Angiosarcoma Treatment & Management
- Author: Belen Carsi, MD, PhD, FRCS; Chief Editor: Dirk M Elston, MD more...
Treatment of soft-tissue angiosarcoma
For stage I angiosarcomas, the National Comprehensive Cancer Network (NCCN) recommends surgery to obtain adequate oncologic margins. For stage II-III disease that can be resected with acceptable functional outcomes, the NCCN also recommends preoperative radiation therapy (category 1) or preoperative chemoradiation or chemotherapy (category 2B). The NCCN lists the following agents as having activity against angiosarcoma:
Ravi et al report exceptional response to treatment with pazopanib in a patient with angiosarcoma that harbored amplification of vascular endothelial growth factor receptor (VEGFR) and that had not responded to sorafenib. These authors suggest that a subset of patients with angiosarcoma with genomic alterations in vascular signaling genes may respond well to pazopanib.
Multiple randomized studies using doxorubicin-based chemotherapy fail to show a survival benefit from neoadjuvant chemotherapy. However, a meta-analysis suggests improved local control and disease-free survival with chemotherapy, but no survival advantage.[12, 25]
Response to preoperative chemotherapy is only 40-50%, with the most active regimens, and toxicity is significant. Consequently, specialists reserve preoperative chemotherapy for patients with high-grade lesions. The regimen is continued in those patients who respond with tumor shrinkage after two to three courses of multiagent chemotherapy after tumor resection.
Pasquier et al reported effective treatment in seven patients with advanced angiosarcoma using the combination of twice-daily propranolol (40 mg) and weekly metronomic vinblastine (6 mg/m2) and methotrexate (35 mg/m2). One patient showed a complete response and three showed very good partial responses. Median progression-free and overall survival was 11 months (range 5–24) and 16 months (range 10–30), respectively.
Offer patients with unresponsive tumors different treatment regimens. Response to neoadjuvant chemotherapy can be observed, but it does not always correlate with radiographic response.
The use of irradiation in conjunction with surgery continues to evolve and results in 80% of local control and excellent functional and cosmetic outcome. However, consider that 50% of angiosarcomas have distant metastases, and irradiation does not improve survival. Better definition of the extent of the disease with the use of MRI helps to further delineate the radiotherapy fields and decrease long-term morbidity. Intraoperative radiation, brachytherapy, or more external beam therapy can complement preoperative external beam radiotherapy.
The disadvantage of preoperative radiation is that a higher wound complication rate may delay surgery (1 wk of healing per 10 Gy of radiation delivered). The advantages of preoperative radiation are as follows:
Optimization for surgery
Smaller volume of external beam fields
Less hypoxic tissue
Potential to reduce the chance of intraoperative implantation
Potential improvement in local control in advanced tumors
Evidence of multicentricity must be sought before making any decision regarding therapy. Patients have presented with lesions affecting as many as 45 different bones. In such cases, consider neoadjuvant chemotherapy.
A chemotherapeutic regimen common for sarcomatous tumors can be administered (ifosfamide and doxorubicin used together or sequentially). If clinical or radiographic improvement is not observed, consider a second regimen with cyclophosphamide, etoposide, and cisplatin. Gemcitabine may be effective as second line or third-line therapy.
The best outcomes are reported with surgery followed by radiotherapy. The role of chemotherapy in cutaneous angiosarcoma has not yet been established, although for patients with metastasis or tumors deemed unresectable, doxorubicin (intraarterial or systemic) is indicated.
Paclitaxel as a single agent has shown substantial activity against angiosarcoma of the scalp or face, even in patients previously treated with chemotherapy or radiation therapy. Further investigation is warranted to define the optimal treatment dose and schedule.
Surgical treatment of angiosarcoma of the soft tissue, retroperitoneum, and abdomen is as follows :
Target obtaining wide surgical margins, with at least 2 cm of unaffected tissue surrounding the tumor. The resection should include skin when applicable and the soft tissue around the angiosarcoma. Include biopsy sites, including the biopsy tract, en bloc with the specimen.
Resection of large lesions can be extremely difficult and sometimes requires amputation for local control; however, local control does not prevent distant relapse
Free surgical margins sometimes have anatomic constraints, especially in retroperitoneal tumors
Surgical treatment of angiosarcoma of bone is as follows:
Surgical resection and radiation therapy are the standard treatment for localized disease
Low-grade lesions lead to similar benefits with either technique
Treat high-grade lesions as malignant bone neoplasms, with a combination of radical en bloc excision followed by radiotherapy and/or chemotherapy
The number of lesions in a limb may render limb salvage impossible, and amputation may be indicated
Surgical treatment of cutaneous angiosarcoma is as follows :
Surgical treatment is contraindicated in tumors extending into vital structures, in those of massive size, or in those with multicentricity
The lesion may be solitary or multicentric and frequently extends laterally throughout the dermis, making gross assessment of surgical margins difficult and necessitating multiple biopsies of the surrounding tissues
In the primary treatment of angiosarcomas of the scalp, recognizing the horizontal and vertical extensions of the tumor is essential, which can only be discerned by microscopic examination of all the margins of the resected specimen; the primary excision of the scalp should be full-thickness, including the pericranium and, if indicated, the outer table of the cranial vault; the margins should be wide (at least 5 cm) on all sides
Young RJ, Brown NJ, Reed MW, Hughes D, Woll PJ. Angiosarcoma. Lancet Oncol. 2010 Oct. 11(10):983-91. [Medline].
Scow JS, Reynolds CA, Degnim AC, Petersen IA, Jakub JW, Boughey JC. Primary and secondary angiosarcoma of the breast: the Mayo Clinic experience. J Surg Oncol. 2010 Apr 1. 101(5):401-7. [Medline].
Babarovic E, Zamolo G, Mustac E, Strcic M. High grade angiosarcoma arising in fibroadenoma. Diagn Pathol. 2011 Dec 20. 6(1):125. [Medline].
Sturgis EM, Potter BO. Sarcomas of the head and neck region. Curr Opin Oncol. 2003 May. 15(3):239-52. [Medline].
Soft Tissue Tumors. Enzinger FM, Weiss SW, eds. Soft Tissue Tumors. 3rd ed. St. Louis, Mo: Mosby; 1995. 648-77.
Toro JR, Travis LB, Wu HJ, Zhu K, Fletcher CD, Devesa SS. Incidence patterns of soft tissue sarcomas, regardless of primary site, in the surveillance, epidemiology and end results program, 1978-2001: An analysis of 26,758 cases. Int J Cancer. 2006 Dec 15. 119(12):2922-30. [Medline].
Adami H, Hunter D, Trichopoulos D, eds. Textbook of Cancer Epidemiology. 2nd ed. Oxford University Press; 2008.
Lezama-del Valle P, Gerald WL, Tsai J, et al. Malignant vascular tumors in young patients. Cancer. 1998 Oct 15. 83(8):1634-9. [Medline].
Mark RJ, Poen JC, Tran LM, Fu YS, Juillard GF. Angiosarcoma. A report of 67 patients and a review of the literature. Cancer. 1996 Jun 1. 77(11):2400-6. [Medline].
Schottenfeld D, Fraumeni J, eds. Cancer. Epidemiology and Prevention. 3rd ed. New York: Oxford University Press; 2006. 763-786/959-974.
Meis-Kindblom JM, Kindblom LG. Angiosarcoma of soft tissue: a study of 80 cases. Am J Surg Pathol. 1998 Jun. 22(6):683-97. [Medline].
Lahat G, Dhuka AR, Hallevi H, Xiao L, Zou C, Smith KD, et al. Angiosarcoma: clinical and molecular insights. Ann Surg. 2010 Jun. 251(6):1098-106. [Medline].
DeVita VT Jr, Hellman S, Rosenberg SA, eds. Cancer: Principles & Practice of Oncology. 8th ed. Philadelphia, Pa: Lippincott Williams & Wilkins; 2008.
Virtanen A, Pukkala E, Auvinen A. Angiosarcoma after radiotherapy: a cohort study of 332 163 Finnish cancer patients. The British Journal of Cancer. Jul 2007. 97:115. [Medline].
Patton KT, Deyrup AT, Weiss SW. Atypical vascular lesions after surgery and radiation of the breast: a clinicopathologic study of 32 cases analyzing histologic heterogeneity and association with angiosarcoma. Am J Surg Pathol. 2008 Jun. 32(6):943-50. [Medline].
Huang J, Mackillop WJ. Increased risk of soft tissue sarcoma after radiotherapy in women with breast carcinoma. Cancer. 2001. Jul 1;92(1):172-80. [Medline].
USA: National Cancer Institute (NCI); 2000-2004. The Surveillance, Epidemiology, and End Results (SEER) Program. Available at http://seer.cancer.gov/.
Wenger DE, Wold LE. Malignant vascular lesions of bone: radiologic and pathologic features. Skeletal Radiol. 2000 Nov. 29(11):619-31. [Medline].
Morgan MB, Swann M, Somach S, et al. Cutaneous angiosarcoma: a case series with prognostic correlation. J Am Acad Dermatol. 2004 Jun. 50(6):867-74. [Medline].
Mullamitha SA, Ton NC, Parker GJ, Jackson A, Julyan PJ, Roberts C, et al. Phase I evaluation of a fully human anti-alphav integrin monoclonal antibody (CNTO 95) in patients with advanced solid tumors. Clin Cancer Res. Apr 2007. 13(7):2128-35. [Medline].
[Guideline] NCCN. National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology: Soft Tissue Sarcoma. Available at https://www.nccn.org/professionals/physician_gls/pdf/sarcoma.pdf. Version 2.2016; Accessed: June 1, 2016.
Ray-Coquard I, Italiano A, Bompas E, Le Cesne A, Robin YM, et al. Sorafenib for patients with advanced angiosarcoma: a phase II Trial from the French Sarcoma Group (GSF/GETO). Oncologist. 2012. 17(2):260-6. [Medline]. [Full Text].
Ravi V, Sanford EM, Wang WL, Ross JS, Ramesh N, Futreal A, et al. Antitumor Response of VEGFR2- and VEGFR3-Amplified Angiosarcoma to Pazopanib. J Natl Compr Canc Netw. 2016 May. 14 (5):499-502. [Medline].
Budd GT. Management of Angiosarcoma. Curr Oncol Rep. 2002. 4(6):515-519. [Medline].
Pasquier E, André N, Street J, Chougule A, Rekhi B, Ghosh J, et al. Effective Management of Advanced Angiosarcoma by the Synergistic Combination of Propranolol and Vinblastine-based Metronomic Chemotherapy: A Bench to Bedside Study. EBioMedicine. 2016 Apr. 6:87-95. [Medline]. [Full Text].
Skubitz KM, Haddad PA. Paclitaxel and pegylated-liposomal doxorubicin are both active in angiosarcoma. Cancer. 2005 Jul 15. 104(2):361-6. [Medline].
Vogt T, Hafner C, Bross K, et al. Antiangiogenetic therapy with pioglitazone, rofecoxib, and metronomic trofosfamidein patients with advanced malignant vascular tumors. Cancer. 2003 Nov 15. 98(10):2251-6. [Medline].
Liekens S, Verbeken E, De Clercq E, Neyts J. Potent inhibition of hemangiosarcoma development in mice by cidofovir. Int J Cancer. 2001 Apr 15. 92(2):161-7. [Medline].