and Methods: We retrospectively reviewed 112 pN2 NSCLC patients who underwent surgery and postoperative radiotherapy (PORT) From January 1999 to February 2008. Seventy-five (67%) patients received segmentectomy or lobectomy and 37 (33%) patients received pneumonectomy. The resection margin was negative in 94 patients, and it was positive or close in 18 patients. Chemotherapy was administered to 103 (92%) patients. Nine (8%) patients received PORT alone. The median radiation dose was 54 Gy (range, 45 to 66), and the fraction size was 1.8~2 Gy. Results: The 2-year overall survival (OS) rate was 60.2% and the disease free survival (DFS) rate was 44.7% for all the patients. Univariate analysis showed that the patients with multiple-station N2 disease had significantly reduced OS and DFS (p=0.047, p=0.007) and the patients with an advanced T stage ($\geq$T3) had significantly reduced OS and DFS (p<0.001, p=0.025). A large tumor size ($\geq$5 cm) and positive lymphovascular invasion reduced the OS (p=0.035, 0.034). Using multivariate analysis, we found that multiple-station N2 disease and an advanced T stage ($\geq$T3) significantly reduced the OS and DFS. Seventy one patients (63.4%) had recurrence of disease. The patterns of failure were loco-regional in 23 (20.5%) patients, distant failure in 62 (55.4%) and combined loco-regional and distant failure in 14 (12.5%) patients. Conclusion: Multiple involvement of mediastinal nodal stations for the pN2 NSCLC patients with PORT was a poor prognostic factor in this study. A prospective study is necessary to evaluate the N2 subclassification and to optimize the adjuvant treatment.

• Radiation Oncology Journal
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• v.17 no.3
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• pp.195-202
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• 1999

Purpose : We peformed this study to evaluate the prognostic factors and the effect of induction chemotherapy in locally advanced non-small cell lung cancer (NSCLC). Materials and Methods : A retrospective analysis was done for 130 patients with locally advanced NSCLC treated with curative radiotherapy alone or induction chemo-radiotherapy from January 1986 to October 1996. Eighty-five patients were treated with radiotherapy alone, forty-five with induction chemotherapy and radiotherapy. Age, sex, performance status, histopathologic type, and stage were evenly distributed in both groups. The patients were treated with 6 MV or 10 MV X-ray. Conventional fractionation with daily fraction size 1$.8\~2.0$ Gy was done. Of the patients, 129 patients received total dose above 59.6 Gy ($56\~66$ Gy, median 60 Gy). Induction chemotherapy regimen were CAP (Cyclo-phosphamide, Adriamycin, Cisplatin) in 6 patients, MVP (Mitomycin, Vinblastine, Cisplatin) in 9 patients, MIC (Mitomycin, Ifosfamide Cisplatin) in 13 patients, and EP (Etoposide, Cisplatin) in 17 patients. Chemotherapy was done in $2\~5$ cycles (median 2). Results : Overall 1-, 2-, and 3-year survival rate (YSR) for all patients were $41.5\%,{\;}13.7\%,{\;}and{\;}7\%$, respectively (median survival time 11 months). According to treatment modality, median survival time, overall 1-, 2-, and 3-YSR were 9 months, $32.9\%,{\;}10.\5%,{\;}6\%$ for radiotherapy alone group, and 14 months, $57.8\%,{\;}20\%,{\;}7.6\%$ for induction chemotherapy group, respectively (f=0.0005). Complete response (CR) to overall treatments was $25\%$ (21/84) in radiotherapy alone and $40.5\%$ (17/42) in induction chemotherapy group (p=0.09). The Prognostic factors affecting overall survival were hemoglobin level (p=0.04), NSE (neuron-specific enolase) level (p=0.004), and respense to overall treatment(p=0.004). According to treatment modalities, NSE (neuron-specific enolase) (p=0.006) and response to overall treatment (p=0.003) were associated with overall survival in radiotherapy alone group, and response to overall treatment (p=0.007) in induction chemotherapy group. The failure Pattern analysis revealed no significant difference between treatment modalities. But, in patients with CR to overall treatment, distant metastasis were found in 11/19 patients with radiotherapy alone, and 3/13 patients with induction chemotherapy and radiotherapy (p=0.07). Locoregional failure patterns were not different between two groups (10/19 vs 6/13). Conclusion : Induction chemotherapy and radiotherapy achieved increased 2YSR compared to radiotherapy alone, At least in CR patients, there was decreased tendency in distant metastasis with induction chemotherapy. But, locoregional failures and long-term survival were not improved. Thus, there is need of more effort to increasing local control and further decreasing distant metastasis.

• Tuberculosis and Respiratory Diseases
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• v.59 no.5
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• pp.510-516
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• 2005

Backgroud : Lung cancer is the leading cause of cancer deaths in Korea and the number of lung cancer deaths is increasing. The higher response rates, decreased toxicity and improved performance status of the first-line treatments have resulted in an increased number of patients becoming candidates for second-line therapy. Several new antineoplastic agents, including gemcitabine, docetaxel and paclitaxel, have recently demonstrated second-line activity. This phase II study evaluated the efficacy and toxicity of gemcitabine and vinorelbine as combination chemotherapy for Korean patients with NSCLC as a second-line treatment. Methods : Sixty response-evaluable patients were enrolled from December 2000 to July 2003. We conducted a phase II study of a combination gemcitabine and vinorelbine chemotherapy for patients with histologically confirmed NSCLC that was stage IIIB and IV disease at the time of diagnosis, and the disease had progressed onward or the patients had relapsed after first-line platinum-based chemotherapy. They were treated with intravenous gemcitabine $1000mg/m^2$ and intravenous vinorelbine $25mg/m^2$ on days 1 and 8. This chemotherapy regimen was repeated every 3 weeks. Results : A total of 215 cycles of treatment were given and the mean number of cycles was 3.6 cycles. All the patients were evaluable for the toxicity profile. The response rate was 10% according to the WHO criteria. The median progression free survival was 3.8 months and the median survival time was 10.1 months. The 1-year survival rate was 32.9%. Grade III and IV neutropenia were seen in 20 (33.3%) and 7 (11.7%) patients, respectively. Conclusion : The combination of gemcitabine and vinorelbine is active and well tolerated as a second-line therapy for patients with advanced nonsmall cell lung carcinoma.

• Tuberculosis and Respiratory Diseases
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• v.58 no.5
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• pp.473-479
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• 2005

Background : Gefitinib targets the epidermal growth factor receptor r(EGFR), and Gefitinib has antitumor activity in patient with non-small cell lung cancer (NSCLC). However, only 10 to 20 percent of patients show a clinical response to this drug, and the molecular mechanisms underlying patient sensitivity to gefitinib are unknown. PTEN (Phosphatase and tensin homolog deleted on chromosome Ten) plays a role for the modulation of the phosphatidylinositol 3-kinase pathway (PI3K), which is involved in cell proliferation and survival, so that it can inhibit cell cycle progression and induce G1 arrest. Therefore, we analyzed the relationship between PTEN expression and gefitinib's responsiveness in patients having advanced non small cell lung cancer that had progressed after previous chemotherapy. Methods : The expression of PTEN was studied by immunohistochemistry in paraffin-embedded tumor blocks that were obtained from 22 patients who had been treated with gefitinib from JAN, 2001 to AUG. 2004. For the evaluation of the relationships between the PTEN expression, the clinical stage and the basal characteristics, those cases that showed the respective antigen expression in >50% of the tumor cells were considered positive. Results : The positive rate of PTEN staining was 55% of the total of 22 patients. There was a significant relationship between the increased expression of PTEN and the response group (p=0.039). However, there was no significant relationship between the expression of PTEN and other clinicopathologic characteristics. Conclusion: The expression of PTEN in patients with advanced non small cell lung cancer that has progressed after previous chemotherapy may play a role in gefitinib's responsiveness.

• Tuberculosis and Respiratory Diseases
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• v.55 no.1
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• pp.98-106
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• 2003

Background : To evaluate the efficacy and safety of gemcitabine and cisplatin chemotherapy in advanced non-small cell lung cancer (NSCLC). Materials and Methods : Forty patients (21 men, 19 women ; age range, 37 to 73 years; median, 63 years) with unresectable stage IIIB to IV NSCLC were evaluated. Patients received cisplatin $60mg/m^2$ (Day 1), gemcitabine $1200mg/m^2$ (Day 1 and 8) every 21 days. Eighteen patients had stage IIIB disease and 22 had stage IV. There were 28 patients of adenocarcinoma (70.0%), 11 of squamous cell carcinoma (27.5%), and one of large cell carcinoma (2.5%). Results : Of 40 patients, no patients showed complete response while 15(37.5%) showed partial response, 7(17.5%) had stable diseases, 18(45%) had progressive diseases. During a total of 195 courses of chemotherapy, grade 3 or more granulocytopenia and thrombocytopenia occured in 12.5% and 2.5% of patients respectively. Non-hematologic toxicity was mild and easily controlled. There was one case of treatment-related death by pneumomia. The median survival was 55 weeks (95% CI, 34~75weeks), and the time to progression was 19 weeks (95% CI, 16~23weeks). One year survival rate was 55% and 2 year survival rate was 10%. Conclusion : The efficacy of cisplatin and gemcitabine combination chemotherapy was acceptable in the treatment of advanced NSCLC.

• Tuberculosis and Respiratory Diseases
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• v.51 no.2
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• pp.108-121
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• 2001

Background : The $p16^{INK4a}$ (p16) twnor suppressor gene is frequently inactivated in hwnan non-small cell lung cancers (NSCLCs), predominantly through homozygous deletion or in association with aberrant promotor hypermethylation. Death-associated protein kinase (DAPK) gene influences interferon $\gamma$-induced apoptotic cell death and has important role in metastasis of lung cancer in animal model. Hypermethylation of promoter region of DAP kinase gene may suppress the expression of this gene. Methods : This study was performed to investigate the aberrant methylation of p16 or DAP kinase in 35 resected primary NSCLCs by methylation-specific PCR (MSP), and demonstrated frequency, diagnostic value and clinical implication of aberrant methylation of two genes. Results : Thirty-two cases were male patients, and 3 cases were female patients with an average age was 57. $8{\pm}10.5$ years. The histologic types of lung cancer were 22 of squamous cell carcinoma, 12 of adenocarcinoma, 1 of large cell carcinoma. Pathologic stages were 11 cases of stage I (1 IA, 10 IB), 13 cases of stage II (1 IIA, 12 IIB), and 11 cases of stage III (9 IIIA, 2 IIIB). Regarding for the cancer tissue, p16 aberrant methylation was noted in 13 case of 33 cases (39.4%), DAP kinase in 21 cases of 35 cases (60%). Age over 55 year was associated with p16 aberrant methylation significantly (p<0.05). Methylation status of two genes was not different by smoking history, histologic type, size of tumor, lymph node metastasis and disease progression of lung cancer. There was no correlation between p16 and DAP kinase hypermethylation. Conclusion: This investigation demonstrates that aberrant methylation of p16 tumor suppressor gene or DAP kinase showed relatively high frequency (74.3%) in NSCLCs, and that these genes could be a biologic marker for early detection of lung cancer.