Angiosarcoma of the Head and Neck

Angiosarcomas are rare, aggressive tumors arising in either blood or lymphatic vessels:
- The scalp and face are the most common sites
Complete surgical resection with wide margins:
- Is preferred for local and locoregional disease:
  - Due to the propensity for insidious local infiltration:
    - Preoperative or postoperative radiation (RT) for almost all patients is recommended
The role of adjuvant chemotherapy is unclear
Neoadjuvant chemotherapy and / or RT:
- May allow some patients with locally advanced lesions:
  - To undergo potentially less mutilating surgery
Angiosarcomas are tumors:
- Arising in either blood or lymphatic vessels:
  - They account for about:
    - 15% of all head and neck sarcomas:
      - 1% of all soft tissue sarcomas
- The scalp and face are the most common sites of origin:
  - In a SEER database series:
    - 434 cases of cutaneous angiosarcomas
    - Reported between 1973 and 2007
    - 270 (72%) arose in the region of the head and neck:
      - Head and neck angiosarcomas tend to be a disease of:
        Older Caucasian men
        With a median age of incidence:
        Of 65 to 70
        A male to female ratio of 2:1
      - The relative Caucasian male predominance, age of incidence, and localization to the face and scalp:
        Has led some to propose that sun exposure contributes to the etiology, but this has not been clearly demonstrated
      - A prior history of radiotherapy to the face or scalp:
        Is elicited in 5% to 20% of patients
Clinical presentation:
- Patients typically present with a blue or purple lesion on the scalp or face:
  - That has been present for several months
- These lesions may appear:
  - Macular, nodular, or plaque-like
    - Diffuse, clinically undetectable intra-dermal spread:
      - Leads to indistinct borders and a high incidence of multicentricity
- Advanced lesions:
  - Can show hemorrhage or ulceration
- Cervical lymphadenopathy:
  - Is found in approximately 10% of patients at the time of presentation
Natural history and prognosis:
- The outlook for these tumors is poor:
  - With five-year survival:
    - Generally less than 40%:
- As an example:
  - In a series of 133 angiosarcomas of the scalp and neck reported to the SEER database between 1973 and 2007:
    - Five and 10-year survival rates were:
      - 34% and 14%, respectively:
        Local recurrence is a major problem
- But distant metastases are also frequent
The most important prognostic factor for survival in patients with head and neck angiosarcoma:
- Is size and the ability to completely resect the tumor:
  - Patients with tumors less than 5 cm in diameter:
    - Have better overall survival and a lower risk of regional recurrence:
In addition:
- Cellular epithelioid morphology:
  - Is emerging as a potentially adverse prognostic factor:
    - As is age 70 and older
Treatment:
- There is limited evidence, other than case series:
  - Upon which to base treatment recommendations for angiosarcoma of the head and neck
- Complete surgical resection with wide margins:
  - Is preferred for local and locoregional disease:
- Although the risk of lymph node spread is higher with angiosarcomas than with other head and neck sarcomas:
  - The overall risk remains lower than what is generally considered an indication for elective lymph node dissection:
    - As a result, most surgeons reserve neck treatment for gross nodal disease only
- Reconstruction is performed immediately following resection; even sizable deficits can be reconstructed using current techniques:
  - Radial forearm and rectus abdominis microvascular free flaps can cover large surface defects with minimal donor site morbidity
  - Smaller defects can be reconstructed using skin grafts, or local or regional flaps
- Some surgeons perform small mapping biopsies along the proposed margins preoperatively:
  - So that disease with subclinical microscopic spread can be identified and appropriate ablative and reconstructive planning undertaken prior to definitive resection
- Due to the propensity for insidious local infiltration:
  - Resection should be combined in nearly all cases by preoperative or postoperative RT:
    - Although randomized trials are not available, the benefits of RT are supported by several small reports
      - As examples:
        In one series of 28 patients with angiosarcoma of the head and neck treated at the University of California, Los Angeles (UCLA):
        Only 1 of 12 patients treated with surgery alone remained disease free compared with four of six who received postoperative RT, with or without chemotherapy
        In a second report of 70 patients with non- metastatic angiosarcoma of the face and scalp:
        Combined therapy with surgery plus RT (versus surgery alone or RT alone) was associated with:
        Improved overall survival (68% versus 32%)
        Disease-specific survival (76% versus 33%)
        As well as better local control
- The role of adjuvant chemotherapy, either alone or concurrent with RT, is unclear:
  - In the above cited series of 70 patients with non-metastatic angiosarcoma, outcomes were not significantly better in those who received any chemotherapy in addition to local therapy:
    - Five-year overall survival 45% versus 39%, p = 0.54)
  - However, interest is increasing in neoadjuvant chemotherapy and / or RT as a component of combined modality therapy, which may allow some patients to undergo potentially less mutilating surgery
- For patients with unresectable tumors or those who refuse surgery, definitive RT or chemoradiation is an option
- Systemic treatment for metastatic angiosarcoma generally follows the same principles as for other anthracycline-sensitive adult-type advanced soft tissue sarcomas:
  - However, in contrast to other soft-tissue sarcomas:
    - Angiosarcomas appear to be particularly responsive to taxanes
  - In addition, promising responses, occasionally dramatic, have been demonstrated in very limited number of angiosarcoma patients with various biologic molecules, including:
    - Bevacizumab, sunitinib, and sorafenib, either as single agents or in combination with chemotherapy
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