Angiosarcoma of the head and neck is an aggressive malignancy with limited therapeutic options when unresectable. We report the case of a 73-year-old male with advanced scalp and neck angiosarcoma characterized by MYC amplification and high tumor mutational burden. He received a multimodal treatment strategy including dual immune checkpoint blockade (nivolumab and ipilimumab) combined with cabozantinib, followed by paclitaxel and subsequent pazopanib. This approach achieved prolonged disease control exceeding 18 months, with manageable toxicities through dose adjustments and supportive care. Genomic profiling guided therapeutic decisions and highlighted the role of MYC amplification and tumor mutational burden as potential biomarkers for treatment response. This case emphasizes the importance of molecular characterization in guiding precision oncology for rare sarcomas and demonstrates the clinical utility of combining immunotherapy with antiangiogenic agents in the management of unresectable angiosarcoma.

1. Fayette J, Martin E, Piperno-Neumann S, et al. Angiosarcomas, a heterogeneous group of sarcomas with specific behavior depending on primary site: A retrospective study of 161 cases. Ann Oncol. 2007;18:2030-2036. doi: 10.1093/annonc/mdm381

2. Young RJ, Brown NJ, Reed MW, Hughes D, Woll PJ. Angiosarcoma. Lancet Oncol. 2010;11(10):983-991. doi: 10.1016/S1470-2045(10)70023-1

3. Shon W, Folpe AL. Immunohistology of vascular neoplasms. Arch Pathol Lab Med. 2015;139(2):268-275. doi: 10.5858/arpa.2013-0582-RA

4. Manner J, Radlwimmer B, Hohenberger P, et al. MYC high level gene amplification is a distinctive feature of angiosarcomas after irradiation or chronic lymphedema. Am J Pathol. 2010;176(1):34-39. doi: 10.2353/ajpath.2010.090637

5. Italiano A, Chen CL, Thomas R, et al. Anti-PD1/PD-L1 activity in angiosarcoma: Results from a retrospective French sarcoma group study. J Clin Oncol. 2020;38(15 Suppl):11511. doi: 10.1200/JCO.2020.38.15_suppl.11511

6. Wagner MJ, Ravi V, Maki RG, et al. Clinical activity of pazopanib in metastatic angiosarcoma: A single-center experience. Cancer. 2020;126(3):438-445. doi: 10.1002/cncr.32554

7. D’Angelo SP, Mahoney MR, Van Tine BA, et al. Nivolumab with or without ipilimumab treatment for metastatic sarcoma (Alliance A091401): Two open-label, non-comparative, phase 2 trial. Lancet Oncol. 2018;19(3):416-426. doi: 10.1016/S1470-2045(18)30006-8

8. Fujisawa Y, Yoshino K, Kadono T, et al. PD-L1 expression in angiosarcoma and its association with clinicopathological factors. Hum Pathol. 2017;59:103-110. doi: 10.1016/j.humpath.2016.09.014

9. Choy E, Butrynski J, Harmon D, et al. Immunotherapy for advanced soft-tissue sarcoma: A review. Clin Sarcoma Res. 2024;14:3. doi: 10.1186/s13023-022-02536-x

10. Wang G, Zhao D, Spring DJ, DePinho RA. Symbiotic tumor microenvironment in cancer immunotherapy: from bench to bedside. Trends Cancer. 2021;7(11):874-889. doi: 10.1016/j.trecan.2021.05.005

11. Yarchoan M, Hopkins A, Jaffee EM. Tumor mutational burden and response rate to PD-1 inhibition. N Engl J Med. 2017;377(25):2500-2501. doi: 10.1056/NEJMc1713444

12. Blay JY, Sleijfer S, Schöffski P. Supportive care in soft tissue sarcoma. Curr Opin Oncol. 2015;27(4):299-306. doi: 10.1097/CCO.0000000000000195

13. Penel N, Bui BN, Bay JO, et al. Phase II trial of weekly paclitaxel for unresectable angiosarcoma: The ANGIOTAX Study. J Clin Oncol. 2008;26(32):5269-5274. doi: 10.1200/JCO.2008.17.3146

14. Van Der Graaf WT, Blay JY, Chawla SP, et al. Pazopanib for metastatic soft-tissue sarcoma (PALETTE): A randomised, double-blind, placebo-controlled phase 3 trial. Lancet. 2012;379(9829):1879-1886. doi: 10.1016/S0140-6736(12)60651-5

15. Schlemmer M, Reichardt P, Verweij J, et al. Paclitaxel in patients with advanced angiosarcomas of the scalp or face: EORTC phase II trial. Cancer. 2008;113(4):832-837. doi: 10.1002/cncr.23666s