The analysis of characteristics of 1624 soft tissue sarcoma cases in 2006~2016 in Henan Province Cancer Hospital, China


 Background To analyze the incidence characteristics of 1624 inpatients with soft tissue sarcoma (STS) during 2006 to 2016 in Henan Province Cancer Hospital.Methods The information of electronic medical record from the first hospitalized patients with STS in Henan Province Cancer Hospital during January 1, 2006 to December 31, 2016 was collected, and descriptive statistics was analyzed on age, gender and pathological type by using SPSS21.0 software.Results There were 1624 inpatients with STS in Henan Province Cancer Hospital in 2006~2016.The top nine pathological subtypes of STS with high constituent ratio were undifferentiated pleomorphic sarcoma (UPS,23.83%),synovial sarcoma(16.69%), liposarcoma(13.67%), fibrosarcoma(10.22%), sarcoma without definite type (8.99%), leiomyosarcoma(7.02%), dermatofibrosarcoma protuberant (5.79%),rhabdomyosarcoma (4.68%) and malignant peripheral nerve sheath tumor(4.25%). The average age of inpatients was 44.71±17.91, and the inpatients aged 35-59 accounted for 47.6%.The number of UPS inpatients reached the peak at the age of 55 to 64; The proportion of rhabdomyosarcoma between 0~4 and 5~9 years old can reach above 46%.In total 1624 inpatients of STS, the number of male and female inpatients were 923 and 701, respectively. The gender ratio was 1.32:1. The proportion of UPS in either male or female inpatients was the highest, accounting for 23.10% and 24.80%, respectively. The number of male inpatients was more than that of female in the top nine pathological subtypes of STS except leiomyosarcoma (the gender ratio was 0.84:1).Conclusion The top three pathological subtypes of STS with high constituent ratio were UPS, synovial sarcoma and liposarcoma.UPS should be paid more attention on the prevention, treatment and research in Henan in future for its highest proportion of STS.


Background
Soft tissue sarcomas (STSs) are rare malignant tumors of mesenchymal origin with high aggressiveness and heterogeneity. More than 50% histopathological subtypes have been identi ed, and may occur in any part of body [1]. STSs are usually derived from bone supporting structures, including muscle, fascia, ber, nerve sheath, fat, lymphoid tissue and blood vessel. STS is account for approximately 0.8% of adult malignant tumor [2] and 5%-7% of children cancers [3], and the study from Japan and England shows that the incidence of soft tissue sarcoma in childhood cancer (aged 0-14) is on the rise [4]. There are good published literatures on the incidence of STS in the western populations, but there is a paucity of data from Asia, particularly on the epidemiology [5,6].It deserves our extensive research due to it is highly hazardous to people for its high invasiveness, recurrence and metastasis.
The data of inpatients with malignant tumors are used to study the pathological subtype proportion and demographic characteristics. Dynamic analysis is carried out to explore the trend of the epidemiology of malignant tumors so as to point out the focus and direction of future work and provide reference for the prevention and treatment of malignant tumors. The epidemiological characteristics of STS have been reported in many literatures both inside and outside the country. In 2018, there were 13040 newly diagnosed STS including the heart site in the United States according to the latest research data released by the American Cancer Society, which included 7,370 male and 5,670 female inpatients, and the sex ratio between males and females was 1.30:1.Moreover, 5150 cases of STS died in the United States in 2018, including 2770 males and 2380 females [2]. Lei Y [7] et al. found that there were 2048 cases of STS diagnosed in Beijing in the past 15 years, with an incidence rate of 1.15/100,000 according to the population-based STS data collected by the Beijing Cancer Registry from 1999 to 2013. The incidence rate of China's population standardization and the world population standardization rate were 0.74/100,000 and 0.86/100,000 respectively. In addition, it was found that the incidence and the common pathological types of STS in Beijing and Taiwan[8] were not the same. However, the characteristics of STS in Henan Province, the north middle of China, have not been reported up to now.
This study was to conduct an epidemiological analysis of the incidence characteristic of STS inpatients for the rst time in Henan Province Cancer Hospital during January 1, 2006 to December 31, 2016. According to the Henan Province Cancer Prevention O ce, the STS patients treated in Henan Province Cancer Hospital is account for about 75% of the province, therefore, analyzing the composition of the age, gender, pathological type of patients with STS in Henan Province Cancer Hospital during the 11 years would provide an reference of the epidemiological statue and time trend of patients with STS in Henan province, and provide clues for the health administrative department to develop effective prevention and control measures for STS.

Subjects
The hospitalized patients with STS for the rst time in Henan Province Cancer Hospital during January 1, 2006 to December 31, 2016 were included. The tumor classi cation criteria were based on the 10th revision of the International Statistical Classi cation of Diseases and Related Health Problems (ICD-10), C47 and C49 in ICD-10 were regarded as inclusion criteria for STS. C47 was a peripheral and autonomic nervous system malignancy, and C49 was other connective tissue and soft tissue malignant tumors. The classi cation criterion for histopathological types was ICD-O-2. Patients with recurrence, incomplete data, non-hospital or visceral STS, such as gastrointestinal stromal tumors and uterine leiomyosarcoma, were excluded in the research. The study was approved by the ethical committee of Zhengzhou University, and all the participating patients signed the informed consent.

Data Source and Collection
The information of electronic medical record of the inpatients with STS meeting the inclusion criteria in Henan Province Cancer Hospital was collected, including admission number (AD), age, gender, date of birth, place of birth, date of admission, date of discharge, location of tumor and pathological subtypes. Certainly, privacy information of the inpatients was not involved. The basic information of electronic medical records was input and stored in Microsoft Excel.

Data Processing and Statistical Analysis
In the latest STS WHO classi cation (2013 edition), the malignant brous histiocytoma (MFH) was renamed undifferentiated pleomorphic sarcoma (UPS). In this study, the cases with pathological diagnosis of MFH before 2013 or UPS after 2013 were uniformly named UPS in order to facilitate statistics.
The inpatients were divided into groups of 5 years old, a total of 18 groups. SPSS21.0 software was used to descriptively analyze the age, sex and pathological types of inpatients with STS. And the ratio of different pathological types was calculated respectively. Microsoft Excel was used to make graphs.

Quality Control
The investigators need to clarify the purpose and signi cance, and clarify the items and precautions of the research before collecting information.
The investigators and the staffs of the medical record department jointly checked and con rmed the information of the original inpatient meeting the inclusion criteria to ensure accurate and completed data.  Table 1 and Figure 1).

General Condition
Inpatient age with STS in Henan Province Cancer Hospital from 2006 to 2016 distributed over a wide range (1-82 yr), with an average age of 44.71±17.91. The number of inpatients with STS increased signi cantly since the age of 15, reached the peak at the age of 45-59, and decreased rapidly after 75 years old. The results showed a single peak distribution. The median age of inpatients with STS was 46 years old, and the inpatients at the age of 35-59 accounted for 47.6% (As shown in Figure 2). The analysis showed that the median age of inpatients with STS of the top nine pathological types varied from 2006 to 2016. It was found that the median age of some inpatients with STS showed different degrees of delay. For instance, the median age of inpatients with UPS, brosarcoma and leiomyosarcoma was delayed 10, 8.5 and 17 years old, respectively. By contrast, the median age of inpatients with some pathological subtypes of STS had a tendency to move forward such as malignant peripheral nerve sheath tumor, which was brought forward by about 10 years old. While the median age of rhabdomyosarcoma was less than 22 years old for containing embryonal rhabdomyosarcoma, which was more common in newborn (As shown in Table 3).

3.2.3
The variation trend of the composition ratio of STS subtypes in all age groups in Henan Province Cancer Hospital From 2006 to 2016, the composition ratio of STS subtypes of different age groups had a certain distribution pattern. For example, the inpatients with UPS and liposarcoma increased with age, and their tumor composition ratio increased continuously. The tumor composition ratio of UPS in the 70-74 age group increased by 20.77% compared with the 0-4 age group, and the tumors proportion of liposarcoma in the 80-85 age group increased by 30.15% compared with the 15-19 age group. Rhabdomyosarcoma accounted for an increasing proportion of tumors with the decrease of age, and the proportion of tumors in 0-4 age group and 5-9 age group can reach more than 46%. Synovial sarcoma was the most common component in the age group of 15-39 with a typical fusiform distribution. Other subtypes of STS composition ratio changes were not signi cant (As shown in Table 4 and Figure 3). UPS, accounting for 23% of STS, was the most common pathological type in males, followed by synovial sarcoma, liposarcoma and brosarcoma, accounting for 15%, 15% and 11% in males, respectively. Similar results were shown in females. The most common type was UPS accounting for 24.80% in females, followed by synovial sarcoma, liposarcoma and sarcoma without de nite type, accounting for 18%, 13% and 9% in females, respectively. As shown in Figure 4.

Gender differences in common pathological subtypes of inpatients with STS in Henan Province Cancer Hospital
Males were signi cantly more susceptible to STS except for leiomyosarcoma among the top nine pathological subtypes of STS in Henan Province Cancer Hospital from 2006 to 2016.UPS was found in 213 males and 174 females, accourting for 13.12% and 10.71% of all inpatients with STS, respectively. Leiomyosarcoma was found in 213 males and 174 females, accourting for 13.12% and 10.71% of all inpatients with STS, respectively. Malignant peripheral nerve sheath tumor was the most prominent sex-speci c subtype with male-to-female ratio was 2:1, followed by dermato brosarcoma (1.69:1), brosarcoma (1.63:1), rhabdomyosarcoma (1.6:1) and leiomyosarcoma (0.84:1).As shown in Table 5.

Discussion
The study analyzed the characteristics of 1624 inpatients with STS excluding visceral sarcoma from Henan Province Cancer Hospital from 2006 to 2016. We found that the top nine were UPS (accounting for 23.83% all STS), synovial sarcoma (16.69%), liposarcoma (13.67%), brosarcoma, sarcoma without de nite type, leiomyosarcoma, dermato brosarcoma protuberant, rhabdomyosarcoma, and malignant peripheral nerve sheath tumor. The number of inpatients with STS in the rst three pathological types accounted for 54.19% of all the inpatients with STS in Henan Province Cancer Hospital. The rst three pathological types of over 45 years old STS inpatients in Beijing were UPS(19.22%), liposarcoma (19.04%) and malignant peripheral nerve sheath tumor (10.18%) [7], the rst three pathological subtypes of STSs in Taiwan were liposarcoma(23%), UPS(18.9%) and leiomyosarcoma(7.6%)[8],and the rst three pathological types of STSs in Japan were UPS(19.46%), well differentiated liposarcoma(19.23%), myxoid/round cell liposarcoma (9.35%) [9].Three results were different from ours. By contrast, Fang's [10] research was consistent with ours. He analyzed information of 1118 patients with STS, and found that the most common rst three pathological types were UPS(35.24%), synovial sarcoma (17.08%) and liposarcoma (16.28%).We speculated that the difference may be due to different data collection methods, because the research in Beijing, Taiwan and Japan was population-based incidence data, and the analysis of STS in Beijing was divided into three age groups: 0-14 years old, 15~44 years old and over 45 years old, in which the rst three pathological types were analyzed in the group of over 45 years old. Particularly, It was noteworthy that synovial sarcoma was the most common diagnosis in foot and ankle malignant soft tissue tumors [11].
Previous studies have shown that the median age of inpatients with STS was 59 years old [12]. The study showed that the average age of inpatients with STS in Henan Province Cancer Hospital was 44.71±17.91 years old, and the peak age of onset was 40-59 years old. Morever, the median age of inpatients with STS has been postponed from 43 years old in 2006 to 51 years old in 2016, which may be related to population aging. However, the peak age of STS in Beijing was 80-84 years old [7], which may be related to the grouping method. The lower peak age in the study may be related to it including embryonal rhabdomyosarcoma with the lower age of onset. The peak age of STS of the extremities in Korea from 2009 to 2011 was 70-89 years old [13], and the peak age of STS in Ireland from 1994 to 2012 was 70-84 years old [14], which were different from the results of the study. The reason may be that the result in Korea mainly studies STS of the extremities, but not the whole body (excluding visceral sarcoma), and the research in Ireland was about the whole body including visceral sarcoma. While in our study, we mainly analyze whole body STS, visceral sarcoma excluded.
We found that the median age of inpatients with UPS was delayed by 10 years old by analyzing the proportion in the rst nine pathology subtypes during the period of 2006 to 2016, and UPS accounted for almost 35% of all inpatients with STS at the age of over 55, which suggested that the important age boundary of UPS was 55 years old. In addition, the present study and published studies manifested that synovial sarcoma was more frequently diagnosed in young patients over 15 years old, which was associated with the comliex nature of synovial sarcoma [15,16]. Meanwhile, we speculated that onset age of malignant peripheral nerve sheath tumor tend to be younger according to the median age of inpatients with malignant peripheral nerve sheath tumor was about 10 years old younger in the study, therefore, we can further speculate that the incidence of malignant nerve sheath tumor with neuro bromatosis type 1 (NF1) may be higher in all subtypes in the future, because the age of onset of NF1was younger [17,18]. Rhabdomyosarcoma was the most common subtype of STS under the age of 20, accounting for 36.67%.The high incidence of different pathological subtypes in all age groups suggested that we need to explore it's possible risk factors in future studies.
We analyzed the gender distribution of STS in Henan Province Cancer Hospital from 2006 to 2016, and found that among 1624 inpatients including 923 males and 701 females, and the ratio of male to female was 1.32:1.Lei Y [7] et al found that the incidence of STS of males in Beijing was higher than that of females, and the incidence rate of both males and females was 1.38:1 on the basis of population-based STS data from 1999 to 2013 collected by the Beijing Cancer Registry. The result was similar with Taiwan, where the gender ratio was 1.34: 1[8]. These were similar to the situation in Henan province. However, the STS surveillance data from 27 countries in Europe showed that the female incidence rate was 5.0/100,000, the male incidence rate was 4.4/100,000, and the female was slightly higher than the male [19]. We hypothesized that the reason was that they included data on internal organs. The incidence of uterine leiomyosarcoma and mammary sarcoma in women was signi cantly higher than that of epididymis sarcoma in male, and the visceral sarcoma data was included in this study, so the incidence of STS in women was higher. In contrast, visceral sarcoma was not included in the study. The study and the protocol were approved by the ethical committee of Zhengzhou University.

Consent for publication
Not applicable.    Figure 1 The trend of inpatients with STS in Henan Province Cancer Hospital in 2006~2016 Figure 2