• Journal of Chest Surgery
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• v.32 no.2
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• pp.144-150
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• 1999

Background: Surgery has been considered the most effective and standard treatment modality in non-small cell lung cancer(NSCLC). However in stage IIIA lung cancer, the role of surgery is still controversial. To evaluate the role of surgery for stage IIIA NSCLC, we investigated the survival after surgery and the prognostic factors. Material and Method: We evaluated 158 consecutive cases of stage IIIA NSCLC patients operated on between 1990 and 1996. There were 130 male patients and 28 female patients, and the mean age was 58.5 years. All patients except one underwent lung resection beyond lobectomy and extended mediastinal dissection. Postoperative adjuvant therapy were undertaken in 145(94.8%) patients. All patients(153) were followed and the mean follow-up period was 21.4months. Result: Twenty nine cases of the postoperative complications developed in 25 patients (15.8%). There were 5 operative mortality cases(3.2%) and the main cause of death was acute respiratory distress syndrome (ARDS). Local or distant recurrences developed in 84 patients(54.9%). The 5-year survival of 153 patients was 29.6% and the median survival time was 18.0 months. The 5-year survival of non N2 disease group(36.8%) was better than that of N2 disease group(26.6%)(p=0.35) and the 5-year survival of squamous cell carcinoma (38.1%) was better than that of adenocarcinoma(25.7%)(p=0.39) however there were no significant differences. Regarding the postoperative adjuvant therapy, in combined therapy group(84 patients), radiotherapy group(37 patients) and chemotherapy group(24 patients), the 5-year survival were 31.3%, 32.4%, and 14.6% respectively. There was no difference of survival between radiotherapy and combined therapy group(p=0.31), however the survival of the combined therapy group was better than the chemotherapy group(p=0.005). The survival of the complete resection group(31.9%) was better than the incomplete resection group(16.6%) however there was no significant difference(p=0.19). Conclusion: These observations indicate that the good 5-year survival(29.6%) in patients with stage IIIA NSCLC result from the agressive surgical treatment including extensive mediastinal nodes dissection.

• Tuberculosis and Respiratory Diseases
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• v.63 no.4
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• pp.382-386
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• 2007

Paraneoplastic limbic encephalitis is a rare disorder that is characterized by personality changes, irritability, depression, seizures, memory loss and dementia, and is commonly associated with small cell lung cancer. The cause is unknown but it is believed to be an autoimmune disorder that develops secondary to a carcinomatous process. We report a patient with the clinical feature consistent with limbic encephalitis. A 64-year-old women developed disorientation, memory loss and general weakness. She was diagnosed with NSCLC (adenocarcinoma) with a brain metastasis 1 year earlier and was treated with radiation and chemotherapy. Although the lung mass and brain metastatic lesions had improved, the brain T2-weighted MRI showed high signal intensity in the right temporal region. This lesion consisted of with limbic encephalitis and was negative to the other viral and immune markers. The patient's symptoms did not improve after steroid treatment. Our case demonstrated that a NSCLC (adenocarcinoma) also can be associated with paraneoplastic limbic encephalitis.

• Tuberculosis and Respiratory Diseases
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• v.39 no.6
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• pp.502-510
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• 1992

Background: Neuron specific enolase (NSE) is a neuronal form of the glycolytic enzyme enolase which was first found in extracts of brain tissue, and later in a variety of APUD cells and neurons of the diffuse endocrine system. SCLC shares many APUD properties with normal neuroendocrine cells. NSE immunostaining and serum NSE measurement may be a useful marker of neuroendocrine differentiation in lung tumors and diagnosis of small cell carcinoma. Methods: NSE immunohistochemical staining was done and at the same time serum NSE levels were measured in 22 small cell lung cancer and 21 non small cell lung cancer which were confirmed histologically. Results: 1) NSE immunoreactivity was detected in 9 of the 18 (50%) small cell lung cancer, in 5 of the 16 non small cell lung cancer. 2) Whereas the mean value in non-small cell lung cancer group was $11.79{\pm}4.47\;ng/ml$, the mean level of serum NSE in small cell lung cancer increased up to $59.3{\pm}77.8\;ng/ml$. In small cell lung cancer patients, mean value of limited disease group was $20.19{\pm}12.91\;ng/ml$, while mean value of extended disease group was $91.9{\pm}94.2\;ng/ml$ showing statistically significant difference. If serum levels above 20 ng/ml were tentatively defined as positive, 16 of 22 (73%) patients with SCLC had positive serum NSE level, but only one patient with NSCLC did. There was no correlation between serum NSE level and immunoreactivity of NSE. Conclusion: These studies indicate that serum NSE measurement may be a useful marker for the diagnosis and disease extent and NSE immunostaining can be used to demonstrate the neuroendocrine components of lung tumor.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.10
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• pp.6115-6120
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• 2013

Introduction: Some non-small cell lung cancer (NSCLC) tumor cells are insensitive to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) -based therapy. This study was conducted to examine the effect of embelin on the sensitivity of the A549 NSCLC cell line to TRAIL receptor2 (TRAILR2) monoclonal antibodies and to investigate the potential mechanisms. Materials and Methods: A549 cells were treated with embelin, TRAILR2 mAb or a combination of both. Cell viability was measured using ATPlite assay and apoptosis rates were determined by flow cytometry with AnnexinV-FITC and propidium iodide staining, with the expression levels of proteins analyzed by Western blotting. Results: The cell survival rate of separate treatments with 100 ng/ml TRAILR2 antibody or 25 uM embelin were $81.5{\pm}1.57%$ and $61.7{\pm}2.84%$, respectively. Their combined use markedly decreased cell viability in A549 cells to $28.1{\pm}1.97%$ (P<0.05). The general caspase inhibitor Z-VAD-FMK could inhibit the embelin-enhanced sensitivity of A549 cells to TRAILR2 mAb ($75.97{\pm}3.17%$)(P<0.05). Both flow cytometry and cell morphological analysis showed that embelin was able to increase TRAIL-induced apoptosis in A549 cells. Combined treatment with embelin and TRAILR2 mAb augmented the activation of initiator caspases and effector caspase. In addition, A549 cells showed increasing levels of TRAILR2 protein and decreasing levels of Bcl-2, survivin and c-FLIP following the treatment with embelin+TRAILR2 mAb. Conclusions: Embelin could enhance TRAIL-induced apoptosis in A549 cells. The synergistic effect of the combination treatment might be due to modulation of multiple components in the TRAIL receptor-mediated apoptotic signaling pathway, including TRAILR2, XIAP, survivin, Bcl-2 and c-FLIP.

• Radiation Oncology Journal
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• v.33 no.3
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• pp.207-216
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• 2015

Purpose: Stereotactic radiosurgery (SRS) has been introduced for small-sized single and oligo-metastases in the brain. The aim of this study is to assess treatment outcome, efficacy, and prognostic variables associated with survival and intracranial recurrence. Materials and Methods: This study retrospectively reviewed 123 targets in 64 patients with non-small cell lung cancer (NSCLC) treated with SRS between January 2006 and December 2012. Treatment responses were evaluated using magnetic resonance imaging. Overall survival (OS) and intracranial progression-free survival (IPFS) were determined. Results: The median follow-up was 13.9 months. The median OS and IPFS were 14.1 and 8.9 months, respectively. Fifty-seven patients died during the follow-up period. The 5-year local control rate was achieved in 85% of 108 evaluated targets. The 1- and 2-year OS rates were 55% and 28%, respectively. On univariate analysis, primary disease control (p < 0.001), the Eastern Cooperative Oncology Group (ECOG) performance status (0-1 vs. 2; p = 0.002), recursive partitioning analysis class (1 vs. 2; p = 0.001), and age (<65 vs. ${\geq}65$ years; p = 0.036) were significant predictive factors for OS. Primary disease control (p = 0.041) and ECOG status (p = 0.017) were the significant prognostic factors for IPFS. Four patients experienced radiation necrosis. Conclusion: SRS is a safe and effective local treatment for brain metastases in patients with NSCLC. Uncontrolled primary lung disease and ECOG status were significant predictors of OS and intracranial failure. SRS might be a tailored treatment option along with careful follow-up of the intracranial and primary lung disease status.

• Radiation Oncology Journal
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• v.33 no.4
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• pp.284-293
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• 2015

Purpose: To determine failure patterns and survival outcomes of T4N0-1 non-small cell lung cancer (NSCLC) treated with definitive radiotherapy. Materials and Methods: Ninety-five patients with T4N0-1 NSCLC who received definitive radiotherapy with or without chemotherapy from May 2003 to October 2014 were retrospectively reviewed. The standard radiotherapy scheme was 66 Gy in 30 fractions. The main concurrent chemotherapy regimen was $50mg/m^2$ weekly paclitaxel combined with $20mg/m^2$ cisplatin or AUC 2 carboplatin. The primary outcome was overall survival (OS). Secondary outcomes were failure patterns and toxicities. Results: The median age was 64 years (range, 34 to 90 years). Eighty-eight percent of patients (n = 84) had an Eastern Cooperative Oncology Group performance status of 0-1, and 42% (n = 40) experienced pretreatment weight loss. Sixty percent of patients (n = 57) had no metastatic regional lymph nodes. The median radiation dose was EQD2 67.1 Gy (range, 56.9 to 83.3 Gy). Seventy-one patients (75%) were treated with concurrent chemotherapy; of these, 13 were also administered neoadjuvant chemotherapy. At a median follow-up of 21 months (range, 1 to 102 months), 3-year OS was 44%. The 3-year cumulative incidences of local recurrence and distant recurrence were 48.8% and 36.3%, respectively. Pretreatment weight loss and combined chemotherapy were significant factors for OS. Acute esophagitis over grade 3 occurred in three patients and grade 3 chronic esophagitis occurred in one patient. There was no grade 3-4 radiation pneumonitis. Conclusion: Definitive radiotherapy for T4N0-1 NSCLC results in favorable survival with acceptable toxicity rates. Local recurrence is the major recurrence pattern. Intensity modulated radiotherapy and radio-sensitizing agents would be needed to improve local tumor control.

• Radiation Oncology Journal
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• v.32 no.3
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• pp.147-155
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• 2014

Purpose: This study was conducted to observe the outcomes of postoperative radiotherapy (PORT) with or without concurrent chemotherapy in resected non-small cell lung cancer (NSCLC) in single institution. Materials and Methods: From 2002 to 2013, 78 patients diagnosed with NSCLC after curative resection were treated with radiotherapy alone (RT, n = 48) or concurrent chemoradiation (CCRT, n = 30). The indications of adjuvant radiation therapy were N2 node positive (n = 31), close or involved resection margin (n = 28), or gross residual disease due to incomplete resection (n = 19). The median radiation dose was 57.6 Gy (range, 29.9 to 66 Gy). Results: Median survival time was 33.7 months (range, 4.4 to 140.3 months). The 5-year overall survival (OS) rate was 49.5% (RT 46% vs. CCRT 55.2%; p = 0.731). The 3-year disease-free survival rate was 45.5% (RT 39.4% vs. CCRT 55.3%; p = 0.130). The 3-year local control rate was 68.1% (RT 64.4% vs. CCRT 77.7%; p = 0.165). The 3-year DMFS rate was 56.1% (RT 52.6% vs. CCRT 61.7%; p = 0.314). In multivariate analysis, age ${\geq}66$ years and pathologic stage III were significant poor prognostic factors for OS. Treatment failure occurred in 40 patients. Four patients had radiologically confirmed grade 3 radiation pneumonitis. Conclusion: In NSCLC, adjuvant RT or CCRT after curative surgery is a safe and feasible modality of treatment. OS gain was seen in patients less than 66 years. Postoperative CCRT showed a propensity of achieving better local control and improved disease-free survival compared to RT alone according to our data.

• Tuberculosis and Respiratory Diseases
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• v.43 no.3
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• pp.331-338
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• 1996

Background : Lung cancer continues to be the leading cause of cancer death in the United States and it's incidence has been rapidly increasing in Korea, too. The overall cure rate for non-small cell lung cancer(NSCLC) is approximately 10%, and the cure is generally achieved by surgery. Unfortunately, however, less than 15% of all patients and less than 25% of those who present with localized disease are candidates for curative surgical resection. So preoperative staging evaluation followed by curative resection has a major role in determining the long tenn prognosis of NSCLC patients. Therefore, we have conducted this study to compare pre-operative and post-operative staging and the long-tenn relapse-free survival rates in NSCLC patients according to its stage. Methods : We analyzed the medical records of 217 NSCLC patients who were operated on for curative resection in Seoul National University Hospital, retrospectively. Among them, 170 patients who were completely resected were selected to determine the long term relapse-free survival rates. Results : Among 217 NSCLC patients, men were 157 and women were 30. The median age was 58 and the difference between men and women was not found. The discrepancy rate between preoperative and postoperative staging was 40.1%. Its major cause was due to the difference of nodal staging. The 3-year relapse-free survival rates were 73%, 53% and 48% in stage I, II and IIIa, respectively. There was no difference of relapse-free duration in recurred patients according to the stage or histologic types. Conclusion : The postoperative pathologic staging determines the long tenn prognosis of patients with NSCLC after surgery, but current preoperative clinical staging can not predict the postoperative pathologic staging correctly. So the improved modality of staging system is required to predict the pathologic staging more correctly.

• Genomics & Informatics
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• v.21 no.3
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• pp.30.1-30.13
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• 2023

Ephs belong to the largest family of receptor tyrosine kinase and are highly conserved both sequentially and structurally. The structural organization of Eph is similar to other receptor tyrosine kinases; constituting the extracellular ligand binding domain, a fibronectin domain followed by intracellular juxtamembrane kinase, and SAM domain. Eph binds to respective ephrin ligand, through the ligand binding domain and forms a tetrameric complex to activate the kinase domain. Eph-ephrin regulates many downstream pathways that lead to physiological events such as cell migration, proliferation, and growth. Therefore, considering the importance of Eph-ephrin class of protein in tumorigenesis, 7,620 clinically reported missense mutations belonging to the class of variables of unknown significance were retrieved from cBioPortal and evaluated for pathogenicity. Thirty-two mutations predicted to be pathogenic using SIFT, Polyphen-2, PROVEAN, SNPs&GO, PMut, iSTABLE, and PremPS in-silico tools were found located either in critical functional regions or encompassing interactions at the binding interface of Eph-ephrin. However, seven were reported in nonsmall cell lung cancer (NSCLC). Considering the relevance of receptor tyrosine kinases and Eph in NSCLC, these seven mutations were assessed for change in the folding pattern using molecular dynamic simulation. Structural alterations, stability, flexibility, compactness, and solvent-exposed area was observed in EphA3 Trp790Cys, EphA7 Leu749Phe, EphB1 Gly685Cys, EphB4 Val748Ala, and Ephrin A2 Trp112Cys. Hence, it can be concluded that the evaluated mutations have potential to alter the folding pattern and thus can be further validated by in-vitro, structural and in-vivo studies for clinical management.

• Journal of Chest Surgery
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• v.51 no.1
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• pp.29-34
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• 2018

Background: We evaluated the feasibility and outcomes of pulmonary resection and mediastinal node dissection (MND) by video-assisted thoracoscopic surgery (VATS) following neoadjuvant therapy for stage IIIA N2 non-small cell lung cancer (NSCLC). Methods: From November 2009 to December 2013, a total of 35 consecutive patients with pathologically or radiologically confirmed stage IIIA N2 lung cancer underwent pulmonary resection and MND, performed by a single surgeon, following neoadjuvant chemoradiation. Preoperative patient characteristics, surgical outcomes, postoperative drainage, postoperative complications, and mortality were retrospectively analyzed. Results: VATS was completed in 17 patients. Thoracotomy was performed in 18 patients, with 13 planned thoracotomies and 5 conversions from the VATS approach. The median age was $62.7{\pm}7.9years$ in the VATS group and $60{\pm}8.7years$ in the thoracotomy group. The patients in the VATS group tended to have a lower diffusing capacity for carbon monoxide (p=0.077). There were no differences between the 2 groups in the method of diagnosing the N stage, tumor response and size after induction, tumor location, or histologic type. Complete resection was achieved in all patients. More total and mediastinal nodes were dissected in the VATS group than in the thoracotomy group (p<0.05). The median chest tube duration was 5.3 days (range, 1 to 33 days) for the VATS group and 7.2 days (range, 2 to 28 days) for the thoracotomy group. The median follow-up duration was 36.3 months. The 5-year survival rates were 76% in the VATS group and 57.8% in the thoracotomy group (p=0.39). The 5-year disease-free survival rates were 40.3% and 38.9% in the VATS and thoracotomy groups, respectively (p=0.8). Conclusion: The VATS approach following neoadjuvant treatment was safe and feasible in selected patients for the treatment of stage IIIA N2 NSCLC, with no compromise of oncologic efficacy.