• Tuberculosis and Respiratory Diseases
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• 제83권1호
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• pp.51-60
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• 2020

Background: Programmed death-ligand 1 (PD-L1) expression is tested by immunohistochemistry (IHC)-22C3, SP263, and SP142. The aim of this study is to evaluate the correlation among the three methods of PD-L1 IHC in non-small cell lung cancer (NSCLC) and clinical significance of PD-L1 expression in lung adenocarcinoma with an epidermal growth factor receptor (EGFR)-tyrosine kinase domain mutation. Methods: The results of 230 patients who were pathologically confirmed as having NSCLC; tested using PD-L1 IHC 22C3, SP263, and SP142 methods; and evaluated via the peptide nucleic acid clamping method to confirm EGFR mutation, were analyzed in this study. Results: 164 patients underwent both the SP263 and 22C3 tests. There was a significant positive correlation between the outcomes of the two tests (Spearman correlation coefficient=0.912, p<0.001), with a derived regression equation as follows: 22C3=15.2+0.884×SP263 (R²=0.792, p<0.001). There was no relationship between the expression of PD-L1 and clinical parameters, including EGFR-tyrosine kinase inhibitor (TKI) mutation. The PD-L1 expression in patients treated with EGFR-TKI yielded a 2-month-shorter progression period than that in the PD-L1-negative group. However, this did not reach statistical significance (PD-L1<1% vs. PD-L1≥1%, 10 months vs. 8 months). Conclusion: The results of the 22C3 and those of SP263 methods were in good correlation with one another. Since the PD-L1 expression is not influenced by the EGFR mutation, it is necessary to perform a PD-L1 test to set the treatment direction in the patients with EGFR-mutant NSCLC.

• Asian Pacific Journal of Cancer Prevention
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• 제15권5호
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• pp.2089-2094
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• 2014

Background: Although many prognostic factors have been identified for lung cancers, new ones are needed to determine the course of the disease. Recently, a high neutrophil to lymphocyte ratio (NLR) prior to surgery or treatment has been shown to be an indicator of prognosis for cancer. The aim of this study was to investigate the value of NLR as a prognostic factor and the correlation between NLR and other probable clinical prognostic factors in non small cell lung cancer patients prior to treatment. Materials and Methods: Data of patients who were diagnosed with non-small cell lung cancer in our institution were retrospectively reviewed. Demographic and clinicopathologic characteristics were recorded. NLR was calculated before the application of any treatment. Results: A total of 299 patients, 270 (90%) males and 29 (10%) females, were included in the study. Age (p<0.001) stage (p<0.001), Eastern Cooperative Oncology Group performance status (p<0.001), weight loss (p<0.001), anemia (p<0.001), histopatology (p<0.001), NLR ${\geq}3$ (p=0.048), NLR ${\geq}4$ (p=0.025) and NLR ${\geq}5$ (p=0.018) were found to be the prognostic factors. Age, anemia, Eastern Cooperative Oncology Group performance status, the stage, NLR (${\geq}5$) were an independent prognostic factors. There was a positive correlation between NLR and the Eastern Cooperative Oncology Group performance status (0.23, p=0.001), the C reactive protein levels (r=0.36, p<0.001). Conclusions: Prior to treatment high NLR was found as an independent poor prognosis factor. Besides, NLR correlated with Eastern Cooperative Oncology Group performance status and the C reactive protein levels.

• Radiation Oncology Journal
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• 제35권1호
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• pp.55-64
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• 2017

Purpose: The outcomes and toxicities of locoregionally recurrent non-small-cell lung cancer (NSCLC) patients treated with curative radiotherapy were evaluated in the modern era. Materials and Methods: Fifty-seven patients receiving radical radiotherapy for locoregionally recurrent NSCLC without distant metastasis after surgery from 2004 to 2014 were reviewed. Forty-two patients were treated with concurrent chemoradiotherapy (CCRT), and 15 patients with radiotherapy alone. The median radiation dose was 66 Gy (range, 45 to 70 Gy). Lung function change after radiotherapy was evaluated by comparing pulmonary function tests before and at 1, 6, and 12 months after radiotherapy. Results: Median follow-up was 53.6 months (range, 12.0 to 107.5 months) among the survivors. The median overall survival (OS) and progression-free survival (PFS) were 54.8 months (range, 3.0 to 116.9 months) and 12.2 months (range, 0.8 to 100.2 months), respectively. Multivariate analyses revealed that single locoregional recurrence focus and use of concurrent chemotherapy were significant prognostic factors for OS (p = 0.048 and p = 0.001, respectively) and PFS (p = 0.002 and p = 0.026, respectively). There was no significant change in predicted forced expiratory volume in one second after radiotherapy. Although diffusing lung capacity for carbon monoxide decreased significantly at 1 month after radiotherapy (p < 0.001), it recovered to pretreatment levels within 12 months. Acute grade 3 radiation pneumonitis and esophagitis were observed in 3 and 2 patients, respectively. There was no chronic complication observed in all patients. Conclusion: Salvage radiotherapy showed good survival outcomes without severe complications in postoperative locoregionally recurrent NSCLC patients. A single locoregional recurrent focus and the use of CCRT chemotherapy were associated with improved survival. CCRT should be considered as a salvage treatment in patients with good prognostic factors.

• Radiation Oncology Journal
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• 제37권3호
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• pp.149-155
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• 2019

In metastatic non-small cell lung cancer (NSCLC), the role of radiotherapy (RT) has been limited to palliation to alleviate the symptoms. However, with the development of advanced RT techniques, recent advances in immuno-oncology therapy targeting programmed death 1 (PD-1) and programmed death ligand 1 (PD-L1) and targeted agents for epidermal growth factor receptor (EGFR) mutation or anaplastic lymphoma kinase (ALK) translocation allowed new roles of RT in these patients. Within this metastatic population, there is a subset of patients with a limited number of sites of metastatic disease, termed as oligometastasis that can achieve long-term survival from aggressive local management. There is no consensus on the definition of oligometastasis; however, most clinical trials define oligometastasis as having 3 to 5 metastatic lesions. Recent phase II randomized clinical trials have shown that ablative RT, including stereotactic ablative body radiotherapy (SABR) and hypofractionated RT, to primary and metastatic sites improved progression-free survival (PFS) and overall survival (OS) in patients with oligometastatic NSCLC. The PEMBRO-RT study, a randomized phase II study comparing SABR prior to pembrolizumab therapy and pembrolizumab therapy alone, revealed that the addition of SABR improved the overall response, PFS, and OS in patients with advanced NSCLC. The efficacy of RT in oligometastatic lung cancer has only been studied in phase II studies; therefore, large-scale phase III studies are needed to confirm the benefit of local ablative RT in patients with oligometastatic NSCLC. Local intensified RT to primary and metastatic lesions is expected to become an important treatment paradigm in the near future in patients with metastatic lung cancer.

• Radiation Oncology Journal
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• 제31권1호
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• pp.34-40
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• 2013

Purpose: To evaluate the predictive factors of radiation pneumonitis (RP) and associated changes in pulmonary function after definitive concurrent chemoradiotherapy (CCRT) in patients with non-small cell lung cancer (NSCLC). Materials and Methods: Medical records of 60 patients with NSCLC who received definitive CCRT were retrospectively reviewed. Dose volumetric (DV) parameters, clinical factors, and pulmonary function test (PFT) data were analyzed. RP was graded according to the CTCAE ver. 4.0. Percentage of lung volume that received a dose of threshold (Vdose) and mean lung dose (MLD) were analyzed for potential DV predictors. PFT changes were calculated as the difference between pre-RT and post-RT values at 3, 6, and 12 months after RT. Results: Twenty-two patients (37%) developed grade ${\geq}2$ RP. Among clinical factors, tumor location in lower lobe was associated with RP. Among the DV parameters, only MLD >15 Gy was associated with grade ${\geq}2$ RP. There were statistically significant decreases in PFT at all points compared with pre-RT values in grade ${\geq}2$ RP group. MLD was associated with forced vital capacity (FVC) and forced expiratory volume in 1 second (FEV1) changes at 6 and 12 months. V10 was associated with FVC changes at 12 months. V20 and V30 were associated with FEV1 changes at 6 months and FVC changes at 12 months. Conclusion: After definitive CCRT in patients with NSCLC, MLD >15 Gy and lower lobe tumor location were predictors of grade ${\geq}2$ RP. Pulmonary functions were decreased after CCRT and the magnitude of changes was associated with DV parameters.

• Journal of Chest Surgery
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• 제52권3호
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• pp.131-140
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• 2019

Background: The purposes of this study were to evaluate the appropriateness of the stage migration of stage IIA non-small cell lung cancer (NSCLC) in the seventh edition of the tumor, node, and metastasis classification for lung cancer to stage IIB lung cancer in the eighth edition, and to identify prognostic factors in patients with eighth-edition stage IIB disease. Methods: Patients with eighth-edition stage IIB disease were subclassified into those with seventh-edition stage IIA disease and those with seventh-edition stage IIB disease, and their recurrence-free survival and disease-specific survival rates were compared. Risk factors for recurrence after curative resection were identified in all included patients. Results: Of 122 patients with eighth-edition stage IIB NSCLC, 101 (82.8%) had seventh-edition stage IIA disease and 21 (17.2%) had seventh-edition stage IIB disease. Nonsignificant differences were observed in the 5-year recurrence-free survival rate and the 5-year disease-specific survival rate between the patients with seventh-edition stage IIA disease and those with seventh-edition stage IIB disease. Visceral pleural invasion was a significant risk factor for recurrence in patients with eighth-edition stage IIB NSCLC. Conclusion: The stage migration from seventh-edition stage IIA NSCLC to eighth-edition stage IIB NSCLC was appropriate in terms of oncological outcomes. Visceral pleural invasion was the only prognostic factor in patients with eighth-edition stage IIB NSCLC.

• The Korean Journal of Medicine
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• 제99권2호
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• pp.96-103
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• 2024

Lung cancer is the leading cause of cancer death in Republic of Korea. After their initial diagnosis, only 10-20% of patients with advanced non-small cell lung cancer (NSCLC) survive for 5 years of longer. Given enormous advances in therapeutics such as novel targeted therapies and immunotherapies, survival rates are improving for advanced patients with NSCLC; 5-year survival rates range from 15% to 50%, contingent upon the biomarker. Detection of the specific molecular alteration as biomarker is thus crucial for identifying subgroups of NSCLC that contain therpapeutically targetable oncogenic drivers. This review examines the process of diagnosing lung adenocarcinoma with dominant biomarkers in order to customize treatment with appropriate targeted therapy.

• Asian Pacific Journal of Cancer Prevention
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• 제16권4호
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• pp.1507-1513
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• 2015

Pemetrexed is an antifolate agent which has been used for treating malignant pleural mesothelioma and non small lung cancer in the clinic as a chemotherapeutic agent. In this study, pemetrexed inhibited cell growth and induced G1 phase arrest in the A549 cell line. To explore the molecular mechanisms of pemetrexed involved in cell growth, we used a two-dimensional polyacrylamide gel electrophoresis (2-DE) proteomics approach to analyze proteins changed in A549 cells treated with pemetrexed. As a result, twenty differentially expressed proteins were identified by ESI-Q-TOF MS/MS analysis in A549 cells incubated with pemetrexed compared with non-treated A549 cells. Three key proteins (GAPDH, HSPB1 and EIF4E) changed in pemetrexed treated A549 cells were validated by Western blotting. Accumulation of GAPDH and decrease of HSPB1 and EIF4E which induce apoptosis through inhibiting phosphorylation of Akt were noted. Expression of p-Akt in A549 cells treated with pemetrexed was reduced. Thus, pemetrexed induced apoptosis in A549 cells through inhibiting the Akt pathway.

• Tuberculosis and Respiratory Diseases
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• 제71권4호
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• pp.259-265
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• 2011

Background: Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors, gefitinib and erlotinib, are effective therapies for non-small cell lung cancer (NSCLC) patients whose tumors harbor somatic mutations in EGFR. The mutations are, however, only found in about 30% of Asian NSCLC patients and all patients ultimately develop resistance to these agents. Ionizing radiation has been shown to induce autophosphorylation of EGFR and activate its downstream signaling pathways. In the present study, we have tested whether the effect of gefitinib treatment can be enhanced after ionizing radiation. Methods: We compared the PC-9 and A549 cell line with its radiation-resistant derivatives after gefitinib treatment with cell proliferation and apoptosis assay. We also analyzed the effect of gefitinib after ionizing radiation in PC-9, A549, and NCI-H460 cells. Cell proliferation was determined by MTT assay and induction of apoptosis was evaluated by flow cytometry. Caspase 3 activation and PARP cleavage were evaluated by western blot analysis. Results: PC-9 cells having mutated EGFR and their radiation-resistant cells showed no significant difference in cell viability. However, radiation-resistant A549 cells were more sensitive to gefitinib than were their parental cells. This was attributable to an increased induction of apoptosis. Gefitinib-induced apoptosis increased significantly after radiation in cells with wild type EGFR including A549 and NCI-H460, but not in PC-9 cells with mutated EGFR. Caspase 3 activation and PARP cleavage accompanied these findings. Conclusion: The data suggest that gefitinib-induced apoptosis could increase after radiation in cells with wild type EGFR, but not in cells with mutated EGFR.

• Asian Pacific Journal of Cancer Prevention
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• 제13권5호
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• pp.2355-2362
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• 2012

The SH2B1 adaptor protein is recruited to multiple ligand-activated receptor tyrosine kinases that play important role in the physiologic and pathologic features of many cancers. The purpose of this study was to assess SH2B1 expression and to explore its contribution to the non-small cell lung cancer (NSCLC). Methods: SH2B1 expression in 114 primary NSCLC tissue specimens was analyzed by immunohistochemistry and correlated with clinicopathological parameters and patients' outcome. Additionally, 15 paired NSCLC background tissues, 5 NSCLC cell lines and a normal HBE cell line were evaluated for SH2B1 expression by RT-PCR and immunoblotting, immunofluorescence being applied for the cell lines. Results: SH2B1 was found to be overexpressed in NSCLC tissues and NSCLC cell lines. More importantly, high SH2B1 expression was significantly associated with tumor grade, tumor size, clinical stage, lymph node metastasis, and recurrence respectively. Survival analysis demonstrated that patients with high SH2B1 expression had both poorer disease-free survival and overall survival than other patients. Multivariate Cox regression analysis revealed that SH2B1 overexpression was an independent prognostic factor for patients with NSCLC. Conclusions: Our findings suggest that the SH2B1 protein may contribute to the malignant progression of NSCLC and could offer a novel prognostic indicator for patients with NSCLC.