• 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.

• Tuberculosis and Respiratory Diseases
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• v.57 no.4
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• pp.345-350
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• 2004

Background : To evaluate the frequency and clinical significance of lymph node micrometastasis in patients of non-small-cell lung cancer pathologically staged to be T1-2,N0. Method : From consecutive 29 patients of non-small-cell lung cancer who received curative operation and routine systemic nodal dissection, we immunohistochemically examined 806 lymph nodes from mediastinal, hilar and peribronchial lesion. All slides were stained with hematoxylin and eosin staining for one section and with cytokeratin AE1/AE3 antibody for another consecutive section of same lymph node to find out micrometastasis. Results : In 806 lymph nodes examined, no tumor cell was seen on hematoxylin and eosin staining and micrometastic foci were shown to be on 0.37%(3) of 806 lymph nodes, in which were upper paratracheal, interlobar and peribronchial lymph node. These three positive stains constitute 10.3%(3) of the 29 patients with non-small-cell lung cancer. Nine patients died from disease progression(4), postoperative complication(3) and concomitant diseases(2). The four patients with disease progression did not show evidence of micrometastasis on their lymph node examination. Conclusion : The frequency of lymph node micrometastasis was in 0.37% of 806 lymph nodes examined. The study results might suggested that routine analysis of micrometastasis on the lymph node didn't give any clinical implication on patients with non-small-cell lung cancer.

• 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.

• Journal of Korean Neurosurgical Society
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• v.64 no.2
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• pp.271-281
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• 2021

Objective : Immune checkpoint inhibitors (ICIs) are approved for treating non-small-cell lung cancer (NSCLC); however, the safety and efficacy of combined ICI and Gamma Knife radiosurgery (GKS) treatment remain undefined. In this study, we retrospectively analyzed patients treated with ICIs with or without GKS at our institute to manage patients with brain metastases from NSCLC. Methods : We retrospectively reviewed medical records of patients with brain metastases from NSCLC treated with ICIs between January 2015 and December 2017. Of 134 patients, 77 were assessable for brain responses and categorized into three groups as follows : group A, ICI alone (n=26); group B, ICI with concurrent GKS within 14 days (n=24); and group C, ICI with non-concurrent GKS (n=27). Results : The median follow-up duration after brain metastasis diagnosis was 19.1 months (range, 1-77). At the last follow-up, 53 patients (68.8%) died, 20 were alive, and four were lost to follow-up. The estimated median overall survival (OS) of all patients from the date of brain metastasis diagnosis was 20.0 months (95% confidence interval, 12.5-27.7) (10.0, 22.5, and 42.1 months in groups A, B, and C, respectively). The OS was shorter in group A than in group C (p=0.001). The intracranial disease progression-free survival (p=0.569), local progression-free survival (p=0.457), and complication rates did not significantly differ among the groups. Twelve patients showed leptomeningeal seeding (LMS) during follow-up. The 1-year LMS-free rate in treated with ICI alone group (69.1%) was significantly lower than that in treated with GKS before ICI treatment or within 14 days group (93.2%) (p=0.004). Conclusion : GKS with ICI showed no favorable OS outcome in treating brain metastasis from NSCLC. However, GKS with ICI did not increase the risk of complications. Furthermore, compared with ICI alone, GKS with ICI may be associated with a reduced incidence of LMS. Further understanding of the mechanism, which remains unknown, may help improve the quality of life of patients with brain metastasis.

• Radiation Oncology Journal
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• v.35 no.2
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• pp.153-162
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• 2017

Purpose: To evaluate intracranial control after surgical resection according to the adjuvant treatment received in order to assess the optimal radiotherapy (RT) dose and volume. Materials and Methods: Between 2003 and 2015, a total of 53 patients with brain oligometastases from non-small cell lung cancer (NSCLC) underwent metastasectomy. The patients were divided into three groups according to the adjuvant treatment received: whole brain radiotherapy (WBRT) ${\pm}$ boost (WBRT ${\pm}$ boost group, n = 26), local RT/Gamma Knife surgery (local RT group, n = 14), and the observation group (n = 13). The most commonly used dose schedule was WBRT (25 Gy in 10 fractions, equivalent dose in 2 Gy fractions [EQD2] 26.04 Gy) with tumor bed boost (15 Gy in 5 fractions, EQD2 16.25 Gy). Results: The WBRT ${\pm}$ boost group showed the lowest 1-year intracranial recurrence rate of 30.4%, followed by the local RT and observation groups, at 66.7%, and 76.9%, respectively (p = 0.006). In the WBRT ${\pm}$ boost group, there was no significant increase in the 1-year new site recurrence rate of patients receiving a lower dose of WBRT (EQD2) <27 Gy compared to that in patients receiving a higher WBRT dose (p = 0.553). The 1-year initial tumor site recurrence rate was lower in patients receiving tumor bed dose (EQD2) of ${\geq}42.3Gy$ compared to those receiving <42.3 Gy, although the difference was not significant (p = 0.347). Conclusions: Adding WBRT after resection of brain oligometastases from NSCLC seems to enhance intracranial control. Furthermore, combining lower-dose WBRT with a tumor bed boost may be an attractive option.

• Tuberculosis and Respiratory Diseases
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• v.85 no.2
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• pp.155-164
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• 2022

Background: The remarkable efficacy of osimertinib in non-small cell lung cancer (NSCLC) with acquired T790M mutation has been widely documented in clinical trials and real-world practice. However, some patients show primary resistance to this drug. Even patients who initially show a favorable response have inconsistent clinical outcomes later. Therefore, the aim of this study was to identify additional clinical predictive factors for osimertinib efficacy. Methods: A prospective cohort of patients with acquired T790M positive stage IV lung adenocarcinoma treated with osimertinib salvage therapy in Hallym University Medical Center were analyzed. Results: Sixty-one eligible patients were analyzed, including 38 (62%) women and 39 (64%) who never smoked. Their mean age was 63.3 years. The median follow-up after treatment with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) was 36.0 months (interquartile range, 24.7-50.2 months). The majority (n=45, 74%) of patients were deceased. Based on univariate analysis, low baseline neutrophil-to-lymphocyte ratios (NLR), age ≥50 years, never-smoking history, stage IVA at osimertinib initiation, and prolonged response to previous TKIs (≥10 months) were associated with a significantly longer progression-free survival (PFS). Multivariate analysis showed that never-smoking status (hazard ratio [HR], 0.54; 95% confidence interval [CI], 0.30-0.98; p=0.041) and a baseline NLR less than or equal to 3.5 (HR, 0.23; 95% CI, 0.12-0.45; p<0.001) were independently associated with a prolonged PFS with osimertinib. Conclusion: Smoking history and high NLR were independent negative predictors of osimertinib PFS in patients with advanced NSCLC developing EGFR T790M resistance after the initial EGFR-TKI treatment.

• Journal of Chest Surgery
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• v.46 no.3
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• pp.192-196
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• 2013

Background: This study focused on the association between preoperative serum carcinoembryonic antigen (CEA) and cytokeratin 19 fragment (Cyfra 21-1) levels and pathologic parameters in patients with resected non-small-cell lung cancer (NSCLC). Materials and Methods: The records of 527 patients who underwent pulmonary resection of NSCLC were reviewed. The association between preoperative serum CEA and Cyfra 21-1 levels and variables that had p-values of less than 0.05 in a t-test or one-way analyses of variance was analyzed by multiple linear regression. Results: The mean serum CEA and Cyfra 21-1 levels prior to surgery were $6.8{\pm}23.1$ mg/dL (range, 0.01 to 390.8 mg/dL) and $5.4{\pm}12.3$ mg/dL (range, 0.65 to 140.2 mg/dL). The serum CEA levels were associated with tumor (T) and lymph node (N) stage and histology. The serum Cyfra 21-1 levels were associated with T stage, tumor size, and histology. Multiple linear regression indicated that serum CEA levels were associated with T (T3/4 vs. T1: ${\beta}$=8.463, p=0.010) and N stage (N2/3 vs. N0: ${\beta}$=9.208, p<0.001) and histology (adenocarcinoma vs. squamous cell: ${\beta}$=6.838, p=0.001), and serum Cyfra 21-1 levels were associated with tumor size (${\beta}$=2.579, p<0.001) and histology (squamous cell vs. adenocarcinoma: ${\beta}$=4.420, p=0.020). Conclusion: Serum CEA level was correlated with T and N stage, and Cyfra 21-1 with tumor size. CEA and Cyfra 21-1 showed histologic correlation. CEA is mainly elevated in adenocarcinoma and Cyfra 21-1 in squamous cell carcinoma. These results might be helpful for predicting pathologic status in preoperative NSCLC.

• Journal of Chest Surgery
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• v.51 no.5
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• pp.312-321
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• 2018

Background: Treatment strategies for octogenarians with lung cancer remain controversial. The purpose of this study was to compare surgical outcomes and survival between octogenarians and younger patients with stage IA and IB lung cancer. Methods: We reviewed the medical records of 34 consecutive octogenarians and 457 younger patients (<70 years) with stage I lung cancer who underwent surgical resection from January 2007 to December 2015. We analyzed the survival and surgical outcomes of the 2 groups according to the lung cancer stage (IA and IB). Results: The only significant differences in the clinicopathological features between the groups were the higher proportion of sublobar resection (56.3% vs. 18.9%) and the smaller number of dissected lymph nodes (LNs) in octogenarians. There was no significant difference in hospital stay (11 days vs. 9 days), pneumonia (5.8% vs 1.9%), or operative mortality (0% vs 0.6%) between the 2 groups. Among patients with stage IA lung cancer, 5-year recurrence-free survival was not significantly different between the octogenarians (n=16) and younger patients (n=318) (86.2% vs. 89.1%, p=0.548). However, 5-year overall survival was significantly lower in octogenarians than in younger patients (79.4% vs. 93.4%, p=0.009). Among patients with stage IB lung cancer, there was no significant difference in 5-year recurrence-free survival (62.1% vs. 73.5%, p=0.55) or overall survival (77.0% vs 85.0%, p=0.75) between octogenarians (n=18) and younger patients (n=139). In multivariable analysis, male sex, the number of dissected LNs, and tumor size were factors related to survival (hazard ratio [HR], 5.795; p=0.017; HR, 0.346, p=0.025; and HR, 1.699; p=0.035, respectively). Conclusion: Surgical outcomes and survival after pulmonary resection for stage I lung cancer were comparable in octogenarians and younger patients. Continued careful selection of octogenarians for pulmonary resection is important to achieve good results.

• Journal of Chest Surgery
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• v.53 no.3
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• pp.114-120
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• 2020

Background: Evidence is lacking on whether the resection of lung parenchymal cancer improves the survival of patients with unexpected pleural metastasis encountered during surgery. We conducted a single-center retrospective study to determine the role of lung resection in the long-term survival of these patients. Methods: Among 4683 patients who underwent lung surgery between 1995 and 2014, 132 (2.8%) had pleural metastasis. After excluding 2 patients who had incomplete medical records, 130 patients' data were collected. Only a diagnostic pleural and/or lung biopsy was performed in 90 patients, while the lung parenchymal mass was resected in 40 patients. Results: The mean follow-up duration was 29.8 months. The 5-year survival rate of the resection group (34.7%±9.4%) was superior to that of the biopsy group (15.9%±4.3%, p=0.016). Multivariate Cox regression analysis demonstrated that primary tumor resection (p=0.041), systemic treatment (p<0.001), lower clinical N stage (p=0.018), and adenocarcinoma histology (p=0.009) were significant predictors of a favorable outcome. Interestingly, primary tumor resection only played a significant prognostic role in patients who received systemic treatment. Conclusion: When pleural metastasis is unexpectedly encountered during surgical exploration, resection in conjunction with systemic treatment may improve long-term survival, especially in adenocarcinoma patients without lymph node metastasis.

• Journal of Chest Surgery
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• v.31 no.2
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• pp.134-141
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• 1998

Primary lung cancer has recently increased progressively in its incidence in Korea. It is clearly evident that surgical resection offers the best offortunity for cure of non-small cell carcinoma. This study was designed to analyse the clinical data of 100 primary non-small cell carcinoma patients who underwent lung resection surgery from January 1992 to July 1995 at the department of Thoracic and Cardiovascular Sugery, Kyungpook National University Hospital. There were 86 males and 14 females(6:1). In the age distribution, the peak incidence was recorded in the seventh decade(43%). The methods of tissue diagnosis were bronchoscopic biopsy in 53 patients(50.5%), percutaneous needle aspiration in 17 patients(16.2%), transbronchial lung biopsy in 11 patients(10.5%), mediastinoscopic biopsy in 2 patients (1.9%), sputum cytology in 2 patients(1.9%), and thoracotomy in 20 patients(19.0%). Fifty-five lobectomies, 22 pneumonectomies, 15 bilobectomies, 2 segmentectomies, 4 sleeve lobectomies, a sleeve pneumonectomy, and a wedge pneumonectomy were performed. Operative mortality occured in 4 cases(sepsis in 2 cases, respiratory failure in 1 case, and acute myocardiac infarction in 1 case). The histologic types of tumor were 67 squamous cell carcinomas, 26 adenocarcinomas, 6 large cell carcinomas, and an adenosquamous cell carcinoma. Eighteen patients with N2 mediastinal lymph node metastases had 8 squamous cell carcinomas(11.9%), 9 adenocarcinomas(34.6%), and a large cell carcinoma(16.7%). The primary tumors in these patients were in the right upper lobe in 4 patients, the right middle and lower lobe in 9 patients, the left upper lobe in 3 patients, and the left lower lobe in 2 patients. With regard to pathologic stages, 45 patients had stage I disease; 13 patients, stage II; 36 patients, stage IIIa; 5 patients, stage IIIb; and 1 patient, stage IV. The overall actuarial survival rate was 77.5% at 12 months, 56.1% at 24 months and 43.7% at 43 months. The actuarial survival rates at 43 months were 81.3% in Stage I, 20.8% in Stage II, 27.9% in Stage IIIa, 25.0% in Stage IIIb and 33.3% in Stage IV. These facts suggest that early detection and surgical resection are recommended for favorable postoperative survival in non-small cell lung cancer.