General Information
Note: Separate PDQ summaries on Childhood Soft Tissue Sarcoma Treatment and Uterine Sarcoma Treatment are also available.
Note: Estimated new cases and deaths from soft tissue sarcoma in the United States in 2008:[1]
- New cases: 10,390.
- Deaths: 3,680.
Note: Some citations in the text of this section are followed by a level of
evidence. The PDQ editorial boards use a formal ranking system to help the
reader judge the strength of evidence linked to the reported results of a
therapeutic strategy. (Refer to the PDQ summary on Levels of Evidence for more
information.)
Soft tissue sarcomas are malignant tumors that may arise in any of the
mesodermal tissues of the extremities (50%), trunk and retroperitoneum (40%),
or head and neck (10%). Rarely, these tumors arise in the gastrointestinal
tract or gastrointestinal stroma, and a small percentage of these are called
gastrointestinal stromal tumors (GISTs). Malignant GISTs can occur from the
esophagus to the rectum but occur most commonly in the stomach and small
intestine. Soft tissue sarcomas occur with greater frequency in patients with:[2]
- von Recklinghausen disease (neurofibromatosis).
- Gardner syndrome.
- Werner
syndrome.
- Tuberous sclerosis.
- Basal cell nevus syndrome.
- Li-Fraumeni
syndrome (p53 mutations).
Soft tissue sarcomas may be heterogeneous, so adequate
tissue should be obtained via either core-needle or incisional biopsy for
microscopic examination to determine histologic type and tumor grade. Careful
planning of the initial biopsy is important to avoid compromising subsequent
curative resection. Since the selection of treatment is determined by the
grade of the tumor, it is essential to have a careful review of the biopsy
tissue by a pathologist who is experienced in diagnosing sarcomas. Complete
staging and treatment planning by a multidisciplinary team of cancer
specialists is required to determine the optimal treatment for patients with this
disease. In most cases, a combined modality approach of preoperative or postoperative radiation therapy is used, rather than the radical surgical procedures that were used in the past.
The role of chemotherapy is less well defined. Because of the evolving nature
of the state of the art in the treatment of this disease, all patients with
such lesions should be included in a clinical trial whenever possible.
The prognosis for patients with adult soft tissue sarcomas depends on several
factors, including the patient’s age and the size, histologic grade, and stage
of the tumor.[3-5] Factors associated with a poorer prognosis include age
older than 60 years, tumors larger than 5 cm, or high-grade
histology.[6]
While low-grade tumors are usually curable by surgery alone,
higher-grade sarcomas (as determined by the mitotic index and by the presence of
hemorrhage and necrosis) are associated with higher local treatment failure
rates and increased metastatic potential.[7] When feasible, wide margin
function-sparing surgical excision is the cornerstone of effective
treatment, with the goal of preservation of a functional extremity.[8,9] This may be facilitated by soft tissue reconstructive surgery.[10] Mohs surgical technique may be considered as an alternative to
wide surgical excision for small, well-differentiated sarcomas when cosmetic
results are considered to be very important, as margins can be assured with
minimal normal tissue removal.[2,11] High-grade soft tissue sarcomas of the
extremities can often be effectively treated while preserving the limb with
combined-modality treatment consisting of preoperative or postoperative
radiation therapy to reduce local recurrence. A phase II trial (SWOG-9119) was conducted of neoadjuvant therapy with DOX/DTIC/IFF for poor prognosis soft tissue sarcoma.[8,12-19] In adults, local
control of high-grade soft tissue sarcomas of the trunk and the head and neck
can be achieved with surgery, often in combination with radiation therapy with
or without chemotherapy.[20]
Effective treatment of retroperitoneal sarcomas
requires removal of all gross disease while sparing adjacent viscera not
invaded by tumor. The prognosis for patients with high-grade retroperitoneal
sarcomas is less favorable than for patients with tumors at other sites, partly
because of the difficulty in completely resecting these tumors and the
limitations placed on high-dose radiation therapy.[2,21] Surgical resection is
the most effective treatment modality for GISTs.[22] Evidence indicates that imatinib mesylate, a tyrosine kinase
inhibitor, induced sustained tumor response in patients with unresectable or
metastatic GIST tumors.[23-25][Level of evidence: 3iiiDiv][26,27]
Several prospective randomized trials have been unable to confirm conclusively
whether doxorubicin-based adjuvant chemotherapy benefits adults with resectable
soft tissue sarcomas. The majority of these studies accrued small numbers of
patients and did not demonstrate a metastasis-free survival or an overall survival
(OS) benefit for adjuvant chemotherapy.[20] A small study of adjuvant chemotherapy
showed a positive impact in disease-free survival and OS in
patients treated with postoperative chemotherapy.[28] There was wide
interstudy variability among the numerous trials, including differences in
therapeutic regimens, drug doses, sample size, tumor site, and histologic
grade. A quantitative meta-analysis of updated data from 1,568 individual
patients from 14 trials of doxorubicin-based adjuvant therapy showed an
absolute benefit from adjuvant therapy of 6% for local relapse-free interval (95% confidence interval [CI],
1–10), 10% for distant
relapse-free interval (95% CI, 5–15), and 10% for recurrence-free survival (95% CI, 5–15); however, there was no OS benefit at 10 years.[29][Level of evidence: 1iiDii] Patients with high-grade tumors (grades 3 or 4) larger than 5 cm in diameter have the greatest tendency for disease to metastasize
and are eligible for prospective clinical trials of adjuvant chemotherapy.
With distant metastases (stage IV), surgery with curative intent is possible
for patients selected for optimal underlying biologic behavior (i.e., patients
with a limited number of metastases, with a long disease-free interval, and
with slow clinical growth) with pulmonary metastases who have undergone or are
undergoing complete resection of the primary tumor.[30-32] Doxorubicin alone
or with dacarbazine is considered the best chemotherapeutic regimen for
advanced sarcoma.[33-35] A randomized trial of 340 patients with advanced
sarcoma showed a higher response rate (32% vs. 17%, P < .002) and longer
time-to-progression (6 vs. 4 months, P < .02) for doxorubicin, dacarbazine,
ifosfamide, and mesna (MAID) versus doxorubicin and dacarbazine
alone.[36][Level of evidence: 1iiDiii] The increased response rate of the MAID
regimen may be justified in preoperative management of younger patients with
borderline resectability, but the increased toxic effects argue against its use
in older patients.[36]
Complete surgical resection is often difficult for sarcomas of the
retroperitoneum because of their large size before detection and anatomic
location.[37,38] Prospective randomized trials have not shown improved
survival with preoperative or postoperative adjuvant chemotherapy for this
subgroup.[29]
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