Surgery Treatment Improved the Overall Survival Rate in Locoregional Myxoid Leiomyosarcoma than Other Myxosarcomas in the United States

Myxosarcomas are rare malignant tumors of soft connective tissues, classified into various subtypes, including myxoid liposarcoma, myxoid chondrosarcoma, and myxoid leiomyosarcoma. In this study, we proposed to study the demographic, tumor characteristics, and overall survival rate and compared the treatment modalities between these cancers. Patient data collected based on locoregional metastasis presentation of the abovementioned tumors with a cutoff study of survival duration up to 10 years were obtained from the SEER database during 1975-2016. Our results indicated that elderly patients and females were more in locoregional myxoid leiomyosarcoma than myxoid liposarcoma and myxoid chondrosarcoma with locoregional metastasis. The white race represented the most patients who suffered from these cancers than other races. The heart is the primary site for the abovementioned cancers, in addition to the female genitals to the myxoid leiomyosarcoma. Myxoid liposarcoma and myxoid chondrosarcoma patients with locoregional metastasis were suffering from grade II, while locoregional myxoid leiomyosarcoma patients with blank grading were due to missed data. Surgery was the most common treatment modality in this study compared with radiotherapy and chemotherapy. Kaplan-Meier analysis showed a significant difference in survival time between the three subtypes by using histology, and myxoid leiomyosarcoma showed prolonged survival than others. Elderly, female, white, unknown grade, surgery, no radiation, and no chemotherapy variables were independent factors associated with overall survival among these cancers. Multivariate analysis also showed significant differences in overall survival between the three tumors by histology, and myxoid leiomyosarcoma was with a better prognosis than others. Multivariate analysis of locoregional myxoid leiomyosarcoma showed the statistical significance of black race, grade, and radiotherapy, indicating them as independent prognostic factors of locoregional myxoid leiomyosarcoma. We conclude that surgery was the primary treatment modality against these cancers than radiotherapy and chemotherapy. And the locoregional myxoid leiomyosarcomas showed a better prognosis and higher survival rate than locoregional myxoid liposarcoma and locoregional myxoid chondrosarcoma.

Myxosarcoma tumors are classified into various subtypes, including myxoid liposarcoma, myxoid chondrosarcoma, and myxoid leiomyosarcoma [17,18]. Myxoid liposarcoma is a subtype of liposarcoma with a low risk of local recurrence than larger tumors [19]. Myxoid liposarcomas represent 5% of soft tissue sarcoma and 10-20% of liposarcoma [20]. However, myxoid liposarcomas may develop metastasis in almost 10% of myxoid liposarcoma patients and constitute 80% of the 5-year overall survival rate and 60% of the 10-year overall survival rate [21]. Myxoid chondrosarcomas are rare in extremities' soft tissues with less than 3% of soft tissue sarcomas [22]. Despite the myxoid chondrosarcomas characterized with a high risk of local recurrence and high spread rate of metastasis, several studies reported a prolonged survival rate of almost 70% of 10-year overall survival [22][23][24]. Myxoid leiomyosarcomas are a subtype of leiomyosarcomas characterized as rare, aggressive, and well-recognized uterus tumors [25]. Myxoid leiomyosarcoma showed a poor prognosis and a worse overall survival rate of 5 years, almost 11% [26].
Directed locoregional therapy on the metastasis pattern with additional treatment of the primary tumors may reduce the primary tumor burden, reduce metastasis prognosis, and improve the overall survival rate than systemic treatment to the distant metastasis [27][28][29]. It is reported that primary tumor resection could promote distant metastasis [30,31] while this hypothesis was drawn by recent studies and elucidated clinically the role of surgery in reducing the distant metastasis and improving the overall survival rate [32,33].
The Surveillance, Epidemiology, and End Results (SEER) is a comprehensive program of incidence, prognosis, and cancer surveillance in the United States (U.S.). SEER is an authoritative program that provides information on cancer statistics in the U.S. to minimize the cancer prognosis on the U.S. population. SEER is supported by the Surveillance Research Program (SRP) in the National Cancer Institute's (NCI's) Division of Cancer Control and Population Sciences (DCCPS). Among 19 registries around the U.S., cancer data has been collected through a coordinated system. These geographic registries reflect about 35% of the U.S. population, which represents the entire U.S. demographics. Data collection started with a few registries in 1973 and expanded to include more areas in the U.S. [34][35][36].
Myxoid liposarcomas, myxoid chondrosarcomas, and myxoid leiomyosarcomas are rare tumors with low incidence and survival data, so a comparison study has also been challenging to clarify. So, we proposed to study the demographic, tumor characteristics, and overall survival rates and to compare the treatment modalities between locoregional metastatic myxoid liposarcomas, locoregional metastatic myxoid chondrosarcomas, and locoregional metastatic myxoid leiomyosarcomas during 1975-2017 in 18 registries of the United States based on SEER database analysis.  [37]. All patients were identified based on the international classification of disease for oncology, third edition (ICD-O-3), using codes of myxoid liposarcoma (8850-8889), myxoid chondrosarcoma (9180-9249), and myxoid leiomyosarcoma (8890-8929). The data extracted from the SEER database in this study was based only on the locoregional metastasis presentation of myxoid liposarcoma, myxoid chondrosarcoma, and myxoid leiomyosarcoma tumors. We obtained a total number of patients of about 1398 of locoregional myxoid liposarcoma, 356 of locoregional myxoid chondrosarcoma, and 129 of locoregional myxoid leiomyosarcoma. Cases with unknown or missing data are included in the descriptive and survival analysis.

Study
Measurement. This study's primary measurement is to identify the locoregional metastasis differences of demographic, tumor characteristics, and survival rates between these three rare myxoid tumors (myxoid liposarcoma, myxoid chondrosarcoma, and myxoid leiomyosarcoma) among 18 registries of the United States during1975-2016. All variables included in this study are based on the cutoff study of survival duration up to 10 years [37].
2.1.3. Variable Study. All patient data are extracted from the SEER database. Demographic data were organized as age at diagnosis, gender, and race. The age variable was studied in two categories (less than 50 and greater than 50) to ease the

Survival Analysis.
Kaplan-Meier analysis of overall survival showed a statistically significant difference between histology subtypes of myxoid liposarcoma, myxoid chondrosarcoma, and myxoid leiomyosarcoma of locoregional metastatic patients with log-rank p < 0:004 (Figure 1). And locoregional metastatic myxoid leiomyosarcoma patients showed prolonged survival (median 85 months) compared with locoregional metastatic myxoid liposarcoma (median 58 months) and locoregional metastatic myxoid chondrosarcoma (median 60 months) (Figure 1). The Kaplan-Meier study indicated that variables of age more than 50 years, female gender, white race, unknown or missed grade, surgery resection, no radiation, and no chemotherapy variables showed statistical significance of overall survival    Table 2). Patients older than 50 showed statistical significance of survival with a median of 58 months of locoregional myxoid liposarcoma, 63 months of locoregional myxoid chondrosarcoma, and 85 months of locoregional myxoid leiomyosarcoma with log-rank p < 0:008 (Table 2, Figure 2), indicating that patients with locoregional myxoid leiomyosarcoma showed prolonged survival than others. Female patients of locoregional myxoid leiomyosarcoma with a median of 85 months showed significantly prolonged survival time compared with locoregional myxoid liposarcoma and locoregional myxoid chondrosarcoma (61 months and 54 months), p < 0:007 (Table 2, Figure 2). And white patients also showed prolonged survival in locoregional myxoid leiomyosarcoma (83 months) compared with locoregional myxoid liposarcoma and locoregional myxoid chondrosarcoma (58 months and 59 months, respectively), p < 0:014 (Table 2, Figure 2). The tumor grade showed that unknown or missed grading in myxoid leiomyosarcoma has significantly higher overall survival (median 85 months) compared with other tumors (63 and 54 median months, respectively), suggesting the inadequate data collection and poor follow-up of patients to their registries, p < 0:017 (Table 2, Figure 2). Among the treatment modalities, surgery resection of myxoid leiomyosarcoma tumors in locoregional metastatic presentation results in prolonged survival time with a median of 84 months compared with locoregional myxoid liposarcoma and locoregional myxoid chondrosarcoma, p < 0:008 (Table 2, Figure 2). The locoregional myxoid leiomyosarcoma patients who were not receiving radiotherapy and chemotherapy showed a significant difference in overall survival time and lived prolonged than other locoregional myxoid liposarcoma patients and locoregional myxoid chondrosarcoma patients with log-rank p < 0:002 and p < 0:009, respectively (Table 2, Figure 2). Multivariate analysis of histology subtype was also meaningful that showed a statistically significant difference of overall survival between myxoid liposarcoma, myxoid chondrosarcoma, and myxoid leiomyosarcoma of locoregional metastatic patients, p < 0:0001, and the locoregional myxoid leiomyosarcoma cases reported better survival time than other cancers ( Figure 3). Based on the abovementioned results and comparing these three tumors, we selected the locoregional myxoid leiomyosarcoma to perform univariate and multivariate analyses. And the univariate analysis of locoregional myxoid leiomyosarcoma showed no statistically significant difference in overall survival (Table 3). Moreover, multivariate analysis showed  7 Oxidative Medicine and Cellular Longevity that black race, with a hazard ratio (0.363), 95% CI (0.154-0.855), p < 0:021; grade IV with a hazard ratio (3.748), 95% CI (1.234-11.384), p < 0:02; and radiotherapy with a hazard ratio (0.529), 95% CI (0.302-0.926), p < 0:026 were independent prognostic factors for locoregional myxoid leiomyosarcoma patients according to data obtained from SEER (Table 3).

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Oxidative Medicine and Cellular Longevity demographic, tumor study, and survival among patients of locoregional myxoid liposarcoma, locoregional myxoid chondrosarcoma, and locoregional myxoid leiomyosarcoma in the U.S. based on data extracted from the SEER database during 1975-2016 [37]. Our demographic analysis of locoregional myxoid leiomyosarcomas showed that most patients were older than 50 compared with locoregional myxoid liposarcomas, and locoregional myxoid chondrosarcoma patients were showing no big difference between age variables according to data reported by SEER, and these results are similar to that reported in literature revealing that myxoid leiomyosarcomas occurred mostly in the elderly [44][45][46]. Myxoid liposarcoma and myxoid chondrosarcoma tumors with locoregional metastasis have mostly male predilection [44,47,48], and the locoregional myxoid leiomyosarcoma tumor has commonly female predilection [49]. Our obtained data indicated that cases of myxoid liposarcomas and myxoid chondrosarcomas with locoregional metastasis were mostly male patients. In contrast, locoregional myxoid leiomyosarcoma patients were mainly female due to myxoid leiomyosarcoma's histological origin, which commonly grows in the uterus [50]. White patients were the most patients suffering from the abovementioned cancers compared with other races, indicating that the white race is more vulnerable to these cancers than other races, as reported in several studies [51,52]. Our data were indicating that the white race represented the most patients suffering from these cancers in the U.S., according to the SEER database. Myxosarcoma tumors can be grown in various body locations but mostly grow in the heart [53,54]. In this study, our analysis indicated that locoregional myxoid liposarcoma and locoregional myxoid chondrosarcoma tumors were primarily located in the heart and locoregional myxoid leiomyosarcoma tumors are located mostly in female genitals and heart too.
Oncology analysis of our data obtained from SEER showed that locoregional myxoid liposarcoma and locoregional myxoid chondrosarcoma patients suffering from tumors have grade II differentiation. In contrast, locoregional myxoid leiomyosarcoma patients with blank or unknown grading showed a higher percentage compared with another grading, suggesting that the higher unknown cases in locoregional myxoid leiomyosarcomas were due to the less number of patient data collection and poor follow-up to their registries during that time of registration, which provides missing data compared with other well-reported cancers; however, grades II, III, and IV were higher in locoregional myxoid leiomyosarcoma compared with grade I.
Surgery is the most common approach of treatment modality used against myxoid liposarcomas, myxoid chondrosarcomas, and myxoid leiomyosarcomas compared to radiotherapy and chemotherapy [55,56]; interestingly, our analysis in this study indicated that the most reported cases of myxoid liposarcomas, myxoid chondrosarcomas, and myxoid leiomyosarcomas with locoregional metastasis were treated with surgery. Meanwhile, in radiotherapy modality, our analysis did not show any statistical significance among myxoid liposarcomas, myxoid chondrosarcomas, and myxoid leiomyosarcomas with locoregional metastasis. And chemotherapy treatment against locoregional metastasis of myxoid liposarcomas, myxoid chondrosarcomas, and myxoid leiomyosarcomas showed statistical significance with a higher percentage of patients who did not receive chemotherapy.
The overall survival rate was better for locoregional localization than distant metastasis, as reported in previous studies [27,57,58]. Our study's overall survival based on Kaplan-Meier analysis showed a statistically significant difference in survival time between patients with locoregional metastasis of myxoid liposarcomas, myxoid chondrosarcomas, and myxoid leiomyosarcomas by using the histology variable. The locoregional metastasis of myxoid leiomyosarcoma showed prolonged survival than locoregional metastatic myxoid liposarcoma and locoregional metastatic myxoid chondrosarcoma. Kaplan-Meier analysis indicated that age older than 50 years, female gender, white patients, unknown or missed grade, surgery, no radiation, and no chemotherapy variables were independent factors associated with overall survival among locoregional metastasis of myxoid liposarcomas, myxoid chondrosarcomas, and myxoid leiomyosarcomas. As reported in the literature, myxoid leiomyosarcomas are associated with a worse prognosis and low overall survival rate [26]; surprisingly, our data extracted from the SEER database of locoregional metastatic myxoid leiomyosarcomas reflected a better prognosis and high survival rate compared with locoregional metastatic myxoid liposarcomas and locoregional metastatic myxoid chondrosarcomas, suggesting that locoregional metastasis is accompanied with prolonged survival and a better prognosis than distant metastasis. Meaningfully, multivariate analysis using Cox hazard proportion analysis between the three subtypes of myxoid liposarcomas, myxoid chondrosarcomas, and myxoid leiomyosarcomas with locoregional metastasis showed also a significant difference in the overall survival rate. However, the locoregional myxoid leiomyosarcoma showed a better survival rate than other abovementioned subtypes, so the univariate and multivariate analyses of locoregional myxoid leiomyosarcoma had been performed, and the results of the univariate study did not show statistical significance of overall survival. The multivariate analysis showed the statistical significance of the black race, tumor grade, and radiotherapy variables of locoregional myxoid leiomyosarcoma, indicating that variables were independent prognostic factors of locoregional myxoid leiomyosarcoma based on the collected data from the SEER database. By comparing the overall survival of three subtypes of locoregional myxoid liposarcomas, locoregional myxoid chondrosarcomas, and locoregional myxoid leiomyosarcomas, the results illustrated that locoregional myxoid leiomyosarcomas have better prognostic and overall survival than the other subtypes.
In conclusion, in this study, we analyzed the demographic, oncology, and survival patterns of myxoid liposarcoma, myxoid chondrosarcoma, and myxoid leiomyosarcoma locoregional metastasis in the U.S. during 1975-2016 based on the SEER database. Our results were similar to the literature, indicating that white patients suffered more from myxoid liposarcoma, myxoid chondrosarcoma, and myxoid leiomyo-sarcoma with locoregional metastasis. The heart was the most common organ to develop locoregional metastasis of myxoid liposarcoma, myxoid chondrosarcoma, and myxoid leiomyosarcoma associated with high-grade differentiations. And surgery was the main approach of treatment modality against these cancers than radiotherapy and chemotherapy. The survival patterns showed that elderly, female, white patients, unknown or missed grade, surgery, radiation, and chemotherapy were dependent factors of overall survival among these cancers. However, locoregional myxoid leiomyosarcomas showed a better prognosis and better survival rate than locoregional myxoid liposarcoma and locoregional myxoid chondrosarcoma based on Kaplan-Meier and Cox hazard proportion studies. Adjuvant radiation and chemotherapy against locoregional leiomyosarcoma based on multicenter randomized clinical trials need further study in the future.

Data Availability
The data used in this study are available in the Surveillance, Epidemiology, and End Results (SEER) database of the National Cancer Institute (http://seer.cancer.gov) and available with the corresponding author.

Conflicts of Interest
The authors declare that there is no conflict of interest.