An Update on Cutaneous Angiosarcoma Diagnosis and Treatment

Other Therapies—Although there have not been large-scale studies performed on alternative treatments, there are several case reports on the use of immune modulators, biologics, β-blockers, and various other therapies in the treatment of CAS. The following studies include small sample sizes of patients with metastatic or locally aggressive disease not amenable to surgical resection, which may affect reported outcomes and survival times.^49-57 In addition, several studies include patients with visceral angiosarcoma, which may not be generalizable to the CAS population. Even so, these treatment alternatives should not be overlooked because there are few agents that are truly efficacious in the treatment of CAS.

Results on the use of VEGF and tyrosine kinase inhibitors have been disappointing. There have been reports of median progression-free survival of only 3.8 months with sorafenib treatment, 3 months with pazopanib, and 6 months with bevacizumab.^49-51 However, one study of patients who were treated with bevacizumab combined with radiation and surgery resulted in a complete response in 2 patients, with no evidence of residual disease at the last follow-up of 8.5 months and 2.1 years.⁵²

Studies on the utility of β-blockers in the treatment of CAS have shown mixed results. Pasquier et al⁵³ evaluated the use of adjunctive therapy with propranolol and vinblastine-based chemotherapy, with a promising median progression-free survival of 11 months compared with an average of 3 to 6 months with conventional chemotherapy regimens. However, in vitro studies reported by Pasquier et al⁵³ indicated that the addition of propranolol to doxorubicin or paclitaxel did not result in increased efficacy. Chow et al⁵⁴ demonstrated that propranolol monotherapy resulted in a reduction of the proliferative index of scalp angiosarcoma by 34% after only 1 week of treatment. This was followed by combination therapy of propranolol, paclitaxel, and radiation, which resulted in substantial tumor regression and no evidence of metastasis after 8 months of therapy.⁵⁴

Immune checkpoint inhibitors have been a recent subject of interest in the treatment of angiosarcoma. Two case reports showed improvement in CAS of the face and primary pleural angiosarcoma with a course of pembrolizumab.^55,56 In another case series, investigators used immune checkpoint inhibitors in 7 patients with cutaneous, breast, or radiation-associated angiosarcoma and found partial response in several patients treated with pembrolizumab and ipilimumab-nivolumab and complete response in 1 patient treated with anti–cytotoxic T-lymphocyte–associated protein 4 antibodies. The authors of this study hypothesized that treatment response was associated with the mutational profile of tumors, including mutational signatures of UV radiation with a large number of C-to-T substitutions similar to melanomas.⁵⁷

Conclusion

Cutaneous angiosarcoma is a rare and aggressive tumor with a poor prognosis due to delayed detection. A thorough skin examination and heightened awareness of CAS by dermatologists may result in early biopsy and shortened time to a definitive diagnosis. Until quality evidence allows for the creation of consensus guidelines, care at a cancer center that specializes in rare and difficult-to-treat tumors and employs a multidisciplinary approach is essential to optimizing patient outcomes. Current knowledge supports surgery with negative margins as the mainstay of treatment, with adjuvant radiation, chemotherapy, and targeted therapies as possible additions for extensive disease. The role of MMS is uncertain, and because of the lack of contiguity in CAS, it may not be an optimal treatment.