• Asian Pacific Journal of Cancer Prevention
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• 제16권16호
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• pp.7359-7363
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• 2015

Background: As a result of significant progress made in treatment of many types of cancers during the last few decades, there have been an increased number of patients who do not experience mortality. We refer to these observations as cure or immune and models for survival data which include cure fraction are known as cure rate models or long-term survival models. Materials and Methods: In this study we used the data collected from 438 female patients with breast cancer registered in the Cancer Research Center in Shahid Beheshti University of Medical Sciences, Tehran, Iran. The patients had been diagnosed from 1992 to 2012 and were followed up until October 2014. We had to exclude some because of incomplete information. Phone calls were made to confirm whether the patients were still alive or not. Deaths due to breast cancer were regarded as failure. To identify clinical, pathological, and biological characteristics of patients that might have had an effect on survival of the patients we used a non-mixture cure rate model; in addition, a Weibull distribution was proposed for the survival time. Analyses were performed using STATA version 14. The significance level was set at $P{\leq}0.05$. Results: A total of 75 patients (17.1%) died due to breast cancer during the study, up to the last follow-up. Numbers of metastatic lymph nodes and histologic grade were significant factors. The cure fraction was estimated to be 58%. Conclusions: When a cure fraction is not available, the analysis will be changed to standard approaches of survival analysis; however when the data indicate that the cure fraction is available, we suggest analysis of survival data via cure models.

• Asian Pacific Journal of Cancer Prevention
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• 제16권17호
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• pp.7923-7927
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• 2015

Background: The Cox PH model is one of the most significant statistical models in studying survival of patients. But, in the case of patients with long-term survival, it may not be the most appropriate. In such cases, a cure rate model seems more suitable. The purpose of this study was to determine clinical factors associated with cure rate of patients with breast cancer. Materials and Methods: In order to find factors affecting cure rate (response), a non-mixed cure rate model with negative binomial distribution for latent variable was used. Variables selected were recurrence cancer, status for HER2, estrogen receptor (ER) and progesterone receptor (PR), size of tumor, grade of cancer, stage of cancer, type of surgery, age at the diagnosis time and number of removed positive lymph nodes. All analyses were performed using PROC MCMC processes in the SAS 9.2 program. Results: The mean (SD) age of patients was equal to 48.9 (11.1) months. For these patients, 1, 5 and 10-year survival rates were 95, 79 and 50 percent respectively. All of the mentioned variables were effective in cure fraction. Kaplan-Meier curve showed cure model's use competence. Conclusions: Unlike other variables, existence of ER and PR positivity will increase probability of cure in patients. In the present study, Weibull distribution was used for the purpose of analysing survival times. Model fitness with other distributions such as log-N and log-logistic and other distributions for latent variable is recommended.

• 응용통계연구
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• 제27권1호
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• pp.21-30
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• 2014

치유율 모형(cure rate model)은 위험 그룹의 단조 감소에 대한 가정이 부적절한 경우에 적용될 수 있다. 예를 들어, 생존 분석에서 위험 그룹은 시간이 경과함에 따라 점점 감소하여 무한대의 시간대에는 영으로 수렴하며 이는 곧 생존 함수가 영으로 수렴함을 의미한다. 하지만 이러한 가정이 적합하지 못한 자료가 의약학, 사회학, 경제학 등에서 종종 발생된다. 즉, 어느 시점에 이르러 더 이상의 생존함수는 감소하지 않고 평행선을 보여주는 경우에 로그 순위검정(log rank test)과 Cox's 비례위험모형(proportional hazard model)의 적용은 바람직하지 못한 결론을 가져오게 된다. 이러한 자료에 대해 치유율 모형(cure rate model)에서는 사건 발생 취약 그룹(susceptible group)과 비취약 그룹(insusceptible group)으로 나누어 취약그룹에 대해서만 일반적인 생존 분석 방법을 적용하는 혼합 모형(mixture model)을 적용해왔다 (Berkson과 Gage, 1952). 본 연구에서는 이러한 치유율 모형을 군집화 구간 중도 절단 자료(clustered interval censored data)에 적용해 보고자 한다. 최근에 Kim과 Jhun (2008)은 구간 중도 절단자료에 대해 치유율 모형을 적용하였으며 본 연구에서는 그들의 방법을 군집화 자료로 확장할 것이다. 실제 자료 분석의 예로 금연자료를 분석할 것이다.

• Communications for Statistical Applications and Methods
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• 제24권4호
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• pp.397-419
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• 2017

A four-parameter extended fatigue lifetime model called the odd Birnbaum-Saunders geometric distribution is proposed. This model extends the odd Birnbaum-Saunders and Birnbaum-Saunders distributions. We derive some properties of the new distribution that include expressions for the ordinary moments and generating and quantile functions. The method of maximum likelihood and a Bayesian approach are adopted to estimate the model parameters; in addition, various simulations are performed for different parameter settings and sample sizes. We propose two new models with a cure rate called the odd Birnbaum-Saunders mixture and odd Birnbaum-Saunders geometric models by assuming that the number of competing causes for the event of interest has a geometric distribution. The applicability of the new models are illustrated by means of ethylene data and melanoma data with cure fraction.

• 응용통계연구
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• 제17권2호
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• pp.253-267
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• 2004

임상시험중에는 소아암연구에서와 같이 환자 중의 상당수에서 사망 또는 재발이 오랜 기간 일어나지 않고 완치된 것으로 보이는 경우가 있다. 이 경우 연구자는 생존함수의 전반적인 비교보다는 치료율의 비교에 더 관심이 있을 것이다. 본고에서는 치료율의 비교를 위한 여러 모수적, 비모수적 방법들을 소개하고, 생존분포, 치료율, 중도절단을 등을 다양하게 설정한 모의실험을 통하여 각 방법들의 검정력과 유의수준을 비교하였다.

• Communications for Statistical Applications and Methods
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• 제25권5호
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• pp.471-488
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• 2018

In this paper, we propose extending proportional hazards frailty models to allow a discrete distribution for the frailty variable. Having zero frailty can be interpreted as being immune or cured. Thus, we develop a new survival model induced by discrete frailty with zero-inflated power series distribution, which can account for overdispersion. This proposal also allows for a realistic description of non-risk individuals, since individuals cured due to intrinsic factors (immunes) are modeled by a deterministic fraction of zero-risk while those cured due to an intervention are modeled by a random fraction. We put the proposed model in a Bayesian framework and use a Markov chain Monte Carlo algorithm for the computation of posterior distribution. A simulation study is conducted to assess the proposed model and the computation algorithm. We also discuss model selection based on pseudo-Bayes factors as well as developing case influence diagnostics for the joint posterior distribution through ${\psi}-divergence$ measures. The motivating cutaneous melanoma data is analyzed for illustration purposes.

• Communications for Statistical Applications and Methods
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• 제24권6호
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• pp.605-625
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• 2017

This paper presents proportional odds cure models to allow spatial correlations by including spatial frailty in the interval censored data setting. Parametric cure rate models with independent and dependent spatial frailties are proposed and compared. Our approach enables different underlying activation mechanisms that lead to the event of interest; in addition, the number of competing causes which may be responsible for the occurrence of the event of interest follows a Geometric distribution. Markov chain Monte Carlo method is used in a Bayesian framework for inferential purposes. For model comparison some Bayesian criteria were used. An influence diagnostic analysis was conducted to detect possible influential or extreme observations that may cause distortions on the results of the analysis. Finally, the proposed models are applied for the analysis of a real data set on smoking cessation. The results of the application show that the parametric cure model with frailties under the first activation scheme has better findings.

• Asian Pacific Journal of Cancer Prevention
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• 제15권22호
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• pp.9673-9678
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• 2014

Background: Breast cancer is a fatal disease and the most frequently diagnosed cancer in women with an increasing pattern worldwide. The burden is mostly attributed to metastatic cancers that occur in one-third of patients and the treatments are palliative. It is of great interest to determine factors affecting time from cancer diagnosis to secondary metastasis. Materials and Methods: Cure rate models assume a Poisson distribution for the number of unobservable metastatic-component cells that are completely deleted from the non-metastasis patient body but some may remain and result in metastasis. Time to metastasis is defined as a function of the number of these cells and the time for each cell to develop a detectable sign of metastasis. Covariates are introduced to the model via the rate of metastatic-component cells. We used non-mixture cure rate models with Weibull and log-logistic distributions in a Bayesian setting to assess the relationship between metastasis free survival and covariates. Results: The median of metastasis free survival was 76.9 months. Various models showed that from covariates in the study, lymph node involvement ratio and being progesterone receptor positive were significant, with an adverse and a beneficial effect on metastasis free survival, respectively. The estimated fraction of patients cured from metastasis was almost 48%. The Weibull model had a slightly better performance than log-logistic. Conclusions: Cure rate models are popular in survival studies and outperform other models under certain conditions. We explored the prognostic factors of metastatic breast cancer from a different viewpoint. In this study, metastasis sites were analyzed all together. Conducting similar studies in a larger sample of cancer patients as well as evaluating the prognostic value of covariates in metastasis to each site separately are recommended.

• Communications for Statistical Applications and Methods
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• 제25권3호
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• pp.245-261
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• 2018

Attempts have been made to define new classes of distributions that provide more flexibility for modelling skewed data in practice. In this work we define a new extension of the generalized gamma distribution (Stacy, The Annals of Mathematical Statistics, 33, 1187-1192, 1962) for Marshall-Olkin generalized gamma (MOGG) distribution, based on the generator pioneered by Marshall and Olkin (Biometrika, 84, 641-652, 1997). This new lifetime model is very flexible including twenty one special models. The main advantage of the new family relies on the fact that practitioners will have a quite flexible distribution to fit real data from several fields, such as engineering, hydrology and survival analysis. Further, we also define a MOGG mixture model, a modification of the MOGG distribution for analyzing lifetime data in presence of cure fraction. This proposed model can be seen as a model of competing causes, where the parameter associated with the Marshall-Olkin distribution controls the activation mechanism of the latent risks (Cooner et al., Statistical Methods in Medical Research, 15, 307-324, 2006). The asymptotic properties of the maximum likelihood estimation approach of the parameters of the model are evaluated by means of simulation studies. The proposed distribution is fitted to two real data sets, one arising from measuring the strength of fibers and the other on melanoma data.

• Biomolecules & Therapeutics
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• 제2권4호
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• pp.376-382
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• 1994

Repeated injections of low-doses of mercuric chloride in rats or mice induce polyclonal activation which includes the induction of anti-glomerular basement membrane (GBM) antibodies and circulating immune complex and it results in nephritis. Because this disease is autoimmune mediated disease resulted from immune dysfunction, immunomodulators are used to control the symptoms or to cure the disease. Irpex lacteus Fr. is a kind of new medicinal fungus. The polysaccharide fraction extracted from submerged fermentation of Irpex lacteus Fr. decreased the serum agglutinin, serolysin and IgM plaque forming cells in normal mice. The hitherto obtained clinical results suggested that it significantly improved the oligourea, edema, and hypertension in patients who have nephritis. To elucidate the action-mechanisms of Irpex lacteus Fr., we established the experimental model of HgCl$_2$induced polyclonal activation by intraperitoneal administrations of HgCl$_2$to mice. To assess the immunomodulating effect of Irpex lacteus fraction, we Investigated its effects on the mitogen induced proliferation and IgM PFC counts of splenic lymphocytes in mice during the treatment of HgCl$_2$. The Irpex lacteus polysaccharide reduced the abnormally increased mitogen induced Iymphocyte proliferation and IgM PFCs to almost normal levels. And the Irpex lacteus polysaccharides prevented the increasement of serum immunoglobulin level induced by HgCl$_2$. These data suggested that the Irpex lacteus polysaccharides might have the immunomodulating activity to prevent and /or improve the HgCl$_2$ induced autoimmune disease.