Postoperative radiotherapy for high-grade primary cardiac spindle cell sarcoma: a rare entity
- 1 Department of Oncology, Section Radiation Oncology, Aga Khan University, Karachi, Pakistan
- 2 Department of Pathology and Laboratory Medicine, Aga Khan University, Karachi, Pakistan
- Correspondence to Dr Tooba Ali; tooba053@gmail.com
Abstract
A patient in her early 20s presented with blood-stained sputum and shortness of breath. Initially, she was treated for pneumonia. Later, upon exacerbation of symptoms, further investigations were done which exhibited a left atrial mass causing compression of contralateral atrium. She underwent surgical resection of the mass, which was initially mistaken as myxoma. However, histopathological correlation revealed spindle cell sarcoma with focal myogenic differentiation. This case report highlights the role of Radiation Therapy in adjuvant setting with promising impact on improving local control after R2 resection. Cardiac spindle cell sarcoma, being one of the rarest cardiac tumours reported to date, warrants establishment of a Rare Tumour Multidisciplinary Team for management of such malignancies.
Background
A primary cardiac tumour is a rare entity with frequency approaching to approximately 0.02% (based on autopsy data).1 Among these, majority are benign and only 25% are malignant.2 Malignant primary cardiac tumours are mostly sarcomas, with angiosarcoma (37%) being the most common and undifferentiated sarcoma as the second most common histology (24%).2 As per extensive literature review, the least reported sarcoma in cardiac region is spindle cell sarcoma.3
Symptoms of cardiac sarcoma depend on tumour site and size. Symptoms range from mild dyspnoea, chest pain and general constitutional symptoms to signs of intracardiac obstruction or systemic embolisation. These tumours are diagnosed using transoesophageal echocardiogram, CT scan or cardiac MRI.4 Evidence-based management of primary spindle cell sarcoma of the heart is relatively lacking; however, the favoured treatment option is complete surgical resection with negative margins, which is only possible in less than 50% of cases due to proximity of the tumour to vital structures.5 Therefore, surgery followed by adjuvant chemotherapy and radiation therapy can be opted.5
The pattern of failure for these tumours includes local as well as distant metastasis mostly within 1 year of diagnosis. Overall prognosis of primary cardiac tumour is poor with median survival approaching up to 6–12 months.6
Case presentation
A woman in her early 20s presented in November 2021 with blood-stained sputum and occasional shortness of breath for the past 2 months. Initially, she was treated for her viral infection/pneumonia. Later, upon progression of symptoms, her chest X-ray was done which reported cardiomegaly and patchy consolidation in the left lower lobe of the lung. Initial conventional echocardiogram was unremarkable; later evaluation with transoesophageal echocardiogram reported severely dilated left atrium with left atrial clot, and moderate mitral regurgitation with ejection fraction of 60%.
She was then referred to tertiary care hospital for further evaluation. On examination, there were fine inspiratory crackles in basal portions of both lungs. On initial workup, ECG displayed prolonged QT interval. CT scan in arterial phase demonstrated a left atrial mass measuring 59×75 mm causing distension of the left atrium with compression effect over the contralateral atrium (figure 1). Soft tissue component of the mass was prolapsing into the left ventricle (25×25 mm), involving right pulmonary veins extending up to posterior mediastinum and abutting the oesophagus.
Preoperative CT of the chest with intravenous contrast, showing a soft tissue mass lesion in the left atrium.
Treatment
The patient then underwent R2 resection (gross residual disease) of the left atrial mass. Intraoperatively, an 8×8 cm locally advanced tumour was identified, and due to proximity to vital vessels, R0 resection was not achievable. Postoperative 18Fluorodeoxyglucose Positron Emission Tomography (PET)/CT scan was done, which showed residual disease (2×1.5 cm), with no evidence of distant metastasis (figure 2). Histopathologically, the mass was consistent with spindle cell sarcoma with focal myogenic differentiation; immunohistochemical staining performed showed focal positivity for desmin and myogenin (figure 3A). The case was discussed in a multidisciplinary tumour board meeting where it was decided to plan for adjuvant chemotherapy and radiation therapy. She received three cycles of ifosfamide and was planned for postoperative radiation therapy.
Preoperative positron emission tomography/CT with intravenous contrast, showing a soft tissue mass lesion in the left atrium.
(A) Immunohistochemical staining focally positive for myogenin. (B) Microscopic representation of malignant spindle cell tumour with areas of necrosis, composed of fascicles of spindle cells exhibiting moderate nuclear pleomorphism, frequent mitotic figures and myxoid stroma.
Postoperative radiation therapy was planned on VMAT (volumetric arc therapy) using a simultaneous integrated boost (SIB) technique on arterial phase radiotherapy planning CT scan7 (figure 4), delivering 6400 cGy in 30 fractions (planning target volume (PTV)6400 cGy at 213 cGy/fraction) to PET-avid residual disease; 6000 cGy (PTV6000 at 200 cGy/fraction) was delivered to intermediate-risk area (surgical bed) and 5400 cGy (PTV5400 cGy at 180 cGy/fraction) was delivered to low-risk area. Figure 5 shows isodose curve lines signifying dose distribution with 95% of the dose being prescribed to delineated PTV. After completion of radiation, she received three more cycles of ifosfamide chemotherapy.
Volumetric arc therapy planning showing planning target volume (PTV) 54 (red), PTV 60 (orange) and PTV 64 (pink).
Isodose curve showing absolute and relative dose distribution curve for the prescribed doses of planning target volume (PTV) 54 (red), PTV 60 (orange) and PTV 64 (pink).
Outcome and follow-up
The patient was then followed for 6 months after completion of adjuvant chemotherapy and radiation; two subsequent PET scans done at 3-month intervals showed a sustained complete metabolic response with no patient-reported radiation-induced toxicity. However, in subsequent follow-up, the patient reported severe headache, nausea and vomiting; MRI of the brain displayed a large heterogeneously enhancing space-occupying lesion in the right frontal lobe measuring 68×58×62 mm and the CT scan of the chest exhibited a large prevascular mediastinal lymph node measuring 28×27 mm, suggestive of distant spread. She was then scheduled for neuronavigation-guided supratentorial craniotomy and excision of the lesion in November 2022. Histopathology of the frontal lesion was consistent with that of primary spindle cell neoplasm with focal myogenic differentiation. She will now be evaluated for palliative radiation to the brain.
Local Recurrence Free Survival following surgical resection and adjuvant chemoradiation is 2 years; however, the patient developed brain metastasis after 9 months of treatment completion (second follow-up) for which she is being managed accordingly with surgical resection and adjuvant whole brain irradiation.
Discussion
Historically, the first report of cardiac tumour stems from mid-16th century by Columbus.8 A malignant primary cardiac tumour is a rare entity with scarce data published to date in terms of its management and disease outcomes.9 The most common malignant cardiac tumours are sarcomas; among those most common are angiosarcomas, having predilection for the right side of the heart.10 Cardiac spindle cell sarcoma is the rarest among cardiac sarcomas, having predilection for cardiac vessels, and is of mesenchymal origin.11
Cardiac tumours can present with symptoms of dyspnoea, tachycardia, fluid overload and syncope, all depending on disease status. Its diagnosis requires transoesophageal echocardiography along with a CT scan or cardiac MRI, which are essential for the assessment of disease extension, involvement of cardiac vessels and distant metastasis. However, the gold-standard modality is histopathological assessment. Cardiac sarcomas are aggressive tumours with up to 80% of patients having distant metastasis at the time of presentation and median survival approaching 9 months.12 Patients with left-sided tumour location have shown better survival as compared to those with right-sided ones, probably due to earlier onset of symptoms and disease diagnosis. Prognosis also depends on tumour necrosis, which solely signifies poor survival.13
First-line treatment consists of surgical resection followed by chemotherapy and radiation therapy, with R0 resection life expectancy improves twice the median survival time. Due to low incidence of cardiac sarcomas, these recommendations are based on data extrapolated from retrospective studies and case reports, with no available prospective data to date.1
In a retrospective analysis of primary cardiac sarcoma carried out in the Netherlands in a dedicated sarcoma expert centre, eight patients were studied who were diagnosed between 2005 and 2019 with a follow-up of a minimum of 12 months. Six patients received adjuvant radiotherapy with doses ranging from 54 to 66 Gy with documented radiation toxicity including dizziness and fatigue. Among these, one patient had R1 resection followed by adjuvant radiation therapy, having a median survival of 12 months with no recurrence. Three patients developed local recurrence with distant metastasis and the median time between local recurrence and distant metastasis was reported to be 16 months (ranging between 3 and 48 months).14
In another case report, a middle-aged woman was diagnosed with undifferentiated pleomorphic sarcoma arising from the left atrium, which was surgically resected; however, the patient presented 11 months later with disease recurrence and was planned for second surgery, but the patient died 3 months after the second surgery due to disease specific cause.9
A retrospective review carried out in Baylor College of Medicine in Houston concluded that patients who underwent adjuvant radiation therapy followed by surgical resection of the tumour had median survival of 47 months as compared with patients who were treated with a single-modality approach with median survival of 25 months.15
Percy et al describe a patient in their 20s with a primary angiosarcoma in the right atrium who received adjuvant radiotherapy to the heart and mediastinum. After the radiation therapy, the patient received adjuvant chemotherapy, which was discontinued upon request of the patient. Thirty-four months after the tumour resection, the patient was asymptomatic and disease free.16
In another case report, primary cardiac angiosarcoma was resected (R1) and was treated with adjuvant radiation therapy of 50 Gy by two oblique anterior fields; the patient’s survival without local recurrence was up to 36 months.17
Romanowska et al signify the role of adjuvant radiotherapy in cardiac sarcoma. Two patients were planned using intensity-modulated radiation therapy with SIB technique at a dose of 54 Gy for PTV and 66 Gy for PTV boost. The patients were followed up to evaluate for cardiac toxicity and local control, which was achieved for up to 32 months for one patient and 47 months for the other patient. Hence, it was concluded that postoperative radiotherapy decreases risk of local recurrence following R1 resection.7
As per a French sarcoma study group, 24 of 124 patients received radiotherapy with improved progression-free survival for those patients.18 In another study group, radiotherapy doses ranging from 45 to 60 Gy were prescribed to 12 patients with primary cardiac sarcoma. Out of these patients, three achieved progression-free survival for 4, 5 and 93 months, respectively.7
The role of radiation therapy in adjuvant setting following primary cardiac spindle cell sarcoma has proven its beneficial effect following R1 resection in a retrospective observational study in which 617 patients diagnosed with cardiac spindle cell sarcoma were reviewed from the National Cancer Database during the period of 2004–2015. The patients were reviewed in terms of overall survival between surgery alone versus surgery followed by adjuvant chemoradiation therapy; median survival doubled in patients receiving postoperative adjuvant therapies, that is, 19 months in adjuvant arm vs 8 months in surgery alone arm with a significant p value of 0.026. However, this did not translate into 5-year overall survival, which was similar between both arms. However, postoperative radiotherapy improved disease-free survival and overall survival following surgical resection.19
In our case, the reason for delivering high dose of radiation therapy was residual disease, which was not resectable due to its proximity with pulmonary vessels. Chemotherapy was offered to reduce the risk of subsequent distant recurrence. On three-dimensional conformal treatment plan, V20 dose of the lung was exceeding the tolerance limit, so it was planned and treated on VMAT technique with SIB technique with dose up to 6000 cGy based on data extrapolated from various case reports and retrospective reviews. However, there is a dire need for establishing a rare cancer multidisciplinary tumour board for the management of cancers in low/middle-income countries to reduce disparity among management options and by having an expert consensus to ensure improved patient outcomes.20
Learning points
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High-grade primary spindle cell sarcoma is one of the rarest types of sarcomas involving the cardiac muscles.
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Literature evidence pertinent to management of cardiac spindle cell sarcoma is limited.
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Radiation to the heart via volumetric arc therapy can be safely administered without compromising vital structures with minimal patient-reported side effects.
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Available literature supports the role of radiation therapy in adjuvant setting following R1/R2 resection as it improves local control, and with the advancements in techniques, precision radiation can be aimed effectively.
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Establishment of a rare cancer multidisciplinary team in lower middle-income countries is the need of the era to improve patient management and record disease outcomes in rare cancers.
Ethics statements
Patient consent for publication
Footnotes
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Twitter @drm_minhas
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Contributors The following authors were responsible for drafting of the text, sourcing and editing of clinical images, investigation results, drawing original diagrams and algorithms, and critical revision for important intellectual content—TA, NA and LK. The following authors gave final approval of the manuscript—TA and NA.
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Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
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Case reports provide a valuable learning resource for the scientific community and can indicate areas of interest for future research. They should not be used in isolation to guide treatment choices or public health policy.
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Competing interests None declared.
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Provenance and peer review Not commissioned; externally peer reviewed.
- © BMJ Publishing Group Limited 2023. No commercial re-use. See rights and permissions. Published by BMJ.
References
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