• Radiation Oncology Journal
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• v.26 no.3
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• pp.160-165
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• 2008

Purpose: In cases of locally advanced non-small cell lung cancer (NSCLC), concurrent chemoradiotherapy(CCRT) is the leading therapeutic modality. However, much controversy exists about the chemotherapeutic regimens and radiation methods. Materials and Methods: During concurrent chemoradiotherapy, three or four cycles of gemcitabine ($500\;mg/m^2$) and cisplatin ($30\;mg/m^2$) were administered every two weeks while 50.4 Gy of irradiation was administered in 28 fractions (once/day, 5 treatment days/week) to the tumor site, mediastinum, and the involved lymph node region. In addition, a booster irradiation dose of 18 Gy in 10 fractions was administered to the primary tumor site unless the disease progressed. Two or three cycles of consolidation chemotherapy were performed with gemcitabine ($1,200\;mg/m^2$, $1^{st}$ and 8th day) and cisplatin ($60\;mg/m^2$) every three weeks. Results: A total of 29 patients were evaluable for modality response. Response and treatment toxicities were assessed after concurrent chemoradiotherapy and consolidation chemotherapy, respectively. One patient (4%) achieved a complete response; whereas 20 patients (69%) achieved a partial response after concurrent chemoradiotherapy. Following the consolidation chemotherapy, three patients (10.3%) achieved complete responses and 21 patients (72.4%) achieved partial responses. The median follow-up period was 20 months (range $3{\sim}39$ months) and the median survival time was 16 months (95% CI; $2.4{\sim}39.2$ months). The survival rates in one, two, and three years after the completion of treatment were 62.7%, 43.9%, and 20%, respectively. Complications associated to this treatment modality included grade 3 or 4 esophagitis, which occurred in 15 patients (51.7%). In addition, an incidence of 24% for grade 3 and 14% for grade 4 neutropenia. Lastly, grade 2 radiation pneumonitis occurred in 6 patients (22%). Conclusion: The response rate and survival time of concurrent chemoradiotherapy with biweekly gemcitabine ($500\;mg/m^2$) and cisplatin ($30\;mg/m^2$) were encouraging in patients with locally advanced NSCLC. However, treatment related toxicities were significant, indicating that further modification of therapy seems to be warranted.

• Tuberculosis and Respiratory Diseases
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• v.45 no.5
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• pp.953-961
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• 1998

Background : In recent years, lung cancer has been one of most common cause of death in Korea. Despite many physician's high degree of pessimism about the gains made in treatment, progressive improvement in the survival of lung cancer by treatment has occurred, particulary in the early stages of the disease. However, a lot of patients refuse treatment or give up in the fight against the disease. This study was done to evaluate factors influencing the compliance to therapy and to lead in the establishment of special programs to enhance compliance in patients with lung cancer. Methods: The medical records of 903 patients, whose ECOG(Eastern Cooperative Oncology Group) performance status was 3 or less and whose medical record was relatively satisfactory, among 1141 patients diagnosed with lung cancer between January 1989 and December 1996 were reviewed retrospectively. Compliance was classified into three groups based on the degree of compliance with physicians practice guideline: (a) compliants; (b) patients who initially complied but gave up of themselves midway during the course of treatment; (c) noncompliants who refused the treatment. Results: The overall compliance rate was 63.9%, which was progressively increased from 57.3-61.3% in 1989 and 1990 to 64.2-67.5% in 1995 and 1996. Age, education level and occupation of patients bore statistically significant relationship with the compliance but sex, marital status and smoking history did not. The compliance was significantly higher in patients without symptoms than with, and was also significantly higher in patients with good performance status. The compliance was significantly high in patients with NSCLC(non-small cell lung cancer) compared to SCLC(small cell lung cancer), but after exclusion of stage I and II, among NSCLC, which had higher compliance to surgery there was no significant difference of compliance by histology. The compliance was significantly lower in advanced stage. Conclusion: To enhance the compliance, special care including education programs about therapy including complication and prognosis are necessary, especially for educationally and economically disadvantaged patients.

• Radiation Oncology Journal
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• v.11 no.2
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• pp.311-319
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• 1993

The retrospective analysis was performed on 37 patients with stage III non small cell lung cancer who received the radiotherapy from Feb. 1986 to Dec. 1990 at the Dept. of Radiation Oncology, National Medical Center. This analysis, with 29 patients $(78.4\%)$ having been followed from 10 to 60 months, was done to know the survival rate and significant prognostic factor. The actuarial 2,5-year survival rates were $20.6\%,6.9\%$ in our all patients and median survival time was 10 months. Of patients with KPS (Karnofsky prformance status) greater than $80\%,$ the 2, 5 year survival rate and median survival time were $29.2\%,9.7\%$ and 13 months, respectively. The 2-year survival rate and median survival time of patients with KPS less than $80\%\;were\;13.7\%$ and 7 months, respectively. The survival difference according to performance status was statisticaly significant $(29.2\%\;vs.\;13.7\%)(p<0.05).$ In stage IIIa, the 2,5-year survival rate and median survival rate and median survival time were $29.2\%,9.7\%$ and 12 months, respectively. The 2-year survival rate and metian survival time of stage IIIb were $8.6\%$ and 10 months, respectively. The survival difference between stage IIIa and IIIb did not show statistical significance (p>0.1). Of the prognostic factors, the difference of survival rate by initial performance status was statistically significant (p<0.05). But the difference of survival rates by pathologic cell type, stage, total radiation dose, radiotherapy response, and cmbination with chemotherapy were not statistically significant.

• Tuberculosis and Respiratory Diseases
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• v.66 no.4
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• pp.280-287
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• 2009

Background: The epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs), became an attractive therapeutic option for advanced non-small-cell lung cancer (NSCLC). Several studies suggested that there might be some different efficacy or response predictors between gefitinib and erlotinib. We compared the efficacy and toxicity of gefitinib and erlotinib in Korean patients with advanced NSCLC and evaluated specific predictors of response for both gefitinib and erlotinib. Methods: We collected the clinical information on patients with advanced NSCLC, who were treated with gefitinib or erlotinib at the Ewha Womans University Hospital, between July 2003 and February 2009. Median survival times were calculated using the Kaplan-Meier method. Results: Eighty-six patients (52 gefitinib vs. 34 erlotinib) were enrolled. Patient median age was 64 years; 53 (62%) subjects were male. Out of the 86 patients treated, 83 received response evaluation. Of the 83 patients, 35 achieved a response and 12 experienced stable disease while 36 experienced progressive disease, resulting in a response rate of 42% and a disease control rate of 57%. After a median follow-up of 502 days, the median progression-free and overall survival time was 129 and 259 days, respectively. Comparing patients by treatment (gefitinib vs erlotinib), there were no significant differences in the overall response rate (44% vs. 39%, p=0.678), median survival time (301 days vs. 202 days, p=0.151), or time to progression (136 days vs. 92 days, p=0.672). Both EGFR-TKIs showed similar toxicity. In a multivariate analysis using Cox regression model, adenocarcinoma was an independent predictor of survival (p=0.006; hazard ratio [HR], 0.487; 95% confidence interval [CI], 0.292-0.811). Analyses of subgroups did not show any difference in response predictors between gefitinib and erlotinib. Conclusion: Comparing gefitinib to erlotinib, there were no differences in the response rate, overall survival, progression-free survival, or toxicity. No specific predictor of response to each EGFR-TKI was identified.

• Tuberculosis and Respiratory Diseases
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• v.42 no.4
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• pp.502-512
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• 1995

Background: One quarter to one third of patients with NSCLC present with primary tumors that although confined to the thorax are too extensive for surgical resection. Until resently standard treatment for these patients had been thoracic radiation, which produces tumor regression in most patients but few cures and dismal 5-year survival rate. The fact that death for most patients with stage III tumors is caused by distant metastases has promped a reevaluation of combined modality treatment approaches that include systemic chemotherapy. Therefore, we report the results observed in a study to evaluate the effect of multimodality treatment in locally advanced non-small cell lung cancer from 1/91 to 8/93 in CNUH. Method: We grouped the patients according to the treatment modalities and evaluated response rate, median survival and the effect of prognostic variables. Among 67 patients evaluated, twenty seven patients classified with group A, received cisplatin and etoposide containing combination chemotherapy alone, eighteen patients, classified with group B, received chemotherapy and radiotherapy, fifteen patients, group C, received neoadjuvant or adjuvant chemotherapy and surgery with/without radiation therapy, seven patients, group D, received only supportive care. Result: The major response rate for group A and B was 37% and 61% respectively. There was no statistically significant difference in response rate between A and B groups(p=0.97). The analysis of prognostic factors showed that differences of age, sex, pathology, blood type, smoking year, stage and ECOG performance did not related to improvement in survival. Median survival time was 8.6 months for group A, 13.4 months for group B, 19.2 months for group C, and 5.4 months for group D, respectively and there was statistically significant difference(p=0.003), suggesting that multimodality therapy was associated with signigicant improvement in survival. Subset survival analysis showed a significant therapeutic effect for earlier stage and good performance state(p=0.007, 0.009, respectively). A possible survival advantages were observed for major response groups. Conclusion: It was suggested that multimodality therapy for the management of patients who had stage III disease, has yielded good median survival and long survival for seleted patients. But, it is necessory to validate above result with further investigation in large scale and in prospective randomized trials.

• 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.56 no.5
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• pp.465-484
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• 2004

Background : Insulin-like growth factor (IGF)-binding protein-3 (IGFBP-3) inhibits the proliferation of non-small cell lung cancer (NSCLC) cells by inducing apoptosis. Methods : In this study, we investigated whether hypermethylation of IGFBP-3 promoter play an important role in the loss of IGFBP-3 expression in NSCLC. We also studied the mechanisms that mediate the silencing of IGFBP-3 expression in the cell lines which have hypermethylated IGFBP-3 promoter. Results : The IGFBP-3 promoter has hypermethylation in 7 of 15 (46.7%) NSCLC cell lines and 16 (69.7%) of 23, 7 (77.8%) of 9, 4 (80%) of 5, 4 (66.7 %) of 6, and 6 (100%) of 6 tumor specimens from patients with stage I, II, IIIA, IIIB, and IV NSCLC, respectively. The methylation status correlated with the level of protein and mRNA in NSCLC cell lines. Expression of IGFBP-3 was restored by the demethylating agent 5'-aza-2'-deoxycytidine (5'-aza-dC) in a subset of NSCLC cell lines. The Sp-1/ Sp-3 binding element in the IGFBP-3 promoter, important for promoter activity, was methylated in the NSCLC cell lines which have reduced IGFBP-3 expression and the methylation of this element suppressed the binding of the Sp-1 transcription factor. A ChIP assay showed that the methylation status of the IGFBP-3 promoter influenced the binding of Sp-1, methyl-CpG binding protein-2 (MeCP2), and histone deacetylase (HDAC) to Sp-1/Sp-3 binding element, which were reversed by by 5'-aza-dC. In vitro methylation of the IGFBP-3 promoter containing the Sp-1/Sp-3 binding element significantly reduced promoter activity, which was further suppressed by the overexpression of MeCP2. This reduction in activity was rescued by 5'-aza-dC. Conclusion : These findings indicate that hypermethylation of the IGFBP-3 promoter is one mechanism by which IGFBP-3 expression is silenced and MeCP2, with recruitment of HDAC, may play a role in silencing of IGFBP-3 expression. The frequency of this abnormality is also associated with advanced stages among the patients with NSCLC, suggesting that IGFBP-3 plays an important role in lung carcinogenesis/progression and that the promoter methylation status of IGFBP-3 may be a marker for early molecular detection and/or for monitoring chemoprevention efforts.

• Radiation Oncology Journal
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• v.22 no.1
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• pp.1-10
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• 2004

Locally advanced (Stage III) non-small cell lung cancer (NSCLC) accounts for approximately one third of all cases of NSCLC. Few patients with locally advanced NSCLC present with disease amenable to curative surgical resection. Historically, these patients were treated with primary thoracic radiation therapy (RT) and had poor long term survival rates, due to both progression of local disease and development on distant metastases. Over the last two decades, the use of multidisciplinary approach has improved the outcome for patients with locally advanced NSCLC. Combined chemoradiotherapy is the most favored approach for treatment of locally advanced unresectable NSCLC. There are two basic treatment protocols for administering combined chemotherapy and radiation, sequential versus concurrent. The rationale for using chemotherapy is to eliminate subclinical metastatic disease while improving local control. Sequential use of chemotherapy followed by radiotherapy has improved median and long term survival compared to radiation therapy alone. This approach appears to decrease the risk of distant metastases,, but local failure rates remain the same as radiation alone. Concurrent chemoradiotherapy has been studied extensively. The potential advantages of this approach may include sensitization of tumor cells to radiation by the administration of chemotherapy, and reduced overall treatment time compared to sequential therapy; which is known to be important for improving local control in radiation biology. This approach Improves survival primarily as a result of improved local control. However, it doesn't seem to decrease the risk of distant metastases probably because concurrent chemoradiation requires dose reductions in chemotherapy due to increased risks of acute morbidity such as acute esophageal toxicity. Although multidisciplinary therapy has led to improved survival rates compared to radiation therapy alone and has become the new standard of care, the optimal therapy of locally advanced NSCLC continues to evolve. The current issues in the multidisciplinary management of locally advanced NSCLC will be reviewed in this report.

• Brain Tumor Research and Treatment
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• v.6 no.2
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• pp.54-59
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• 2018

Background Leptomeningeal metastasis (LM) is an uncommon, but devastating complication of advanced cancer and has no standard treatment. Herein, we analyzed the clinical characteristics and outcomes of patients with solid tumors who were diagnosed with LM. Methods Between January 2007 and December 2017, we retrospectively analyzed the medical records of patients with solid tumors who were diagnosed with LM. Results A total of 58 patients were enrolled in this study. The median age of patients was 51 years (range, 27-72 years), and 62.1% had a poor Eastern Cooperative Oncology Group (ECOG) performance status (PS) (>2). The common types of primary tumor were breast cancer (39.7%), gastric cancer (25.9%), and non-small cell lung cancer (20.7%). Forty-two patients (72.4%) were diagnosed with LM by MRI of the brain and/or spine and cerebrospinal fluid (CSF) analysis, 14 were diagnosed by CSF analysis alone, and 2 were diagnosed by MRI alone. Treatments for LM were performed in 53 patients (91.4%), and best supportive care was provided for 5 patients (8.6%). Intrathecal chemotherapy, radiotherapy, and systemic chemotherapy were administered in 43 (74.1%), 17 (29.3%), and 24 (41.4%) patients, respectively. The median overall survival of the entire cohort was 2.4 months (95% confidence interval, 1.0-3.7). In the analysis of prognostic factors for survival, a good ECOG PS (${\leq}2$), administration of systemic chemotherapy after LM diagnosis, and a prior history of brain radiation were associated with prolonged survival. Conclusion Although the prognosis of LM in patients with solid tumors is poor, systemic chemotherapy might improve survival in selected patients with a good PS.

• Tuberculosis and Respiratory Diseases
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• v.66 no.1
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• pp.20-26
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• 2009

Background: $^{18}F$-Fluorodeoxyglucose positron emission tomography (FDG-PET) is widely used for the diagnosis and staging of non-small cell lung cancer (NSCLC). The aim of this study is to determine whether the bone marrow hypermetabolism seen on FDG-PET predicts a response to chemotherapy in patients with NSCLC. Methods: We evaluated the patients with advanced NSCLC and who were treated with combination chemotherapy. For determination of the standardized uptake value (SUV) of the bone marrow (BM SUV) on FDG-PET, regions of interest (ROIs) were manually drawn over the lumbar vertebrae (L1, 2, 3). ROIs were also drawn on a homogenous transaxial slice of the liver to obtain the bone marrow/ liver SUV ratio (BM/L SUV ratio). The response to chemotherapy was evaluated according to the Response Evaluation Criteria in Solid Tumor (RECIST) criteria after three cycles of chemotherapy. Results: Fifty-nine NSCLC patients were included in the study. Multivariate analysis was performed using a logistic regression model. The BM SUV and the BM/L SUV ratio on FDG-PET were not associated with a response to chemotherapy in NSCLC patients (p=0.142 and 0.978, respectively). Conclusion: The bone marrow hypermetabolism seen on FDG-PET can not predict a response to chemotherapy in NSCLC patients.