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1.
Cancer Research and Treatment ; : 1112-1119, 2020.
Article | WPRIM | ID: wpr-831143

ABSTRACT

Purpose@#The introduction of immune checkpoint inhibitors represents a major advance in the treatment of lung cancer, allowing sustained recovery in a significant proportion of patients. Nivolumab is a monoclonal anti–programmed death cell protein 1 antibody licensed for the treatment of locally advanced or metastatic non-small cell lung cancer (NSCLC) after prior chemotherapy. In this study, we describe the demographic and clinical outcomes of patients with advanced NSCLC treated with nivolumab in the Korean expanded access program. @*Materials and Methods@#Previously treated patients with advanced non-squamous and squamous NSCLC patients received nivolumab at 3 mg/kg every 2 weeks up to 36 months. Efficacy data including investigator-assessed tumor response, progression data, survival, and safety data were collected. @*Results@#Two hundred ninety-nine patients were treated across 36 Korean centers. The objective response rate and disease control rate were 18% and 49%, respectively; the median progression-free survival was 2.1 months (95% confidence interval [CI], 1.87 to 3.45), and the overall survival (OS) was 13.2 months (95% CI, 10.6 to 18.9). Patients with smoking history and patients who experienced immune-related adverse events showed a prolonged OS. Cox regression analysis identified smoking history, presence of immune-related adverse events as positive factors associated with OS, while liver metastasis was a negative factor associated with OS. The safety profile was generally comparable to previously reported data. @*Conclusion@#This real-world analysis supports the use of nivolumab for pretreated NSCLC patients, including those with an older age.

2.
Article | WPRIM | ID: wpr-831069

ABSTRACT

Purpose@#Osimertinib is a third-generation, irreversible, oral epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) that potently and selectively inhibits both EGFR sensitizing mutation and EGFR T790M and has demonstrated efficacy in non-small cell lung cancer (NSCLC) central nervous system (CNS) metastases. We present results of a subgroup analysis of Korean patients from the pooled data of two global phase II trials: AURA extension (NCT01802632) and AURA2 (NCT02094261). @*Materials and Methods@#Enrolled patients had EGFR T790M-positive NSCLC and disease progression during or after EGFR-TKI therapy. Patients received osimertinib 80 mg orally once daily until disease progression. The primary endpoint was objective response rate (ORR). @*Results@#In total, 66 Korean patients received osimertinib treatment with a median treatment duration of 19 months. In the evaluable-for-response population (n=62), ORR was 74% (95% confidence interval [CI], 61.5 to 84.5) and median duration of response was 9.8 months (95% CI, 7.1 to 16.8). In the full analysis set (n=66), median progression-free survival was 10.9 months (95% CI, 8.3 to 15.0; data cutoff November 1, 2016), and median overall survival was 29.2 months (95% CI, 24.8 to 35.7; data cutoff May 1, 2018). Eight patients with CNS metastases were evaluable for response, none of whom showed CNS progression. The most common adverse events were rash (53%), cough (33%), paronychia, diarrhea, and decreased appetite (each 32%). @*Conclusion@#Efficacy and safety profiles of osimertinib in this subgroup are consistent with the global phase II pooled population, which supports osimertinib as a recommended treatment for Korean patients with T790M positive NSCLC.

3.
Cancer Research and Treatment ; : 1052-1063, 2019.
Article in English | WPRIM | ID: wpr-763174

ABSTRACT

PURPOSE: The relationship between head and neck squamous cell carcinoma (HNSCC) and subtypes of tropomyosin-related kinase (Trk) has not been studied in-depth. In this study, we evaluated the expression patterns of TrkA, TrkB, and panTrk and their clinicopathological significance as well as association with p16 expression and human papilloma virus (HPV) status. MATERIALS AND METHODS: Total of 396 radically resected oropharyngeal (n=121) and non-oropharyngeal (n=275) HNSCCs were included. Immunohistochemistry for TrkA, TrkB, and panTrk was performed. In addition, p16 immunohistochemistry was performed to assess the HPV status. Using HPV-negative HNSCC cell lines, FaDu and CAL27, HPV type 16 E6/E7 gene was transfected, and then changes of TrkA and TrkB expression were analyzed. RESULTS: In the clinical samples of HNSCC, high expression of TrkA and panTrk were more associated with oropharyngeal and p16 positive squamous cell carcinoma (SCC). In patients with completely resected (R0-resected) oropharyngeal SCC, high TrkA expression was related to superior overall survival and recurrence-free survival (RFS). In patients with R0-resected oral cavity SCC, high panTrk was related to poor RFS. In HPV type E6/E7 gene-transfected FaDu and CAL27 cell lines, increase of TrkA expression was observed. CONCLUSION: It seems that expression pattern of panTrk and TrkA differed according to anatomical sites of HNSCC and was closely related to p16 expression and patient prognosis. Trk expression should be considered in the context of anatomical site, p16 expression or HPV status and Trk subtypes.


Subject(s)
Carcinoma, Squamous Cell , Cell Line , Epithelial Cells , Head , Humans , Immunohistochemistry , Mouth , Neck , Papillomaviridae , Papillomavirus Infections , Phosphotransferases , Prognosis
4.
Article in English | WPRIM | ID: wpr-719422

ABSTRACT

PURPOSE: Head and neck squamous cell carcinoma (HNSCC) is a deadly disease in which precision medicine needs to be incorporated. We aimed to implement next-generation sequencing (NGS) in determining actionable targets to guide appropriate molecular targeted therapy in HNSCC patients. MATERIALS AND METHODS: Ninety-three tumors and matched blood samples underwent targeted sequencing of 244 genes using the Illumina HiSeq 2500 platform with an average depth of coverage of greater than 1,000×. Clinicopathological data from patients were obtained from 17 centers in Korea, and were analyzed in correlation with NGS data. RESULTS: Ninety-two of the 93 tumors were amenable to data analysis. TP53 was the most common mutation, occurring in 47 (51%) patients, followed by CDKN2A (n=23, 25%), CCND1 (n=22, 24%), and PIK3CA (n=19, 21%). The total mutational burden was similar between human papillomavirus (HPV)–negative vs. positive tumors, although TP53, CDKN2A and CCND1 gene alterations occurred more frequently in HPV-negative tumors. HPV-positive tumors were significantly associated with immune signature-related genes compared to HPV-negative tumors. Mutations of NOTCH1 (p=0.027), CDKN2A (p < 0.001), and TP53 (p=0.038) were significantly associated with poorer overall survival. FAT1 mutations were highly enriched in cisplatin responders, and potentially targetable alterations such as PIK3CA E545K and CDKN2A R58X were noted in 14 patients (15%). CONCLUSION: We found several targetable genetic alterations, and our findings suggest that implementation of precision medicine in HNSCC is feasible. The predictive value of each targetable alteration should be assessed in a future umbrella trial using matched molecular targeted agents.


Subject(s)
Biomarkers , Carcinoma, Squamous Cell , Cisplatin , Epithelial Cells , Head , Humans , Korea , Molecular Targeted Therapy , Neck , Precision Medicine , Statistics as Topic
5.
Yonsei Medical Journal ; : 525-534, 2019.
Article in English | WPRIM | ID: wpr-762083

ABSTRACT

PURPOSE: Standard treatment for cases of non-small cell lung cancer (NSCLC) exhibiting acquired drug resistance includes tumor rebiopsy, epidermal growth factor receptor (EGFR) mutation testing (e.g., for T790M mutations), and the subsequent administration of third-generation EGFR-tyrosine kinase inhibitors (EGFR-TKIs). However, rebiopsies are typically invasive, costly, and occasionally not feasible. Therefore, the present study aimed to assess rebiopsy procedures by analyzing real-world data collected by the ASTRIS study of patients with resistant NSCLC. MATERIALS AND METHODS: The present study used statistical models to evaluate data collected by the ASTRIS trial (NCT02474355) conducted at Yonsei Cancer Center, including the rebiopsy success rate, incidence of T790M mutations in collected tissue and plasma samples, and association of administered osimertinib treatment efficacy. RESULTS: In a total of 188 screened patients, 112 underwent rebiopsy. An adequate tumor specimen was obtained in 95 of these patients, the greatest majority of whom (43.8%) were subjected to bronchoscopy. T790M mutations were detected in 53.3% of successfully EGFR-tested rebiopsy samples. A total of 88 patients received osimertinib treatment, and the objective response rate and median progression-free survival time was 44.3% and 32.7 weeks, respectively, among the treated patients overall, but 57.8% and 45.0 weeks, and 35.2% and 20.4 weeks among patients who exhibited T790M-positive tissue (n=45) and plasma (n=54) samples, respectively. CONCLUSION: Approximately 60% of patients in the analyzed real-world cohort were eligible for tissue rebiopsy upon NSCLC progression. Osimertinib activity was higher in patients in whom T790M mutations were detected in tissues rather than in plasma samples.


Subject(s)
Bronchoscopy , Carcinoma, Non-Small-Cell Lung , Cohort Studies , Disease-Free Survival , Drug Resistance , Humans , Incidence , Models, Statistical , Phosphotransferases , Plasma , ErbB Receptors , Treatment Outcome
6.
Radiation Oncology Journal ; : 153-162, 2017.
Article in English | WPRIM | ID: wpr-44437

ABSTRACT

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) ± boost (WBRT ± 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 ± 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 ± 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 ≥42.3 Gy 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.


Subject(s)
Appointments and Schedules , Brain , Carcinoma, Non-Small-Cell Lung , Humans , Lung Neoplasms , Lung , Metastasectomy , Neoplasm Metastasis , Radiotherapy , Radiotherapy, Adjuvant , Recurrence , Retrospective Studies
7.
Article in English | WPRIM | ID: wpr-6984

ABSTRACT

PURPOSE: The purpose of this study was to evaluate the benefits of adjuvant treatment for curatively resected thoracic esophageal squamous cell carcinoma (ESCC) and determine the optimal adjuvant treatments. MATERIALS AND METHODS: One hundred ninety-five patients who underwent a curative resection for thoracic ESCC between 1994 and 2014 were reviewed retrospectively. Postoperatively, the patients received no adjuvant treatment (no-adjuvant group, n=68), adjuvant chemotherapy (AC group, n=62), radiotherapy (RT group, n=41), or chemoradiotherapy (CRT group, n=24). Chemotherapy comprised cisplatin and 5-fluorouracil administration every 3 weeks. The median RT dose was 45.0 Gy (range, 34.8 to 59.4 Gy). The overall survival (OS), disease-free survival (DFS), locoregional recurrence (LRR), and distant metastasis (DM) rates were estimated. RESULTS: At a median follow-up duration of 42.2 months (range, 6.3 to 215.2 months), the 5-year OS and DFS were 37.6% and 31.4%, respectively. After adjusting for other clinicopathologic variables, the AC and CRT groups had a significantly better OS and DFS compared to the no-adjuvant group (p < 0.05). The LRR rate was significantly lower in the RT and CRT groups than in the no-adjuvant group (p < 0.05), whereas no significant difference was observed in the AC group. In the no-adjuvant and AC groups, 25% of patients received high-dose salvage RT due to LRR. The DM rates were similar. The anastomotic stenosis and leakage were similar in the treatment groups. CONCLUSION: Adjuvant treatment might prolong survival after an ESCC resection, and RT contributes to a reduction of the LRR. Overall, the risks and benefits should be weighed properly when selecting the optimal adjuvant treatment.


Subject(s)
Carcinoma, Squamous Cell , Chemoradiotherapy , Chemotherapy, Adjuvant , Cisplatin , Constriction, Pathologic , Disease-Free Survival , Drug Therapy , Epithelial Cells , Esophageal Neoplasms , Fluorouracil , Follow-Up Studies , Humans , Neoplasm Metastasis , Radiotherapy , Recurrence , Retrospective Studies , Risk Assessment
8.
Article in English | WPRIM | ID: wpr-6982

ABSTRACT

PURPOSE: The recent discovery and characterization of an oncogenic ROS1 gene rearrangement has raised significant interest because small molecule inhibitors are effective in these tumors. The aim of this study was to determine frequency and clinicopathological features associated with ROS1 rearrangement in patients with cholangiocarcinoma (CCA). MATERIALS AND METHODS: A total of 261 patients who underwent surgery for CCA between October 1997 and August 2013 were identified from an international, multi-institutional database. ROS1 rearrangement was evaluated by break-apart fluorescence in situ hybridization using tissue microarrays of these patients. RESULTS: Of 261 CCA evaluated, three cases (1.1%) showed ROS1 rearrangement by fluorescence in situ hybridization (FISH), all of which were derived from intrahepatic origin. ROS1 protein expression was observed in 38 samples (19.1%). Significantly larger tumor size was observed in ROS1 immunohistochemistry (IHC)–negative patients compared with ROS1 IHC–positive patients. ROS1 FISH–positive patients had a single tumor with a median size of 4 cm and well-to-moderate differentiation. Overall, there was no difference in terms of baseline characteristics, overall survival, and recurrence-free survival between ROS1-positive and -negative patients. CONCLUSION: ROS1 rearrangement was detected in 1.1% of CCA patients. Although rare, conduct of clinical trials using ROS1 inhibitors in these genetically unique patients is warranted.


Subject(s)
Cholangiocarcinoma , Fluorescence , Gene Rearrangement , Humans , Immunohistochemistry , In Situ Hybridization , In Situ Hybridization, Fluorescence , Incidence
9.
Article in English | WPRIM | ID: wpr-61892

ABSTRACT

PURPOSE: We investigated ¹⁸F-fluorodeoxyglucose positron emission tomography (PET)-derived parameters as prognostic indices for disease progression and survival in locally advanced nasopharyngeal carcinoma (NPC) and the effect of high-dose radiotherapy for a subpopulation with PET-based poor prognoses. MATERIALS AND METHODS: Ninety-seven stage III and Iva-b NPC patients who underwent definitive treatment and PET were reviewed. For each primary, nodal, and whole tumor, maximum standardized uptake value, metabolic tumor volume, and total lesion glycolysis (TLG) were evaluated. RESULTS: Based on the C-index (0.666) and incremental area under the curve (0.669), the whole tumor TLGwas the most useful predictorfor progression-free survival (PFS); thewhole tumor TLG cut-off value showing the best predictive performance was 322.7. In multivariate analysis, whole tumor TLG was a significant prognostic factor for PFS (hazard ratio [HR], 0.3; 95% confidence interval [CI], 0.14 to 0.65; p=0.002) and OS (HR, 0.29; 95% CI, 0.11 to 0.79; p=0.02). Patients with low whole tumor TLG showed the higher 5-year PFS in the subgroup for only patients receiving intensity modulated radiotherapy (77.4% vs. 53.0%, p=0.01). In the subgroup of patients with high whole tumor TLG, patients receiving an EQD₂≥ 70 Gy showed significantly greater complete remission rates (71.4% vs. 33.3%, p=0.03) and higher 5-year OS (74.7% vs. 19.6%, p=0.02). CONCLUSION: Our findings demonstrated that whole tumor TLG could be an independent prognostic factor and high-dose radiotherapy could improve outcomes for NPC showing high whole tumor TLG.


Subject(s)
Disease Progression , Disease-Free Survival , Electrons , Glycolysis , Humans , Multivariate Analysis , Positron-Emission Tomography , Prognosis , Radiotherapy , Radiotherapy Dosage , Radiotherapy, Intensity-Modulated , Tumor Burden
10.
Article in Korean | WPRIM | ID: wpr-161392

ABSTRACT

The rearrangement of c-ros oncogene 1 (ROS1) has been recently identified as an important molecular target in non small cell lung cancer (NSCLC). ROS1 rearrangement and epidermal growth factor receptor (EGFR) mutation were mutually exclusive each other in previous studies, and the clinical implication of co-existence of the two genetic alterations has not been determined. We report a case of 46-year-old female never-smoker NSCLC patient whose tumor harbored ROS1 rearrangement and EGFR mutation concomitantly. She had undergone curative surgery for stage IIIA NSCLC, and the recurrence in left pleura and brain occurred at 2 years after the surgery. She received several lines of chemotherapy including docetaxel plus carboplatin, erlotinib, pemetrexed, and gemcitabine. Erlotinib therapy showed a favorable treatment response with progression-free survival of 9.5 months and partial response of tumor on radiologic evaluations. This case represents a successful erlotinib treatment in a NSCLC patient with concurrent ROS1 rearrangement and EGFR mutation.


Subject(s)
Adenocarcinoma , Brain , Carboplatin , Carcinoma, Non-Small-Cell Lung , Disease-Free Survival , Drug Therapy , Female , Humans , Lung , Middle Aged , Oncogenes , Pleura , ErbB Receptors , Recurrence , Small Cell Lung Carcinoma , Erlotinib Hydrochloride , Pemetrexed
11.
Yonsei Medical Journal ; : 854-864, 2013.
Article in English | WPRIM | ID: wpr-99053

ABSTRACT

PURPOSE: The main objective of this study was to evaluate the association between polymorphisms of the target genes of pemetrexed and clinical outcomes in non-small cell lung cancer (NSCLC) patients treated with pemetrexed. MATERIALS AND METHODS: We assessed polymorphisms at 8 sites in 4 genes [thymidylate synthase (TS), dihydrofolate reductase (DHFR; 1610, 680, 317, intron 1), methylenetetrahydrofolate reductase (MTHFR; 677, 1298), glycinamide ribonucleotide formyl transferase (GARFT; 2255)] associated with pemetrexed metabolism using polymerase chain reaction, gene scanning, and restriction fragment length polymorphism analysis in 90 patients with adenocarcinoma of the lung. RESULTS: Survival was significantly longer with pemetrexed in patients with TS 3RGCC/3RGCC or 3RGGC/3RGGC compared with the other groups (PFS; 5.2 months vs. 3.7 months, p=0.03: OS; 31.8 months vs. 18.5 months, p=0.001). Patients with DHFR 680CC experienced fatigue more frequently (50% vs. 8.6%, p=0.008). Polymorphisms of MTHFR and GARFT were not significantly associated with clinical outcomes of pemetrexed. CONCLUSION: The TS genotype was associated with survival and one DHFR polymorphism was associated with fatigue in NSCLC patients treated with pemetrexed. Further large prospective studies are required to identify other biomarkers that affect patients being treated with pemetrexed for adenocarcinoma of the lung.


Subject(s)
Adenocarcinoma/drug therapy , Adult , Aged , Aged, 80 and over , Antimetabolites, Antineoplastic/pharmacology , Female , Glutamates/pharmacology , Guanine/analogs & derivatives , Humans , Lung Neoplasms/drug therapy , Male , Methylenetetrahydrofolate Reductase (NADPH2)/genetics , Middle Aged , Pharmacogenetics , Phosphoribosylglycinamide Formyltransferase/genetics , Polymorphism, Single Nucleotide , Tetrahydrofolate Dehydrogenase/genetics , Thymidylate Synthase/genetics
12.
Yonsei Medical Journal ; : 865-874, 2013.
Article in English | WPRIM | ID: wpr-99052

ABSTRACT

PURPOSE: This study was designed to determine the relationship of cigarette smoking to the frequency and qualitative differences among KRAS mutations in lung adenocarcinomas from Korean patients. MATERIALS AND METHODS: Detailed smoking histories were obtained from 200 consecutively enrolled patients with lung adenocarcinoma according to a standard protocol. EGFR (exons 18 to 21) and KRAS (codons 12/13) mutations were determined via direct-sequencing. RESULTS: The incidence of KRAS mutations was 8% (16 of 200) in patients with lung adenocarcinoma. KRAS mutations were found in 5.8% (7 of 120) of tumors from never-smokers, 15% (6 of 40) from former-smokers, and 7.5% (3 of 40) from current-smokers. The frequency of KRAS mutations did not differ significantly according to smoking history (p=0.435). Never-smokers were significantly more likely than former or current smokers to have a transition mutation (G-->A or C-->T) rather than a transversion mutation (G-->T or G-->C) that is known to be smoking-related (p=0.011). In a Cox regression model, the adjusted hazard ratios for the risk of progression with epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) were 0.24 (95% CI, 0.14-0.42; p<0.001) for the EGFR mutation and 1.27 (95% CI, 0.58-2.79; p=0.537) for the KRAS mutation. CONCLUSION: Cigarette smoking did not influence the frequency of KRAS mutations in lung adenocarcinomas in Korean patients, but influenced qualitative differences in the KRAS mutations.


Subject(s)
Adenocarcinoma/drug therapy , Adult , Aged , Aged, 80 and over , Asians/genetics , Female , Humans , Incidence , Lung Neoplasms/drug therapy , Male , Middle Aged , Mutation , Mutation Rate , Proportional Hazards Models , Proto-Oncogene Proteins/genetics , ErbB Receptors/antagonists & inhibitors , Smoking/adverse effects , Treatment Outcome , ras Proteins/genetics
13.
Article in English | WPRIM | ID: wpr-48226

ABSTRACT

BACKGROUND: Plasminogen activator inhibitor type 1 (PAI-1), an important regulator of plasminogen activator system which controls degradation of extracellular membrane and progression of tumor cells, and PAI-1 gene polymorphic variants have been known as the prognostic biomarkers of non-small cell lung cancer patients. Recently, experimental in vitro study revealed that transforming growth factor-beta1 initiated PAI-1 transcription through epithelial growth factor receptor (EGFR) signaling pathway. However, there is little clinical evidence on the association between PAI-1 A15T gene polymorphism and prognosis of Korean population with pulmonary adenocarcinoma and the influence of activating mutation of EGFR kinase domain. METHODS: We retrospectively reviewed the medical records of 171 patients who were diagnosed with pulmonary adenocarcinoma and undergone EGFR mutation analysis from 1995 through 2009. RESULTS: In all patients with pulmonary adenocarcinoma, there was no significant association between PAI-1 A15T polymorphic variants and prognosis for overall survival. However, further subgroup analysis showed that the group with AG/AA genotype had a shorter 3-year survival time than the group with GG genotype in patients with EGFR mutant-type pulmonary adenocarcinoma (mean survival time, 24.9 months vs. 32.5 months, respectively; p=0.015). In multivariate analysis of 3-year survival for patients with pulmonary adenocarcinoma harboring mutant-type EGFR, the AG/AA genotype carriers had poorer prognosis than the GG genotype carriers (hazard ratio, 7.729; 95% confidence interval, 1.414-42.250; p=0.018). CONCLUSION: According to our study of Korean population with pulmonary adenocarcinoma, AG/AA genotype of PAI-1 A15T would be a significant predictor of poor short-term survival in patients with pulmonary adenocarcinoma harboring mutant-type EGFR.


Subject(s)
Adenocarcinoma , Biomarkers , Carcinoma, Non-Small-Cell Lung , Genotype , Humans , Medical Records , Membranes , Multivariate Analysis , Phosphotransferases , Plasminogen Activator Inhibitor 1 , Plasminogen Activators , Plasminogen , Polymorphism, Single Nucleotide , Prognosis , ErbB Receptors , Retrospective Studies
15.
Article in English | WPRIM | ID: wpr-196073

ABSTRACT

Transglutaminase 2 (TG2), a cross-linking enzyme, is involved in drug resistance and in the constitutive activation of nuclear factor kappa B (NF-kappaB). We investigated the association of non-small cell lung cancer (NSCLC) treatment efficacy with TG2 and NF-kappaB expression in 120 patients: 102 with adenocarcinoma and 18 with other histologic types. All patients underwent surgery; 88 received adjuvant chemotherapy, with 28 receiving platinum-based doublet chemotherapy as first-line treatment and 29 receiving epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) therapy. Patients' TG2 and NF-kappaB expression values were calculated semiquantitatively. The median TG2 value was 50 (range, 0-300) and the median NF-kappaB value was 20 (range, 0-240). Disease-free survival did not differ between the low- and high-TG2 groups. Among patients who received palliative platinum-based doublet chemotherapy, progression free survival (PFS) was longer in the low-TG2 group than in the high-TG2 group (11.0 vs. 7.0 months; P=0.330). Among those who received EGFR-TKI therapy, PFS was also longer in the low-TG2 group than in the high-TG 2 group (11.0 vs. 2.0 months; P=0.013). Similarly, in EGFR wild-type patients treated with EGFR-TKI, PFS was longer in patients with low TG2 expression (9.0 vs. 2.0 months; P=0.013). TG2 expression levels can predict PFS in patients with NSCLC treated with EGFR-TKI.


Subject(s)
Adenocarcinoma/drug therapy , Adult , Aged , Aged, 80 and over , Antineoplastic Agents/therapeutic use , Carcinoma, Non-Small-Cell Lung/drug therapy , Disease-Free Survival , Female , GTP-Binding Proteins/biosynthesis , Humans , Lung Neoplasms/drug therapy , Male , Middle Aged , NF-kappa B/biosynthesis , Protein Kinase Inhibitors/therapeutic use , ErbB Receptors/antagonists & inhibitors , Transglutaminases/biosynthesis , Treatment Outcome
16.
Yonsei Medical Journal ; : 111-117, 2012.
Article in English | WPRIM | ID: wpr-95036

ABSTRACT

PURPOSE: Elevated C-reactive protein (CRP) is associated with poor prognosis in several tumor types. The purpose of this study was to investigate serum CRP as a prognostic marker in small cell lung cancer (SCLC). MATERIALS AND METHODS: The pretreatment serum CRP level was measured in 157 newly diagnosed SCLC patients, and correlation between serum CRP level and other clinical parameters was analyzed. Multivariate analyses were performed to find prognostic markers using Cox's proportional hazards model. RESULTS: The initial CRP concentration was within the normal range in 72 (45.9%) patients and elevated in 85 (54.1%) patients. There was a significant correlation between serum CRP level and the extent of disease (p<0.001), weight loss (p=0.029) and chest radiation (p=0.001). Median overall survival (OS) in the normal CRp group was significantly longer than with the high CRp group (22.5 months vs. 11.2 months, p<0.001). Extent of disease (p<0.001), age (p=0.025), and performance status (p<0.001) were additional prognostic factors on univariate analysis. On multivariate analysis, elevated serum CRp level was an independent prognostic factor for poor survival (HR=1.8; p=0.014), regardless of the extent of disease (HR=3.7; p<0.001) and performance status (HR=2.2; p<0.001). CONCLUSION: High level of CRP was an independent poor prognostic serum marker in addition to previously well-known prognosticators in patients with SCLC.


Subject(s)
Aged , Aged, 80 and over , Biomarkers/blood , C-Reactive Protein/metabolism , Female , Humans , Kaplan-Meier Estimate , Lung Neoplasms/blood , Male , Middle Aged , Predictive Value of Tests , Prognosis , Small Cell Lung Carcinoma/blood
17.
Gut and Liver ; : 118-121, 2012.
Article in English | WPRIM | ID: wpr-196145

ABSTRACT

Synchronous esophageal and gastric cancers with the pathologic features of a squamous cell carcinoma are extremely rare. A 57-year-old male visited our hospital with a history of hematemesis and was diagnosed with a synchronous cancer. He underwent a staging work-up, and the resectable lesion in the stomach was operated on following radiologic and endoscopic evaluations. The pathologic examination revealed a synchronous cancer consisting of squamous cell carcinoma in the distal esophagus and the cardia of the stomach. We report a case of a synchronous cancer that was successfully treated by surgical resection followed by concurrent chemoradiotherapy. We also discuss the hypothesis regarding the origin and presentation of the synchronous cancer and highlight the importance of careful surveillance by physicians at the time of diagnosis.


Subject(s)
Carcinoma, Squamous Cell , Cardia , Chemoradiotherapy , Esophageal Neoplasms , Esophagus , Hematemesis , Humans , Male , Middle Aged , Stomach , Stomach Neoplasms
18.
Yonsei Medical Journal ; : 1128-1135, 2012.
Article in English | WPRIM | ID: wpr-183503

ABSTRACT

PURPOSE: Mutations in the epidermal growth factor receptor (EGFR) have been confirmed as predictors of the efficacy of treatment with EGFR-tyrosine kinase inhibitors (TKIs). We investigated whether polymorphisms of the EGFR gene were associated with clinical outcomes in non-small cell lung cancer (NSCLC) patients treated with EGFR-TKI. MATERIALS AND METHODS: A polymorphic dinucleotide repeat in intron 1 [CA simple sequence repeat in intron 1(CA-SSR1)] in intron 1 and single nucleotide polymorphisms (SNP-216) in the promoter region of the EGFR gene were evaluated in 71 NSCLC patients by restriction fragment length polymorphism and DNA sequencing. The relationship between genetic polymorphisms and clinical outcomes of treatment with EGFR-TKIs was evaluated. RESULTS: SNP-216G/T polymorphisms were associated with the efficacy of EGFR-TKI. The response rate for the SNP-216G/T tended to be higher than that for G/G (62.5% vs. 27.4%, p=0.057). The SNP-216G/T genotype was also associated with longer progression-free survival compared with the GG genotype (16.7 months vs. 5.1 months, p=0.005). However, the length of CA-SSR1 was not associated with the efficacy of EGFR-TKI. CONCLUSION: SNP-216G/T polymorphism was a potential predictor of clinical outcomes in NSCLC patients treated with EGFR-TKI.


Subject(s)
Adult , Aged , Aged, 80 and over , Female , Genotype , Humans , Introns/genetics , Kaplan-Meier Estimate , Lung Neoplasms/drug therapy , Male , Middle Aged , Polymorphism, Single Nucleotide/genetics , Protein Kinase Inhibitors/therapeutic use , ErbB Receptors/antagonists & inhibitors , Treatment Outcome
19.
Yonsei Medical Journal ; : 352-357, 2012.
Article in English | WPRIM | ID: wpr-154808

ABSTRACT

PURPOSE: Anaplastic thyroid cancer is known to have a poor prognosis due to its aggressive and rapid metastasis with median survival of less than 6 months. Multimodal treatment involving surgery and chemoradiotherapy has been used to improve the survival of patients. Here, we retrospectively review of treatment outcome of 13 consecutive patients who were treated at a single center. MATERIALS AND METHODS: We retrospectively reviewed medical records of 13 anaplastic thyroid cancer patients who received multidisciplinary treatment between 2006 and 2010. Kaplan-Meier survival curve was used to analyze progression-free survival and overall survival of patients. RESULTS: The median patient age at diagnosis was 69 years, and six patients had stage IVc diseases. Eight patients received primary surgery followed by radiotherapy or concurrent chemoradiotherapy (CCRT). Five patients received weekly doxorubicin-based definitive CCRT, but only one patient's condition remained stable, while the rest experienced rapid disease progression. The median progression-free survival was 2.8 months (95% CI, 1.2-4.4 months), and the median overall survival was 3.8 months (95% CI, 3.0-4.6 months). CONCLUSION: Patients with anaplastic thyroid cancer showed poor prognosis despite multimodality treatment. Therefore, identification of novel therapeutic targets is warranted to take an effective mode of treatment.


Subject(s)
Aged , Aged, 80 and over , Antineoplastic Agents/therapeutic use , Combined Modality Therapy , Disease-Free Survival , Doxorubicin/therapeutic use , Female , Humans , Male , Middle Aged , Retrospective Studies , Thyroid Neoplasms/drug therapy , Treatment Outcome
20.
Yonsei Medical Journal ; : 931-939, 2012.
Article in English | WPRIM | ID: wpr-228779

ABSTRACT

PURPOSE: The prognostic and predictive value of pretreatment serum levels of carcinoembryonic antigen (CEA) and cytokeratin-19 fragments (CYFRA 21-1) were assessed in advanced non-small cell lung cancer (NSCLC) patients treated with gefitinib or erlotinib. MATERIALS AND METHODS: Pretreatment CEA and CYFRA 21-1 were measured in 123 advanced NSCLC patients receiving gefitinib or erlotinib. High CEA levels (h-CEA) were significantly associated with females, patients with adenocarcinoma, and non-smokers. RESULTS: Low CYFRA 21-1 levels (l-CYFRA) were significantly associated with a good performance status (ECOG PS 0-1). The overall response rate (RR) was 27.6%, and higher RR was associated with adenocarcinoma, h-CEA, and epidermal growth factor receptor (EGFR) mutation. Patients with h-CEA had significantly longer progression-free survival (PFS) (p=0.021). Patients with l-CYFRA had significantly longer PFS and overall survival (p=0.006 and p<0.001, respectively). Of note, h-CEA and l-CYFRA had good prognosis in patients with unknown EGFR mutation status or patients with squamous cell carcinoma (p=0.021 and p=0.015, respectively). A good ECOG PS (HR=0.45, p=0.017), h-CEA (HR=0.41, p=0.007), l-CYFRA 21-1 (HR=0.52, p=0.025), and an EGFR mutation (HR=0.22, p<0.001) were independently predictive of a longer PFS. CONCLUSION: h-CEA and l-CYFRA 21-1 may be prognostic and predictive serum markers for higher response and longer survival in patients with advanced NSCLC receiving gefitinib or erlotinib, especially in patients with unknown EGFR mutation status or patients with squamous cell carcinoma.


Subject(s)
Adenocarcinoma , Biomarkers , Carcinoembryonic Antigen , Carcinoma, Non-Small-Cell Lung , Carcinoma, Squamous Cell , Disease-Free Survival , Erlotinib Hydrochloride , Female , Humans , Keratin-19 , Prognosis , ErbB Receptors
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