• Tuberculosis and Respiratory Diseases
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• v.71 no.6
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• pp.425-430
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• 2011

Background: High 2-[$^{18}F$] fluoro-2-deoxy-D-glucose (FDG) uptake on positron emission tomography-computed tomography (PET-CT) is a prognostic factor for poor survival in non-small cell lung cancer (NSCLC), especially in Stage I. We determined whether the high FDG uptake value of a primary tumor was associated with recurrence and death in patients with resected Stage I and Stage II NSCLC. Methods: We identified consecutive patients who underwent complete surgical resection for Stage I and II NSCLC between 2006 and 2009, who had preoperative PET-CT, and reviewed clinical records retrospectively. FDG uptake was measured as the maximal standardized uptake value (SUVmax) for body weight. Patients were divided into two groups based on SUVmax: (i) above or (ii) below the cut-off value (SUVmax=5.9) determined by a receiver operating characteristic (ROC) curve. Results: Of 57 patients who were enrolled consecutively, 32 (56%) had Stage I NSCLC and 25 (44%) had Stage II. The 5-year recurrence-free survival (RFS) for patients with high (${\geq}5.9$) and low (<5.9) SUVmax were 31% and 57%, respectively (p=0.014). The 5-year overall survival (OS) rates were 39% and 60%, respectively (p=0.029). In univariate analyses, SUVmax (p=0.014), T staging (p=0.025), and differentiation of tumor tissue (p=0.034) were significantly associated with RFS. But, multivariate analyses did not show that SUVmax was an independently significant factor for RFS (p=0.180). Conclusion: High FDG uptake on PET-CT is not an independent prognostic factor for poor outcomes (disease recurrence in patients with resected Stage I and II NSCLC).

• Tuberculosis and Respiratory Diseases
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• v.80 no.2
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• pp.187-193
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• 2017

Background: Third-generation tyrosine kinase inhibitors of the epidermal growth factor receptor (EGFR-TKIs) have proved efficacious in treating non-small cell lung cancer (NSCLC) patients with acquired resistance resulting from the T790M mutation. However, since almost 50% patients with the acquired resistance do not harbor the T790M mutation, retreatment with first- or second-generation EGFR-TKIs may be a more viable therapeutic option. Here, we identified positive response predictors to retreatment, in patients who switched to a different EGFR-TKI, following initial treatment failure. Methods: This study retrospectively reviewed the medical records of 42 NSCLC patients with EGFR mutations, whose cancers had progressed following initial treatment with gefitinib or erlotinib, and who had switched to a different first-generation EGFR-TKI during subsequent retreatment. To identify high response rate predictors in the changed EGFR-TKI retreatment, we analyzed the relationship between clinical and demographic parameters, and positive clinical outcomes, following retreatment with EGFR-TKI. Results: Overall, 30 (71.4%) patients received gefitinib and 12 (28.6%) patients received erlotinib as their first EGFR-TKI treatment. Following retreatment with a different EGFR-TKI, the overall response and disease control rates were 21.4% and 64.3%, respectively. There was no significant association between their overall responses. The median progression-free survival (PFS) after retreatment was 2.0 months. However, PFS was significantly longer in patients whose time to progression was ${\geq}10months$ following initial EGFR-TKI treatment, who had a mutation of exon 19, or whose treatment interval was <90 days. Conclusion: In patients with acquired resistance to initial EGFR-TKI therapy, switched EGFR-TKI retreatment may be a salvage therapy for individuals possessing positive retreatment response predictors.

• 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.76 no.5
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• pp.218-225
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• 2014

Background: Small cell lung cancer (SCLC) is an extremely aggressive tumor with a poor clinical course. Although many efforts have been made to improve patients' survival rates, patients who survive longer than 2 years after chemotherapy are still very rare. We examined the baseline characteristics of patients with long-term survival rates in order to identify the prognostic factors for overall survivals. Methods: A total of 242 patients with cytologically or histologically diagnosed SCLC were enrolled into this study. The patients were categorized into long- and short-term survival groups by using a survival cut-off of 2 years after diagnosis. Cox's analyses were performed to identify the independent factors. Results: The mean patient age was 65.66 years, and 85.5% were males; among the patients, 61 of them (25.2%) survived longer than 2 years. In the multivariate analyses, CRP (hazard ratio [HR], 2.75; 95% confidence interval [CI], 1.25-6.06; p=0.012), TNM staging (HR, 3.29; 95% CI, 1.59-6.80; p=0.001), and progression-free survival (PFS) (HR, 11.14; 95% CI, 2.98-41.73; p<0.001) were independent prognostic markers for poor survival rates. Conclusion: In addition to other well-known prognostic factors, this study discovered relationships between the long-term survival rates and serum CRP levels, TNM staging, and PFS. In situations with unfavorable conditions, the PFS would be particularly helpful for managing SCLC patients.

• Tuberculosis and Respiratory Diseases
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• v.69 no.4
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• pp.271-278
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• 2010

Background: Recent studies have demonstrated that the epidermal growth factor receptor (EGFR) genotype is the most important predictive marker to EGFR-tyrosine kinase inhibitors (TKIs) and first-line gefitinib treatment will be approved in the near future for use in non-small cell lung cancer (NSCLC) patients with the EGFR mutation. Direct sequencing is known to be the standard for detecting EGFR mutations; however, it has limited sensitivity. Peptide nucleic acids (PNA)-mediated PCR clamping method is a newly introduced method for analyzing EGFR mutations with increased sensitivity and stability. Methods: A total of 71 NSCLC patients were analyzed for EGFR mutations using the PNA-mediated PCR clamping technique. Sixty-nine patients were analyzed for clinicopathologic correlation with EGFR genotype; 2 patients with indeterminate results were excluded. In order to determine EGFR-TKI drug response, 57 patients (42 gefitinib, 15 erlotinib) were included in the analysis. Results: The EGFR mutation rate was 47.8%. Being female, a non-smoker, and having adenocarcinoma were favorable clinicopathologic factors, as expected. However, more than a few smokers (33.3%), male (28.1%), and patients with non-adenocarcinoma (28.6%) had the EGFR mutation. Having a combination of favorable clinicopathologic factors did not increase the EGFR mutation rate significantly. Drug response to EGFR-TKIs showed significant differences depending on the EGFR genotype; ORR was 14.3% for wild type vs 69.0% for mutant type; DCR is 28.6% for wild type vs 96.6% for mutant type. The median EGFR-TKI treatment duration is 7.6 months for mutant type group and 1.4 months for wild type group. Conclusion: EGFR genotype determined using the PNA-mediated PCR clamping method is significantly correlated with the clinical EGFR-TKI responses and PNA-mediated PCR.

• Journal of Chest Surgery
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• v.46 no.1
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• pp.49-55
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• 2013

Background: The aim of this study was to determine the survival rate of patients with non-small cell lung cancer (NSCLC) who were preoperatively diagnosed with a negative N2 lymph node, but postoperatively confirmed as a positive N2 node based on a pathological evaluation. Materials and Methods: The hospital records of 248 patients from 1994 to 2009 with resected primary NSCLC who were preoperatively diagnosed with negative N2 lymph node, were retrospectively reviewed. Of these, after surgery, there were 148 (59.7%) patients with pathological N0, 54 (21.8%) with pathological N1 and 46 (18.5%) with pathological N2. Results: The median follow-up period was 24 months (range, 1 to 132 months). The 5-year disease free survival rates were 60% in pN0, 44% in pN1, and 29% in pN2. The 5-year overall survival rates were 63.1% in pN0, 51.9% in pN1, and 33.5% in pN2. There were no statistically significant differences between pN1 and pN2 (p=0.326 and p=0.106, respectively). Thirty-three (71.7%) of the 46 pN2 patients had single-zone metastasis, and 13 patients (28.3%) had multiple-zone metastases over the two nodal zone metastasis. There were no statistical differences in the 5-year disease free survival rate and the 5-year overall survival rates between the two groups. Conclusion: The 5-year disease free survival and the overall survival rate of the patients with unsuspected N2 disease were statistically similar with that of the patients with pathological N1 disease. There was no statistically significant difference between the patients with a single-zone metastasis and a multiple zone metastasis.

• 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.

• Radiation Oncology Journal
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• v.31 no.4
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• pp.185-190
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• 2013

Purpose: We evaluated the effect of early chemoradiotherapy on the treatment of patients with limited stage small cell lung cancer (LS-SCLC). Materials and Methods: Between January 2006 and December 2011, thirty-one patients with histologically proven LS-SCLC who were treated with two cycles of chemotherapy followed by concurrent chemoradiotherapy and consolidation chemotherapy were retrospectively analyzed. The chemotherapy regimen was composed of etoposide and cisplatin. Thoracic radiotherapy consisted of 50 to 60 Gy (median, 54 Gy) given in 5 to 6.5 weeks. Results: The follow-up period ranged from 5 to 53 months (median, 22 months). After chemoradiotherapy, 35.5% of the patients (11 patients) showed complete response, 61.3% (19 patients) showed partial response, 3.2% (one patient) showed progressive disease, resulting in an overall response rate of 96.8% (30 patients). The 1-, 2-, and 3-year overall survival (OS) rates were 66.5%, 41.0%, and 28.1%, respectively, with a median OS of 21.3 months. The 1-, 2-, and 3-year progression free survival (PFS) rates were 49.8%, 22.8%, and 13.7%, respectively, with median PFS of 12 months. The patterns of failure were: locoregional recurrences in 29.0% (nine patients), distant metastasis in 9.7% (three patients), and both locoregional and distant metastasis in 9.7% (three patients). Grade 3 or 4 toxicities of leukopenia, anemia, and thrombocytopenia were observed in 32.2%, 29.0%, and 25.8%, respectively. Grade 3 radiation esophagitis and radiation pneumonitis were shown in 12.9% and 6.4%, respectively. Conclusion: We conclude that early chemoradiotherapy for LS-SCLC provides feasible and acceptable local control and safety.

• Tuberculosis and Respiratory Diseases
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• v.75 no.2
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• pp.52-58
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• 2013

Background: More than half of cases for advanced non-small-cell lung cancer (NSCLC) occur in elderly patients with a median age at diagnosis of 70 years. The aim of our study was to examine the clinical features and prognostic factors contributing to mortality in elderly patients with advanced NSCLC. Methods: Following a retrospective review of clinical data, 122 patients aged 70 years and over with a histopathological diagnosis of locally advanced (stage IIIB, n=32) and metastatic (stage IV, n=90) NSCLC between 2005 and 2011 were enrolled. Results: The median age was 76 years (interquartile range, [IQR], 72-80 years), and 85 (70%) patients were male. Fifty-seven (46%) patients had never smoked, and 17 (19%) were in a malnourished state with a body mass index (BMI) of <$18.5kg/m^2$. The initial treatments included chemotherapy (40%) and radiotherapy (7%), but 57% of the patients received supportive care only. The 1-year survival rate was 32%, and the 3-year survival rate was 4%, with a median survival duration of 6.2 months (IQR, 2.5-15.3 months). Male gender (hazard ratio [HR], 2.2; 95% confidence interval [CI], 1.3-3.9; p=0.005), low BMI (HR, 2.3; 95% CI, 1.3-3.9; p=0.004), and supportive care only (HR, 1.9; 95% CI, 1.2-2.9; p=0.007) were independent predictors of shorter survival based on a Cox proportional hazards model. Conclusion: Elderly patients with advanced NSCLC had a poor prognosis, particularly male patients, those with a low BMI, and those who received supportive care only.

• Tuberculosis and Respiratory Diseases
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• v.73 no.6
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• pp.303-311
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• 2012

Background: This study was designed to analyze the efficacy of gefitinib as a second-line therapy, according to the clinical characteristics in Korean patients with non-small-cell lung cancer (NSCLC). Methods: In this Phase IV observational study, we recruited patients, previously failed first-line chemotherapy, who had locally advanced or metastatic NSCLC, and who were found to be either epidermal growth factor receptor (EGFR) mutation-positive or satisfied 2 or more of the 3 characteristics: adenocarcinoma, female, and non-smoker. These patients were administered with gefitinib 250 mg/day, orally. The primary endpoints were to evaluate the objective response rate (ORR) and to determine the relationship of ORRs, depending on each patient's characteristics of modified intent-to-treat population. Results: A total of 138 patients participated in this study. One subject achieved complete response, and 42 subjects achieved partial response (ORR, 31.2%). The subgroup analysis demonstrated that the ORR was significantly higher in patients with EGFR mutation-positive, compared to that of EGFR mutation-negative (45.8% vs. 14.0%, p=0.0004). In a secondary efficacy variable, the median progression-free survival (PFS) was 5.7 months (95% confidence interval, 3.9~8.4 months) and the 6-month PFS and overall survival were 49.6% and 87.9%, respectively. The most common reported adverse events were rash (34.4%), diarrhea (26.6%), pruritus (17.5%), and cough (15.6%). Conclusion: Gefitinib was observed in anti-tumor activity with favorable tolerability profile as a second-line therapy in these selected patients. When looking at EGFR mutation status, EGFR mutation-positive showed strong association with gefitinib by greater response and prolonged PFS, compared with that of EGFR mutation-negative.