Angiosarcoma: History of Prior Radiation Therapy is an Adverse Prognostic Factor

Abstract

Angiosarcoma is a rare and aggressive malignancy with poor prognosis and limited literature describing treatment management and prognostic factors. Recent evidence on this disease is conflicting regarding the prognosis in patients with radiation (RT) induced angiosarcoma versus primary angiosarcoma. We aim to characterize treatment related factors and the impact of prior RT on the prognosis of patients with angiosarcoma. Patients with a pathologic diagnosis of angiosarcoma between the years 2008-2017 were retrospectively reviewed. Patients with metastatic disease at diagnosis were excluded. To minimize selection bias, patient and treatment specific factors including age, race, sex, prior RT, grade, tumor size, anatomic site, nodal stage, surgical margins, chemotherapy, and treatment modality were analyzed using multivariate Cox modeling to evaluate factors associated with local control (LC) and overall survival (OS). Treatment modalities were grouped as surgery alone, surgery + RT, or non-surgical. A P-value < 0.05 was considered statistically significant. A total of 65 patients were identified. The median age at diagnosis was 68 (36 - 93) years. The median follow up was 17.9 (2.1-191.7) months. The most common anatomic site was breast (n = 17), followed by extremity (12), scalp (11), head/neck (11), trunk (9), and liver (5). The most common treatment modality was surgery alone (n = 27), followed by surgery + RT (n = 26), and non-surgical (Ex. Definitive Chemo-RT) (n = 12). Chemotherapy was used in 33 patients. A total of 19 patients had a history of prior RT. The 2-year LC and OS was 65.3% and 58.9%, respectively. On multivariate analysis, prior RT was significantly associated with decreased LC (HR 76.71, 95% CI 5.93-991.88, p < 0.001) and OS (HR 2.97, 95% CI 1.18-7.44, p < 0.001). When compared to patients undergoing surgery + RT, patients receiving non-surgical management had decreased LC (HR 45.9, 95 % CI 4.01-525.22, p = 0.002) and OS (HR 3.82, 95% CI 1.16-12.59, p = 0.028). However, there was no difference in LC or OS between patients receiving surgery alone vs surgery + RT. Additionally, deep tumors were associated with poor OS (HR 2.28, 95% CI 1.02-5.12, p = 0.045), but not with LC. Chemotherapy was not associated with LC or OS. There were no differences in OS between different anatomic sites. At 2-years, the LC in patients with history of prior RT was 44.7 % vs 72.4% in patients without prior RT (p = 0.018). Similarly, the 2-yr OS was 45.0 % in patients with prior RT vs 65.1% in patients without prior RT (p = 0.006). Patients with history of prior RT and those receiving non-surgical treatment have adverse outcomes. These findings are potentially due to compromise of clinical care and selection bias in RT induced angiosarcoma. Despite such, genomic differences between RT induced angiosarcoma and primary angiosarcoma need to be characterized to evaluate the underlying biological differences which may guide the future treatment management in these patients.