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Asia-Pacific Journal of Clinical Oncology 2015; 11: 221–227
doi: 10.1111/ajco.12179
ORIGINAL ARTICLE
Survival of lung cancer patients in a resource-limited country Soon Hin HOW,1 Teck Han NG,1 Yeh Chunn KUAN,1 Abdul Rahman JAMALLUDIN2 and Abdul Rani FAUZI1 Departments of 1Internal Medicine and 2Public Health, Kulliyyah of Medicine, International Islamic University Malaysia, Kuantan, Pahang, Malaysia
Abstract Aim: Data on lung cancer survival are lacking in developing countries. Our objectives were to describe the survival of our lung cancer patients and to determine independent prognostic factors affecting survival. Method: All patients diagnosed with lung cancer from August 2007 to August 2010 were recruited from a single referral hospital of the state of Pahang, Malaysia. Detailed demographic data, ECOG (Eastern Cooperation Oncology Group) performance status, stage of disease and treatment were recorded. The date of histology or cytology confirmation was used as the date of entry. Survival time was calculated from the date of entry to the date of death. Results: One hundred forty-nine patients were included for survival analysis. The median age was 62 years and patients were predominantly males (78%) and smokers (78%). The majority had non-small cell lung cancer (NSCLC) (94%); only six patients (4%) had small cell lung cancer. All patients presented with stage 3 or stage 4 disease. Overall median survival was 18 weeks. “No definitive treatment” and “ECOG 3–4” were the significant independent predictors of death, with the hazard ratios of 2.1 (95% confidence interval [CI] 1.4, 3.0) and 1.6 (95% CI 1.1, 2.3) times, respectively. Among NSCLC patients on treatment, 1- and 2-year survival rates were 27% and 15%, respectively. Conclusion: The majority of lung cancer patients in Pahang presented with advanced disease. No definitive treatment and ECOG 3–4 were independent poor prognostic factors. Key words: factors, lung cancer, median survival, outcome.
INTRODUCTION In Malaysia, lung cancer is the most common cancer among men (16.3%), third most common cancer among women (5.4%)1 and accounted for most of the cancer deaths in 2001.2 Hooi et al. looked at the survival of surgically treated patients in a single tertiary referral center and reported fairly good 5-year survival of 29% and median survival of 27 months.3 Most of the patients Correspondence: Dr Yeh Chunn Kuan MBBS, Department of Internal Medicine, Kulliyyah of Medicine, International Islamic University Malaysia, Jalan Sultan Ahmad Shah, 25200 Kuantan, Pahang, Malaysia. Email: [email protected] Conflict of interest: none Accepted for publication 5 January 2014.
© 2014 Wiley Publishing Asia Pty Ltd
in Malaysia present with advanced disease when surgery is no longer an option, and even among patients who are operable, more than half have refused surgery.4 Chemotherapy with or without radiotherapy is the treatment of choice in this group of patients.5 Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) has been shown to improve overall survival in lung cancer patients with EGFR mutation,6 but it costs more than US $2000/month, which is unaffordable to most of our patients. Despite recent development in the treatment of advanced lung cancer with proven survival benefit, some patients still opt for alternative treatment. Loh et al.7 showed that patients who have opted out from cancer-specific therapy have a shorter survival. There are no survival data for patients with advanced lung cancer in Malaysia. Several studies have shown that
222
treating physicians tend to overestimate the survival of patients with advanced cancer.8 Furthermore, most of the survival data are extrapolated from developed countries, which have been shown to be higher than developing or nondeveloped countries.9,10 Patient survival data in clinical trials may be better than real-life studies because study protocols demand more attentive healthcare and closer follow-up. It is also necessary for cancer patients to know about survival data relevant to their diseases so that they can make informed decisions about their treatment plans and other aspects of their personal lives. Due to a lack of data on lung cancer survival in resource-limited countries like Malaysia, we started the Hospital Tengku Ampuan Afzan (HTAA) lung cancer registry in August 2007. In this study, our objectives were to describe the survival of lung cancer patients in HTAA and to determine the independent prognostic factors affecting lung cancer survival.
METHODS This was a 3-year prospective study carried out at HTAA, Kuantan, Pahang, from August 2007 to August 2010. HTAA is a tertiary referral hospital for Pahang and the only center providing lung cancer treatment in Pahang. This study received the approval of the Ethics Committee of International Islamic University Malaysia. All consecutive patients who were suspected to have lung cancer from the respiratory clinic, medical and respiratory wards, and bronchoscopy suites, and who gave their informed consent were recruited. The definite diagnosis of lung cancer was based on histological or cytological examination. The patients with the diagnoses of lung secondaries, mesothelioma, inconclusive histological diagnosis or unknown outcome were excluded from the survival analysis. The date of histology or cytology confirmation was used as the date of entry. For patients who were not hospitalized, the date of death was ascertained by telephone contact or by making an enquiry through the National Registration Department of Malaysia. Survival time was defined as the time from the date of histological or cytological confirmation to the date of death. The patients’ detailed demographic data, occupation, smoking history, underlying lung disease, socioeconomic status, staging, ECOG (Eastern Cooperation Oncology Group) performance status, treatment and treatment outcome were recorded. Nonsmokers were defined as those who have smoked less than 100 cigarettes before the date of diagnosis. Staging was based on the Interna-
© 2014 Wiley Publishing Asia Pty Ltd
SH How et al.
tional Staging System for Lung Cancer, 6th Edition, using computed tomography (CT) thorax and upper abdomen with or without endobronchial ultrasound, CT brain, bone scan or positron emission tomography scan. The performance status of the patients at presentation was classified according to the ECOG. The treatment of advanced lung cancer was divided into two groups: (1) supportive care (i.e. no definitive treatment), which included radiotherapy for symptomatic relief but without chemotherapy or targeted therapy, and (2) definitive treatment with either chemotherapy or targeted therapy or both, with or without radiotherapy. The standard of care for non-small cell lung cancer (NSCLC) during this period was cisplatin and gemcitabine as first-line chemotherapy and docetaxel or pemetrexed as second-line therapy. Bevacizumab was not included due to its high cost. Concurrent chemoradiotherapy was not administered as radiotherapy facility was not available in this hospital. Patients who required sequential or palliative radiotherapy were referred to another hospital for further treatment. Targeted therapy refers to EGFR TKI such as erlotinib and gefitinib. Analysis was performed using IBM SPSS Statistics for Windows, version 20 (IBM: International Business Machines Corp., Armonk, NY, USA). The Kaplan– Meier method was used to estimate overall survival, and log-rank test was used to test the survival differences in each subgroup. Multivariate analysis was performed using Cox proportional hazard regression model to determine the independent prognostic factors affecting survival. A P-value of less than 0.05 was determined as statistically significant.
RESULTS Patient characteristics A total of 226 patients were recruited. Seventy-seven of them were excluded from analysis due to the following reasons: 41 had inconclusive histology, 13 had no histological diagnosis, 6 had no survival outcome, 8 had histology consistent with secondary metastases to the lung and 9 were diagnosed or suspected to have mesothelioma. Among the 149 patients included for survival analysis, age ranged from 23 to 84 years, with a median age of 62 (interquartile range 19) years and they were predominantly males (78%). The majority of our patients were of Malay ethnicity (68%), followed by Chinese (29%). Eight patients had chronic lung diseases (one lung fibrosis, one asthma and six chronic obstructive pulmonary disease).
Asia-Pac J Clin Oncol 2015; 11: 221–227
223
Survival of lung cancer patients
Disease characteristic Out of the 149 patients, 140 (94%) had NSCLC, 6 patients (4%) had small cell lung cancer (SCLC), 2 had neuroendocrine tumor and 1 had carcinoid tumor. Among the patients with NSCLC, 57% were adenocarcinoma, 20% were squamous cell carcinoma, 15% were poorly differentiated carcinoma and the others were bronchioloalveolar carcinoma (1 patient), adenosquamous carcinoma (1 patient) and large cell lung cancer (1 patient). Overall, 78% were smokers or ex-smokers. There was significantly more female than male nonsmokers (79% vs 6%, P < 0.001). None of the patients presented with early stage lung cancer (i.e. stage 1 and stage 2). The majority of our patients presented with advanced stage 3B (51%) and stage 4 (46%) diseases. A large proportion of our patients had ECOG performance status of 1 at presentation (45%). Only 70 (47%) patients received definitive treatment. Table 1 shows the demography and clinical presentation of the female and male patients with lung cancer.
Overall survival At review, 95% of the patients had passed away. Of the 149 patients, 21% survived 30 days or less and 15% of the patients survived for more than a year. Overall median survival was 18 weeks (95% confidence interval [CI] 8, 21). Patients with SCLC had shorter median survival of 6 weeks (95% CI 0, 26) compared to NSCLC of 18 weeks (95% CI 15, 21). Patients who had ECOG 1–2 had significantly longer survival than patients with ECOG 3–4 (29 weeks vs 12 weeks, P < 0.001) and
Table 1 Demography, clinical presentation, treatment and median survival among male and female lung cancer patients Male (n = 116) Race Malay : Chinese : Others Smoking Yes : No Age (years)
Asia-Pacific Journal of Clinical Oncology 2015; 11: 221–227
doi: 10.1111/ajco.12179
ORIGINAL ARTICLE
Survival of lung cancer patients in a resource-limited country Soon Hin HOW,1 Teck Han NG,1 Yeh Chunn KUAN,1 Abdul Rahman JAMALLUDIN2 and Abdul Rani FAUZI1 Departments of 1Internal Medicine and 2Public Health, Kulliyyah of Medicine, International Islamic University Malaysia, Kuantan, Pahang, Malaysia
Abstract Aim: Data on lung cancer survival are lacking in developing countries. Our objectives were to describe the survival of our lung cancer patients and to determine independent prognostic factors affecting survival. Method: All patients diagnosed with lung cancer from August 2007 to August 2010 were recruited from a single referral hospital of the state of Pahang, Malaysia. Detailed demographic data, ECOG (Eastern Cooperation Oncology Group) performance status, stage of disease and treatment were recorded. The date of histology or cytology confirmation was used as the date of entry. Survival time was calculated from the date of entry to the date of death. Results: One hundred forty-nine patients were included for survival analysis. The median age was 62 years and patients were predominantly males (78%) and smokers (78%). The majority had non-small cell lung cancer (NSCLC) (94%); only six patients (4%) had small cell lung cancer. All patients presented with stage 3 or stage 4 disease. Overall median survival was 18 weeks. “No definitive treatment” and “ECOG 3–4” were the significant independent predictors of death, with the hazard ratios of 2.1 (95% confidence interval [CI] 1.4, 3.0) and 1.6 (95% CI 1.1, 2.3) times, respectively. Among NSCLC patients on treatment, 1- and 2-year survival rates were 27% and 15%, respectively. Conclusion: The majority of lung cancer patients in Pahang presented with advanced disease. No definitive treatment and ECOG 3–4 were independent poor prognostic factors. Key words: factors, lung cancer, median survival, outcome.
INTRODUCTION In Malaysia, lung cancer is the most common cancer among men (16.3%), third most common cancer among women (5.4%)1 and accounted for most of the cancer deaths in 2001.2 Hooi et al. looked at the survival of surgically treated patients in a single tertiary referral center and reported fairly good 5-year survival of 29% and median survival of 27 months.3 Most of the patients Correspondence: Dr Yeh Chunn Kuan MBBS, Department of Internal Medicine, Kulliyyah of Medicine, International Islamic University Malaysia, Jalan Sultan Ahmad Shah, 25200 Kuantan, Pahang, Malaysia. Email: [email protected] Conflict of interest: none Accepted for publication 5 January 2014.
© 2014 Wiley Publishing Asia Pty Ltd
in Malaysia present with advanced disease when surgery is no longer an option, and even among patients who are operable, more than half have refused surgery.4 Chemotherapy with or without radiotherapy is the treatment of choice in this group of patients.5 Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) has been shown to improve overall survival in lung cancer patients with EGFR mutation,6 but it costs more than US $2000/month, which is unaffordable to most of our patients. Despite recent development in the treatment of advanced lung cancer with proven survival benefit, some patients still opt for alternative treatment. Loh et al.7 showed that patients who have opted out from cancer-specific therapy have a shorter survival. There are no survival data for patients with advanced lung cancer in Malaysia. Several studies have shown that
222
treating physicians tend to overestimate the survival of patients with advanced cancer.8 Furthermore, most of the survival data are extrapolated from developed countries, which have been shown to be higher than developing or nondeveloped countries.9,10 Patient survival data in clinical trials may be better than real-life studies because study protocols demand more attentive healthcare and closer follow-up. It is also necessary for cancer patients to know about survival data relevant to their diseases so that they can make informed decisions about their treatment plans and other aspects of their personal lives. Due to a lack of data on lung cancer survival in resource-limited countries like Malaysia, we started the Hospital Tengku Ampuan Afzan (HTAA) lung cancer registry in August 2007. In this study, our objectives were to describe the survival of lung cancer patients in HTAA and to determine the independent prognostic factors affecting lung cancer survival.
METHODS This was a 3-year prospective study carried out at HTAA, Kuantan, Pahang, from August 2007 to August 2010. HTAA is a tertiary referral hospital for Pahang and the only center providing lung cancer treatment in Pahang. This study received the approval of the Ethics Committee of International Islamic University Malaysia. All consecutive patients who were suspected to have lung cancer from the respiratory clinic, medical and respiratory wards, and bronchoscopy suites, and who gave their informed consent were recruited. The definite diagnosis of lung cancer was based on histological or cytological examination. The patients with the diagnoses of lung secondaries, mesothelioma, inconclusive histological diagnosis or unknown outcome were excluded from the survival analysis. The date of histology or cytology confirmation was used as the date of entry. For patients who were not hospitalized, the date of death was ascertained by telephone contact or by making an enquiry through the National Registration Department of Malaysia. Survival time was defined as the time from the date of histological or cytological confirmation to the date of death. The patients’ detailed demographic data, occupation, smoking history, underlying lung disease, socioeconomic status, staging, ECOG (Eastern Cooperation Oncology Group) performance status, treatment and treatment outcome were recorded. Nonsmokers were defined as those who have smoked less than 100 cigarettes before the date of diagnosis. Staging was based on the Interna-
© 2014 Wiley Publishing Asia Pty Ltd
SH How et al.
tional Staging System for Lung Cancer, 6th Edition, using computed tomography (CT) thorax and upper abdomen with or without endobronchial ultrasound, CT brain, bone scan or positron emission tomography scan. The performance status of the patients at presentation was classified according to the ECOG. The treatment of advanced lung cancer was divided into two groups: (1) supportive care (i.e. no definitive treatment), which included radiotherapy for symptomatic relief but without chemotherapy or targeted therapy, and (2) definitive treatment with either chemotherapy or targeted therapy or both, with or without radiotherapy. The standard of care for non-small cell lung cancer (NSCLC) during this period was cisplatin and gemcitabine as first-line chemotherapy and docetaxel or pemetrexed as second-line therapy. Bevacizumab was not included due to its high cost. Concurrent chemoradiotherapy was not administered as radiotherapy facility was not available in this hospital. Patients who required sequential or palliative radiotherapy were referred to another hospital for further treatment. Targeted therapy refers to EGFR TKI such as erlotinib and gefitinib. Analysis was performed using IBM SPSS Statistics for Windows, version 20 (IBM: International Business Machines Corp., Armonk, NY, USA). The Kaplan– Meier method was used to estimate overall survival, and log-rank test was used to test the survival differences in each subgroup. Multivariate analysis was performed using Cox proportional hazard regression model to determine the independent prognostic factors affecting survival. A P-value of less than 0.05 was determined as statistically significant.
RESULTS Patient characteristics A total of 226 patients were recruited. Seventy-seven of them were excluded from analysis due to the following reasons: 41 had inconclusive histology, 13 had no histological diagnosis, 6 had no survival outcome, 8 had histology consistent with secondary metastases to the lung and 9 were diagnosed or suspected to have mesothelioma. Among the 149 patients included for survival analysis, age ranged from 23 to 84 years, with a median age of 62 (interquartile range 19) years and they were predominantly males (78%). The majority of our patients were of Malay ethnicity (68%), followed by Chinese (29%). Eight patients had chronic lung diseases (one lung fibrosis, one asthma and six chronic obstructive pulmonary disease).
Asia-Pac J Clin Oncol 2015; 11: 221–227
223
Survival of lung cancer patients
Disease characteristic Out of the 149 patients, 140 (94%) had NSCLC, 6 patients (4%) had small cell lung cancer (SCLC), 2 had neuroendocrine tumor and 1 had carcinoid tumor. Among the patients with NSCLC, 57% were adenocarcinoma, 20% were squamous cell carcinoma, 15% were poorly differentiated carcinoma and the others were bronchioloalveolar carcinoma (1 patient), adenosquamous carcinoma (1 patient) and large cell lung cancer (1 patient). Overall, 78% were smokers or ex-smokers. There was significantly more female than male nonsmokers (79% vs 6%, P < 0.001). None of the patients presented with early stage lung cancer (i.e. stage 1 and stage 2). The majority of our patients presented with advanced stage 3B (51%) and stage 4 (46%) diseases. A large proportion of our patients had ECOG performance status of 1 at presentation (45%). Only 70 (47%) patients received definitive treatment. Table 1 shows the demography and clinical presentation of the female and male patients with lung cancer.
Overall survival At review, 95% of the patients had passed away. Of the 149 patients, 21% survived 30 days or less and 15% of the patients survived for more than a year. Overall median survival was 18 weeks (95% confidence interval [CI] 8, 21). Patients with SCLC had shorter median survival of 6 weeks (95% CI 0, 26) compared to NSCLC of 18 weeks (95% CI 15, 21). Patients who had ECOG 1–2 had significantly longer survival than patients with ECOG 3–4 (29 weeks vs 12 weeks, P < 0.001) and
Table 1 Demography, clinical presentation, treatment and median survival among male and female lung cancer patients Male (n = 116) Race Malay : Chinese : Others Smoking Yes : No Age (years)
