Myung Hee Chang

Sungkyunkwan University, Seoul, Seoul, South Korea

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Publications (26)68.02 Total impact

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    ABSTRACT: OBJECTIVES:: There is no confirmed treatment strategy for primary intestinal diffuse large B-cell lymphoma (DLBL). In this retrospective study, the purpose is to find an appropriate treatment strategy in patients with primary intestinal DLBL undergoing surgery followed by chemotherapy or chemotherapy alone. METHODS:: Seventy-six patients were newly diagnosed with DLBL and received treatment between March 2004 and June 2011. Forty-seven patients were treated with surgical resection followed by rituximab combined with cyclophosphamide, adriamycin, vincristine, and prednisolone (R-CHOP), and 29 patients were treated with R-CHOP chemotherapy alone. RESULTS:: The characteristics of the patients were as follows: the median age was 56.5 years (range, 15 to 85 y) with a female to male ratio of 1.00:1.45. There was no significant difference in patient characteristics between the 2 groups. The estimated 3-year progression-free survival rates (PFS) and overall survival rates (OS) of surgery followed by R-CHOP (surgery/R-CHOP) and R-CHOP alone (R-CHOP) groups were 92.2% and 74.8% (P=0.009) and 94.2% and 80.7% (P=0.049), respectively. In univariate analysis, significant differences were seen in estimated PFS and OS rates when comparing Lugano stages I and II1 with II2 and IIE (P=0.006 and 0.036), low and low-intermediate risk with high-intermediate risk (P=0.004 and 0.000), and surgery/R-CHOP group with R-CHOP group (P=0.009 and 0.049), respectively. In multivariate analysis, there were no independent predictive factors for survival. CONCLUSIONS:: Patients treated with surgery followed by R-CHOP seemed to have a higher survival rate than those treated with R-CHOP alone. There were no significant prognostic factors for survival, but there were possible prognostic factors such as Lugano stage, International Prognostic Index risk, and treatment modality for PFS and OS.
    American journal of clinical oncology 12/2012; · 2.21 Impact Factor
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    ABSTRACT: Little is known about outcomes in the use of third-line chemotherapy in cases of advanced gastric cancer (AGC). The primary aim of this retrospective study was to evaluate outcomes of docetaxel-based chemotherapy in patients with AGC that progressed after both oxaliplatin-based and irinotecan-based regimens. Eligible patients were those with AGC who had previous chemotherapy including fluoropyrimidine and oxaliplatin as well as fluoropyrimidine and irinotecan and who received subsequent docetaxel-based chemotherapy. Thirty-five patients were retrospectively recruited from 5 medical centers in Korea. Patients received either weekly or 3 weekly with docetaxel +/- cisplatin. Thirty-one out of 35 patients were evaluated for treatment response. A total of 94 cycles of chemotherapy (median, 2; range, 1 to 7) were administered. The overall response rate was 14.3%, and the disease control rate was 45.7%. The median progression-free survival (PFS) was 1.9 months (95% confidence interval [CI], 1.1 to 2.7 months). The median overall survival (OS) was 3.6 months (95% CI, 2.8 to 4.4 months). PFS and OS were significantly prolonged in patients of the Eastern Cooperative Oncology Group, with performance status of 0 or 1 in multivariate analysis (PFS: hazard ratio[HR], 0.411; 95% CI, 0.195 to 0.868; p=0.020 and OS: HR, 0.390; 95% CI, 0.184 to 0.826; p=0.014, respectively). Four of the 35 patients enrolled in the study died due to infection associated with neutropenia. Our findings suggest that salvage docetaxel-based chemotherapy is a feasible treatment option for AGC patients with good performance status (PS), whereas chemotherapy for patients with poor PS (PS≤2) should be undertaken with caution for those who previously failed oxaliplatin- and irinotecan-based regimens.
    Cancer Research and Treatment 12/2012; 44(4):235-41. · 1.96 Impact Factor
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    ABSTRACT: Chang MH, Lee K, Lee K‐Y, Kim YS, Kim YK, Kang J‐H. Prognostic role of integrin β1, E‐cadherin, and rac1 expression in small cell lung cancer. APMIS 2012; 120: 28–38.Integrin β1 mediates cellular adhesion to the extracellular matrix (ECM) and is correlated with highly invasive and metastatic behavior in small cell lung cancer (SCLC). E‐cadherin (ECAD) is a calcium‐dependent cell–cell adhesion receptor that restricts invasion of cells and reduces metastasis. Rac1 is involved in the regulation of the actin cytoskeleton, adhesion, migration, invasion, and tumor metastasis. The aim of this study was to examine integrin β1, ECAD and rac1 expression in SCLC and to analyze the prognostic value of these markers in patients with SCLC. We analyzed integrin β1, ECAD, and rac1 expression in 112 SCLC tissues by immunohistochemical staining. Correlative analyses between integrin β1, ECAD, and rac1 expression and cliniopathological factors were performed. A total of 65 patients had extensive disease (ED) (58%), and 47 had limited disease (LD) (42%). The median follow‐up duration was 61 months (range: 14–117 months), and the median progression free survival (PFS) and overall survival (OS) were 6.1 months (range: 4.8–7.4 months) and 9.7 months (range: 8.1–11.3 months), respectively. The expression of integrin β1, ECAD, and rac1 protein was observed in 64, 73, and 99 of SCLC tissues, respectively. The correlative analyses between integrin β1, ECAD, or rac1 expression and various clinical parameters did not show any statistical significance. However, the ECAD expression was associated with OS in the entire cohort. In contrast, the expression of integrin β1 and rac1 was not associated with PFS or OS. In a subgroup analysis, patients with less than two metastasis had significantly longer OS (p = 0.047) if their tumors expressed integrin β1 compared to those without integrin β1 expression. In addition, OS was longer for patients with ECAD positive tumors compared to those whose tumors did not express ECAD in males (p = 0.032) and patients who never smoked (p 0.001). Multivariate analysis showed that LD (p = 0.004), overall response rate (p = 0.003), and expression of ECAD (p = 0.015) were the independent good prognostic factors for OS. LD (p = 0.024), overall response rate (p 0.001), and less than two metastasis (p = 0.003) were prognostic factors for longer PFS. These results suggest that ECAD expression may be useful as a prognostic indicator in patients with SCLC.
    Apmis 01/2012; 120(1). · 2.07 Impact Factor
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    ABSTRACT: Integrin β(1) mediates cellular adhesion to the extracellular matrix (ECM) and is correlated with highly invasive and metastatic behavior in small cell lung cancer (SCLC). E-cadherin (ECAD) is a calcium-dependent cell-cell adhesion receptor that restricts invasion of cells and reduces metastasis. Rac1 is involved in the regulation of the actin cytoskeleton, adhesion, migration, invasion, and tumor metastasis. The aim of this study was to examine integrin β(1) , ECAD and rac1 expression in SCLC and to analyze the prognostic value of these markers in patients with SCLC. We analyzed integrin β(1) , ECAD, and rac1 expression in 112 SCLC tissues by immunohistochemical staining. Correlative analyses between integrin β(1) , ECAD, and rac1 expression and cliniopathological factors were performed. A total of 65 patients had extensive disease (ED) (58%), and 47 had limited disease (LD) (42%). The median follow-up duration was 61 months (range: 14-117 months), and the median progression free survival (PFS) and overall survival (OS) were 6.1 months (range: 4.8-7.4 months) and 9.7 months (range: 8.1-11.3 months), respectively. The expression of integrin β(1) , ECAD, and rac1 protein was observed in 64, 73, and 99 of SCLC tissues, respectively. The correlative analyses between integrin β(1) , ECAD, or rac1 expression and various clinical parameters did not show any statistical significance. However, the ECAD expression was associated with OS in the entire cohort. In contrast, the expression of integrin β(1) and rac1 was not associated with PFS or OS. In a subgroup analysis, patients with less than two metastasis had significantly longer OS (p = 0.047) if their tumors expressed integrin β(1) compared to those without integrin β(1) expression. In addition, OS was longer for patients with ECAD positive tumors compared to those whose tumors did not express ECAD in males (p = 0.032) and patients who never smoked (p < 0.001). Multivariate analysis showed that LD (p = 0.004), overall response rate (p = 0.003), and expression of ECAD (p = 0.015) were the independent good prognostic factors for OS. LD (p = 0.024), overall response rate (p < 0.001), and less than two metastasis (p = 0.003) were prognostic factors for longer PFS. These results suggest that ECAD expression may be useful as a prognostic indicator in patients with SCLC.
    Apmis 01/2012; 120(1):28-38. · 2.07 Impact Factor
  • Annals of Hematology 11/2011; 91(7):1135-8. · 2.87 Impact Factor
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    ABSTRACT: Recombinant human erythropoietin (rhEPO) has been successfully used for correcting renal anemia. However, recent studies have raised some concerns about the safety of rhEPO treatment due to its immunogenic side effect - pure red cell aplasia (PRCA). We now report a case of development of anti-EPO neutralizing antibodies (Abs) implicated in thrombocytopenia as well as erythrocytopenia. A 35-year-old man had a history of administering rhEPO (epoetin alfa, epoetin beta and darbepoetin alfa) for 2years to treat renal anemia. The hematological parameters were collected. Anti-EPO, anti-platelet, and anti-thrombopoietin (TPO) Ab assays were performed to test the presence of autoreactive Abs. After performing antibody assays due to severe resistance to rhEPO treatment, a high titer of anti-EPO neutralizing Abs was detected. However, unexpectedly, this patient also showed thrombocytopenia rather than PRCA. We investigated the cause of the marked thrombocytopenia and found anti-TPO Abs in patient serum. To our best knowledge, this is the first report of the development of anti-TPO Abs during rhEPO treatment for anemia.
    International immunopharmacology 10/2011; 11(12):2237-41. · 2.21 Impact Factor
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    ABSTRACT: Triple-negative breast cancer (TNBC) exhibits a distinct pattern of recurrence characterized by a rapidly rising rate in the first 2 years with a peak at 2-3 years, followed by a decline over the next 5 years. However, some TNBC patients exhibit indolent clinical behavior. The aim of this study was to investigate clinical characteristics and outcomes of metastatic TNBCs. In addition, we were to find out the marker which could divide TNBCs into a few subgroups according to different clinical features. We retrospectively analyzed the clinicopathologic characteristics and outcomes of patients with metastatic TNBC who received palliative treatment between 1999 and 2007. The median relapse-free survival (RFS) and overall survival (OS) of 152 patients were 24 and 20 months, respectively. Divided TNBCs based on a RFS of 36 months, the patients with a RFS of ≥36 months had a better disease control rate (DCR), progression-free survival (PFS), and OS than those with a RFS of <3 years. Cox-regression multivariate analysis for RFS and OS revealed EGFR positivity and a low BRCA1 score as an independent risk factor for OS. The patients with a RFS ≥ 3 years had a significantly better DCR, PFS, and OS than patients who had a RFS < 3 years. BRCA1 and EGFR expression may be candidate determinants to distinguish RFS. A prospective clinical trial for different therapeutic strategies is needed for each subgroup.
    Cancer Chemotherapy and Pharmacology 09/2011; 68(3):753-61. · 2.80 Impact Factor
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    ABSTRACT: Hereditary protein S (PS) deficiency (Gene ID: 5627; MIM # 176880) is a notable risk factor for recurrent venous thrombosis, inherited as an autosomal-dominant trait, either homozygous or heterozygous. It may be caused by point mutations in the gene (PROS1) encoding PS, which contains 15 exons on the chromosome 3q11.2. Only a few point mutations associated with the PROS1 gene in patients with hereditary PS deficiency have been reported. A 60-year-old woman was admitted for deep vein thrombosis (DVT) of the right lower extremity. Upon coagulation examination, both the free PS antigen level and the total PS antigen level were decreased, so the DNA-PCR products of all 15 exons, including the exon-intron boundaries of the PROS1, gene were directly sequenced. A substitution from guanine to adenine at position +5 of the donor splice site of intron 10 (c.1155+5G>A) was identified. Further familial study was performed, and the patient's older sister was revealed to have the same mutation; she was already taking warfarin due to diagnosed pulmonary thromboembolism. Here we report a G to A transition at position +5 of intron 10 from the splice donor site as a rare case of a patient with type I hereditary PS deficiency in Korea.
    Annals of clinical and laboratory science 01/2011; 41(4):397-400. · 0.88 Impact Factor
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    ABSTRACT: In patients with nonsmall cell lung cancer (NSCLC), several studies have demonstrated a positive correlation between somatic mutation in the epidermal growth factor receptor (EGFR) tyrosine kinase domain and clinical outcomes with the use of EGFR tyrosine kinase inhibitors (TKIs). However, some patients with wild-type (WT) EGFR also responded to EGFR TKIs and remained stable. Recently, amphiregulin (AR) has been suggested as a predictive marker for EGFR TKIs in patients with WT EGFR-positive NSCLC. The objective of the current study was to evaluate the association between AR expression and the efficacy of using EGFR TKIs in the treatment of patients with WT EGFR-positive NSCLC. Seventy-three patients with WT EGFR-positive NSCLC received treatment with gefitinib or erlotinib between May 2005 and December 2008. AR expression was assessed by immunohistochemistry. The clinical response to EGFR TKIs was reassessed for all patients as follows: 16 of 73 patients had a partial response (21.9%), 12 patients had stable disease (16.5%), and 45 patients had progressive disease (61.6%). AR expression was positive in 24 of 40 patients (60%). The ability to achieve disease control did not differ significantly between AR-positive patients and AR-negative patients (P = .188). At a median follow-up of 25.4 months (range, 10.5-53.3 months), progression-free survival was 8.1 weeks in AR-positive patients and 4 weeks in AR-negative patients (P = .025), and overall survival was significantly longer in AR-positive patients than in AR-negative patients (12.2 months vs 4.1 months; P = .001). The current results suggested that patients with WT EGFR-positive NSCLC who have AR-positive tumors may benefit clinically from treatment with EGFR TKIs, indicating that AR expression may be a potential marker for the selection of EGFR-TKI treatment for patients with WT EGFR-positive NSCLC.
    Cancer 01/2011; 117(1):143-51. · 5.20 Impact Factor
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    ABSTRACT: For patients with refractory bone and soft tissue sarcoma (STS), treatment options have been limited. Ifosfamide is an alkylating agent with well-demonstrated efficacy against STS, and dose-dependent activity. The aim of this retrospective study was to evaluate the response rate, progression-free survival (PFS), progression-free rate (PFR), and median duration of response to high-dose ifosfamide (HDI) as at least second-line chemotherapy for patients with advanced bone sarcoma and STS. Thirty metastatic, unresectable sarcoma patients who were treated with HDI chemotherapy between May 1999 and November 2007 were included in the analysis. In total, 106 cycles (median 3 cycles; range 1-8 cycles) were administered. Twenty-one patients received treatment as second-line chemotherapy, and 9 patients as third-line treatment. HDI was given at a dose of 2 g/m(2) over 3 h, and at a dose of 2 g/m(2) per day; continuous infusion was administered on 6 consecutive days (2 g/m(2)/6 days) every 3 weeks. After a median follow-up of 49 months (range 10-114), median PFS was 2.9 months (range 0.4-9.3) and median overall survival 8.7 months (range 0.4-57.8). The 3- and 6-month PFR were 47% (SE 9.1%) and 20% (SE 7.3%), respectively. Median response duration of HDI was 2.9 months (range 0.7-7.6). Of the 28 evaluable patients, 2 (7%) achieved complete response, 5 (18%) partial response, and 4 (14%) stable disease, and overall disease control was 39%. Two responders out of 7 (28.5%) and 4 patients out of 11 (36%) with controlled disease by HDI had a synovial sarcoma. Two patients were not evaluable because they were switched to another treatment due to ifosfamide-induced encephalopathy. Grade 3-4 neutropenia was seen in 13 (43%) patients, and treatment-related death was observed in one patient. HDI at a total dose of 14 g/m(2) with mesna is still an active salvage regimen, particularly in patients with synovial sarcomas.
    Oncology 01/2011; 80(3-4):257-61. · 2.17 Impact Factor
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    ABSTRACT: Cisplatin has been the cornerstone of the chemotherapy regimen for urothelial carcinoma. Excision repair cross-complementation group 1 (ERCC1) is a key component of the platinum-DNA repair machinery responsible for nucleotide excision repair. Recent reports have suggested that ERCC1 is a predictive and prognostic marker in solid cancers treated with platinum-based chemotherapy. We performed this study to determine whether or not immunohistochemical expression of ERCC1 can predict objective tumor response and cancer-specific survival in patients with advanced urothelial carcinoma treated with cisplatin-based chemotherapy. We performed a retrospective analysis of 89 patients with advanced or recurrent urothelial cancer, who had undergone treatment at Samsung Medical Center between May 2001 and August 2007. Pretherapeutic biopsy samples from 89 patients with a known tumor response were available. ERCC1 expression was assessed by immunohistochemistry. Of the 89 patients, ERCC1 expression was positive in 49 patients (55%). The overall response rate after chemotherapy was 68.5% (95% CI 54.8-74.8%). Among 61 patients who obtained a response, 27 were negative for ERCC-1 expression and 34 were positive (p = 0.61). Median duration of follow-up was 53.7 months (range 14.4-152.3 months). Progression-free survival (PFS) was 10.6 months for ERCC-1-negative patients and 8.4 months for ERCC-1-positive patients (p = 0.03); the difference in overall survival between patients with ERCC-1-negative tumors and ERCC-1-positive tumors (p = 0.73) was not statistically significant. Other than ERCC1 expression, there was no independent prognostic factor for PFS. These results suggest a negative contribution by ERCC1expression to PFS in metastatic urothelial carcinoma patients treated with cisplatin-based chemotherapy.
    Apmis 12/2010; 118(12):941-8. · 2.07 Impact Factor
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    ABSTRACT: K-ras proto-oncogene is commonly mutated in colorectal cancer (CRC) and has been associated with predictive markers for anti-EGFR (epidermal growth factor receptor) therapy. However, the prognostic role of K-ras status is still unclear. The aim of this study was to evaluate the association between k-ras status and addition of oxaliplatin to fluorouracil plus leucovorin (FOLFOX) chemotherapy in CRC patients with curative surgical resection. Sixty-six patients with stage II or III CRC were treated with FOLFOX or fluorouracil plus leucovorin (FL) followed by curative surgery between January 2004 and October 2007. K-ras status was assessed by direct sequencing. Fifteen patients (22.7%) had K-ras mutations of codon 12 (11/15) or codon 13 (4/15). There were no significant differences in clinicopathological parameters, such as age, sex, stage, or adjuvant regimen between the wild-type K-ras and mutant K-ras. With a median follow-up of 41.6 months (range 25.1-72.3 months), median disease-free survival (DFS) and overall survival (OS) were not reached. With regard to K-ras status, DFS and OS were not statistically different (P = 0.269 and P = 0.917, respectively). Even in the group treated with FOLFOX only, neither DFS (P = 0.651) nor OS (P = 0.265) was significantly different according to K-ras status. With the exception of tumor location in DFS and OS, no differences in other variables were observed. Proximal colon cancer patients had a longer DFS than distal CRC patients (P = 0.079); this trend was maintained only in the wild-type K-ras group (P = 0.051). These results showed that K-ras status was not associated with clinical outcome in patients treated with adjuvant FOLFOX.
    Cancer Chemotherapy and Pharmacology 10/2010; 68(2):317-23. · 2.80 Impact Factor
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    ABSTRACT: We analyzed the responses to first line treatment and clinical outcomes of metastatic breast cancer patients treated with palliative doxorubicin/cyclophosphamide (AC) according to molecular cancer subtype. A retrospective analysis was performed for 110 metastatic breast cancer patients selected on the basis of palliative AC treatment and the availability of immunohistochemical data for estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 (HER-2/neu) status. Of the 110 patients analyzed, 71 (64.5%) were hormone receptor positive (HR+), 14 (12.7%) were HER2+, and 25 (22.7%) were triple negative (TN). There were no differences in age, stage at diagnosis, total number of cycles of palliative chemotherapy, incidence of visceral metastasis, and metastatic sites with the exception of liver among breast cancer subtypes. The overall response rates to AC were 55.9% for the HR+ subgroup, 42.9% for the HER2+ subgroup, and 56.5% for the TN subgroup. The progression-free survival (PFS) in patients with HER2+ and TN were significantly shorter than in the HR+ (median PFS, 9.1 vs 8.1 vs 11.5 months, respectively; p = 0.0002). The overall survival (OS) was 25.4 months in the TN subgroup and 27.3 months in HER2+ subgroup. The median OS for these two groups was significantly shorter than for patients in the HR+ subgroup (median, 38.5 months; 95% CI, 30.1-46.9 months; p < 0.0001). The response to palliative AC chemotherapy did not differ among breast cancer subtypes. Despite chemosensitivity for palliative AC, the TN subtype has a shorter overall survival than non-TN subtypes. Innovative treatment strategies should be developed to slow the course of disease.
    BMC Cancer 10/2010; 10:527. · 3.33 Impact Factor
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    ABSTRACT: Interdigitating dendritic cell sarcoma (IDCS) is an extremely rare malignancy derived from antigen-presenting cells, with 55 cases reported thus far. A standard treatment modality is still being debated. This report describes a 56-year-old female who presented with right tonsillar enlargement and right submandibular swelling for 6 months. Treatment with empiric antibiotics did not result in improvement of her symptoms. Fine needle aspiration of the tonsil revealed no malignant cells. Tonsillectomy was eventually performed due to persistent symptoms. Based on microscopic findings, immunohistochemical stains, and review of the literature, the present case was finally diagnosed as IDCS of the tonsil with cervical lymph node involvement. The patient received four cycles of CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone) chemotherapy, and a clinically complete response was achieved followed by adjuvant radiation.
    Asia-Pacific Journal of Clinical Oncology 09/2010; 6(3):144-8. · 0.91 Impact Factor
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    ABSTRACT: Pemetrexed is one of the standard second-line therapies in advanced non-small cell lung cancer (NSCLC). Currently, there are no standard cytotoxic treatments beyond second-line therapy. We evaluated the efficacy and safety of pemetrexed as a salvage regimen in heavily pretreated NSCLC patients. We also analyzed thymidylate synthase (TS) expression in tumor tissues to determine whether TS expression is correlated with the clinical efficacy of pemetrexed. One hundred and ten NSCLC patients who received pemetrexed as third- or fourth-line therapy at the Samsung Medical Center between June 2006 and June 2008 were retrospectively reviewed. TS expression was analyzed by immunohistochemical staining in 55 NSCLC tissue specimens. The relationships between TS expression and clinicopathological factors were evaluated. Univariate and multivariate analyses were performed to define the predictive factors and prognostic significances. The median age of patients in this study was 59 years (range: 24-84), 50.9% were men, and 27 (24.6%) were smokers or previous smokers. Sixty-five patients (59.1%) received pemetrexed as third-line treatment, and 95 (86.4%) had non-squamous cell carcinoma. Platinum-based chemotherapy (84.6%) was the most common first-line therapy, and EGFR TKIs [erlotinib (17.3%) or gefitinib (43.6%)] were a common second-line therapy. The median time from date of diagnosis to the date of the first pemetrexed treatment was 12.8 months (range: 1.8-62.2 months) and the median number of pemetrexed treatments was 4 (range 1-22). Eighteen patients achieved PR (16.3%), 41 patients SD (37.3%), and 43 patients PD (39.1%), with a disease control rate of 53.6%. The median follow-up duration was 16.1 months, the median progression-free survival (PFS) was 3.2 months (95% CI: 1.9-4.5 months), and the median overall survival (OS) was 11.6 months (95% CI: 9.0-14.1 months). Male gender was the only independent variable for poor PFS (HR=1.673, 95% CI: 1.103-2.535), with poor performance status (HR=2.454, 95% CI: 1.405-4.287) and history of smoking (HR=1.856, 95% CI: 1.087-3.168) being independent adverse factors for OS. Thirteen of 55 tumor tissues (23.6%) showed TS expression; however, there were no significant correlations between TS expression and the clinicopathological factors. Pemetrexed was suggested as a third- or fourth-line therapy due to its favorable efficacy and tolerable toxicity. Further studies are warranted to define the adequate sequence of salvage treatments, especially in patients with adenocarcinoma lung cancer.
    Lung cancer (Amsterdam, Netherlands) 09/2010; 69(3):323-9. · 3.14 Impact Factor
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    ABSTRACT: Insulin-like growth factor receptor-1 (IGFR-1) is a cellular membrane receptor which is overexpressed in many tumors and seems to play a critical role in anti-apoptosis. The insulin-like growth factor binding protein-3 (IGFBP-3) is known as a growth suppressor in multiple signaling pathways. The aim of this study was to determine IGFR-1 and IGFBP-3 expression in small-cell lung cancer (SCLC) and analyze the prognostic value in patients with SCLC. We analyzed IGFR-1 and IGFBP-3 expression in 194 SCLC tissues by immunohistochemical staining. Correlative analyses between IGFR-1 and IGFBP-3 expression in SCLC and clinicopathologic factors were performed. A total of 117 patients had extensive disease (ED) (60.3%) and 77 had limited disease (39.7%). With the median follow-up duration of 49.5 months (24-82 months), the median progression-free survival (PFS) and overall survival (OS) were 7.2 months [95% confidence interval (CI): 6.4-8.0 months] and 14.4 months (95% CI: 12.7-16 months), respectively. IGFR-1 expression was observed in 154 of the 190 tumor tissues, whereas there was no IGFBP-3 expression. Multivariate analysis showed that stage (p < 0.001), response rate (p < 0.001), and lactate dehydrogenase (LDH) levels (p < 0.001) were the independent prognostic factors for PFS, and age (p = 0.014), LDH level (p < 0.001), and stage (p < 0.001) for OS. The IGFR-1 positivity was not associated with PFS or OS in the entire cohort. Subgroup analysis revealed that OS was significantly longer in patients with IGFR-1-positive tissue than IGFR-1-negative tissue in SCLC-ED (p = 0.034). These results suggest that IGFR-1 expression may be useful as a prognostic marker in patients with SCLC-ED.
    Apmis 12/2009; 117(12):861-9. · 2.07 Impact Factor
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    ABSTRACT: One hundred and twenty-two patients in whom the CA 15-3 level showed either a decline (92 patients) or an acute surge followed by a decline (30 patients) after chemotherapy were included. The clinical characteristics between the two groups and the CA 15-3 kinetics using receiver operating characteristic curves were analyzed. Patients with a surge had a significantly higher risk of disease progression than patients without a surge (P=0.004; odds ratio 2.62; 95% CI 1.45–4.72). The clinicopathologic characteristics were significantly different between the two groups with respect to the distribution of ER, PR, and HER2 status, relapse-free survival, and the severity and extent of the involved organs. For patients with a surge, a CA 15-3 slope threshold >−0.0038 was chosen with a sensitivity of 80.0% and a specificity of 80.4%. The area under the curve was 0.847 (95% CI 0.771–0.906; P=0.0001). A significant correlation between PFS and CA 15-3 slope was shown with Cox-regression modeling (P=0.036; hazard ratio [HR], 2.1; 95% CI 1.01–4.14).These kinetics may serve as a good predictive marker of treatment response and response duration.
    Breast Cancer Research and Treatment 11/2009; 118(1):89-97. · 4.47 Impact Factor
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    ABSTRACT: A retrospective analysis to compare the treatment outcomes of two regimens with different doses of methotrexate (MTX). Seventy-two patients, newly diagnosed with primary central nervous system lymphoma between 1995 and 2006, were included. All patients were treated with one of the two different MTX regimens depending on when the diagnosis was made. Thirty-six patients diagnosed between 1995 and 2002 were treated with 1 g/m(2) of intravenous MTX (HD-MTX 1 g/m(2), cohort 1). The other 36 patients, diagnosed between 2003 and 2006, received 3.5 g/m(2) of intravenous MTX (HD-MTX 3.5 g/m(2), cohort 2). The median age was 47 years (range, 17-78 years) and 42 patients (58.3%) were male. The median overall survival (OS) and progression-free survival (PFS) of all patients was 90.3 and 52.9 months, respectively. Although OS and PFS was not statistically different between the two cohorts, cohort 2 achieved higher complete response/unconfirmed complete response rates than cohort 1 at an evaluation conducted between completion of intravenous MTX therapy and the initiation of radiotherapy (52.8% vs. 16.7%, respectively; p = 0.005). Furthermore, there were no deaths within 6 months of MTX therapy for the cohort 2, whereas there were eight deaths by 6-months for cohort 1 (p = 0.003). Even though cohort 2 failed to show superior survival outcomes compared with cohort 1 after sequential brain radiotherapy and intravenous cytarabine, the higher early CR/CRu rate of cohort 2 compared with cohort 1 might indicate that a high dose of MTX is desirable.
    Leukemia & lymphoma 08/2009; 50(7):1110-8. · 2.61 Impact Factor
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    ABSTRACT: The optimal treatment for non-small cell lung cancer (NSCLC) patients with asymptomatic brain metastasis is still controversial. This study aimed to analyze the outcome for various treatment modalities including chemotherapy only, upfront whole brain radiotherapy (WBRT) or stereotactic radiosurgery (SRS) in NSCLC patients with asymptomatic brain metastases. We retrospectively reviewed the medical records of patients with histopathologically proven NSCLC and synchronous asymptomatic brain metastasis between January 2003 and December 2007. From the database, 741 NSCLC patients were identified to have been diagnosed of brain metastases during initial staging or follow-up between January 2003 and December 2007. Of 741 NSCLC patients, 135 (18%) NSCLC patients were identified to have synchronous brain metastasis without associated symptoms. Of the 129 patients included in the analysis, 78 (57.8%) patients received systemic chemotherapy only, 27 (20.0%) upfront WBRT followed by chemotherapy and 24 (17.8%) patients received upfront SRS and chemotherapy. There was no significant difference in overall survival among three groups (systemic chemotherapy alone, 13.9 versus upfront SRS followed by chemotherapy, 22.4 versus upfront WBRT followed by chemotherapy, 17.7 months, respectively; P=0.86). Subset analysis of 110 adenocarcinoma patients showed that the median OS for patients treated with upfront SRS was longer than those of upfront WRBT (29.3 months versus 17.7 months; P=0.01) or chemotherapy alone (29.3 months versus 14.6 months; P=0.04). This study suggested a potential role of systemic chemotherapy alone or upfront SRS followed by chemotherapy instead of WBRT as an initial treatment of NSCLC patients with synchronous, asymptomatic brain metastases. The optimal treatment modality, however, needs to be defined in prospective trials for this subset of patients.
    Lung cancer (Amsterdam, Netherlands) 08/2009; 68(2):258-63. · 3.14 Impact Factor
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    ABSTRACT: We investigated the value of Epstein-Barr virus (EBV) DNA load in unfractionated whole blood for the diagnosis and prognosis of EBV-associated lymphoma. From July 2004 to July 2007, we compared EBV DNA loads in 101 patients with lymphoma and 105 control individuals. The median copy number of EBV was higher in patients with EBV-positive lymphoma (p<0.001). In patients with natural killer (NK)/T-cell lymphomas, the median EBV DNA load at presentation was significantly related to the stage (p = 0.011) and response (p = 0.026). The newly proposed classification model for NK/T cell lymphoma showed EBV DNA load differed significantly between patients with upper and extra-upper aerodigestive tracts (p = 0.017). In 16 patients with NK/T-cell lymphoma monitored serially, EBV DNA load correlated well with the treatment response and clinical course. Further prospective studies are required to evaluate the diagnosing and monitoring role of whole blood EBV DNA for uniformly treated patients.
    Leukemia & lymphoma 07/2009; 50(5):757-763. · 2.61 Impact Factor