Primary cardiac tumors are rare, with an overall incidence of 0.001–0.02% [
We present a case series of 39 patients with PCS in attempt to characterize and better understand disease presentation, location, treatment modalities, and overall survival of patients with PCS. We highlight patterns of metastatic disease, histologic subtypes, and the barriers to improvements in overall survival of PCS patients.
The University of Michigan Electronic Medical Record Search Engine (EMERSE) was searched using the terms “cardiac sarcoma” and “heart” plus “sarcoma” to identify patients with a diagnosis of primary cardiac sarcoma treated at our institution between 1992 and 2017. Patients with sarcomas originating within the pulmonary vasculature or great vessels were not included in this analysis. Details regarding demographics, clinical presentation, pathologic features, treatment protocols, and outcome were extracted from clinical records. All research was approved by the University of Michigan Institutional Review Board (HUM00068553).
Descriptive statistics, such as median and range, were calculated for continuous variables, and frequencies were presented for categorical variables. To compare two categorical variables, a frequency table was created and analyzed using the chi-squared test or Fisher’s exact test. Overall survival (OS) was estimated by the Kaplan–Meier method and compared using the log-rank test. Statistical significance was defined as a two-sided
Thirty-nine patients with PCS presenting to the University of Michigan between 1992 and 2017 were identified. Median age at diagnosis was 41 years. Patient demographics and brief outline of disease characteristics are summarized in Table
Patient demographics and disease characteristics.
No. of patients (%) | |
---|---|
Male | 13 (33) |
Female | 26 (67) |
Median tumor size in cm (range) | 6.5 (1.7–16) |
Median no. of total chemotherapy regimens | 2 (range 1–6) |
Primary tumor location | |
Right heart | 16 (41) |
Left heart | 18 (46) |
Pericardium | 5 (13) |
Histology | |
Angiosarcoma | 14 (36) |
High-grade undifferentiated pleomorphic sarcoma | 10 (26) |
Leiomyosarcoma | 5 (13) |
Intimal sarcoma | 3 (8) |
Fibrosarcoma | 2 (4) |
Other | 5 (13) |
Metastatic disease present at diagnosis | 18 (46) |
Sites of metastases | |
Lung | 10 (55) |
Bone | 7 (39) |
Liver | 5 (28) |
Brain | 4 (22) |
Pancreas | 1 (5) |
Adrenal | 1 (5) |
Treatment | |
Surgery | 25 (58) |
R0 | 3 (12) |
R1 | 9 (36) |
R2 | 11 (44) |
Unknown | 2 (8) |
Chemotherapy | 28 (72) |
Radiation to cardiac tumor | 3 (8) |
Median age in years (range) | 41 (2–77) |
All patients were symptomatic at time of diagnosis, most frequently with dyspnea (
Angiosarcoma was the most common tumor histology and was more commonly located on the right side of the heart (
Primary cardiac histology by tumor location.
Metastatic disease was present in 18/39 (46%) of PCS patients at the time of diagnosis. The distribution of metastases at the time of disease diagnosis is listed in Table
Twelve patients developed brain metastases, 4 of whom had brain metastases at initial diagnosis. All presented with neurologic symptoms. Median time from diagnosis of PCS to diagnosis of brain metastases was 8.5 months (range 0–75.8 months). Left-sided cardiac tumors were more commonly associated with brain metastases (9/12,
Twenty-five patients (64%) underwent surgical resection of their PCS. Eleven of the twenty-five (11/25, 44%) patients had evidence of metastatic disease at diagnosis. An R0 resection was obtained in only 3 patients (12%), all of whom had left atrial tumors. Nine patients had R1 resections, 11 patients had R2 resections, and the surgical margin in 2 patients was unknown. Five patients with solitary brain metastases underwent craniotomy as primary management of their metastatic disease.
In total, 11 patients (26%) received radiation therapy. Three patients had radiation to the primary cardiac tumor, one to alleviate superior vena cava syndrome and two to optimize clinical status prior to systemic chemotherapy. Eight patients received radiation therapy to brain metastases (5 whole brain and 3 stereotactic radiotherapy). Four patients received radiation therapy after resection of solitary brain metastases. Four patients received radiation therapy alone for multifocal brain metastases. Two of these patients received palliative radiation to symptomatic lesions in the bone and lung.
Twenty-eight patients (72%) received chemotherapy, with a median of 2 regimens (range 1–6). Twenty-one patients (75%) who received chemotherapy had resection of their primary tumor. Two patients received neoadjuvant chemotherapy followed by resection, R0, and R1. Figure
Baseline cardiac MRI shows a large, heterogeneous mass in the pericardial space with a large effusion and compression of the left atrium (a). Neoadjuvant chemotherapy with doxorubicin/ifosfamide ×12 cycles and gemcitabine/docetaxel ×6 cycles resulted in near complete response (b).
Most patients received systemic therapy with palliative intent. Seventeen patients (61%) received doxorubicin plus ifosfamide (AI) as first-line therapy with a mean of 5 cycles (range 0.5–9). Ten patients received gemcitabine and docetaxel (GT) as first (
The median OS for patients who underwent surgery was 14.0 months (range 1–79 months), compared to 8.2 months (range 0–33 months;
Overall Survival of cardiac sarcoma patients (
Survival differences were not statistically significant based on the presence of metastatic disease at diagnosis, tumor location, or tumor histology because, in part, of our small sample size.
We present our single-institution experience with primary cardiac sarcoma with several notable findings: a high incidence of metastatic disease to the brain as compared to sarcomas originating in other locations, pattern of metastatic spread associated with location of sarcoma origin within the heart, predilection of certain histologies to originate in the right versus left heart, and association of multimodality therapy with improved patient survival despite the lack of a standardized treatment approach.
We found brain metastases occurred quickly and frequently in our PCS patients. Thirty-one percent (12/39) of our PCS patients developed brain metastases, compared to 1–8% in noncardiac sarcomas [
The prevalence of brain metastases in sarcoma is increasing due to prolonged survival from multimodal therapies that have poor CNS penetration [
The management of brain metastases is largely dependent on the number of lesions and patient performance status. Surgical intervention is considered with solitary metastases, while radiation therapy is preferred for multifocal disease or in patients with marginal performance status. Metastasectomy of brain metastases is reported to result in increased post-brain metastases survival to about 9 months, compared with 2.7 months for those who did not receive surgical intervention [
Surgical resection is the preferred management for localized sarcomas. As compared to other sarcomas, PCS patients are more likely to have advanced stage or inoperable primary tumor at presentation. Barriers to complete resection include anatomic location and declining performance status due to tumor at presentation. Given the difficulty in achieving complete resection with cardiac tumors, autotransplantation has been explored to allow for complete resection and optimal reconstruction. Ramlawi et al. reported on their institutional experience with cardiac transplant in 34 patients with left-sided cardiac tumors [
Nearly 50% of our patients had evidence of metastatic disease at time of presentation, which is higher than the reported 20–30% in several case series [
Surgery alone, however, is not enough to prevent primary tumor recurrence or distant metastases. Most patients who undergo complete (R0) resections without metastatic disease will relapse, highlighting the need for systemic therapy [
In our patient cohort, those who received chemotherapy alone and those who underwent surgical resection and received systemic chemotherapy had a survival advantage (
Primary cardiac sarcomas are rare, confer increased risk of brain metastases, are associated with shorter survival duration, and have a higher disease-specific mortality compared to soft tissue sarcomas arising in extracardiac sites. Increased mortality may be due to the difficulty with complete resection and high disease and symptom burden at presentation, making aggressive multimodal therapy difficult. Multidisciplinary care incorporating surgery, radiation, and systemic therapy when appropriate constitutes ideal management. Based on our findings, we recommend brain imaging at the time of primary cardiac sarcoma diagnosis given the incidence of brain metastases. Furthermore, our results suggest a role for aggressive multimodal therapy including resection and systemic therapy, even in the metastatic setting, to improve outcomes.
The data sets generated and analyzed to support the findings of this study may be available from the corresponding author upon request.
The authors declare that there are no conflicts of interest regarding the publication of this paper.