• Tuberculosis and Respiratory Diseases
• /
• 제68권4호
• /
• pp.212-217
• /
• 2010

Background: Acyl protein thioesterase-1 (APT1) is a cytosolic protein that may function in the depalmitoylation of numerous proteins, including the Ras family. However, the clinical role of depalmitoyl thioesterase in human cancer is not known. We evaluated the APT1 expression in lung cancer tissue and its clinicopathological findings according APT1 expression pattern. Methods: APT1 expression was examined by immunohistochemistry in the tumor tissue from 79 patients, who had undergone curative surgical removal of the primary lesion; all patients had been diagnosed with stage I non-small cell lung cancer between 1993 and 2004, at Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea. Results: The APT1 expression was seen in 50 out of 79 (63.3%) cases. The positive APT1 expression was significantly related with histologic subtype and T stage, but was not influenced by differentiation. The positive APT1 expression was not significantly related to patient age, gender, or smoking history. The median follow-up duration was 10.0 years; the 5-year survival rate was 71.0%. The positive APT1 expression group showed significantly worse overall survival and worse disease-free survival without statistical significance. Conclusion: We conclude that positive APT1 expression in stage I lung cancer after surgery is closely associated with overall survival. To evaluate APT1 as a prognostic marker in lung cancer, comprehensive studies on advanced stage cases are needed.

• Asian Pacific Journal of Cancer Prevention
• /
• 제14권7호
• /
• pp.4403-4408
• /
• 2013

Background: Chronic inflammation is considered as an important factor in the pathogenesis of lung cancer. The presence of inflammatory cells and higher levels of pro-inflammatory cytokines in the tumor microenvironment and their surrounding tissues is gaining much importance in research. Materials and Methods: One hundred ninety NSCLC cases and 200 age, smoking and sex matched controls were evaluated for association of IL-8 -251 (rs4073) and IL-8 -845 (rs2227532) in our population. Restriction fragment length polymorphism (RFLP) was used followed by direct sequencing for the detection of SNPs. Results: The IL-8 -845 polymorphism was not found in our population. No significant association was observed between the IL-8 -251 AT genotypes and IL-8 -25 AA genotypes and NSCLC (p=0.05) in our population. The IL-8 -251 A allele was also non-significant (p=0.05) in NSCLC patients. Conclusions: In conclusion, this report reveals lack of association between IL-8 - 251 A/T polymorphism and NSCLC in our Kashmir Valley population.

• Asian Pacific Journal of Cancer Prevention
• /
• 제15권24호
• /
• pp.10967-10970
• /
• 2015

Objective: To analyze the efficacy and survival associated factors of gefitinib combined with cisplatin and gemcitabine for advanced non-small cell lung cancer. Materials and Methods: A total of 57 patients with advanced non-small cell lung cancer (NSCLC), who received platinum-based chemotherapy regimens for more than 1 cycle, were treated with gefitinib combined with cisplatin and gemcitabine until disease progression. Efficacy, survival time and adverse reactions were observed. The Kaplan-Meier method was adopted for analysis of survival and Cox regression for associated influencing factors. Results: The patients were followed up until October 31, 2013, and the median follow-up time was 19 months. Of 57 patients, there were 4 (7.0%) with complete remission (CR), 8 (14.0%) with partial remission, 31 (54.4%) with stable disease, and 14 (24.6%) with disease progression. The remission rate was 21.1% and the disease control rate was 75.4%. The median progression-free survival (PFS) time and the median overall survival time were 10 months and 15.2 months. The one-year, two-year and three-year survival rates were 47.4%, 23.3% and 10.0%. Gender and pathological types were the independent risk factors influencing PFS time (P=0.028, P=0.009). Tumor pathological type and early efficacy were independent factors for the prognosis (P=0.018, P=0.000). Adverse reactions were mostly rashes of I~II degree and diarrhea and slightly increasing level of aminopherase. The skin adverse event incidence of III degree or above was 1.8% (1/57) and brain metastasis was foudn in 31.6% (18/57). Conclusions: Gefitinib combined with cisplatin andgemcitabine, is effective for patients with IIIb~IV NSCLC who received multiple cycles of chemotherapy.

• Asian Pacific Journal of Cancer Prevention
• /
• 제14권2호
• /
• pp.701-705
• /
• 2013

Polymorphisms in XPG are considered to contribute to the clinical outcome of patients receiving platinum drug chemotherapy. We aimed to investigate the role of five potential SNPs of XPG gene on the response to platinum-based chemotherapy in advanced Chinese NSCLC patients. A total of 451 patients with newly diagnosed and histopathologically confirmed primary NSCLC were consecutively collected. XPG rs2296147, rs4150261, rs17655, rs1047768 and rs2094258 were genotyped by the Taqman real-time polymerase chain reaction (PCR). In our study, we found patients carrying rs1057768 TT genotype had a significantly lower treatment response when compared with the CC genotype (OR=0.38, 95% CI=0.18-0.78). Patients carrying rs1047768 TT genotype showed a significantly short median PFS (11.2 months) and OS (13.6 months) than CC genotype, and the hazard ratios (HR) for PFS and OS were 2.06 (1.01-4.50) and 2.29 (1.21-2.49), respectively. Moreover, we found a significant decreased risk of death from NSCLC among patients carrying the rs2296147 TT genotype when compared with the CC genotype, the HR (95% CI) for OS being 0.50 (0.27-0.95). In conclusion, our study found that polymorphisms in rs1047768 C/T and rs2296147 C/T are associated with response to platinum-based chemotherapy in advanced NSCLC, and XPG polymorphisms could be predictive of prognosis.

• Journal of Korean Neurosurgical Society
• /
• 제50권4호
• /
• pp.385-387
• /
• 2011

Leptomeningeal metastasis is a devastating complication of advanced stage cancer. It is frequently accompanied by hydrocephalus and intracranial hypertension that must be treated by ventriculoperitoneal shunts. However, there are actual risks of peritoneal seeding or accumulation of malignant ascites after the cerebrospinal fluid diversion procedure, though it has not been reported. Here, we present the case of a patient with non-small cell lung cancer with leptomeningeal metastasis in whom malignant ascites developed after a subduroperitoneal shunt.

• Asian Pacific Journal of Cancer Prevention
• /
• 제13권5호
• /
• pp.2157-2162
• /
• 2012

Objective: The PI3K/PTEN/AKT/mTOR signaling pathway has been implicated in resistance to cisplatin. In the current study, we determined whether common genetic variations in this pathway are associated with platinum-based chemotherapy response and clinical outcome in advanced non-small cell lung cancer (NSCLC) patients. Methods: Seven common single nucleotide polymorphisms (SNPs) in core genes of this pathway were genotyped in 199 patients and analyzed for associations with chemotherapy response, progression-free survival (PFS) and overall survival (OS). Results: Logistic regression analysis revealed an association between AKT1 rs2494752 and response to treatment. Patients carrying heterozygous AG had an increased risk of disease progression after two cycles of platinum-based chemotherapy compared to those with AA genotype (Adjusted odds ratio (OR)=2.18, 95% confidence interval (CI): 1.00-4.77, which remained significant in the stratified analyses). However, log-rank test and cox regression detected no association between these polymorphisms in the PI3K pathway genes and survival in advanced NSCLC patients. Conclusions: Our findings suggest that genetic variants in the PI3K/PTEN/AKT/mTOR pathway may predict platinum-based chemotherapy response in advanced NSCLC patients in a Chinese population.

• Asian Pacific Journal of Cancer Prevention
• /
• 제15권16호
• /
• pp.6799-6804
• /
• 2014

Background: Chemotherapy is the mainstay of treatment for the majority of patients with advanced non-small cell lung cancer (NSCLC) without driver mutations and many receive therapies beyond first-line. Second-line chemotherapy has been disappointing both in terms of response rate and survival and we know relatively little about the prognostic factors. Materials and Methods: One thousand and eight patients with advanced NSCLC who received second-line chemotherapy after progression were reviewed in Shanghai Pulmonary Hospital, China, from September 2005 to July 2010. We analyzed the effects of potential prognostic factors on the outcomes of second-line chemotherapy (overall response rate, ORR; progression free survival, PFS; overall survival, OS). Results: The response and progression free survival of first-line chemotherapy affects the ORR, PFS and OS of second-line chemotherapy (ORR: CR/PR 15.4%, SD 10.1%, PD2.3%, p<0.001; PFS: CR/PR 3.80 months, SD 2.77 months, PD 2.03 months, p<0.001; OS: CR/PR 11.60 months, SD 10.33 months, PD 6.57 months, p=0.578, p<0.001, p<0.001, respectively). On multivariate analysis, better response to first-line therapy (CR/PR: HR=0.751, p=0.002; SD: HR=0.781, p=0.021) and progression within 3-6 months (HR=0.626, p<0.001), together with adenocarcinoma (HR=0.815, p=0.017), without liver metastasis (HR=0.541, p=0.001), never-smoker (HR=0.772, p=0.001), and ECOG PS 0-1 (HR=0.745, p=0.021) were predictors for good OS following second-line chemotherapy. Conclusions: Patients who responded to first-line chemotherapy had a better outcome after second-line therapy for advanced NSCLC, and the efficacy of first-line chemotherapy, period of progression, histology, liver metastasis, smoking status and ECOG PS were independent prognostic factors for OS.

• Radiation Oncology Journal
• /
• 제24권4호
• /
• pp.230-236
• /
• 2006

목 적: 국소진행성 비소세포폐암 환자에 대한 매주 paclitaxel 항암화학요법과 방사선치료 동시 요법의 안정성과 효과를 알아보고 재발 양상 및 생존율을 분석하고자 하였다. 대상 및 방법: 1999년 10월부터 2004년 9월까지 국소진행성 비소세포폐암으로 진단받고 근치적 목적으로 항암화학방사선 동시요법을 시행 받은 환자 23명을 대상으로 후향적 분석을 시행하였다. 방사선치료는 일일 1회 1.8 Gy씩 주5회 분할 조사하여 $7{\sim}8$주에 걸쳐 총 선량 $55.8{\sim}64.8$ (median 64.8) Gy를 조사하였다. 항암화학요법은 매주 paclitaxel 50 또는 $60\;mg/m^2$ 용량으로 방사선치료 1일, 8일, 15일, 22일, 29일 36일째에 투여하였다. 항암화학방사선 동시요법을 마친 4주 후부터 paclitaxel $135\;mg/m^2$와 cisplatin $75\;mg/m^2$ 용량으로 3주 간격으로 3주기의 공고 항암화학요법을 추가 시행하였다. 결 과: 동시 항암화학방사선요법을 시행받은 23명의 환자 중 3명이 도중에 환자 임의로 치료를 중단하였고 1명이 5,580 cGy까지 방사선치료를 시행 받고 세균성 폐렴으로 사망하였다. 주된 급성 부작용은 방사선 식도염으로 4명(17%)의 환자에서 2도의 식도염이 관찰되었으며 3도 이상의 부작용은 관찰되지 않았다. 16명의 환자가 추가 공고 항암화학요법을 시행 받았으며 공고 항암화학요법 중의 급성 부작용으로 3도 이상의 호중구 감소증이 8명(50%)의 환자에서 관찰되었으며 그중 한 명은 패혈증으로 사망하였다. 동시 항암화학방사선요법을 끝까지 시행 받은 20명의 환자에서 치료에 대한 반응을 조사할 수 있었으며 완전 관해 4명(20%), 부분 관해 14명(70%)으로 전체 관해율은 90%이었다. 관해를 보인 환자들 중 추적 관찰이 가능했던 16명 중 14명에서 재발이 확인되었고 국소 재발이 9명(56%), 국소 재발과 원격 전이가 3명(19%), 원격 전이가 2명(13%)이었다. 동시 항암화학방사선요법을 끝까지 시행받은 환자들에서의 무진행 생존 기간의 중앙값은 9.5개월이었으며, 2년 무진행 생존율은 18%이었다. 재발된 환자 중 11명에서 2차(second-line) 또는 3차(third-line) 항암화학요법이 시행되었다. 전체 환자 23명의 중앙 생존 기간은 21개월, 2년 및 5년 생존율은 각각 43%, 33%였다. 다변량 분석을 시행했을 때 환자의 나이, 수행 능력, 종양의 크기는 무진행 생존율에 영향을 주는 유의한 예후 인자로 나타났다. 결 론: 국소진행성 비소세포폐암 환자에서 paclitaxel 매주 투여 항암화학요법과 방사선치료 동시요법은 안전하고 종양의 관해율도 높았다. 그러나 국소 재발률이 높고 특히 종양의 크기가 큰 환자에서 예후가 나쁜 것을 알 수 있었다. 따라서 향후 부작용은 증가시키지 않으면서 국소제어율을 향상시키기 위한 노력이 필요하다.

• Tuberculosis and Respiratory Diseases
• /
• 제58권4호
• /
• pp.344-351
• /
• 2005

배 경 : Gemcitabine, paclitaxel, docetaxel, vinorelbine, irrinotecan 새로운 항종양제의 출현으로 일차 치료의 효과가 증대 되고 있고 재발시에도 좋은 신체 활동도를 보이고 있어서 이차 치료의 대상군도 늘어나는 효과를 보이고 있다. 치료의 필요성은 증대 되고 있지만 현재까지 표준 치료가 확립되지 않은 상황에서 Gemcitabine과 Vinorelbine 모두 독성이 강하지 않아서 혼합 요법이 가능한 장점이 있고 비소세포폐암에 대한 효과도 입증이 되어있어서 본 연구는 반응이 없거나 반응을 보인후에 재발된 진행된 비소세포 폐암에 gemcitabine과 vinorelbine 혼합 요법을 시행하여서 치료 반응률과 생존율 그리고 부작용을 평가하였다. 대상 및 방법 : 2000년 6월부터 2004년 3월까지 충남대학교병원에 내원하여 진행성 비소세포 폐암 IIIA/IIIB, IV로 진단을 받고 일차 항암화학요법치료를 받은 환자중에 초기 치료에 반응이 없거나, 치료에 반응이 있었으나 병이 진행된 환자로 추적 관찰 기간이 6개월 이상인 환자를 대상으로 생존율과 반응률 그리고 독성을 분석하였다. 결 과 : 총 치료 반응률은 17%, 반응 유지기간의 중앙값은 3.1개월(1-10개월)이었고 생존기간의 중앙값은 8.2개월(1-23개월) 그리고 1년 생존율은 35%였다. 항암화학요법에 의한 독성은 3도 이상의 중성구 감소가 12%, 오심과 구토가 12.5% 였다. 결 론 : 일차 치료에 반응이 없거나 재발한 비소세포 폐암환자의 이차 치료로 gemcitabine과 vinorelbine 혼합요법은 효과적이라고 생각되며 향후 3상 연구를 통한 다른 약제와의 비교 연구가 필요하다고 생각된다.

• Tuberculosis and Respiratory Diseases
• /
• 제85권2호
• /
• pp.155-164
• /
• 2022

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