• Title/Summary/Keyword: Proportional hazards

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Genetic Variants of NBS1 Predict Clinical Outcome of Platinum-based Chemotherapy in Advanced Non-small Cell Lung Cancer in Chinese

  • Xu, Jia-Li;Hu, Ling-Min;Huang, Ming-De;Zhao, Wan;Yin, Yong-Mei;Hu, Zhi-Bin;Ma, Hong-Xia;Shen, Hong-Bing;Shu, Yong-Qian
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.3
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    • pp.851-856
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    • 2012
  • Objective: NBS1 plays a key role in the repair of DNA double-strand break (DSB). We conducted this study to investigate the effect of two critical polymorphisms (rs1805794 and rs13312840) in NBS1 on treatment response and prognosis of advanced non-small cell lung cancer (NSCLC) patients with platinum-based chemotherapy. Methods: Using TaqMan methods, we genotyped the two polymorphisms in 147 NSCLC patients. Odds ratios (ORs) and their 95% confidential intervals (CIs) were calculated as a measure of difference in the response rate of platinum-based chemotherapy using logistic regression analysis. The Kaplan-Meier and log-rank tests were used to assess the differences in progression-free survival (PFS) and overall survival (OS). Cox proportional hazards model was applied to assess the hazard ratios (HRs) for PFS and OS. Results: Neither of the two polymorphisms was significantly associated with treatment response of platinum-based chemotherapy. However, patients carrying the rs1805794 CC variant genotype had a significantly improved PFS compared to those with GG genotype (16.0 vs. 8.0 months, P = 0.040). Multivariable cox regression analysis further showed that rs1805974 was a significantly favorable prognostic factor for PFS [CC/CG vs. GG: Adjusted HR = 0.62, 95% CI: 0.39-0.99; CC vs. CG/GG: Adjusted HR = 0.56, 95% CI: 0.32-0.97). Similarly, rs13312840 with a small sample size also showed a significant association with PFS (CC vs. CT/TT: Adjusted HR = 25.62, 95% CI: 1.53-428.39). Conclusions: Our findings suggest that NBS1 polymorphisms may be genetic biomarkers for NSCLC prognosis especially PFS with platinum-based chemotherapy in the Chinese population.

Gamma Knife Radiosurgery for Brain Metastases from Breast Cancer

  • Jo, Kyung Il;Im, Young-Hyuck;Kong, Doo Sik;Seol, Ho Jun;Nam, Do-Hyun;Lee, Jung-Il
    • Journal of Korean Neurosurgical Society
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    • v.54 no.5
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    • pp.399-404
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    • 2013
  • Objective : The authors conducted a retrospective cohort study to determine prognostic factors and treatment outcomes of brain metastases (BM) from breast cancer (BC) after Gamma Knife radiosurgery (GKS). Methods : Pathologic and clinical features, and outcomes were analyzed in a cohort of 62 patients with BM from BC treated by GKS. The Kaplan- Meier method, the log-rank test, and Cox's proportional hazards model were used to assess prognostic factors. Results : Median survival after GKS was 73.0 weeks (95% confidence interval, 46.0-100.1). HER2+ [hazard ratio (HR) 0.441; p=0.045], Karnofsky performance scale (KPS) ${\geq}70$ (RR 0.416; p=0.050) and systemic chemotherapy after GKS (RR 0.282; p=0.001) were found to be a favorable prognostic factor of overall survival. Actuarial local control (LC) rate were $89.5{\pm}4.5%$ and $70.5{\pm}6.9%$ at 6 and 12 months after GKS, respectively. No prognostic factors were found to affect LC rate. Uni- and multivariate analysis revealed that the distant control (DC) rate was higher in patients with; a small number (${\leq}3$) of metastasis (HR 0.300; p=0.045), no known extracranial metastasis (p=0.013, log-rank test), or the HER2+ subtype (HR 0.267; p=0.027). Additional whole brain radiation therapy and metastasis volume were not found to be significantly associated with LC, DC, or overall survival. Conclusion : The treatment outcomes of patients with newly diagnosed BM from BC treated with GKS could be affected primarily by intrinsic subtype, KPS, and systemic chemotherapy. Therapeutic strategy and prognosis scoring system should be individualized based on considerations of intrinsic subtype in addition to traditionally known parameters related to stereotactic radiosurgery.

Risk Factors for Clinical Metastasis in Men Undergoing Radical Prostatectomy and Immediate Adjuvant Androgen Deprivation Therapy

  • Taguchi, Satoru;Fukuhara, Hiroshi;Kakutani, Shigenori;Takeshima, Yuta;Miyazaki, Hideyo;Suzuki, Motofumi;Fujimura, Tetsuya;Nakagawa, Tohru;Igawa, Yasuhiko;Kume, Haruki;Homma, Yukio
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.24
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    • pp.10729-10733
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    • 2015
  • Background: Adjuvant androgen deprivation therapy (ADT) is a treatment option for prostate cancer (PC) patients after radical prostatectomy (RP). Although it can achieve a good progression-free survival rate, some patients still develop clinical metastasis. We here investigated risk factors of clinical metastasis in post-prostatectomy patients who received immediate adjuvant ADT. Materials and Methods: We identified 197 patients with non-metastatic PC who underwent RP at our institution between 2000 and 2012, followed by adjuvant ADT. The associations of various clinicopathologic factors with clinical metastasis (primary endpoint) and cancer-specific survival (secondary endpoint) were assessed. Multivariate analysis was conducted using a Cox proportional hazards model. Median follow-up was 87 months after RP. Results: Nine (4.6%) patients developed clinical metastasis and six (3.0%) died from PC. Eight of nine metastatic patients had a pathologic Gleason score (GS) 9 and developed bone metastasis, while the remaining one had pathologic GS 7 and developed metastasis only to para-aortic lymph nodes. On multivariate analyses, pathologic GS ${\geq}9$ and regional lymph node metastasis (pN1) were independent predictors of clinical metastasis and pathologic GS ${\geq}9$ was an independent predictor of cancer-specific death. Conclusions: Pathologic GS ${\geq}9$ and pN1 were independent predictors of clinical metastasis in post-prostatectomy patients who received immediate adjuvant ADT. Furthermore, pathologic GS ${\geq}9$ was an indispensable condition for bone metastasis, which may imply that patients with GS ${\leq}8$ on adjuvant ADT are unlikely to develop bone metastasis.

Metastatic Axillary Lymph Node Ratio (LNR) is Prognostically Superior to pN Staging in Patients with Breast Cancer -- Results for 804 Chinese Patients from a Single Institution

  • Xiao, Xiang-Sheng;Tang, Hai-Lin;Xie, Xin-Hua;Li, Lai-Sheng;Kong, Ya-Nan;Wu, Min-Qing;Yang, Lu;Gao, Jie;Wei, Wei-Dong;Xie, Xiaoming
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.9
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    • pp.5219-5223
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    • 2013
  • The number of axillary lymph nodes involved and retrieved are important prognostic factors in breast cancer. The purpose of our study was to investigate whether the lymph node ratio (LNR) is a better prognostic factor in predicting disease-free survival (DFS) for breast cancer patients as compared with pN staging. The analysis was based on 804 breast cancer patients who had underwent axillary lymph node dissection between 1999 and 2008 in Sun Yat-Sen University Cancer Center. Optimal cutoff points of LNR were calculated using X-tile software and validated by bootstrapping. Patients were then divided into three groups (low-, intermediate-, and high-risk) according to the cutoff points. Predicting risk factors for relapse were performed according to Cox proportional hazards analysis. DFS was estimated using the Kaplan-Meier method and compared by the log-rank test. The 5-year DFS rate decreased significantly with increasing LNRs and pN. Univariate analysis found that the pT, pN, LNR, molecule type, HER2, pTNM stage and radiotherapy well classified patients with significantly different prognosis. By multivariate analysis, only LNR classification was retained as an independent prognostic factor. Furthermore, there was a significant prognostic difference among different LNR categories for pN2 category, but no apparent prognostic difference was seen between different pN categories in any LNR category. Therefore, LNR rather than pN staging is preferable in predicting DFS in node positive breast cancer patients, and routine clinical decision-making should take the LNR into consideration.

Influences of Continuance Intention and Past Behavior on Active Users' Knowledge Sharing Continuance and Frequency: Naver Knowledge-iN case (지속의도와 과거행위가 핵심 사용자의 지식공유 지속여부 및 빈도에 미치는 효과: 네이버 지식인 사례)

  • Kang, Minhyung
    • Knowledge Management Research
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    • v.21 no.3
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    • pp.67-87
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    • 2020
  • Maintaining active users who repeatedly share high-quality knowledge is critical for the success of online Q&A sites. This study suggests two paths that lead to active users' continuous knowledge sharing: 1) elaborated decision process, represented by continuance intention, and 2) automated cognitive process, represented by past behavior. The direct and moderating effects of continuance intention and past behavior were verified by analyzing subjective intention data and objective behavior data of 333 active users of Naver Knowledge-iN. Using Cox proportional hazards regression and negative binomial regression, the influences of continuance intention and past behavior on two types of continuous knowledge sharing were examined. The results showed that only past behavior was significantly influential on knowledge sharing continuance and as to the frequency of knowledge sharing, both continuance intention and past behavior's influences were significant. It was also confirmed that past behavior negatively moderates continuance intention's effect on the frequency of knowledge sharing. In order to maintain active users' continuous knowledge sharing, it is important to habituate knowledge sharing through repetitive knowledge sharing behavior. And in order to increase the frequency of knowledge sharing, in addition to the habituation, appropriate benefits that can increase the continuance intention should be provided.

Exploitation of the Dose/Time-Response Relationship for a New Measure of DNA Repari in the Single-Cell Gel Electrophoresis (Comet) Assay

  • Kim, Byung-Soo;Edler, Lutz;Park, Jin-Joo;Fournier, Dietrich Von;Haase, Wulf;Sautter-Bihl, Mare-Luise;Hagmuller, Egbert;Gotzes, Florian;Thielmann, Heinz Walter
    • Toxicological Research
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    • v.20 no.2
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    • pp.89-100
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    • 2004
  • The comet assay (also called the single-cell gel electrophoresis assay) has been widely used for detecting DNA damage and repair in individual cells. Since the conventional methods of evaluating comet assay data using frequency statistics are unsatisfactory we developed a new quantitative measure of DNA damage/repair that is based on all information residing in the dose/time-response curves of a comet experiment. Blood samples were taken from 25 breast cancer patients before undergoing radiotherapy. The comet assay was performed under alkaline conditions using isolated lymphocytes. Tail DNA, tail length, tail moment and tail inertia of the comet were measured for each patient at four doses of $\gamma$-rays (0, 2, 4 and 8 Gy) and at four time points after irradiation (0, 10, 20 and 30 min) using 100 cells each. The resulting three-dimensional dose-time response surface was modeled by multiple regression, and the second derivative, termed 2D, on dose and time was determined. A software module was programmed in SAS/AF to compute 2D values. We applied the new method successfully to data obtained from cancer patients to be assessed for their radiation sensitivity. We computed the 2D values for the four damage measures, i.e., tail moment, tail length, tail DNA and tail inertia, and examined the pairwise correlation coefficients of 2D both on the log scale and the unlogged scale. 2D values based on tail moment and tail DNA showed a high correlation and, therefore, these two damage measures can be used interchangeably as far as DNA repair is concerned. 2D values based on tail inertia have a correlation profile different from the other 2D values which may reflect different facets of DNA damage/repair. Using the dose-time response surface, other statistical models, e.g., the proportional hazards model, become applicable for data analysis. The 2D approach can be applied to all DNA repair measures, Le., tail moment, tail length, tail DNA and tail inertia, and appears to be superior to conventional evaluation methods as it integrates all data of the dose/time-response curves of a comet assay.

Pesticides and Cancer Incidence - The Kangwha Cohort Study - (농약사용과 암발생과의 관계)

  • Sull, Jae-Woong;Yi, Sang-Wook;Sohn, Tae-Yong;Jee, Sun-Ha;Nam, Chung-Mo;Ohrr, Hee-Chul
    • Journal of Preventive Medicine and Public Health
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    • v.35 no.1
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    • pp.24-32
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    • 2002
  • Objective : Few studies have examined the relationship between the risk of cancer and exposure to pesticides in Korea or in other East Asian that have until recently used chlorophenoxy herbicides. The aim of this study was to evaluate the relationship between the exposure to pesticides and cancer incidence. Methods : We conducted a prospective cohort study with a follow-up period of 13 years (1985-1998). The subjects included 2,687 male and 3,589 female Kangwha Island residents, Koreans aged fifty-five or more as of March 1985, who received a personal health interview and completed a health examination survey. A Cox proportional hazards models were used to estimate relative risks(RR). Results : At baseline, the mean age of the study participants in 1985 was 66.4 for males and 67.1 for females. During the 13 years follow-up, a total of 300 incidents of cancer in males and 140 in females developed. In males, the total cancer incidence in the highest group was RR, 1.4 (95%. CI=1.0-1.9), p for trend=0.041, for digestive organ cancer Incidence in the highest group, RR, 1.5 (95% CI=1.0-2.3), p for trend=0.057, for stomach cancer, incidence in the highest group, RR, 1.6 (95% CI=0.9-2.8), p for trend=0.094, for gallbladder cancer incidence in the highest group, RR, 9.1 (95% CI=1.1-77.0), p for trend=0.014 were elevated according to the higher frequency of pesticide use per year. In particular, the risk of gallbladder cancer was very high. Although not significant, the risk of liver cancer was higher than in the non-exposed group (in the highest group, RR, 2.0(95% CI=0.7-5.9)). In females, although not significant, breast cancer incidence in the highest exposure group was higher than in the non-exposed group (in the highest group, RR, 4.7 (95% CI=0.5-27.9)). Conclusions : This study demonstrates that Korean farmers who use pesticides, particularly males, have a significantly higher total cancer incidence, particularly from digestive organ cancers such as, stomach, gallbladder, and liver cancer. In particular, the risk of gallbladder cancer was very high.

The Prognostic Value of the Preoperative Lymphocyte Count in Patients with Gastric Cancer (위암환자에서 수술 전 말초혈액 림프구 수와 예후)

  • Kang, Shin-Yong;Yu, Wan-Sik;Chung, Ho-Young;Park, Sung-Hun
    • Journal of Gastric Cancer
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    • v.9 no.1
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    • pp.26-30
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    • 2009
  • Purpose: The aim of this study was to evaluate the prognostic value of the peripheral blood lymphocyte count before surgery in those patients with gastric cancer. Materials and Methods: The study group was comprised of a series of 1,054 patients who underwent curative gastrectomy. The appropriate lymphocyte count cutoff value was determined. The prognostic factors were evaluated by univariate and multivariate analyses. Results: The lymphocyte count cutoff value was 1,500/ul. The patients were classified into two groups: Group A had a lymphocyte count $\geq$ 1,500/ul (n=765) and Group B had a lymphocyte count <1,500/ul (n=289). There were statistically significant differences between the groups according to their age (P<0.001), the tumor stage (P=0.038) and the tumor size (P<0.001). The 5- and 10-year survival rates of Group A were 80.1% and 76.6%, respectively and those of Group B were 72.4% and 63.5%, respectively (P=0.002). When multivariate analysis was performed by the Cox proportional hazards model, the lymphocyte count was not an independent prognostic factor. Conclusion: Although the prognosis of patients with a high lymphocyte count was better than that of the patients with a low lymphocyte count, our results did not support using the preoperative peripheral blood lymphocyte count as an independent prognostic factor for patients with gastric cancer.

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Association between BMI and Mortality - Kangwha cohort study - (BMI와 사망과의 관련성 - 강화 코호트 연구 -)

  • Yoon, Soo-Jin;Yi, Sang-Wook;Kim, Soh-Yoon;Lee, Soon-Young;Park, Yun-Hee;Sohn, Tae-Yong;Ohrr, Hee-Choul
    • Journal of Preventive Medicine and Public Health
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    • v.33 no.4
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    • pp.459-468
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    • 2000
  • Objectives : To investigate the association between BMI and Mortality. Methods : This study was based on the analysis and assembly of the 'Kangwha Cohort Study', previously conducted by the Department of Preventive Medicine, Yonsei University. A total of 2,696 males and 3,595 females were followed for almost ten years and ten months from March 1985 to January 1996, a total of whom 2,420 died during this period. The Cox's proportional hazards regression model was used to analyze this data. Results : We found a U-shaped relationship between BMI and mortality among the aged men in the Kangwha cohort. The hazard ratio of dying was adjusted for age, marital status, occupation, self cognitive health level, chronic disease, smoking, and alcohol frequency, then sorted by body mass index into the following groups; less than 10.5, 18.5 to less than 21.0, 21.0 to less than 23.5, 23.5 to less than 26.0 and greater than or equal to 26. The corresponding ratios for men were 1.81(1.50-2.19, 95%CI), 1.31(1.14-1.51, 95%CI), 1.0(referent), 1.05(0.87-1.26, 95%CI) and 1.39(1.09-1.76, 95%CI), respectively. And for women, 1.46(1.19-1.78), 1.12(0.95-1.31, 95%CI), 1.0(referent), 1.00(0.84-1.20, 95%CI) and 1.09(0.89-1.34, 95%CI), respectively. Conclusions : The risk of death among aged men in Kangwha increased in the under and overweight groups. The relationship between BMl and mortality has been well studied in Western populations, but little is known about the association between BMI and mortality in our country. So, on the basis of this study, it is apparent that more studies of the relationship between BMI and mortality will be needed for future work.

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The Role of Surgical Resection in the Treatment of Newly-Diagnosed Supratentorial Lobar Glioblastoma in Adults (성인에서 천막상부, 두개엽에 위치한 원발성 교모세포종의 치료에서 종양 절제의 역할)

  • Rhee, Jong Joo;Ahn, Jae Sung;Jeon, Sang Ryong;Kim, Jeong Hoon;Ra, Young Shin;Kim, Chang Jin;Lee, Jung Kyo;Kwun, Byung Duk
    • Journal of Korean Neurosurgical Society
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    • v.30 no.sup2
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    • pp.221-227
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    • 2001
  • Objective : The therapeutic impact of tumor resection in glioblastomas is poorly defined and still questionable. Therefore, we conducted the current study to verify the role of tumor resection in the treatment of these highly malignant tumors. Methods : A retrospective study was performed(1990-1999) to compare the treatment results of surgical resection plus radiotherapy(130 patients) with those of stereotactic biopsy plus radiotherapy(19 patients) in glioblastomas. Only adult patients with supratentorial, de novo glioblastoma located in one lobe were included. Survival time/rate was analysed with Kaplan-Meier method, and prognostic variables were obtained from the univariate log-rank test and the multivariate Cox's proportional hazards model. Results : The resection group and the biopsy group did not differ in terms of age, gender, duration of symptoms, presenting symptoms, tumor location, tumor side, tumor size, and the frequency of midline shift. Patients in the biopsy group more often were found to have worse preoperative Karnofsky performance status(KPS)(p=0.001). On univariate analysis, age, KPS, and tumor side were associated with survival(p=0.0053, 0.0001, and 0.0331 respectively). Median survival time and 1-year survival rate were also statistically improved by tumor resection ; resection group - 13 months and 61.2%, and biopsy group - 8 months and 19.7%, respectively(p=0.0001). In patients with midline shift of the tumor, resection was highly effective comparing to biopsy(p=0.0001), but in patients without midline shift, external beam radiation alone was as effective as tumor resection(p=0.0605). Other prognostic variables did not affect survival. On multivariate analysis after variable selection, survival was independently associated with KPS(p=0.001), but not the surgical resection(p=0.2837). Even in biopsy group with midline shift of the tumor, survival rate was not different from that seen after tumor resection(p=0.3505). Conclusions : Radiotherapy alone was as effective as tumor resection plus radiotherapy in patients without midline shift of the tumor. Although there was not statistically significant, tumor resection looked like effective in patients with midline shift. For supratentorial, lobar glioblastoma patients without mass effect of the tumor, biopsy with radiotherapy is one of rational treatment strategies. We consider that tumor resection should be performed in patients with pretreatment midline shift.

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