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###  Agent Orange Brief

**Prepared by the Environmental Agents Service (131)**

D4 VA Central Office, Washington, DC 20420 Aug. 2002

#### 

> **AGENT ORANGE AND SOFT TISSUE SARCOMAS**

**What are soft tissue sarcomas?**

Soft tissue sarcomas are a group of different types of malignant tumors
that arise from body tissues such as muscle, fat, blood and lymph
vessels and connective tissues (that is, distinct from hard tissue such
as bone or cartilage). These tumors are relatively rare.

In regulations, VA has defined the term \"soft tissue sarcoma\" to
include adult fibrosarcoma; dermatofibrosarcoma protuberans, malignant
fibrous histiocytoma, liposarcoma; leiomyosarcoma; epithelioid
leiomyosarcoma (malignant leiomyoblastoma); rhabdomyosarcoma;
ectomesenchymoma; angiosarcoma (hemangiosarcoma and lymphangiosarcoma);
proliferating (systemic) angioendotheliomatosis; malignant glomus tumor;
malignant hemangiopericytoma; synovial sarcoma (malignant synovioma);
malignant giant cell tumor of tendon sheath; malignant schwannoma,
including malignant schwannoma with rhabdomyoblastic differentiation
(malignant Triton tumor), glandular and epithelioid malignant
schwannomas; malignant mesenchymoma; malignant granular cell tumor;
alveolar soft part sarcoma; epithelioid sarcoma; and clear cell sarcoma
of tendons and aponeuroses. (See 56 [Fed. Reg.]{.underline} 51651,
October 15, 1991).

**Why are Vietnam veterans concerned about soft tissue sarcomas?**

The possibility that exposure to phenoxy herbicides, such as Agent
Orange, may have caused rare forms of cancer in humans such as soft
tissue sarcomas was suggested in 1979 and 1981 by small scale studies
conducted in Sweden. These studies showed that persons reporting
occupational exposure to phenoxy herbicides may have a 5 to 6 fold
higher risk of developing soft tissue sarcomas as compared to persons
without such exposure.

**Have more recent research results supported or conflicted with the
Swedish studies finding regarding soft tissue sarcomas?**

A number of scientific studies of soft tissue sarcomas among people who
may have been exposed to herbicides and/or dioxins have been published
in the past few years. Some studies suggested a possible association
between these exposures and an increased risk of some cancers, but none
showed an increased risk of soft tissue sarcomas of the magnitude cited
by the Swedish researchers, and the majority of these investigations
showed no association at all.

Mortality studies conducted by Massachusetts and West Virginia indicated
that there might be a link between service in Vietnam and soft tissue
sarcomas. However, the small number of deaths in the West Virginia study
makes it possible that these findings were the results of chance rather
than real association.

A New York State study showed that fewer Vietnam veterans died of soft
tissue sarcomas than Vietnam-era veterans who did not serve in Vietnam.
A study in New Zealand of soft tissue sarcomas and exposure to phenoxy
herbicides and chlorophenols, a National Cancer Institute study of
agricultural herbicide use and risk of lymphomas and soft tissue
sarcomas in Kansas, a western Washington State study, the Department of
Veterans Affairs (VA) Vietnam veterans mortality study, two VA studies
of the relationship between soft tissue sarcomas and military service in
Vietnam, and the Centers for Disease Control Selected Cancers Study have
not supported the findings of the Swedish researchers. The VA studies
were published in the [Journal of Occupational Medicine]{.underline} in
December 1986, and the [Journal of the National Cancer
Institute]{.underline} in October 1987. Very few cases of soft tissue
sarcomas are appearing in the Agent Orange Registry. Research on soft
tissue sarcomas and other cancers is continuing.

**What did the Veterans\' Advisory Committee on Environmental Hazards
conclude about the relationship between herbicides and soft tissue
sarcomas?**

This VA committee, established by law, met on May 16-17, 1990, to review
scientific literature relating to whether there is a significant
statistical association between exposure to a dioxin-containing
herbicide and subsequent development of soft tissue sarcomas. After
considering more than eighty articles, the Advisory Committee concluded
that it was as least as likely as not that such an association existed.

Committee members noted that work done in Sweden was strongly compelling
for an association while studies done elsewhere not showing an
association were also very strong. Members observed that \"positive\"
studies tended to be confined to one geographic area of the world
whereas studies involving Vietnam veterans did not find such an
association. Several Committee members noted they did not believe that
the scientific evidence demonstrated a causal association.

**How did VA respond to the Advisory Committee\'s finding?**

The day after the meeting, Secretary Derwinski announced that VA would
recognize, as service-connected, soft tissue sarcomas based on exposure
to dioxin-containing herbicides.

Final rule implementing the Secretary\'s decision was published in the
[Federal Register]{.underline} in October 1991. (See 56
[Fed. Reg.]{.underline} 51651, October 15, 1991).

**How did Public Law 102-4 help Vietnam veterans who suffer with soft
tissue sarcomas?**

To a large extent, Public Law 102-4, the Agent Orange Act of 1991,
enacted February 6, 1991, codified (established in law) the Secretary\'s
decision. However, since there are significant differences in the
eligibility requirements for service connection under the rule and the
presumptions of service connection established under Public Law 102-4,
the rule implementing the new statute was published separately in the
[Federal Register]{.underline}. (For proposed rule, see 57 [Fed.
Reg.]{.underline} 30707, July 10, 1992; for final rule see 58 [Fed.
Reg.]{.underline} 29107, May 19, 1993).

**What did the National Academy of Sciences (NAS) conclude about soft
tissue sarcomas (STS) in its 1993 report, entitled
[Veterans and Agent Orange
- Health Effects of Herbicides Used in Vietnam]{.underline}?**

The 832-page NAS report contained the following statements:

> The strongest evidence for an association between STS and exposure to
> phenoxy herbicides come from a series of case-control studies
> involving a total of 506 cases conducted by Hardell and colleagues in
> Sweden \... that show an association between STS and exposure to
> phenoxy herbicides, chloropenols, or both. Although these studies have
> been criticized, the committee feels that there is insufficient
> justification to discount the consistent pattern of elevated risks,
> and the clearly described and sound methods employed.
>
> These findings are supported by a significantly increased risk in the
> NIOSH study \... for the production workers most highly exposed to
> TCDD \... , and a similar increased risk in the IARC cohort \... for
> deaths that occurred between 10 and 19 years after the first exposure
> \.... These are the two largest, as well as the most highly exposed
> occupational cohorts.
>
> Some studies in other occupational, environmental, and veterans group
> showed an increased risk for STS, but the results were commonly
> nonsignificant possibly because of small sample sizes related to the
> relative rarity of STS in the population, except for males in Zone R
> of Seveso. The risk of this group was significantly elevated and is
> consistent with the findings supporting an association\....
>
> Evidence is sufficient to conclude that there is a positive
> association between exposure to herbicides (2,4-D; 2,4,5-T and its
> contaminant TCDD; cacodylic acid; and picloram) and soft tissue
> sarcoma.

**What did the NAS conclude regarding soft tissue sarcomas in its 1996
update?**

In the 1996 update, the NAS commented that reports issued since the
publication of **Veterans and Agent Orange** provide "additional
evidence for an association" between exposure to herbicides and soft
tissue sarcomas.

**What did the NAS conclude regarding soft tissue sarcomas in its 1998
update?**

The 1998 update contained the following statement, "No new evidence has
been produced to change the committee's earlier judgment that evidence
is sufficient to conclude that a positive statistical association exists
between exposure" to the herbicides considered in this report and soft
tissue sarcomas.

**What did the NAS conclude regarding soft tissue sarcomas in its 2000
update?**

The 2000 update contained the following statement, "There is no
information contained in the research reviewed for this report to change
the conclusion that there is sufficient evidence to conclude that an
association exists between exposure to herbicides and soft tissue
sarcoma."

**Where can a veteran get additional information on this subject?**

Information on soft tissue sarcomas and related matters can be obtained
at VA medical center libraries, from the Registry Physicians at every VA
medical center, or from the Environmental Agents Service (131),
Department of Veterans Affairs, 810 Vermont Avenue, N.W., Washington, DC
20420.

**Where can a veteran obtain additional information about Agent
Orange-related issues**?

The following Agent Orange fact sheets (including the one you are
reading) are available on the World Wide Web at
[www.va.gov/agentorange](http://www.va.gov/agentorange). Hard copies can
be obtained from local VA medical centers or from the VA Central Office
at the Environmental Agents Service (131), Department of Veterans
Affairs, 810 Vermont Avenue N.W., Washington, DC 20420. The briefs are
A1 -- General Information, A2 - Class Action Lawsuit, B1 -- Registry, B2
-- Health Care Eligibility, B3 -- VA Disability Compensation, B4 -- VA
Information on Agent Orange and Related Matters, C1 -- The Problems
Encountered in Research, C2 - Vietnam Related Research - VA Efforts, C3
-- Vietnam Related Research and Non-VA Efforts, D1 -- Birth Defects, D2
-- Chloracne, D3 -- Non-Hodgkin's Lymphoma, D5 -- Peripheral Neuropathy,
D6 -- Hodgkin's Disease, D7 -- Porphyria Cutanea Tarda, D8 -- Multiple
Myeloma, D9 -- Respiratory Cancers, D10 -- Prostate Cancer, D11 -- Spina
Bifida, and D12 -- Diabetes.

**This fact sheet was prepared in early August 2002 and does not include
any subsequent developments.**