Estimation of Survival Rates in Patients with Lung Cancer in West Azerbaijan , the Northwest of Iran

Among all diseases, a majority of human effort has been allocated to fight with cancer (Amirimoghadam, 2012). Cancer is one of the major causes of morbidity, mortality and disability worldwide (Haghshenas et al., 2013). Lung cancer is a very common disease with an increasing trend (Bollschweiler et al., 2002). In Iran, after cardiovascular diseases and accidents, cancer is the third leading cause of death (Mousavi et al., 2009). Lung cancer is an important and fatal cancer a five-year survival rate of only 13% after the time of diagnosis (OZLU and BULBUL, 2005; Haraguchi et al., 2012). Cancers in Iran as a whole imposed 662.2 Disability Adjusted Life Years (DALY) per hundred thousand people and after the gastric cancer, the lung cancer is in the second important fatal cancerwith 56.3 DALY (Bollschweiler et al., 2002). According to classification of the America Cancer Society, there are two types of lung cancer: (a) small cell carcinoma (SCC) and (b) non-small cell carcinoma (NSCC), there are many forms of this cancer. This type of lung cancer is defined according to the type of cells in


Introduction
Among all diseases, a majority of human effort has been allocated to fight with cancer (Amirimoghadam, 2012).Cancer is one of the major causes of morbidity, mortality and disability worldwide (Haghshenas et al., 2013).Lung cancer is a very common disease with an increasing trend (Bollschweiler et al., 2002).In Iran, after cardiovascular diseases and accidents, cancer is the third leading cause of death (Mousavi et al., 2009).Lung cancer is an important and fatal cancer a five-year survival rate of only 13% after the time of diagnosis (OZLU and BULBUL, 2005;Haraguchi et al., 2012).Cancers in Iran as a whole imposed 662.2 Disability Adjusted Life Years (DALY) per hundred thousand people and after the gastric cancer, the lung cancer is in the second important fatal cancerwith 56.3 DALY (Bollschweiler et al., 2002).
According to classification of the America Cancer Society, there are two types of lung cancer: (a) small cell carcinoma (SCC) and (b) non-small cell carcinoma (NSCC), there are many forms of this cancer.This type of lung cancer is defined according to the type of cells in the lung tissue (Macdonald et al., 2004).The three main subtypes of NSCC are adenocarcinoma, squamous-cell carcinoma and large-cell carcinoma (Horn et al., 2012).
SCC involves dense neurosecretory granules (Rosti et al., 2006).Most cases arise in the larger airways (primary and secondary bronchi) (Collins et al., 2007).SCC is the most common type of lung cancer and has rapid growth and metastasis rate, and spreads to other organs easily.About 67% of cases have metastatic disease at time of diagnosis.This type of lung cancer is strongly associated with smoking (Horn et al., 2012).NSCC is often treated with surgery, while SCC usually responds better to chemotherapy and radiotherapy (Chapman et al., 2009).
Lung cancer is one of the main causes of death among known cancers and has the highest mortality rates compared to the cancers of breast, prostate and other multiple cancers (a person that getting more than one type of cancer) (Zahir and Mirtalebi, 2012).Unfortunately, it takes a very long time until the lung cancer symptoms become evident.Therefore, in most cases the disease is diagnosed in advanced stages (Fauci, 2008;Silvestri et al., 2009).
Survival rate of patients with any type of cancer is one of the most important indicators in disease control and evaluation of treatment methods (Klein, 2005).Taghipour et al reported a mean survival time of 8.5 months for patients with lung cancer.They reported that only 25% of patients had survived more than one year (Zahir and Mirtalebi, 2012).Drech Gross et al reported a median survival time of 6.5 months for patients with lung cancer and a one-year survival rate of 30% (Grose et al., 2014).Santro et al obtained median survival time of 15.7 months.They estimated median survival time of patients 14.9 and 22.1 months for smokers and non-smokers, respectively (Santoro et al., 2011).Mathew et al reporteda median survival time of 15.2 months with 5-years survival rate of 11% in patients with lung cancer (Schabath et al., 2014).Goksel et al also reporteda median survival of 16.9 months with 5-year survival rate of 9% (Goksel et al., 2013).
West Azerbaijan province is in the northwest of Iran.Until now, no comprehensive study has conducted to examine the lung cancer survival rate and its associated risk factors.This is the first study conducted in this province to estimate survival rate of patients with lung cancer and to determine its associated predictive factors.

Materials and Methods
In this retrospective cohort study, demographic and biological information of all patients with lung cancer admitted to university hospitals of West Azerbaijan province was obtained from 2007 to 2014.Demographic variables included age at time of diagnosis, and gender.Biological variables includedEastern Cooperative Oncology Group (ECOG) performance, smoking, tumor type, tumor stage, metastasis, and blood hemoglobin concentration.The patients were followed by the June 2014 and their information obtained from medical records and through phone calls and home visits.The patients who lost to follow up or diedfor reasons other than lung cancer or was alive at the end of the study were considered as censored.The duration of survival time was measured in months from the time of diagnosis until the end of the study period.The event of interest was death from lung cancer.
The data were analyzed using Stata and R software.Survival rates were estimated by Kaplan-Meier method and compared by Log-rank test to assess the effect of various variables on the patients' survival time.In addition,simple and multiple Cox's regression analyses were performed.
The assumption of hazard proportionality was checked by the Schenofeld residual test.The assumption was not rejected for any variable.Significance level for statistical tests was 0.05.

Results
Of the 355 patients under study, 240 died and 115 were censored.About 72.1% of the patients (256 cases) were males and 27.9% (99 cases) were females (male to female ratio was 2.6).The mean age at time of diagnosis was 63.5±13.5 (ranged from 11 to 91 years).The mean age at time of diagnosis for men and women was 65.0±12.4and 59.4±15.5 years, respectively (p=0.002).The mean and median survival time of patients was13 and 4.8 months, respectively.The mean and median survival time for men was 12.5 and 8.1 months and that of women was13.910.1 months, respectively.The Log-rank test did not show any significant difference between the survival time in men and women (p=0.350).
According to the results of Kaplan-Meier method, 1, 2, and 3 years survival rate of patients was 39%, 18%, and 0.07%, respectively (Figure 1).One-year survival rate was 38% for men and 41% for women, which log-rank test did Lung cancers based on histological classification are divided into three types of NSCC, SCC and carcinoid tumor.In this study, 71.8% of cases had NSCC, 9%had SCC and 19.3% had carcinoid tumor.The mean and standard deviation of blood hemoglobin was 11.9 (±2.2) mg/dl for men and was 11.2±1.9mg/dl for women.Other characteristics of the patients are given in Table 1.
The results of univariate Cox regression showed that male patients, whose blood hemoglobin level was less than 14 mg/dl had a higher survival rate compared to male subjects with a blood hemoglobin level more than 14 md/ dl (p=0.021,HR=1.44).This variable was not significant for females (p=0.507,HR=1.23).
To evaluate the effect of variables on survival time, unadjusted univariate Cox's regression was used.The results showed that age at diagnosis time, smoking status, tumor type, treatment, and metastasis had a significant effect on the survival time (Table 2).In addition, multiple Cox regression was used to estimate the adjusted effects of potential risk factors on survival time.In multiple Cox regression the ECOG performance, smoking status and treatment was significantly associated with survival time of patients with lung cancer.Unlike univariate regression, the adjusted association between lung cancer and age at the time diagnosis, tumor stage, and metastasis was not statistically significant in multiple regression analysis (Table 2).

Discussion
The results of this study indicated that age at the time of diagnosis, ECOG performance, smoking status, stage group, treatment, and metastasis had a significant effect on the patients' survival probability.
Based on our results, the mean age at the time diagnosis was consistent with to results of other studies conducted in Iran and other countries (Arrieta et al., 2012;Zahir and Mirtalebi, 2012).Although sex is one of the effective factors on survival time, in the current study, the sex was not significantly related to survival time as was reported by Zahir Mirtalebi et al. (2012).However, some studies have indicated that survival time in women is more than in men (Battafarano et al., 2002;Puri et al., 2010).
In this study, we indicated a significant reverse association between age at diagnosis and survival time, so that the survival time decreased with age.The hazard ratio for patients older than 75 years was more than two fold higher than patients aged 60 years or younger.Similar studies confirm such a finding (Puri et al., 2010;Zahir and Mirtalebi, 2012).
According to our findings,there was a significant association between ECOG performance and survival time.The patients in group V had the lowest survival time and followed by patients in group III.
In the current study, the most common type of lung cancer was SCC and adenocarcinomaand carcinoid were in the second and third most common lung cancers.There was no significant association between tumor type and survival rate.This finding was consistent with the results of similar to other studies conducted in Iran (Zahir and Mirtalebi, 2012;Hajmanoochehri et al., 2014) but inconsistent with the results of studies carried out in other countries.Some studies in other countries have reported  (Haraguchi et al., 2012;Jiang et al., 2012).There was a significant association betweentumor stage and survival time.Approximately, 68% of patients were in the stage IV.Patients with tumor stage IV had a hazard ratio of 1.4 compared to those with tumor stages I, II, or III.The results of study performed by Kawaguchi et Al confirmed our results (Kawaguchi et al., 2010).
Subjects who received chemotherapy, radiotherapy, or underwent surgery had longer survival time than those subjects who did not receive any treatment.This finding was consistent with the results of similar studies (Berghmans et al., 2005;Zahir and Mirtalebi, 2012).
Mitsudomietal (Mitsudomi et al., 2010) and Kawaguchi etal (Kawaguchi et al., 2010) reported that smoking had a significant effect onthe survival time.It should be mentioned that from 96 non-smoker patients, 75 patients were with stage IV tumors, and only 21 patients were in other tumor stages.
Metastasis was another factor that had a significant effecton the survival time.Patients who had metastases had a median survival time of 5.8 months while the median survival time of the patients without metastases was 12.2 months.
In conclusion, the survival time of the patients with lung cancer is very short while early diagnosis of disease may improve the life expectancy in patients with lung cancer although effective treatment is not available for this cancer.

Table 1 . Demographic and Clinical Characteristics of Patients with lung Cancer
Figure 1.Kaplan-