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Primary Cardiac Sarcoma: Clinical Characteristics and Prognostic Factors Over the Past 2 Decades.

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Ayrton Bangolo  *
,Pierre Fwelo,Kritika M Iyer,Sarah Klinger,Lorena Tavares,
Shraboni Dey,
Angel Ann Chacko,Myat Hein,Samyukta Gudena,Gbenga Lawal,Barath P. Sivasubramanian,Zekordavar Rimba,Kinjal Hirpara,Merajunnissa Merajunnissa,Swathi Veliginti,Georgemar Arana,Dily T. Sathyarajan,Sachin Singh,Tanvi Shetty,Kshitij Bhardwaj,Sayed Hashemy,Roberto L. Duran,Sung H. Kim,Candice M. Hipolito,Kibo Yoon,Vrusha Patel,Aseel Alshimari,Pugazhendi Inban,Saaniya Yasmeen,Krushika Devanaboyina,Gulshan Kumar,Saran Preet,Mishgan Akhtar,Ayanleh Abdi,Navya Nalajala,Syed F.M. Rizvi,Bhavna Gupta,
Simcha Weissman

This version is not peer-reviewed

Submitted:

21 April 2023

Posted:

28 April 2023

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Abstract
Background: Primary cardiac sarcomas (PCS) are extremely rare malignant tumors involving the heart. Only isolated case reports have been described. There is a paucity of data on the epidemiological characteristics of PCS. This study has the objective of investigating the epidemiologic characteristics, survival outcomes, and independent prognostic factors of PCS. Methods: We enrolled a total of 362 patients with PCS, between 2000 and 2017, by retrieving the Surveillance, Epidemiology, and End Results (SEER) database. We analyzed demographics, clinical characteristics, and overall mortality (OM) as well as cancer-specific mortality (CSM) of PCS. Variables with a p-value < 0.1 in the univariate Cox regression were incorporated into the multivariate Cox model to determine the independent prognostic factors, with a hazard ratio (HR) of greater than 1 representing adverse prognostic factors. Results: Crude analysis revealed a high OM in age 80+ (HR=5.958, 95% CI 3.357-10.575, p=0), followed by age 60-79 (HR=1.429, 95% CI 1.028-1.986, p=0.033); and PCS with distant metastases (HR=1.888, 95% CI 1.389-2.566, p=0). Patients that underwent surgical resection of the primary tumor and patients with malignant fibrous histiocytomas (HR=0.657, 95% CI 0.455-0.95, p=0.025) had a better OM (HR=0.606, 95% CI 0.465-0.791, p=0). The highest cancer-specific mortality was observed in age 80+ (HR=5.037, 95% CI 2.606-9.736, p=0) and patients with distant metastases (HR=1.953, 95% CI 1.396-2.733, p=0). Patients with malignant fibrous histiocytomas (HR=0.572, 95% CI 0.378-0.865, p=0.008) and those who underwent surgery (HR=0.581, 95% CI 0.436-0.774, p=0) had a lower CSM. Multivariate Cox proportional hazard regression analyses revealed higher OM in the age group 80+ (HR=13.261, 95% CI 5.839-30.119, p=0) and advanced disease with distant metastases (HR=2.013, 95% CI 1.355-2.99, p=0.001). Lower OM was found in patients with rhabdomyosarcoma (HR=0.364, 95% CI 0.154-0.86, p=0.021) and widowed patients (HR=0.506, 95% CI 0.263-0.977, p=0.042). Multivariate Cox proportional hazard regression analyses of CSM also revealed higher mortality in the same groups, and lower mortality in patients with Rhabdomyosarcoma. Conclusion: In this United States population-based retrospective cohort study using the SEER database, we found that cardiac rhabdomyosarcoma was associated with the lowest CSM and OM. Furthermore, as expected, age and advanced disease at diagnosis were independent factors predicting poor prognosis. Surgical resection of the primary tumor showed lower CSM and OM in the crude analysis but when adjusted for covariates in the multivariate analysis, it did not significantly impact the overall mortality or the cancer-specific mortality. These findings allow for treating clinicians to recognize patients that should be referred to palliative/hospice care at the time of diagnosis and avoid any surgical interventions as they did not show any differences in mortality. Surgical resection in patients with poor prognoses should be reserved as a palliative measure rather than an attempt to cure the disease.
Keywords: 
Subject: Public Health and Healthcare  -   Public Health and Health Services

1. Introduction

Primary cardiac sarcomas (PCS) are the most common malignancies affecting the heart, however overall, only 15 percent of cardiac neoplasms are malignant [1]. PCS remain a rare entity in the literature that have mainly been reported by the means of case reports [2,3,4,5,6]. Almost exclusively, PCS do not arise from benign neoplasms but are believed to arise de novo [7].
Signs and symptoms associated with PCS mostly depend on the location of the tumor [8]. PCS involving the left atrium can present with symptoms mitral regurgitation as they tend to grow into the left atrial lumen and cause mitral insufficiency symptoms such as dyspnea, orthopnea, pulmonary edema and hemoptysis. Some patients can present with thrombi in the general circulation, including neurologic thrombi [9]. PCS in the right atrium can present with symptoms of tricuspid stenosis and with thrombi into the pulmonary circulation causing pulmonary emboli [9]. PCS in the left ventricle may present with rhythm abnormalities and conduction aberrations as they may be intramural. Those that are intracavitary can present with systemic emboli and outflow obstruction [9].
Echocardiogram is the initial testing modality to assess a PCS. Location and sometimes type of cardiac tumors can be suggested by the echocardiogram. Detailed anatomic images and information on chemical microenvironment within the tumor can be provided by cardiac Magnetic Resonance Imaging (CMRI) and if not available a cardiac Computed tomography can be used [10]. A coronary angiogram should be performed to map blood vessels supplying tumors, that will then help to decide on the excision technique that will be most likely to be successful.
Cardiac tumors resectable on imaging are managed by complete open excision, as the tumor will be biopsied after excision. This will also help prevent complications of cardiac biopsy such as embolization [8]. For unresectable or diffuse tumors based on imaging, if the benefit outweighs the risk, a percutaneous cardiac biopsy can be performed with risks of cardiac perforation. Right sided tumors can benefit from intracardiac echocardiographic-guided biopsy with greater level of precision, therefore lower risk of cardiac perforation [11].
PCS are known to proliferate rapidly and be locally invasive by infiltrating the myocardium and obstructing cardiac blood flow. Complete resection is the treatment of choice, but the disease has a high recurrence rate and a high mortality rate with a median survival of 6 to 12 months [3]. Neoadjuvant or adjuvant chemotherapy has been inconsistently used with no proven benefits [3].
Studies addressing the prognostic factors associated with PCS are scarce. One of the largest studies on the subject was carried out by Yin and colleagues. The study looked at patients with PCS over a period of 42 years [12]. Nevertheless, adequate power studies addressing baseline epidemiology characteristics and independent prognostic factors of patients with PCS over the past 2 decades alone remain pauce.
To fill in the gap in the literature, using a large United States (US) population-based dataset, we aimed to evaluate the overall clinical characteristics as well as independent prognostic factors among patients diagnosed with PCS.

2. Materials and Methods

2.1. Study design

This retrospective study enrolled patients with a diagnosis of PCS retrieving the SEER research plus database, Nov 2020 submission (http://www.seer.cancer.gov). The SEER database is sponsored by the United States National Cancer Institute (US NCI) and has information on nearly 28% of the U.S. population [3].

2.2. Data selection

2.2.1. Inclusion Criteria:

All patients with PCS diagnosed from 2000 to 2017 were selected in our cohort based on, (1) Primary site [c38.0] and (2) histological type [ICD-O-3: 8800-8805,8810,8811,8815,8825,8830,8840,8850,8852,8855,8890,8891,8895,8896,8900-8902,8910,9040, 9041, 9043, 9120,9130,9180,9240] [9]. The above-mentioned ICD-9 and/or ICD-10 and/or ICD-0-3 codes were used to extract data regarding these patients from the SEER database.

2.2.2. Exclusion Criteria:

We excluded patients with an unknown age at diagnosis, race, stage of the PCS, unknown histologic type, or patients diagnosed during autopsies.

2.3. Study Variables

2.3.1. Main exposure

Age at diagnosis is the main predictor of mortality in this study. Age was classified into 0-39, 40-59, 60-79, 80+.

2.3.2. Outcomes

Overall mortality was defined by death of any causes at the end of the study, whereas Cancer-specific mortality was defined by death related to complications of PCS at the end of the study.

2.3.3. Survival months

Reported date of last follow up by December 31st, 2017, and date of death as reported in the SEER registry were used to calculate survival time starting from the date of diagnosis in terms of overall mortality. In terms of cancer-specific mortality, the reported date of last follow up and the date of cancer associated death were used to calculate PCS specific mortality, starting from the date of PCS diagnosis.

2.3.4. Sociodemographic and tumor characteristics

Baseline characteristics obtained in our cohort are as follows: Age at diagnosis, gender, race/ethnicity (non-Hispanic white, non-Hispanic black, Hispanic, and others), year of diagnosis, histological type, stage at diagnosis (localized, regional, and distant), geographic residential area, yearly income, marital status, year of diagnosis, surgery, and radiation, and well as chemotherapy. Histologic subtypes included are as follows: Leiomyosarcoma/spindle cell sarcoma, angiosarcoma, rhabdomyosarcoma, malignant fibrous histiocytomas, synovial sarcomas, osteosarcoma/Chondrosarcoma and Sarcoma, NOS. There were not enough cases of liposarcoma in the database, thus these patients were excluded. “Sarcoma, NOS '' indicates no tumor subtype in patient records.

2.4. Statistical analysis

The fact that Hazard rates are proportional overtime constitute the basis of Cox proportional hazard regression model. In order to be able to determine independent prognostic factors influencing the OM and CSM, variables that had a p value of less than 0.1 in the univariate analysis were incorporated in the multivariate analysis adjusting for covariates. Deleterious prognostic factors are associated with a hazard ratio (HR) of more than 1. The threshold of statistical significance was defined by a p value of <0.005, with a confidence interval of 95%. The software used to carry out the statistical test was STATA 17, and all the tests were two-sided.

3. Results

We ultimately enrolled a total of 362 patients with a primary diagnosis of PCS. Table 1 summarizes the baseline characteristics of patients included in our cohort. Patients with higher revenue and yearly income $75,000+ and those living in populated metropolitans (1 million people) were more likely to be diagnosed. Male patients (50.83%) slightly more represented than their female counterpart. The other two well represented groups were age range 40-59 (37.85%) and non-Hispanic whites (58.84%). The most encountered histologic subtype was angiosarcoma (42.51%), which represented nearly half the cases. The majority of diagnoses were made at the advanced disease stage, with distant metastases (38.67%). Married patients constituted the majority of the study (54.42%), followed by single patients (26.80%). Most patients underwent surgical resection of the primary tumor (65.47%). There was a steady number of new cases from 2000 to 2017 with an average of 20 new cases per year.
Crude analysis of factors associated with all-cause mortality and PCS related mortality among US patients between 2000 and 2017 is demonstrated in Table 2. Age 80+ (HR=5.958, 95% CI 3.357-10.575, p=0), followed by age 60-79 (HR=1.429, 95% CI 1.028-1.986, p=0.033); and PCS with distant metastases (HR=1.888, 95% CI 1.389-2.566, p=0) have the highest overall mortality. Patients that underwent surgical resection of the primary tumor and patients with malignant fibrous histiocytomas (HR=0.657, 95% CI 0.455-0.95, p=0.025) had a better OM (HR=0.606, 95% CI 0.465-0.791, p=0). The highest cancer specific mortality was observed in age 80+ (HR=5.037, 95% CI 2.606-9.736, p=0) and patients with distant metastases (HR=1.953, 95% CI 1.396-2.733, p=0). Patients with malignant fibrous histiocytomas (HR=0.572, 95% CI 0.378-0.865, p=0.008) and those who underwent surgery (HR=0.581, 95% CI 0.436-0.774, p=0) had a lower CSM.
Table 3 summarizes the results of multivariate cox proportional hazard regression analyses of characteristics influencing all-cause mortality and CSM of patients with PCS diagnosed between 2000 and 2017. The following groups were found to have a higher overall mortality: age 80+ (HR=13.261, 95% CI 5.839-30.119, p= 0), followed by age 60-79 (HR=1.916, 95% CI 1.213-3.025, p=0.005); and advanced disease with distant metastasis (HR=2.013, 95% CI 1.355-2.99, p=0.001), followed by regional involvement (HR=1.518, 95% CI 1.041-2.214, p=0.03). Lower OM rate was observed in patients with rhabdomyosarcoma (HR=0.364, 95% CI 0.154-0.86, p=0.021) and widowed (HR=0.506, 95% CI 0.263-0.977, p=0.042). Age 80+ (HR=11.177, 95% CI 4.449-28.08, p=0) and advanced disease with distant metastases (HR=2t.117, 95% CI 1.37-3.271, p=0.001) have the highest cancer specific mortality. Patients with rhabdomyosarcoma (HR=0.344, 95% CI 0.128-0.929, p=0.035) have a lower CSM.

4. Discussion

Primary cardiac sarcomas are rare. In this United States based population cohort using the SEER database, we found that age at diagnosis, and advanced disease with metastasis are associated with poor prognosis. Surgical intervention of the primary tumor was associated with lower mortality in the crude analysis but did not make any difference in the multivariate analysis. Patients with malignant fibrous histiocytoma had the best prognosis in the crude analysis but not in the multivariate analysis, whereas rhabdomyosarcoma had the best prognosis in the adjusted multivariate analysis. Angiosarcoma was the most encountered histologic subtype.
Prior literature has demonstrated that rhabdomyosarcomas make up approximately 20% of malignant sarcomas of the heart and are usually multifocal [14]. Our study had different findings, with rhabdomyosarcoma representing only 3.31% of our cohort. Sarcomatous tumors of the heart proliferate rapidly causing myocardial replacement and can lead to widespread metastatic disease [14]. Angiosarcomas, the most common subtype in adults, are aggressive, rapidly invading adjacent structures, and 47% to 89% of patients present with lung, liver, or brain metastases by the time of diagnosis [15,16]. This rapid proliferation and high representation of angiosarcoma might be the reason most patients in our cohort were diagnosed at advanced disease stage with distant metastases.
Most of our patients were diagnosed between 40 and 59 years old, which differs from findings in the study by Yin et al. where patients were mostly diagnosed between 20 and 40 years old [12]. However, a similar trend for seen in the study by Hammami et al. where patients were diagnosed between 31 and 60 years old [17]. The majority of patients in our cohort were white, representing more than half of the population in this study, which is in adequacy with the literature [12,17]. This trend can be explained by the disparity in healthcare access between the races [18].
Patients living in crowded areas and those with a higher annual revenue were most likely to be diagnosed with PCS in our cohort. Metropolitans with a crowded population tend to be better served medically with higher accessibility to advanced imaging techniques and better expertise. Likewise, patients with higher revenue are more likely to have better insurance coverage and means of affording other out of pocket medical expenses, thus increasing their diagnosis yield. Previous observational studies carried out on cancer patients have found a better outcome in married patients compared to their nonmarried counterparts, in terms of OM and CSM [19,20,21,22,23,24,25,26,27,28,29]. Better spousal and social supports were possible explanations of that better survival. However, that observation did not hold true in our cohort. Furthermore, widowed patients had a better OM compared to other marital status.
Surgical resection is the mainstay of treatment for PCS. Despite the overall poor survival, patients who do undergo complete resection have better outcomes compared with those who undergo incomplete resection. The roles of radiation, chemotherapy, cardiomyopathy, and cardiac transplantation, including auto-transplantation, are still controversial due to the rarity of the disease, lack of standardized therapies, and scarcity of data in the literature [30]. The study by Yin et. al found that chemotherapy and surgical resection were associated with better prognosis [12]. Half of the patients in our cohort underwent chemotherapy and more than half underwent surgical resection of the primary tumor. Our study revealed a better prognosis for patients with surgical resection in the crude analysis. However, these results were not sustained in the adjusted multivariate analysis. Neither surgical resection, nor chemotherapy were associated with better prognosis in our cohort.
As stated above, complete resection is the treatment of choice for PCS even though most patients develop recurrent disease that is fatal despite complete resection. The study by Centofanti et al., that enrolled patients from 1980 to 1997, found that effective palliation is possible with resection of malignant tumors and effective adjuvant therapy may improve prognosis [f]. The study by Bakaeen et al [g], that enrolled patients from 1975 to 2002, revealed that there was good local tumor control with surgery, but no effect was found on the mortality given the metastatic nature of the PCS at the time of surgery. Ramlawi et al., enrolling patients from 1990 to 2015 in their single institution study, found a 1 year post operative mortality rate of 35 % [h]. Kosuga et al., that carried out a study between 1978 and 1999, found a poor prognosis of malignant PCS if only debulked but a great benefit of aggressive surgery if carried out with palliative intentions until adjuvant therapy is available [i]. The study by Raaf et. Al published in 1994 concluded that surgical resection, adjuvant chemotherapy and radiation therapy can also symptoms and prolong survival [j].
As evidenced by the above-mentioned studies overtime, surgical resection remains the mainstay of treatment in patients with PCS. There are currently contrasting and mixed data showing the benefits of adjuvant chemotherapy or radiation in survival of patients with PCS. As stated earlier, in our cohort, when adjusting for covariates to avoid confounding factors, surgery of primary, adjuvant chemotherapy and radiation did not influence mortality. Therefore, we propose that those treatment modalities should only be reserved for palliative purposes and in an effort to improve the patient's quality of life. We hope to encourage clinicians to avoid exposing patients with PCS, especially those with advanced age and or disease, from side effects of radiation, chemotherapy, and surgery if those are not done with the intention to alleviate the patient's suffering. In the era of emergence of immunotherapy in the treatment of refractory solid tumors, particularly Chimeric Antigen Receptor (CAR) T Cell therapy, promising data have emerged in the treatment of sarcomas [k].
Certain limitations must be considered when interpreting the results of this study. Our study was mainly carried out on PCS, this makes it difficult to generalize our results to metastatic cardiac sarcomas. Information gathered on patients that underwent surgery was not complete. We were unable to find out if patients underwent complete or incomplete resection. Furthermore, the SEER database publicly available does not provide information on comorbidities. However, this study has the merit of collecting data from the largest cancer database in the USA. We were also able to enroll an adequate sample size despite the rarity of the pathology.

5. Conclusion

Data on PCS are very pauce in the literature mainly due to the scarcity of the pathology. A dismal prognosis is associated with PCS given its aggressive behavior. As one could expect, advanced age and advanced disease with metastasis are independent factors of poor prognosis, as evidenced in our cohort over the past 2 decades. No positive prognostic value was observed after resecting the primary tumor. Rhabdomyosarcoma was the histologic type with the best prognosis. Furthermore, adjuvant chemotherapy and radiation did not affect mortality. Given the aggressive nature and dismal prognosis of PCS, treatment of such patients should mainly focus on improving the quality of life. Clinicians should weigh the pros and cons of proceeding with such therapies as the side effects might worsen the patient’s quality of life without prolonging survival. We propose that, for the elderly and those with advanced disease, the above-mentioned therapies should only be carried out with the intention of palliation. With newer and promising data of CAR T cell therapy on solid tumors, including sarcomas, we hope that more clinical trials involving patients with PCS will be carried out, as the need to find new treatment modalities for this dismal pathology is urging.

Author Contributions

Ayrton Bangolo searched the literature, wrote, and revised the manuscript. Pierre Fwelo extracted and analysed the data, revised, and edited the manuscript. Kritika M. Iyer, Sarah Klinger, Lorena Tavares, Shraboni Dey, Angel Ann Chacko, Myat Hein, Samyukta Gudena, Gbenga Lawal, Barath P. Sivasubramanian, Zekordavar Rimba, Kinjal Hirpara, Merajunnissa, Swathi Veliginti, Georgemar Arana, Dily T. Sathyarajan, Sachin Singh, Tanvi Shetty, Kshitij Bhardwaj, Sayed Hashemy, Roberto L. Duran, Sung H. Kim, Candice M. Hipolito, Kibo Yoon, Vrusha Patel, Aseel Alshimari, Pugazhendi Inban, Saaniya Yasmeen, krushika Devanaboyina, Gulshan Kumar, Saran Preet, Mishgan Akhtar, Ayanleh Abdi, Navya Nalajala, Syed F.M. Rizvi revised and edited the manuscript. Bhavna Gupta, Sameh Elias and Simcha Weissman revised and approved the final version and are the article’s guarantors. All authors certify that they contributed sufficiently to the intellectual content and data analysis. Each author has reviewed the final version of the manuscript and approves it for publication.

Funding

No Funding was received.

Data Availability Statement

The data used and/or analyzed in this study are available in the Surveillance, Epidemiology, and End Results (SEER) Database of the National Cancer Institute (http://seer.cancer.gov).

Conflicts of Interest

No potential conflict of interest was reported by the authors.

Statement of Ethics

The SEER Dataset was a public-use dataset, of which the informed consent was waived.

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Table 1. Demographic and Clinicopathologic characteristics of US patients with Primary cardiac sarcoma between 2000 and 2017.
Table 1. Demographic and Clinicopathologic characteristics of US patients with Primary cardiac sarcoma between 2000 and 2017.
Characteristics
N= %
Total 362 100
Gender
Female 178 49.17
Male 184 50.83
Age at diagnosis, y.o
0-39 116 32.04
40-59 137 37.85
60-79 86 23.76
80+ 23 6.35
Race
Non-Hispanic white 213 58.84
Non-Hispanic black 44 12.15
Hispanic 68 18.78
Other 37 10.22
Histopathology
Angiosarcoma 172 42.51
Rhabdomyosarcoma 12 3.31
Malignant fibrous histiocytomas 51 14.09
Leiomyosarcomas/spindle cell sarcomas 42 11.60
Sarcoma, NOS 38 10.50
Synovial sarcomas 14 3.87
Osteosarcoma/Chondrosarcoma 33 9.12
Tumor stage
Localized 96 26.52
Regional 110 30.39
Distant 140 38.67
Unknown 16 4.42
Living area
Counties in metropolitan areas of 1 million persons 215 59.39
Counties in metropolitan areas of 250,000 to 1 million persons 79 21.82
Counties in metropolitan areas of 250,000 persons 27 7.46
Nonmetropolitan counties adjacent to a metropolitan area 15 4.14
Nonmetropolitan counties not adjacent to a metropolitan area 26 7.18
Income per year
$< $45,000 18 4.97
$45,000-54,999 57 15.75
$55,000-64,999 81 22.38
$65,000-74,999 90 24.86
$75,000+ 116 32.04
Marital Status
Married 197 54.42
Single 97 26.80
Divorced/separated 33 9.12
Widowed 21 5.80
Unknown 14 3.87
Chemotherapy
No 181 50.00
Yes 181 50.00
Radiation
No 285 79.83
Yes 72 20.17
Surgery
No 123 33.98
Yes 237 65.47
Unknown 2 0.55
Year of diagnosis
2000 17 4.70
2001 20 5.52
2002 13 3.59
2003 13 3.59
2004 26 7.18
2005 11 3.04
2006 13 3.59
2007 23 6.35
2008 9 2.49
2009 32 8.84
2010 22 6.08
2011 28 7.73
2012 14 3.87
2013 20 5.52
2014 28 7.73
2015 20 5.52
2016 23 6.35
2017 30 8.29
Table 2. Crude analysis of factors associated with all-cause mortality and Primary Cardiac Sarcoma related mortality among US patients between 2000 and 2017.
Table 2. Crude analysis of factors associated with all-cause mortality and Primary Cardiac Sarcoma related mortality among US patients between 2000 and 2017.
Characteristics Overall Mortality.
Crude Proportional
Hazard ratio
(95 % confidence interval)		 Primary Cardiac Sarcoma mortality.
Crude Proportional
Hazard ratio
(95% confidence interval)
Gender
Female 1.00 (reference) 1,00 (reference)
Male 0.964 (0.758-1.226) 0.995 (0.766-1.293)
Age at diagnosis, y.o
0-39 1.00 (reference) 1.00 (reference)
40-59 1.212 (0.911-1.615) 1.258 (0.925-1.712)
60-79 1.429 (1.028-1.986) ** 1.35 (0.939-1.941)
80+ 5.958 (3.357-10.575) *** 5.037 (2.606-9.736) ***
Race
Non-Hispanic white 1.00 (reference) 1.00 (reference)
Non-Hispanic black 1.222 (0.851-1.754) 1.257 (0.851-1.857)
Hispanic 0.833 (0.602-1.154) 0.827 (0.578-1.182)
Other 1.063 (0.685-1.648) 1.212 (0.77-1.906)
Histopathology
Angiosarcoma 1.00 (reference) 1.00 (reference)
Rhabdomyosarcoma 0.608 (0.283-1.307) 0.501 (0.204-1.231)
Malignant fibrous histiocytomas 0.657 (0.455-0.95) ** 0.572 (0.378-0.865) ***
Leiomyosarcomas/spindle cell sarcomas 0.787 (0.535-1.16) 0.734 (0.48-1.123)
Sarcoma, NOS 0.965 (0.64-1.456) 0.853 (0.539-1.349)
Synovial sarcomas 0.535 (0.271-1.056) 0.608 (0.307-1.203)
Osteosarcoma/Chondrosarcoma 0.987 (0.646-1.507) 0.932 (0.589-1.474)
Tumor stage
Localized 1.00 (reference) 1.00 (reference)
Regional 1.334 (0.964-1.846) 1.386 (0.972-1.976)
Distant 1.888 (1.389-2.566) *** 1.953 (1.396-2.733) ***
Living area
Counties in metropolitan areas of 1 million persons 1.00 (reference) 1.00 (reference)
Counties in metropolitan areas of 250,000 to 1 million persons 1.01 (0.747-1.366) 0.993 (0.714-1.381)
Counties in metropolitan areas of 250,000 persons 1.037 (0.662-1.623) 1.051 (0.648-1.703)
Nonmetropolitan counties adjacent to a metropolitan area 1.666 (0.923-3.007) 1.614 (0.846-3.081)
Nonmetropolitan counties not adjacent to a metropolitan area 1.128 (0.721-1.766) 1.16 (0.716-1.88)
Income per year
$< $45,000 1,00 (reference) 1.00 (reference)
$45,000-54,999 0.72 (0.372-1.392) 0.842 (0.392-1.805)
$55,000-64,999 0.689 (0.363-1.309) 0.774 (0.367-1.632)
$65,000-74,999 0.601 (0.316-1.144) 0.729 (0.346-1.534)
$75,000+ 0.624 (0.332-1.172) 0.755 (0.363-1.569)
Marital Status
Married 1.00 (reference) 1.00 (reference)
Single 0.854 (0.643-1.135) 0.783 (0.572-1.071)
Divorced/separated 1.121 (0.728-1.726) 1.121 (0.707-1.778)
Widowed 1.203 (0.717-2.019) 1.207 (0.694-2.099)
Chemotherapy
No 1.00 (reference) 1.00 (reference)
Yes 0.928 (0.724-1.19) 0.956 (0.729-1.253)
Radiation
No 1.00 (reference) 1.00 (reference)
Yes 0.931 (0.7-1.24) 0.937 (0.688-1.278)
Surgery
No 1.00 (reference) 1.00 (reference)
Yes 0.606 (0.465-0.791) *** 0.581 (0.436-0.774) ***
*** p<.01, ** p<.05.
Table 3. Multivariate cox proportional hazard regression analyses of factors affecting all-cause mortality and Primary Cardiac Sarcoma related mortality among US patients between 2000 and 2017.
Table 3. Multivariate cox proportional hazard regression analyses of factors affecting all-cause mortality and Primary Cardiac Sarcoma related mortality among US patients between 2000 and 2017.
Characteristics Overall Mortality.
Adjusted proportional Hazard ratio (95% confidence interval)		 Primary Cardiac Sarcoma mortality.
Adjusted proportional Hazard ratio (95% confidence interval)
Gender
Female 1.00 (reference) 1.00 (reference)
Male 0.952 (0.692-1.309) 0.917 (0.649-1.296)
Age at diagnosis, y.o
0-39 1.00 (reference) 1.00 (reference)
40-59 1.201 (0.847-1.703) 1.173 (0.81-1.699)
60-79 1.916 (1.213-3.025) *** 1.61 (0.976-2.657)
80+ 13.261 (5.839-30.119) *** 11.177 (4.449-28.08) ***
Race
Non-Hispanic white 1.00 (reference) 1.00 (reference)
Non-Hispanic black 1.446 (0.919-2.276) 1.557 (0.962-2.52)
Hispanic 1.051 (0.691-1.597) 1.015 (0.645-1.596)
Other 1.174 (0.709-1.944) 1.379 (0.814-2.336)
Histopathology
Angiosarcoma 1.00 (reference) 1.00 (reference)
Rhabdomyosarcoma 0.364 (0.154-0.86) ** 0.344 (0.128-0.929) **
Malignant fibrous histiocytomas 0.668 (0.422-1.056) 0.62 (0.373-1.029)
Leiomyosarcomas/spindle cell sarcomas 0.751 (0.458-1.229) 0.705 (0.411-1.207)
Sarcoma, NOS 1.376 (0.818-2.314) 1.322 (0.75-2.33)
Synovial sarcomas 0.603 (0.271-1.341) 0.738 (0.329-1.657)
Osteosarcoma/Chondrosarcoma 1.355 (0.792-2.316) 1.37 (0.758-2.476)
Tumor stage
Localized 1.00 (reference) 1.00 (reference)
Regional 1.518 (1.041-2.214) ** 1.574 (1.042-2.379) **
Distant 2.013 (1.355-2.99) *** 2.117 (1.37-3.271) ***
Living area
Counties in metropolitan areas of 1 million persons 1.00 (reference) 1.00 (reference)
Counties in metropolitan areas of 250,000 to 1 million persons 0.999 (0.692-1.44) 0.927 (0.624-1.377)
Counties in metropolitan areas of 250,000 persons 0.654 (0.372-1.148) 0.586 (0.318-1.082)
Nonmetropolitan counties adjacent to a metropolitan area 1.16 (0.556-2.421) 1.007 (0.444-2.283)
Nonmetropolitan counties not adjacent to a metropolitan area 1.226 (0.663-2.268) 1.434 (0.743-2.771)
Income per year
$< $45,000 1.00 (reference) 1.00 (reference)
$45,000-54,999 1.049 (0.48-2.292) 1.531 (0.62-3.781)
$55,000-64,999 0.856 (0.379-1.93) 1.207 (0.475-3.069)
$65,000-74,999 0.778 (0.339-1.787) 1.158 (0.448-2.991)
$75,000+ 0.812 (0.353-1.864) 1.199 (0.463-3.104)
Marital Status
Married 1.00 (reference) 1.00 (reference)
Single 0.834 (0.573-1.215) 0.681 (0.451-1.028)
Divorced/separated 1.27 (0.746-2.163) 1.183 (0.664-2.108)
Widowed 0.506 (0.263-0.977) ** 0.576 (0.282-1.18)
Chemotherapy
No 1.00 (reference) 1.00 (reference)
Yes 0.97 (0.704-1.337) 1.047 (0.739-1.484)
Radiation
No 1.00 (reference) 1.00 (reference)
Yes 0.94 (0.674-1.313) 0.829 (0.578-1.188)
Surgery
No 1.00 (reference) 1.00 (reference)
Yes 0.735 (0.508-1.062) 0.724 (0.489-1.072)
*** p<.01, ** p<.05.
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