Angiosarcoma Symptoms, Treatment and Answers to All Your Questions

What is a sarcoma?

Sarcomas are rare cancers occurring in the body’s soft and supporting tissues. Although rare, this important group includes more than fifty types. Sarcoma cells may arise from soft tissue (%80) or bone (%20). Soft tissues may include fat, muscle, and blood and lymphatic vessels.

What is angiosarcoma?

Among soft tissue sarcomas, those arising from blood vessels are called angiosarcomas. They may develop in subcutaneous tissues in many body regions, including the trunk, head and neck, and breast. The best-known cause is radiotherapy for breast cancer or lymphoma; they may occur in the irradiated area approximately 8-10 years later. On microscopic examination, stains identifying vascular structures, such as CD31 and Factor 8, are positive.

How are angiosarcomas treated?

LOCAL treatment methods for sarcomas

Surgery

The main sarcoma treatment is complete removal of the cancerous area. Surgery aims to remove it with surgical margins entirely surrounded by normal, cancer-free tissue. However, complete removal may be impossible depending on location and adherence to surrounding structures. Radiotherapy may also be an option when disease remains at the surgical margin.

Radiotherapy

Radiotherapy treats cancer using high energy. It damages cancer cells by creating breaks in DNA, the genetic expression of our cells. In angiosarcoma, it may be an option for patients unsuitable for surgery or with disease at the surgical margin.

Ablation

These are local methods for destroying small tumors, also called nonsurgical cancer treatments . Destroying a tumor by freezing is called cryoablation, while using high-energy radio waves is called radiofrequency ablation. These procedures use imaging guidance such as ultrasound or CT. They may treat inoperable tumors or target metastases in sarcomas that have spread to a limited number of sites.

Embolization

Embolization aims to destroy cancer cells by cutting off the cancerous tissue’s blood supply. When performed with chemotherapy, it is called chemoembolization; when performed with small radioactive beads, radioembolization .

SYSTEMIC treatment methods for sarcomas

Chemotherapy

The group of drugs used to kill cancer cells is called chemotherapy . Some damage cancer-cell DNA and others prevent DNA production, causing cell death. In angiosarcoma, chemotherapy may relieve symptoms and prolong survival in patients with disseminated disease, or shrink locally confined inoperable tumors to make surgery possible.

Chemotherapy agents proven effective in angiosarcoma

• Paclitaxel
• Doxorubucin
• Liposomal doxorubicin
• Ifosfamide
• Gemcitabine

Whether these chemotherapy drugs are used alone or together depends on the patient’s general condition.

A promising combination of propranolol, a heart and blood pressure drug, with the chemotherapy drug vinblastine

Vinblastine, used since 1958, is one of our oldest chemotherapy drugs. It works by inhibiting cell division. Propanolol (commonly known by the trade name Dideral) is among our oldest drugs for heart disease and high blood pressure. Propanolol acts on beta receptors in blood vessels, which have many functions including vessel contraction. Because angiosarcoma arises from blood vessel cells, a clinical study followed laboratory findings demonstrating that propanolol increased chemotherapy effectiveness in angiosarcoma. The study included 7 previously treated patients with recurrent, disseminated disease. Combined vinblastine and propanolol produced disease-free survival of 11 months and overall survival of 16 months, a promising result for patients who had received multiple treatment lines.

In the study published by Pasquier and colleagues, patients with angiosarcoma received propranolol 2 times daily at 40 mg, weekly metronomic vinblastine (6 mg/m2) and methotrexate (35 mg/m2). All 7 responded; 1 patient had a complete response, and 3 had a very good partial response. Following this development, in January 2017 propranolol received orphan drug status in Europe for treating soft tissue sarcoma.

Note: Orphan drug status is granted to support clinical trials of agents to be tested in rare diseases, meaning that studies of such drugs will receive public funding.

Targeted Therapies

These drugs suppress cancer-cell growth signals. Some prevent growth by blocking signals for new blood vessel formation.

Antiangiogenic and molecular targeted treatments

Vascular Epithelial Growth Factor (VEGF) is one of the most important factors in tumor blood vessel formation in many cancers. Increased vascularization contributes to tumor growth and progression; blocking VEGF receptor pathways suppresses this transformation. Targeted therapy uses anticancer drugs directed against living or growing cancer cells. Some prevent growth signals reaching cancer cells, some reduce their nourishment through the bloodstream, and others strengthen immunity to recognize and attack them. This slows cancer growth or kills more cancer cells. Targeted therapy may be combined with other cancer treatments.

Pazopanib (Votrient®)

Pazopanib is a multiple tyrosine kinase inhibitor that slows or stops cancer-cell development. It also prevents formation of new blood vessels supporting cancer growth. A total daily tablet dose of 800 mg is taken once daily, 1 hour before or 2 hours after food (on an empty stomach).

Sorafenib (Neksavar®)

Sorafenib blocks new blood vessels feeding the cancer (angiogenesis) and growth-signaling molecules within cancer cells. It does so by inhibiting various tyrosine kinases important for cell growth and survival.

Subgroup analyses in two phase II studies including patients with different sarcomas showed greater activity in angiosarcoma than other sarcomas, with disease-free survival of 5 months. Skin side effects are the most important problem with sorafenib. Dose reductions made it tolerable.

Bevacizumab (Altuzan®)

Bevacizumab is an antibody that binds circulating VEBFs and their receptors, preventing their interaction. Its effectiveness in combination with Doxorubucin chemotherapy has been demonstrated

Olaratumab (Lartruvo)

Olaratumab is an immunoglobulin G1 antibody. By binding the platelet-derived growth factor receptor (PDGFRA), elevated in sarcomas, it suppresses cancer-cell growth and increased vascularization. Its study demonstrated efficacy with doxorubicin chemotherapy in patients previously unable to receive chemotherapy. Olaratumab, showing an additional 12-month survival benefit in phase II research, received FDA approval with doxorubucin in October 2016. Common side effects are reduced blood counts and mouth sores.

Sunitinib (Sutent®)

Sunitinib is a multiple tyrosine kinase inhibitor that blocks tyrosine kinase in intracellular VEGF receptor pathways and in other receptors triggering cancer-cell growth and division. It therefore attacks growing blood vessels and other targets helping cancer cells grow. It is taken once daily at 50 mg with food or before eating.

Immunotherapy

The immune system is the body’s natural defense against infection and disease. Immunology and oncology have been linked since the late 19th century, when surgeon William Coley reported tumor shrinkage after injecting killed bacteria into sarcomas. Immunotherapy works by increasing immune system activity, enabling recognition and destruction of cancer cells. Studies in angiosarcoma continue, but no immunotherapy approach has yet been approved.