Brain radiotherapy and anlotinib had a good intracranial control on primary cardiac angiosarcoma with multiple metastases: a case report

Brain radiotherapy and anlotinib had a good intracranial control on primary cardiac angiosarcoma with multiple metastases: a case report | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Case Report Brain radiotherapy and anlotinib had a good intracranial control on primary cardiac angiosarcoma with multiple metastases: a case report Ying-Ying Ma, Zhi-Ke Li, Zi-Yi Liao, Yang Peng, Dai-Yuan Ma This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-2788054/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Primary cardiac angiosarcoma (PCA) is a relatively rare and fatal disease with poor prognosis. It remains controversial whether its survival can be improved with additional treatment besides complete surgical excision. In this case,we presented a 52-year-old man with PCA in the right atrial who underwent a palliative resection, but suffered from metastases of the brain, lung and liver rapidly. He accepted multi-mode combination therapy including first-line chemotherapy, second-line anlotinib which was not only concurrent with brain radiotherapy but also concurrent with immunotherapy in the end. Although anlotinib combined with brain radiotherapy had a effectively control on the intracranial lesions, progression free survival was 5 months. But overall survival didn’t significantly prolonged, for he only survived for 12 months. In conclusion, the treatment for those metastatic PCA still needs further exploration. Primary cardiac angiosarcoma PD-1 anlotinib brain metastases radiotherapy Figures Figure 1 Figure 2 Figure 3 Introduction Primary cardiac angiosarcoma (PCA) is a rare cardiac tumor, accounting for about 33% of all primary malignant cardiac neoplasms (Liu等, 2018) . The mainly characteristics of PCA are highly invasive, rapid progression with a poor prognosis. For management, surgical resection is the preferred method. The median survival time for primary cardiac malignant tumor is 6–11 months (Antonuzzo等, 2009) , and the median survival time for operable ones is 14 months, while for unoperable ones is only 3.8 ± 2.5 months (Jang等, 2016) . The other management strategies include chemotherapy, radiotherapy, immunotherapy, targeted therapy or a combination of them. At present, there’s still no consensus for its treatment. Here, we reported a case of right atrium angiosarcoma with rapidly multiple metastases. The patient was treated with multi-mode combination therapy, anlotinib combined with brain radiotherapy had a effectively control on the intracranial lesions, progression free survival (PFS) was 5 months. And overall survival (OS) was 12 months. This may indicated that combination therapy could be effective for PCA, which still needs further research. Case Presentation A 52-year-old man admitted to our hospital in January 2021, he complained with chest tightness and pain for 7 days. Heart ultrasound showed pericardial fluid collection. A thoracic Computed Tomography scan (CT) showed a malignant tumor of the right atrium (about 3.5×3.2 cm); with a small amount of pleural effusion (FIGURE 1 A). He underwent palliative resection of the right atrial tumor on February 2, 2021. The pathology was angiosarcoma, which was positive for CD31, CD34, ERG, and Ki-67 (about 40% expression) (FIGURE 2 ). Then only 1 month later, he developed with cough and hemoptysis, chest CT showed multiple metastases in the pericardium, right upper lobe of lung, thoracic vertebra and right pleura (FIGURE 1 B). Therefore, he received 1 cycle of IE regimen (epirubicin 100 mg d1-2 + ifosfamide 3.0 g d1-5) on April 16, 2021. After the chemotherapy, limb edema and myelosuppression (IV degree) happened, so he received rhG-CSF (150.0 ug d1-6) since April 24 and discharged. The patient represented to our hospital with dizziness and headache on May 19, 2021. The abdomen CT scan revealed multiple liver lesions and the magnetic resonance imaging (MRI) of head found multiple brain metastases, mainly in the left parietal lobe (FIGURE 3 A). Subsequently, he started brain radiotherapy (PTV:30 Gy/10 Fx, P-GTV: 52 Gy/12 Fx) synchronized with anlotinib (10 mg,d1-14,q3w) on June 2, 2021. After brain radiotherapy, his dizziness and headache relieved significantly, and the evaluation was partial response (PR) based on the Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1 (FIGURE 3 B). Then he accepted 4 cycles of chemotherapy plus targeted therapy (paclitaxel 210 mg d1, anlotinib 10 mg d1-d14, q3w) since July 4, 2021. After 2 cycles,the evaluation was partical response (PR) (FIGURE 3 C) on August 27, 2021. But after 4 cycles, metastases lesions in the pericardium, lung, thoracic vertebra and liver were progressed, while the brain matastases lesions were decreased. So the comprehensive evaluation was progressive disease (PD) (FIGURE 3 D). During this period, he developed hemoptysis, so the treatment of anlotinib was temporarily discontinued on October 20, 2021. Then, he underwent 2 cycles of immunotherapy with tirelizumab (an anti-body against programmed cell death protein 1) since October 27, 2021. Then the patient self-administered with anlotinib, but unfortunately, he died on December 28, 2021 and survived for about 12 months. Discussion Cardiac neoplasm was firstly reported in 1559 by Dr. Realdo Colombus, while clinical diagnosis of primary cardiac sarcoma was firstly reported until 1934 (Barnes等, 1934) . Nearly 90% of PCA occurs in the right atrium, which usually grows rapidly and infiltrates the myocardium, invades the vena cava, tricuspid valve, atrium and other adjacent structures (M等, 2001) , so it often accompanied with pericardial effusion and half of the patients are complicated with pericardial tamponage. These pathological changes can lead to chest tightness, chest pain and other related symptoms. Due to the characteristics of highly invasive and rapid progression, PCA often has a poor prognosis, and about 66%-89% of patients have metastases when diagnosis (Koo等, 2021) , the most common metastatic sites are lung and bone, occasionally liver and brain (Jain等, 2015),(Waness等, 2015) . The patient repeatedly presented with chest tightness, chest pain and pericardial effusion immediately followed by multiple systemic metastases in lung, liver, brain and other organs, which was consistent with the reports and indicated a poor survival. The main diagnostic methods for PCA include echocardiography, CT, MRI and so on. For primary and secondary cerebral angiosarcoma, the diagnosis is usually based on CT or MRI, which show well circumscribed tumors with hemorrhage and surrounding edema. After resection of the heart tumor, drugs active in the central nervous system (CNS) or radiotherapy could be theoretically useful for the prevention of brain metastasis. However, Once it progress to the brain, drugs can’t penetrate the CNS effectively (Espana等, 1980) , thus these patients have a worse survival. In the review by Drosos E (Drosos等, 2020) , the mean overall survival for brain metastasis from angiosarcoma was 7.2 months, while PFS was 1.5 months, those ones originated from heart is even worse. In this case, although the disease progressed rapidly, after brain radiotherapy and anlotinib was given, the patient's PFS was 5 months, and the intracranial lesions were evaluated as PR and controled well untill he died. This indicated that brain radiotherapy combined with anlotinib may be a good control for brain metastases from PCA. As reported, combination therapy including palliative surgery, radiotherapy, adjuvant chemotherapy, and immunotherapy may improve the survival rate of some PCA patients (Kakizaki等, 1997) . Xuan Li (Li等, 2022) et al. reported a case of multiple metastatic cardiosarcoma who underwent chemoradiotherapy (epirubicin 10 mg, qd, ifosfamide 5g, qd) and immunotherapy (pembrolizumab 100 mg, qd) for 4 cycles and radiotherapy for rib metastases (20 Gy/5 fx) resulted in significant regression of primary lesions and metastatic ones. Xin Fang (Fang and Zheng, 2021) et al. also reported a patient with multiple metastatic cardiosarcoma (with no brain lesions) who was treated with chemotherapy of gemcitabine combined with docetaxe for 8 cycles, then synchronous radiotherapy with 5 cycles of anlotinib and the overall survival was 23 months. These indicated that radiotherapy plus anlotinib may have a good efficiacy in PCA. In our case, brain radiotherapy combined with anlotinib had a good control on intracranial lesions, but this seems not to translate into OS benefits. Thus, PCA with brain metastasis may have a worse survival, and the value of anlotinib plus radiotherapy in these patients still needs further research. Conclusion PCA is a relatively rare and fatal disease with poor prognosis, especially when brain metastasis happens. Combination therapy for brain metastatic ones may be helpful, anlotinib and anlotinib combination therapy may have a bright future, which needs further research. Abbreviations PCA: Primary cardiac angiosarcoma; PFS: progression free survival; OS: overall survival; IE: ifosfamide and epirubicin; CT: Computed Tomography; MRI: The magnetic resonance imaging; PR: partical response; PD: progressive disease; CNS: Central nervous system Declarations Funding information: This work was supported by the Dr Pioneer Foundation of North Sichuan Medical College (Grant number CBY21-QD18) Acknowledgements Not applicable Conflict of interest None. Authors’ contributions Ying-Ying Ma performed the bibliographic search and wrote the manuscript, Zhi-Ke Li, Zi-Yi Liao, Yang-Peng, and Dai-Yuan Ma revised the manuscript; Zi-Yi Liao and Yang-Peng took part to the patient therapy as Registrars. All authors read and approved the final manuscript. Funding This work was supported by the Dr Pioneer Foundation of North Sichuan Medical College (Grant number CBY21-QD18) Availability of data and materials all the Patient’s data and medical images can be found on the database of Affiliated Hospital of North Sichuan Medical College Ethics approval and consent to participate The research related to human use has been complied with all the relevant national regulations, institutional policies and in accordance with the tenets of the Helsinki Declaration, and has been approved by the Medical Ethics Committee of Affliated Hospital of North Sichuan Medical College. Consent for publication The patient provided informed consent for publication of this case report and accompanying images Competing interests The author declare that they have no competing interest. Author details 1 Department of Oncology, Affiliated Hospital of North Sichuan Medical College, Nanchong, China. References Liu CW, Zhao YX, Yin ZY, et al. Right atrial epithelioid angiosarcoma with multiple pulmonary metastasis confirmed by multimodality imaging-guided pulmonary biopsy: A case report and literature review. Medicine. 2018;97(30):e11588. Antonuzzo L, Rotella V, Mazzoni F, et al. Primary cardiac angiosarcoma: a fatal disease. Case Rep Med. 2009;2009:591512. Jang Y, Kim J, Shim JW, et al. Primary cardiac angiosarcoma: a prolonged response to surgical resection followed by concurrent chemoradiotherapy with docetaxel. Springerplus. 2016;5:648. Barnes AR, Beaver DC, Snell AM. Primary sarcoma of the heart - Report of a case with electrocardiographic and pathological studies. Am Heart J. 1934;9:480–91. Silver MD, Gotlieb AI, Schoen FJ. Cardiovascular pathology. In: Cohn LH, editor. Cardiac Surgery in the Adult, 4e. Churchill Livingstone. Philadelphia: Elsevier; 2001. pp. 399–598. Koo J, Knight-Perry J, Galambos C, et al. Pediatric metastatic cardiac angiosarcoma successfully treated with multimodal therapy: case report and review of literature. J Pediatr Hematol Oncol. 2021;43(2):E203–6. Jain A, Simon S, Elangovan I. (18)F-fluoro-deoxyglucose positron emission tomography-computed tomography in initial assessment and diagnosis of right atrial angiosarcoma with widespread visceral metastases: A rare case report and review of the literature. Indian J nuclear medicine: IJNM : official J Soc Nuclear Med India. 2015;30(1):51–4. Waness A, Batoon AA, Mirza I, et al. Elusive Cardiac Angiosarcoma in a Young Pregnant Female: Rare Presentation With Fatal Outcome. Cardiol Res. 2015;6(3):292–6. Espana P, Chang P, Wiernik PH. Increased incidence of brain metastases in sarcoma patients. Cancer. 1980;45(2):377–80. Drosos E, Kalyvas A, Komaitis S, et al. Angiosarcoma-related cerebral metastases: a systematic review of the literature. Neurosurg Rev. 2020;43(4):1019–38. Kakizaki S, Takagi H, Hosaka Y. Cardiac angiosarcoma responding to multidisciplinary treatment. Int J Cardiol. 1997;62(3):273–5. Li X, Lan L, Hu HJ. Case report: Primary cardiac angiosarcoma with multiple metastases. Front Cardiovasc Med. 2022;9:941967. Fang X, Zheng S. Primary cardiac angiosarcoma: a case report. J Int Med Res. 2021;49(8):03000605211033261. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-2788054","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Case Report","associatedPublications":[],"authors":[{"id":190982782,"identity":"0230abfb-45dd-4920-aef7-cfa37948a0c5","order_by":0,"name":"Ying-Ying Ma","email":"","orcid":"","institution":"Affiliated Hospital of North Sichuan Medical College","correspondingAuthor":false,"prefix":"","firstName":"Ying-Ying","middleName":"","lastName":"Ma","suffix":""},{"id":190982784,"identity":"7cf2e45c-143e-4cf1-b83c-4d1866f6cda1","order_by":1,"name":"Zhi-Ke Li","email":"","orcid":"","institution":"Affiliated Hospital of North Sichuan Medical College","correspondingAuthor":false,"prefix":"","firstName":"Zhi-Ke","middleName":"","lastName":"Li","suffix":""},{"id":190982785,"identity":"e16fad73-b2ec-4bfb-ba8a-52c1c7cf4ab8","order_by":2,"name":"Zi-Yi Liao","email":"","orcid":"","institution":"Affiliated Hospital of North Sichuan Medical College","correspondingAuthor":false,"prefix":"","firstName":"Zi-Yi","middleName":"","lastName":"Liao","suffix":""},{"id":190982786,"identity":"dea21729-cc51-4f2b-ab74-6fb7023512bd","order_by":3,"name":"Yang Peng","email":"","orcid":"","institution":"Affiliated Hospital of North Sichuan Medical College","correspondingAuthor":false,"prefix":"","firstName":"Yang","middleName":"","lastName":"Peng","suffix":""},{"id":190982787,"identity":"a81589d6-f4e5-48f9-8384-93a1f1d757e8","order_by":4,"name":"Dai-Yuan Ma","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAoklEQVRIiWNgGAWjYFCCBMYDDBUScvKkaGE4wHDGwtiwgSQtjG0ViUCNRALd9hyDw7zzJBIYG5gfPrpBjBazM28MDs7cJpHHzsBmbJxDlJYbOQYHPm6TKGZs4GGTJl5L4hyJxIYDJGn52ECSljPPCg7OOCZhbNhMtF+OJ298zFNTJyfP3vzwMVFaGBg4DCA0M3HKQYD9AfFqR8EoGAWjYGQCAFXcNBzikMVDAAAAAElFTkSuQmCC","orcid":"","institution":"Affiliated Hospital of North Sichuan Medical College","correspondingAuthor":true,"prefix":"","firstName":"Dai-Yuan","middleName":"","lastName":"Ma","suffix":""}],"badges":[],"createdAt":"2023-04-07 03:14:14","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-2788054/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-2788054/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":35738537,"identity":"37ec08c2-6fa8-455a-838a-a27ea36cf7b0","added_by":"auto","created_at":"2023-04-13 23:22:03","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":699200,"visible":true,"origin":"","legend":"\u003cp\u003eThe computed tomography (CT) of PCA: (A) Before resection of the heart tumor (about 3.5×3.2cm) on May 18，2021; (B) recurred lesions after operation on March 31, 2021; (C) After 2 cycles of anlotinib on August 27, 2021, the evaluation was PR; (D) After 4 cycles of anlotinib on October 24, 2021, the evaluation was PD.\u003c/p\u003e","description":"","filename":"floatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-2788054/v1/6d296d0daa06338e3753b178.png"},{"id":35738539,"identity":"53d727b0-ea6b-40ce-8343-1f3aa10ec181","added_by":"auto","created_at":"2023-04-13 23:22:03","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":1629201,"visible":true,"origin":"","legend":"\u003cp\u003eResults of immunohistochemistry of the tumors: (A) Positive for CD31, ×100; (B) Positive for CD34, ×100; (C) Positive for ERG, ×100; (D) Positive for Ki-67(Abou40%),×100.\u003c/p\u003e","description":"","filename":"floatimage2.png","url":"https://assets-eu.researchsquare.com/files/rs-2788054/v1/f17bab067f60fdc10dcee7cc.png"},{"id":35738538,"identity":"97d3aee5-8715-4fce-8362-6d6979b07ff1","added_by":"auto","created_at":"2023-04-13 23:22:03","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":734826,"visible":true,"origin":"","legend":"\u003cp\u003eThe magnetic resonance imaging (MRI) of the brain lesions: (A) Before brain radiotherapy on May 19, 2021; (B) After anlotinib synchronized with brain radiotherapy on July 5, 2021; (C) After 2 cycles of anlotinib synchronized with on August 30, 2021; (D) After 4 cycles of anlotinib synchronized with on October 24, 2021.\u003c/p\u003e","description":"","filename":"floatimage3.png","url":"https://assets-eu.researchsquare.com/files/rs-2788054/v1/146a79d491810e2822d82cb8.png"},{"id":35859514,"identity":"931711a4-e3c9-4d9e-a866-86053a41d33e","added_by":"auto","created_at":"2023-04-17 09:29:58","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":3410935,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-2788054/v1/8ebc7d29-cc80-4695-a922-4bd096b819bc.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Brain radiotherapy and anlotinib had a good intracranial control on primary cardiac angiosarcoma with multiple metastases: a case report","fulltext":[{"header":"Introduction","content":"\u003cp\u003ePrimary cardiac angiosarcoma (PCA) is a rare cardiac tumor, accounting for about 33% of all primary malignant cardiac neoplasms\u003csup\u003e(Liu等, 2018)\u003c/sup\u003e. The mainly characteristics of PCA are highly invasive, rapid progression with a poor prognosis. For management, surgical resection is the preferred method. The median survival time for primary cardiac malignant tumor is 6\u0026ndash;11 months \u003csup\u003e(Antonuzzo等, 2009)\u003c/sup\u003e, and the median survival time for operable ones is 14 months, while for unoperable ones is only 3.8\u0026thinsp;\u0026plusmn;\u0026thinsp;2.5 months\u003csup\u003e(Jang等, 2016)\u003c/sup\u003e. The other management strategies include chemotherapy, radiotherapy, immunotherapy, targeted therapy or a combination of them. At present, there\u0026rsquo;s still no consensus for its treatment.\u003c/p\u003e \u003cp\u003eHere, we reported a case of right atrium angiosarcoma with rapidly multiple metastases. The patient was treated with multi-mode combination therapy, anlotinib combined with brain radiotherapy had a effectively control on the intracranial lesions, progression free survival (PFS) was 5 months. And overall survival (OS) was 12 months. This may indicated that combination therapy could be effective for PCA, which still needs further research.\u003c/p\u003e"},{"header":"Case Presentation","content":"\u003cp\u003eA 52-year-old man admitted to our hospital in January 2021, he complained with chest tightness and pain for 7 days. Heart ultrasound showed pericardial fluid collection. A thoracic Computed Tomography scan (CT) showed a malignant tumor of the right atrium (about 3.5\u0026times;3.2 cm); with a small amount of pleural effusion (FIGURE \u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eA). He underwent palliative resection of the right atrial tumor on February 2, 2021. The pathology was angiosarcoma, which was positive for CD31, CD34, ERG, and Ki-67 (about 40% expression) (FIGURE \u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). Then only 1 month later, he developed with cough and hemoptysis, chest CT showed multiple metastases in the pericardium, right upper lobe of lung, thoracic vertebra and right pleura (FIGURE \u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eB). Therefore, he received 1 cycle of IE regimen (epirubicin 100 mg d1-2\u0026thinsp;+\u0026thinsp;ifosfamide 3.0 g d1-5) on April 16, 2021. After the chemotherapy, limb edema and myelosuppression (IV degree) happened, so he received rhG-CSF (150.0 ug d1-6) since April 24 and discharged. The patient represented to our hospital with dizziness and headache on May 19, 2021. The abdomen CT scan revealed multiple liver lesions and the magnetic resonance imaging (MRI) of head found multiple brain metastases, mainly in the left parietal lobe (FIGURE \u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003eA). Subsequently, he started brain radiotherapy (PTV:30 Gy/10 Fx, P-GTV: 52 Gy/12 Fx) synchronized with anlotinib (10 mg,d1-14,q3w) on June 2, 2021. After brain radiotherapy, his dizziness and headache relieved significantly, and the evaluation was partial response (PR) based on the Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1 (FIGURE \u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003eB). Then he accepted 4 cycles of chemotherapy plus targeted therapy (paclitaxel 210 mg d1, anlotinib 10 mg d1-d14, q3w) since July 4, 2021. After 2 cycles,the evaluation was partical response (PR) (FIGURE \u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003eC) on August 27, 2021. But after 4 cycles, metastases lesions in the pericardium, lung, thoracic vertebra and liver were progressed, while the brain matastases lesions were decreased. So the comprehensive evaluation was progressive disease (PD) (FIGURE \u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003eD). During this period, he developed hemoptysis, so the treatment of anlotinib was temporarily discontinued on October 20, 2021. Then, he underwent 2 cycles of immunotherapy with tirelizumab (an anti-body against programmed cell death protein 1) since October 27, 2021. Then the patient self-administered with anlotinib, but unfortunately, he died on December 28, 2021 and survived for about 12 months.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eCardiac neoplasm was firstly reported in 1559 by Dr. Realdo Colombus, while clinical diagnosis of primary cardiac sarcoma was firstly reported until 1934 \u003csup\u003e(Barnes等, 1934)\u003c/sup\u003e. Nearly 90% of PCA occurs in the right atrium, which usually grows rapidly and infiltrates the myocardium, invades the vena cava, tricuspid valve, atrium and other adjacent structures\u003csup\u003e(M等, 2001)\u003c/sup\u003e, so it often accompanied with pericardial effusion and half of the patients are complicated with pericardial tamponage. These pathological changes can lead to chest tightness, chest pain and other related symptoms. Due to the characteristics of highly invasive and rapid progression, PCA often has a poor prognosis, and about 66%-89% of patients have metastases when diagnosis\u003csup\u003e(Koo等, 2021)\u003c/sup\u003e, the most common metastatic sites are lung and bone, occasionally liver and brain\u003csup\u003e(Jain等, 2015),(Waness等, 2015)\u003c/sup\u003e. The patient repeatedly presented with chest tightness, chest pain and pericardial effusion immediately followed by multiple systemic metastases in lung, liver, brain and other organs, which was consistent with the reports and indicated a poor survival.\u003c/p\u003e \u003cp\u003eThe main diagnostic methods for PCA include echocardiography, CT, MRI and so on. For primary and secondary cerebral angiosarcoma, the diagnosis is usually based on CT or MRI, which show well circumscribed tumors with hemorrhage and surrounding edema.\u003c/p\u003e \u003cp\u003eAfter resection of the heart tumor, drugs active in the central nervous system (CNS) or radiotherapy could be theoretically useful for the prevention of brain metastasis. However, Once it progress to the brain, drugs can\u0026rsquo;t penetrate the CNS effectively\u003csup\u003e(Espana等, 1980)\u003c/sup\u003e, thus these patients have a worse survival. In the review by Drosos E\u003csup\u003e(Drosos等, 2020)\u003c/sup\u003e, the mean overall survival for brain metastasis from angiosarcoma was 7.2 months, while PFS was 1.5 months, those ones originated from heart is even worse. In this case, although the disease progressed rapidly, after brain radiotherapy and anlotinib was given, the patient's PFS was 5 months, and the intracranial lesions were evaluated as PR and controled well untill he died. This indicated that brain radiotherapy combined with anlotinib may be a good control for brain metastases from PCA.\u003c/p\u003e \u003cp\u003eAs reported, combination therapy including palliative surgery, radiotherapy, adjuvant chemotherapy, and immunotherapy may improve the survival rate of some PCA patients \u003csup\u003e(Kakizaki等, 1997)\u003c/sup\u003e. Xuan Li \u003csup\u003e(Li等, 2022)\u003c/sup\u003eet al. reported a case of multiple metastatic cardiosarcoma who underwent chemoradiotherapy (epirubicin 10 mg, qd, ifosfamide 5g, qd) and immunotherapy (pembrolizumab 100 mg, qd) for 4 cycles and radiotherapy for rib metastases (20 Gy/5 fx) resulted in significant regression of primary lesions and metastatic ones. Xin Fang\u003csup\u003e(Fang and Zheng, 2021)\u003c/sup\u003eet al. also reported a patient with multiple metastatic cardiosarcoma (with no brain lesions) who was treated with chemotherapy of gemcitabine combined with docetaxe for 8 cycles, then synchronous radiotherapy with 5 cycles of anlotinib and the overall survival was 23 months. These indicated that radiotherapy plus anlotinib may have a good efficiacy in PCA. In our case, brain radiotherapy combined with anlotinib had a good control on intracranial lesions, but this seems not to translate into OS benefits. Thus, PCA with brain metastasis may have a worse survival, and the value of anlotinib plus radiotherapy in these patients still needs further research.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003ePCA is a relatively rare and fatal disease with poor prognosis, especially when brain metastasis happens. Combination therapy for brain metastatic ones may be helpful, anlotinib and anlotinib combination therapy may have a bright future, which needs further research.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003ePCA: Primary cardiac angiosarcoma; PFS: progression free survival; OS: overall survival; IE: ifosfamide and epirubicin; CT: Computed Tomography; MRI: The magnetic resonance imaging; PR: partical response; PD: progressive disease; CNS: Central nervous system\u0026nbsp;\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eFunding information: \u003c/strong\u003eThis work was supported by the Dr Pioneer Foundation of North Sichuan Medical College (Grant number CBY21-QD18)\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflict of interest\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNone.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026rsquo; contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eYing-Ying Ma performed the bibliographic search and wrote the manuscript, Zhi-Ke Li, Zi-Yi Liao, Yang-Peng, and Dai-Yuan Ma revised the manuscript; Zi-Yi Liao and Yang-Peng took part to the patient therapy as Registrars. All authors read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis work was supported by the Dr Pioneer Foundation of North Sichuan Medical College (Grant number CBY21-QD18)\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eall the Patient\u0026rsquo;s data and medical images can be found on the database of Affiliated Hospital of North Sichuan Medical College\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe research related to human use has been complied with all the relevant national regulations, institutional policies and in accordance with the tenets of the Helsinki Declaration, and has been approved by the Medical Ethics Committee of Affliated Hospital of North Sichuan Medical College.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe patient provided informed consent for publication of this case report and\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eaccompanying images\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe author declare that they have no competing interest.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor details\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003csup\u003e1\u003c/sup\u003eDepartment of Oncology, Affiliated Hospital of North Sichuan Medical College, Nanchong, China.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eLiu CW, Zhao YX, Yin ZY, et al. 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In: Cohn LH, editor. Cardiac Surgery in the Adult, 4e. Churchill Livingstone. Philadelphia: Elsevier; 2001. pp. 399\u0026ndash;598.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKoo J, Knight-Perry J, Galambos C, et al. Pediatric metastatic cardiac angiosarcoma successfully treated with multimodal therapy: case report and review of literature. J Pediatr Hematol Oncol. 2021;43(2):E203\u0026ndash;6.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eJain A, Simon S, Elangovan I. (18)F-fluoro-deoxyglucose positron emission tomography-computed tomography in initial assessment and diagnosis of right atrial angiosarcoma with widespread visceral metastases: A rare case report and review of the literature. Indian J nuclear medicine: IJNM : official J Soc Nuclear Med India. 2015;30(1):51\u0026ndash;4.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWaness A, Batoon AA, Mirza I, et al. Elusive Cardiac Angiosarcoma in a Young Pregnant Female: Rare Presentation With Fatal Outcome. Cardiol Res. 2015;6(3):292\u0026ndash;6.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eEspana P, Chang P, Wiernik PH. Increased incidence of brain metastases in sarcoma patients. Cancer. 1980;45(2):377\u0026ndash;80.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDrosos E, Kalyvas A, Komaitis S, et al. Angiosarcoma-related cerebral metastases: a systematic review of the literature. Neurosurg Rev. 2020;43(4):1019\u0026ndash;38.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKakizaki S, Takagi H, Hosaka Y. Cardiac angiosarcoma responding to multidisciplinary treatment. Int J Cardiol. 1997;62(3):273\u0026ndash;5.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLi X, Lan L, Hu HJ. Case report: Primary cardiac angiosarcoma with multiple metastases. Front Cardiovasc Med. 2022;9:941967.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFang X, Zheng S. Primary cardiac angiosarcoma: a case report. J Int Med Res. 2021;49(8):03000605211033261.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Primary cardiac angiosarcoma, PD-1, anlotinib, brain metastases, radiotherapy","lastPublishedDoi":"10.21203/rs.3.rs-2788054/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-2788054/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003ePrimary cardiac angiosarcoma (PCA) is a relatively rare and fatal disease with poor prognosis. It remains controversial whether its survival can be improved with additional treatment besides complete surgical excision. In this case,we presented a 52-year-old man with PCA in the right atrial who underwent a palliative resection, but suffered from metastases of the brain, lung and liver rapidly. He accepted multi-mode combination therapy including first-line chemotherapy, second-line anlotinib which was not only concurrent with brain radiotherapy but also concurrent with immunotherapy in the end. Although anlotinib combined with brain radiotherapy had a effectively control on the intracranial lesions, progression free survival was 5 months. But overall survival didn\u0026rsquo;t significantly prolonged, for he only survived for 12 months. In conclusion, the treatment for those metastatic PCA still needs further exploration.\u003c/p\u003e","manuscriptTitle":"Brain radiotherapy and anlotinib had a good intracranial control on primary cardiac angiosarcoma with multiple metastases: a case report","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2023-04-13 23:21:58","doi":"10.21203/rs.3.rs-2788054/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"33b80130-92cc-4d90-93c7-041757f2dde3","owner":[],"postedDate":"April 13th, 2023","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2023-06-07T03:59:14+00:00","versionOfRecord":[],"versionCreatedAt":"2023-04-13 23:21:58","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-2788054","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-2788054","identity":"rs-2788054","version":["v1"]},"buildId":"J0_U0BvcaRcwD8yVFaRlm","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}