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INTRODUCTION
Recently, the incidence of some hematologic malignancies such as lymphoma and multiple myeloma (MM) has been gradually increasing, but hematologic malignancies still comprise a relatively lower proportion of the whole cancer incidence compared to other major solid cancers [1]. However, insufficient basic data exist on hematologic malignancies in Korea.
Several large-scale studies on hematologic malignancies were widely conducted in Korea [2-4]. The first nationwide study was conducted from 1999 to 2008 to analyze the statistics of hematologic malignancy in Korea, provided that significant research data about the overall status of hematologic malignancies were available at that time; however, the study used data from the last 10 to 20 years [2]. Moreover, the studies on myeloid malignancy and lymphoid malignancy, from 1999 to 2012, offered more detailed analysis data compared to the previous study [3, 4].
An Annual Report of Cancer Statistics for 2015 was the latest research data on the incidence of hematologic malignancies in Korea [5]. According to the report, the number of people who have been diagnosed with hematologic malignancies has gradually increased despite the lower incidence proportion of hematologic malignancies in overall cancer [5].
This study aimed to present a diverse range of background information on hematologic malignancy by analyzing longitudinal big data from the National Health Insurance Service (NHIS) from 2005 to 2015 for an improvement in national public health-care.
MATERIALS AND METHODS
1. Data source and research subjective disease codes
This study presented the claims from the NHIS in Korea from 2003 to 2015. To minimize diagnostic errors, data from 2003 and 2004 were not considered. The main objects were seven codes of hematologic malignancy defined by the Korean Classification of Disease-6 (KCD-6) [6]. During the study, hospitalized individuals designated with the seven codes of hematologic malignancy and one code of other diseases related to hematologic malignancy were included (Table 1). The claims were sorted in chronological order, and the first day of the claim was defined as the first day of diagnosis. Information about sex and age of the patients was ob-tained. Patients’ ages were analyzed in units of 10 years. This study was approved by the Institutional Review Board of the NHIS Ilsan Hospital (2017-01-001) and Kyung Hee University Hospital (2018-08-027) .
2. Incidence and prevalence analysis
A crude incidence rate (CIR) is defined as the number of new patients in a specified population during a year per 100,000 people. It was calculated using the following formula:
The age-standardized incidence rate (ASR) is defined as the weighted average incidence rate of the age-specific rate. The standard population for the ASR in our study was obtained from the midyear population of Korea in 2000. The annual percentage change (APC) is an indication of the changes in the annual ASRs, indicating the annual increase or decrease rate of cancer incidence rate. The prevalence rate (PR) is defined as the number of patients who have the disease in a specified population during a year per 100,000 people. It was calculated using the following formula:
3. Other diseases related to hematologic malignancy
The status of new patients diagnosed with myelodysplastic syndrome (MDS) (D46) among the disease codes related to hematologic malignancy in the KCD-6 (Table 1) was investigated.
RESULTS
1. Annual new patients’ status of hematologic malignancy: C90 to C96
The number of new patients in the study was 52,757, and this number gradually increased from 2005 to 2015 (total increase rate, 56.7%; 5,875/3,749) (Fig. 1). In this study, the number of cases of myeloid leukemia (C92) was the highest (46.5%) followed by those of MM and malignant plasma cell neoplasm (C90) (25.3%) and lymphoid leukemia (C91) (18.5%). Regarding sex, the number of males newly diagnosed with hematologic malignancy was higher than that of females in all hematologic malignancy codes except other and unspecified malignant neoplasms of the lymphoid, hematopoietic, and related tissue (C96). Moreover, the highest difference in number was observed in myeloid leukemia (C92) (Table 2). Regarding age distributions, the age group with the largest number of new patients was patients in their 60s (20.0%, 10,542/52,757), followed by patients in their 70s (19.1%, 10,066/52,757). The age group under 9 years constituted the largest proportion in lymphoid leukemia (C91) during the study (22.3%, 2,177/9,759).
2. Crude incidence rate and age-standardized incidence rate
From 2005 to 2011, acute myeloblastic leukemia (C920) showed the highest CIR (up to 2.65), and after 2012, MM (C900) showed the highest CIR (up to 2.89). The CIR of chronic myeloid leukemia, BCR/ABL-positive (C921), ranged from 0.83 (in 2009) to 1.05 (in 2015). Acute lymphoid leukemia (C910) was the code with a CIR of greater than 1 during the study (Table 3). During the study, there were three codes with ASR>1. Among them, the ASR of acute myeloblastic leukemia (C920) decreased from 2.16 in 2005 to 1.97 in 2015, and the APC was -1.88 (P <0.05). In chronic myeloid leukemia, BCR/ABL-positive (C921), the ASR remained around 0.7. The ASR of MM (C900) increased from 1.40 in 2005 to 1.65 in 2015, and the APC was 2.17 (P <0.05). The ASR of acute lymphoid leukemia (C910) was not statistically significant during the study (Table 4).
3. Prevalence rate
During the study, the PR of all hematologic malignancy codes (C90 to C96) was maintained or increased (Table 5), and the code with the largest PR difference was C900 of MM, which showed an increase by 2.59 times from 4.92 in 2005 to 12.75 in 2015. The codes with a PR greater than 10 were C900 of MM and C921 of chronic myeloid leukemia, BCR/ABL-positive.
4. The current incidence state of myelodysplastic syndrome (D46)
Among the five subcodes of MDS (D46), D467 of other MDS had the highest number of new diagnoses (70.1%, 11,346/16,034) and showed a gradual increase in the study. Regarding sex, except for refractory anemia without ring sideroblasts, so stated (D460), the number of new male patients was higher than that of females in most disease codes (Table 6).
DISCUSSION
In the analysis of the current status of hematologic malignancy from 2005 to 2015, the number of new patients diagnosed with hematologic malignancy, with increased PR, increased for 10 years. According to a previous study in Korea from 1999 to 2008, the number of new patients showed an increase of approximately 69.1% (8,006/4,735) for total hematologic malignancies [2]. In another study from 1999 to 2012 [3], a rate of increase was approximately 42.8% (1,257/880) for AML and approximately 106.9% (813/393, from 2003 to 2012) for MDS. In this context, a continuous reporting system of the current status of hematologic malignancy in Korea should be firmly established, such as the systems in international studies on hematologic malignancy. Moreover, studies should expand their scope including not only some major cancers but also other minor cancers such as hematologic malig-nancies.
According to sex, the number of new patients diagnosed with C codes was higher in males than in females. Our results with high male proportions were consistent with those of the previous studies in Korea, Europe, and the USA [2, 3, 7, 8]. Regarding age, the number of new patients aged 50 to 69 years was the highest except in lymphoid leukemia (C91), where young children are more likely to be diagnosed with lymphoid leukemia (C91) than adults [2, 9]. Nevertheless, as most of the newly diagnosed patients were elderly people, new patients might increase continuously in the future.
The increasing CIR during the study was similar to that of the previous studies [2, 3, 7, 8], and it is likely that this will continue in the future because of the aging population. Furthermore, the increasing PR is likely to continue due to an increased survival rate [3, 10].
The code of other MDS (D467) had the largest proportion (70.8%) among MDS (D46) in our study. In the previous studies on the incidence of MDS in Japan, 73% of the cases were also coded as MDS not otherwise specified [11]. MDS is a heterogeneous group of myeloid disease [12], and the classification of the KCD-6 system does not correspond to the World Health Organization (WHO) classification [13], which is one of the possible reasons regarding the mismatch between the diagnosis and claim codes.
Our study has a limitation, that is, we were not able to include the medical records, which are not integrated in the NHIS claims data, of individual patients. However, a systemic nationwide study was possible through coded data, and this can be useful to illustrate the general status of hematologic malignancies in Korea. Additionally, as mentioned above, the classification of the KCD-6 system does not correspond to the WHO classification. Therefore, a more reliable analysis result will be generated and provided when the classification system is revised, considering the WHO classification.
In summary, our study showed the increasing incidence and prevalence of hematologic malignancies including leukemia and MDS. Therefore, further investigation is required. It is also necessary to consider introducing a continuous reporting system in Korea, such as the Surveillance, Epidemiology, and End Results report from the National Cancer Institute in the USA [7] and the HAEMACARE project from the European HAEMACARE Working Group [8]. This nationwide data could contribute in the studies of hematologic malignancies and would be useful in the improvement of national public healthcare.
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