Retrospective Appraisal of Cancer Patients from Vientiane Capital City , Lao People ’ s Democratic Republic ( PDR ) , Seeking Treatment in Thailand

Estimates from the GLOBOCAN (2008) database show the cancer burden is higher in the developing parts of the world than in advanced economies both in terms of incidence (56% of new cancers in 2008 occurred within developing regions) and mortality (63% of cancer deaths were in developing regions) (Ferlay et al., 2010). Further, it is predicted that by 2020, approximately 60% of all new cancer cases will occur in the least developed nations. Compared to advanced economies where early diagnosis and access to systemic therapy is prolonging life, in low and middle-income countries cancer patients typically present and are diagnosed late and as a consequence, mortality rates are high (Gyorki et al., 2012). Within the Association of Southeast Asian Nations


Introduction 5436
and epidemiological transitions characterized by the burden of undernutrition and infectious disease alongside overnutrition and a rise in chronic non-communicable diseases including cancer (Dans et al., 2011). As Lao PDR becomes increasingly urbanized and the population has increasing exposure to risk factors for cancer, the future burden is expected to increase. The health system, however, remains orientated primarily towards infectious disease and reliable epidemiological data about the patterns and burden of cancer and related risk factors are scarce (Lua et al., 2011). This poses a major challenge to an already overstretched health system in terms of planning and resource allocation. In recognition of this, Lao PDR is beginning to respond to the current and potential future cancer burden. In June 2008, for example, the Cancer Center was established at the Mittaphab Hospital in the capital, Vientiane. The first hospital-based cancer registry (pathology) in the country was established at the local University of Health Sciences using data from hospitals in Vientiane and was first published in 2010. The only hospitals in the country which can perform some limited cancer surgery are six tertiary level public hospitals in Vientiane. There are no comprehensive diagnostic or cancer treatments available and facilities for chemotherapy and radiotherapy are nonexistent. Most cancer patients do not receive proper treatment and die at home.
Despite the increasing cancer burden in Lao PDR, there are no population-based cancer registries, making it extremely difficult to determine the national cancer burden and prevalence. This lack of data is compounded by the fact that due to the limited capacity to diagnose and treat cancer, patients are known to cross national borders, often to neighboring Thailand, in order to obtain diagnosis and care (Lua et al., 2011). In this study we sought to estimate some of the otherwise largely unknown parameters of the cancer burden in Lao PDR by analysing records from Srinagarind Hospital, Khon Kaen University, in Northeast Thailand. The estimated cancer statistics for the most recent year reported in the present study can provide a useful benchmark for the planning and evaluation of cancer control programmes in the country.

Materials and Methods
This was a retrospective descriptive study of all Lao patients attending Srinagarind Hospital, Khon Kaen University, for cancer treatment during the period 11 March 1988 to 1 December 2010. Secondary data of 847 cancer cases treated with surgery, radiation and chemotherapy were extracted from the Srinagarind Hospital cancer registry. The data comprised sex, age, residence, marital status, religion; date of diagnosis; method of diagnosis; tumor site and type of treatment. The data were analysed using descriptive statistics (frequency distributions, means and standard deviations), linear trend analysis and chi square for determining age and gender differences in method of cancer diagnosis, cancer stage and cancer sites.
Ethical clearance was received from the Ethical Committee of the University of Health Sciences. Permission to use the cancer registry data from the Srinagarind Hospital, Khon Kaen University was also obtained from the local authority. All the data was deidentified, routine in nature and collected with the intent of eventually becoming publicly available, thus individual consent was not required. Figure 1 shows the number of Lao cancer patients registered at the Srinagarind Hospital, Khon Kaen University by year from 1988-2010. The number of patients increased steadily from eight cases in 1988 to 42 cases in 1994, but fluctuated over the remaining years, sometimes declining from one year to the next. Nevertheless, there was an overall increase in the number of cases over the entire period (R 2 =0.677; p<0.001).

Socio-demographic characteristics of cancer patients
The socio-demographic characteristics of the cancer patients are summarised in Table 1. The sex ratio of cancer patients was 0.96, and their mean (SD) age was 45.2 (18.89) years (range <1-93 years). The highest proportion of cancer patients was in the age group 45-49 years (12.2%) and the lowest proportion was among the age group >85 years (0.2%). Most patients (81.7%) were married and almost all were Buddhists (98.6%).

Method of cancer diagnosis and cancer stage
The main recorded method of diagnosis was histology of the primary tumour (65.2%), followed by endoscopy and radiology (15.6%) and blood cytology (6.3%). The results show that there was a statistically significant gender difference in the method of cancer diagnosis, with   specific histology being the primary method of diagnosis for female cancer patients (χ 2 =29.602; p<0.001). Table 2 summarizes the methods used in the diagnosis of cancer. Table 3 shows the stage (where known) at which cancer was diagnosed. For the majority of cases (70.2%) the cancer stage was not recorded, but of those for whom the stage was known, very few were at an early stage (7.5% at stage 0 and 1), and the majority (54.0%) were at the most serious stage (stage IV).

Distribution of cancer sites by socio-demographic characteristic of patients
Among male patients, the most common cancer sites were the liver (16.1%), blood (12.3%) and nasopharynx (10.6%), but there were some age differences. For example, the incidence of liver cancer was relatively higher (24%) in the 45-64 year age group, and the incidence of blood cancer was particularly high (26.2%) in the 0-44 year age group (See Table 4). Among female patients, the most common cancer site was the cervix (22.2%), followed by breast (14.6%) and blood (8.1%). The incidence of cervical cancer and breast cancer were

Discussion
Lao PDR does not have a population-based cancer register and the cancer burden in the country is largely unknown. To estimate cancer incidence and cancer mortality in 2008 for Lao PDR, the IARC used data from China and Thailand (IARC, 2008). Furthermore, treatment facilities remain underdeveloped and cancer patients in Lao PDR seek treatment in neighbouring countries, such as Thailand (Lua et al., 2011). This study represents the first attempt to analyze the secondary data of cancer patients receiving treatment in Thailand. The patient data came from the cancer registry of Srinagarind Hospital; a tertiary-level, University-based hospital in Northeast Thailand. This hospital is easy to access from Vientiane, the capital of Lao PDR, where most of the patients came from and is known for its quality of its care.
The present study shows an increasing trend in the number of Lao cancer patients from Vientiane registered at the Srinagarind Hospital over a recent period of more than 20 years suggesting a steady rise in the number of cases. This is consistent with the rising cancer rate in countries globally. For example, between 1994 and 2003 in Ireland, the average annual increase in the incidence of cancer was 2.7% (2.5% for males and 2.8% for females) (National Cancer Registry Ireland, 2006). In France, cancer incidence had increased by 63% over a 20-year period with 170,000 new cases in 1980 rising to 278,000 in 2000 (Remontet et al., 2003). Similarly, in less developed contexts the incidence of cancer has also increased. In Sri Lanka for example, the cancer incidence rose from 10,925 in 2001to 13,372 in 2005(Cancer Registry, 2009). Using actual data for the period 1989-2000 and basing predictions on data from nine registries for the period 1998-2000, Sriplung et al. (2006) estimated that in Thailand the number of cancer cases would increase from 45,873 cases in 1990 to 102,665 cases in 2008 (Sriplung et al., 2006). In Nepal, it was estimated that cancer cases would increase by 90% between 2000 and 2015 (Sathian et al., 2010). The increasing trend of cancer cases is also consistent with that seen in other ASEAN countries (Ferlay et al., 2010;Kimman et al., 2012). While the present study suggests a steady rise in Lao cancer cases, there have been marked variations in the annual number of Lao patients attending Srinagarind Hospital for cancer treatment. One possible explanation for this is that patients' choice of treatment centre outside Lao PDR has increased over time. Alternative cancer treatment centres are now available in other places in Thailand (for example, Udon Thani which is closer to Lao PDR than Khon Kaen) and in other neighboring countries such as Cambodia and Vietnam. Travel to these countries has also been facilitated in recent years by a relaxation of travel restrictions.
The mean (SD) age of the cancer patients in the present study was 45.2 (18.891) years, which is similar to that reported in other studies conducted in South East Asia . However, some authors have found a higher mean age of cancer patients (Hertz et al., 2005). In the present study, the commonest method of diagnosis was by histology of the primary tumor (65.2%). This is consistent with previous studies (Mutuma et al., 2006;Tracey et al., 2010). For example, Attasara found that in 2008, 88.7% of males and 87.7% of females cancers were diagnosed by histology, and basis of diagnosis for all cases registered 2000-2002 was 86% histology verification respectively. In our study however, there was a statistically significant gender difference in the method of cancer diagnosis, with specific histology being the primary method of diagnosis for female cancer patients. This might be explained by the low awareness of cancer among female patients and their health seeking behavior. The second most frequent method of diagnosis in our study was by endoscopy and radiology, a finding which was also similarly reported elsewhere (Attasara, 2005).
According to the World Health Rankings Live Longer Live Better in 2011, liver cancer in Lao PDR was estimated to account for 1,155 (2.77%) of the total deaths. The age adjusted death rate was 35.14 per 100,000 population, which is the fourth highest death rate for this disease globally. In this study, the leading cancer site in the male patients was the liver (16.1%). This is consistent with the type of cancer found to have the highest incidence (45-50% of all cancers) in the northeastern region of Thailand (Nakhon Phanom, Udon Thani and Khon Kaen provinces) which borders Lao PDR and has a similar lifestyle and culture (Hertz et al., 2005). Using epidemiological data from GLOBOCAN (2008). Kimman et al. (2012) also found high rates of liver cancer. In a study of mortality data from 2007-2008 in Lao PDR, Lua et al. (2011) found liver cancer to be the most frequent cause of cancer related mortality (52.2 per 100,000). In our study, blood cancer was the second leading type of male cancer, which is different from the findings of a Sri Lankan study which reported that crude rate of blood cancer was 2.9% (Cancer Registry, 2009). Among female patients, the most common cancer site was the cervix (22.2%). This finding is consistent with WHO estimates for Lao PDR (WHO/ICO, 2010). Kimman et al. (2012) also reported high cervical cancer incidence rates in Lao PDR. This finding is in contrast to the northeastern region of Thailand, however, where the most common cancer for females between 1998 and 2000 was liver cancer (24.2-32.4% of all cancers) (Attasara, 2005;Sriplung et al., 2006). Liver cancer was also reported to be the leading cause of mortality from cancer in the Lao PDR in the Lua et al. (2011) study. In the aforementioned study in Thailand, cervical cancer was the second most common cancer (Attasara, 2005). For female patients, the second common cancer site was the breast. Within the ASEAN region, breast cancer has been identified as the most frequently diagnosed cancer and the leading cause of cancer mortality (Kimman et al., 2012). Our study also revealed that over half (54.0% of total, 75.3% males and 40.7% females) of the patients were at the last stage of cancer. These figures are much higher than those for patients at stage IV of colon and rectum cancer (19.9%) and oral cavity cancer (6.5%) reported in Thailand (Kamnerdsupaphon et al. 2008). Studies in other lower-middle income countries, however, have reported that most patients present at an advanced stage of disease (Gyorki et al., 2012). Reasons for delayed presentation typically include low levels of awareness, lack of access to health care, lack of early detection, and use of alternative health care models. The diagnosis of advanced cancer is usually difficult for patients and their family and can cause anxiety and uncertainty. However, even if treatment is no longer able to cure or stop the growth of cancer there are alternatives for care, such as treatments which slow tumor growth and manage pain and other symptoms of cancers. Understanding the stage of cancer helps patients and doctors to develop a personalized treatment plan, which takes into account individual needs, goals, and preferences. The present study found that the stage of cancer could not be identified in a high proportion of the patients (70.2%) so that for many this source of guidance in the development of a treatment plan was not available. This finding was in contrast to studies carried out in advanced countries. In New Zealand, for example, Stevens et al. (2008) found much fewer cases of unknown staging (25.2% unknown in all sex), and in the United States too, Utah residents diagnosed between 1996-2000 the stage of disease at diagnosis of liver and intrahepatic bile duct was reported as unknown in 37.5% (Utah Cancer Registry and Utah Department of Health, 2012).
Cancer control includes a range of interventions and treatment selection should be based on life expectancy and expected benefit for the patients. In advanced economies, a combination of early detection and therapy has contributed to a constant decline in cancer mortality rates since the 1980s . Some tumors may be cured with anticancer therapy, even at an advanced stage, and quality of life can be improved or maintained. This study suggested that the most common types of treatment were surgery and supportive care from families and relatives. However, the previous studied in the Northern Thailand (Kamnerdsupaphon et al., 2008) found that the most common primary treatment was surgery (43.1%) followed by chemotherapy, and radiation therapy (19.7% and 14.8% Asian Pacific Journal of Cancer Prevention, Vol 14, 2013 5439 DOI:http://dx.doi.org/10.7314/APJCP.2013.14.9.5435 Retrospective Appraisal of Cancer Patients from Vientiane, Lao PDR, Treated in Thailand respectively). The main determinant of outcomes is largely due to access comprehensive health systems whereas in low and lower middle income countries, health systems are often struggling with the dual burden of infectious and chronic diseases alongside suboptimal resources, poor data and inadequate surveillance of risk factors (Dans et al., 2011). Correcting this inequity requires a restructuring of health-care to maximize resources and attain a balance between interventions for infectious and non-communicable diseases. In Lao PDR, failure to address prevention, treatment and care of cancer patients means that those who can afford to do so are likely to continue to travel overseas for healthcare, perpetuating in-country inequalities. Further, the on-going recurrent cost of patient travel abroad is likely to be unsustainable and potentially catastrophic over the long-term especially for those on lower incomes (Kangas, 2010). Seeking cancer care abroad may also create a lack of trust in the domestic health care system, fracture the continuum of care and provide a distorted picture of health care needs for policy makers. As such, Lao PDR cannot await control of communicable diseases before it begins to deal with cancer and other non-communicable diseases.
As with all studies, our study has some limitations. Considerable caution is required in generalizing the findings this study as they based only on those patients in Vientiane who wanted and were able to go to Khon Kaen for treatment. While accurate data on the incidence of cancer in Vientiane are unavailable, data derived from the registration of new cases at Srinagarind Hospital in Thailand can only provide a very crude underestimate as it does not capture the number of new cases who remain within Lao PDR or those who travel to other places outside of the country for treatment.
In conclusion, this study highlighted the increasing burden of cancer in Vientiane Capital City, Lao PDR, and the limited cancer treatment health facilities available in the country as a whole. The unfavorable pattern of late stage of cancer diagnosis among male and female patients suggests a need for improved cancer control interventions, the establishment of a nation-wide system of cancer registration and the development of a modern array of cancer treatment options. Lao PDR needs to adopt a stepwise approach starting with the control of the most common risk factors and education to increase awareness of the early signs and symptoms of common cancers. These initiatives should be coupled with quality treatments and palliative care for advanced cases.
The health-care system has evolved to deal with the acute infectious diseases. Health care providers and health infrastructure have not been designed to deliver chronic care services required for treatment and control of non-communicable diseases such as cancer. To respond appropriately, accurate data are required. The issue of inadequate incidence data must be addressed alongside improving surveillance for risk factors, and outcomes. Lao PDR has begun to respond with the Cancer Center but to progress cancer control and care, national leadership, political will and financing are needed. The global recognition of the increasing burden of non-communicable diseases provides an opportunity for the international community and the ASEAN leadership support national will. Without action, premature death will continue and hinder or even reverse economic progress. In addition, those who cannot afford to seek care overseas will be further disadvantaged and remain invisible in the public health system.