General Information About Adult Soft Tissue Sarcoma
Adult soft tissue sarcoma is a disease in which malignant (cancer) cells form in
the soft tissues of the body.
The soft tissues of the body include the muscles, tendons (bands of fiber that connect muscles to bones), fat, blood vessels, lymph vessels, nerves, and tissues around joints. Adult soft tissue sarcomas can form almost anywhere in the body, but are most common in the legs, abdomen, arms, and trunk.
There are many types of soft tissue sarcoma. One type that forms in the wall of the stomach, intestines, or rectum is called a gastrointestinal stromal tumor (GIST). The cells of each type of sarcoma look different under a microscope, based on the type of soft tissue in which the cancer began.
Having certain inherited disorders can increase the risk of developing adult soft tissue sarcoma.
Anything that increases your risk of getting a disease is called a risk factor. Risk factors for soft tissue sarcoma include the following inheriteddisorders:
- Retinoblastoma.
- Neurofibromatosis type 1 (von Recklinghausen disease or NF1).
- Tuberous sclerosis.
- Familial adenomatous polyposis (FAP).
- Li-Fraumeni syndrome.
- Werner syndrome.
- Basal cell nevus syndrome.
Other risk factors for soft tissue sarcoma include past treatment with radiation therapy during childhood or for the following types of cancer:
- Retinoblastoma.
- Breast cancer.
- Lymphoma.
- Cervical cancer.
Possible signs of adult soft tissue sarcoma include a lump or swelling in soft tissue of the body.
A sarcoma may appear as a painless lump under the skin, often on an arm or a leg. Sarcomas that begin in the abdomen may not cause symptoms until they become very large. As the sarcoma grows larger and presses on nearby organs, nerves, muscles, or blood vessels, symptoms may include:
Other conditions may cause the same symptoms that soft tissue sarcomas do. A doctor should be consulted if any of these problems occur.
Adult soft tissue sarcoma is diagnosed with a biopsy.
If a soft tissue sarcoma is suspected, a biopsy will be done. The type of biopsy that is done will be based on the size and location of the tumor. There are two types of biopsy that may be used:
- Incisional biopsy: The removal of part of a lump or a sample of tissue.
- Core biopsy: The removal of tissue using a wide needle.
Samples will be taken from the primary tumor, lymph nodes, and other suspicious areas. A pathologist views the tissue under a microscope to look for cancer cells and to
find out the grade of the tumor. The grade of a tumor depends on how abnormal the cancer cells look under a microscope and how quickly the cells are dividing. High-grade tumors usually grow and spread more quickly than low-grade tumors. Because soft tissue sarcoma can be hard to diagnose, patients should ask to have biopsy samples checked by a pathologist who has experience in diagnosing soft tissue sarcoma.
Certain factors affect treatment options and prognosis (chance of recovery).
The treatment options and prognosis (chance of recovery) depend on the following:
- The type of soft tissue sarcoma.
- The size, grade, and stage of the tumor.
- Where the tumor is in the body.
- Whether the entire tumor is removed by surgery.
- The patient's age and general health.
- Whether the cancer has recurred (come back).
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Stages of Adult Soft Tissue Sarcoma
After adult soft tissue sarcoma has been diagnosed, tests are done to find out if cancer cells have spread within the soft tissue or to other parts of the body.
The process used to find out if cancer has spread within the soft tissue or to other
parts of the body is called staging. Staging of soft tissue sarcoma is also based on the grade and size of the tumor, whether it is superficial (close to the skin's surface) or deep, and whether it has spread to the lymph nodes or other parts of the body. The information gathered from the
staging process determines the stage of the disease. It is important to know
the stage in order to plan treatment.
The following tests and
procedures may be used in the staging process:
- Physical exam and history: An exam of the body to check general signs of health, including checking for signs of disease, such as lumps or anything else that seems unusual. A history of the patient’s health habits and past illnesses and treatments will also be taken.
- X-rays: An x-ray is a type of energy beam that can go through the body onto film, making pictures of areas inside the body.
- Laboratory tests: Medical procedures that test samples of tissue, blood, urine, or other substances in the body. These tests help to diagnose disease, plan and check treatment, or monitor the disease over time.
- CT scan (CAT scan): A procedure that makes a series of detailed pictures of areas inside of the body, taken from different angles. The pictures are made by a computer linked to an x-ray machine. A dye may be injected into a vein or swallowed to help the organs or tissues show up more clearly. This procedure is also called computed tomography, computerized tomography, or computerized axial tomography.
- MRI (magnetic resonance imaging): A procedure that uses a magnet, radio waves, and a computer to make a series of detailed pictures of areas inside the body. This procedure is also called nuclear magnetic resonance imaging (NMRI).
The results of these tests are viewed together with the results of
the tumor biopsies to determine the stage of the soft tissue sarcoma.
There are three ways that cancer spreads in the body.
The three ways that cancer spreads in the body are:
- Through tissue. Cancer invades the surrounding normal tissue.
- Through the lymph system. Cancer invades the lymph system and travels through the lymph vessels to other places in the body.
- Through the blood. Cancer invades the veins and capillaries and travels through the blood to other places in the body.
When cancer cells break away from the primary (original) tumor and travel through the lymph or blood to other places in the body, another (secondary) tumor may form. This process is called metastasis. The secondary (metastatic) tumor is the same type of cancer as the primary tumor. For example, if breast cancer spreads to the bones, the cancer cells in the bones are actually breast cancer cells. The disease is metastatic breast cancer, not bone cancer.
The following stages are used for adult soft tissue sarcoma:
Stage I
In stage I, the tumor is any size, low-grade (likely to grow and spread slowly), and may be either superficial (close to the skin's surface) or deep.
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| Pea, peanut, walnut, and lime show tumor sizes. |
Stage II
In stage II, the tumor is high-grade (likely to grow and spread quickly) and either:
- 5 centimeters or smaller and can be superficial (close to the skin's surface) or deep; or
- larger than 5 centimeters and superficial.
Stage III
In stage III, the tumor is high-grade, larger than 5 centimeters, and deep.
Stage IV
In stage IV, the tumor is any size, any grade, and has spread to nearby lymph nodes or to other parts of the body.
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Recurrent Adult Soft Tissue Sarcoma
Recurrent adult soft tissue sarcoma is cancer that has recurred (come back) after it has been treated. The cancer may come back in the same soft tissue or in other parts of the body.
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Treatment Option Overview
There are different types of treatment for patients with adult soft tissue sarcoma.
Different types of treatments are available for patients with adult soft tissue sarcoma. Some treatments are standard (the currently used treatment), and some are being tested in clinical trials. A treatment clinical trial is a research study meant to help improve current treatments or obtain information on new treatments for patients with cancer. When clinical trials show that a new treatment is better than the standard treatment, the new treatment may become the standard treatment. Patients may want to think about taking part in a clinical trial. Some clinical trials are open only to patients who have not started treatment.
Three types of standard treatment are used:
Surgery
Surgery is the most common treatment for adult soft tissue sarcoma. For some soft-tissue sarcomas, removal of the tumor in surgery may be the only treatment needed. The following surgical procedures may be used:
- Mohs microsurgery: A procedure in which the tumor is cut from the skin in thin layers. During surgery, the edges of the tumor and each layer of tumor removed are viewed through a microscope to check for cancer cells. Layers continue to be removed until no more cancer cells are seen. This type of surgery removes as little normal tissue as possible and is often used where appearance is important, such as on the skin.
- Wide local excision: Removal of the tumor along with some normal tissue around it.
- Limb-sparing surgery: Removal of the tumor in an arm or leg without amputation, so the use and appearance of the limb is saved. Radiation therapy or chemotherapy may be given first to shrink the tumor. The tumor is then removed in a wide local excision. Tissue and bone that are removed may be replaced with a graft using tissue and bone taken from another part of the patient's body, or with an implant such as artificial bone.
- Amputation: Surgery to remove part or all of a limb or appendage, such as an arm or leg.
- Lymphadenectomy: Removal of the lymph nodes that contain cancer.
Radiation therapy or chemotherapy may be given before or after surgery to remove the tumor. When given before surgery, radiation therapy or chemotherapy will make the tumor smaller and reduce the amount of tissue that needs to be removed during surgery. Treatment given before surgery is called neoadjuvant therapy. When given after surgery, radiation therapy or chemotherapy will kill any remaining cancer cells. Treatment given after the surgery, to lower the risk that the cancer will come back, is called
adjuvant therapy.
Radiation therapy
Radiation therapy is a cancer treatment that uses high-energy x-rays or other types of radiation to kill cancer cells or keep them from growing. There are two types of radiation therapy. External radiation therapy uses a machine outside the body to send radiation toward the cancer. Internal radiation therapy uses a radioactive substance sealed in needles, seeds, wires, or catheters that are placed directly into or near the cancer. The way the radiation therapy is given depends on the type and stage of the cancer being treated.
Fast neutron radiation therapy is a type of high-energy external radiation therapy. A radiation therapy machine aims tiny, invisible particles, called neutrons, at the cancer cells to kill them. Fast neutron radiation therapy uses a higher-energy radiation than the x-ray type of radiation therapy. This allows the same amount of radiation to be given in fewer treatments.
Chemotherapy
Chemotherapy is a cancer treatment that uses drugs to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. When chemotherapy is taken by mouth or injected into a vein or muscle, the drugs enter the bloodstream and can reach cancer cells throughout the body (systemic chemotherapy). When chemotherapy is placed directly into the spinal column, an organ, or a body cavity such as the abdomen, the drugs mainly affect cancer cells in those areas (regional chemotherapy). The way the chemotherapy is given depends on the type and stage of the cancer being treated.
New types of treatment are being tested in clinical trials.
This summary section describes treatments that are being studied in clinical trials. It may not mention every new treatment being studied. Information about clinical trials is available from the NCI Web site.
High-dose chemotherapy with stem cell transplant
High-dose chemotherapy with stem cell transplant is a method of giving high doses of chemotherapy and replacing blood-forming cells destroyed by the cancer treatment. Stem cells (immature blood cells) are removed from the blood or bone marrow of the patient or a donor and are frozen and stored. After the chemotherapy is completed, the stored stem cells are thawed and given back to the patient through an infusion. These reinfused stem cells grow into (and restore) the body's blood cells.
Targeted therapy
Targeted therapy is a type of treatment that uses drugs or other substances to find and attack specific cancer cells without harming normal cells. Imatinib (Gleevec) is a type of targeted therapy called a tyrosine kinase inhibitor. It finds and blocks an abnormalprotein on cancer cells that causes them to divide and grow. Targeted therapy may be used for gastrointestinal stromal tumors that cannot be removed by surgery or that have spread to other parts of the body.
Patients may want to think about taking part in a clinical trial.
For some patients, taking part in a clinical trial may be the best treatment choice. Clinical trials are part of the cancer research process. Clinical trials are done to find out if new cancer treatments are safe and effective or better than the standard treatment.
Many of today's standard treatments for cancer are based on earlier clinical trials. Patients who take part in a clinical trial may receive the standard treatment or be among the first to receive a new treatment.
Patients who take part in clinical trials also help improve the way cancer will be treated in the future. Even when clinical trials do not lead to effective new treatments, they often answer important questions and help move research forward.
Patients can enter clinical trials before, during, or after starting their cancer treatment.
Some clinical trials only include patients who have not yet received treatment. Other trials test treatments for patients whose cancer has not gotten better. There are also clinical trials that test new ways to stop cancer from recurring (coming back) or reduce the side effects of cancer treatment.
Clinical trials are taking place in many parts of the country. See the Treatment Options section that follows for links to current treatment clinical trials. These have been retrieved from NCI's clinical trials database.
Follow-up tests may be needed.
Some of the tests that were done to diagnose the cancer or to find out the stage of the cancer may be repeated. Some tests will be repeated in order to see how well the treatment is working. Decisions about whether to continue, change, or stop treatment may be based on the results of these tests. This is sometimes called re-staging.
Some of the tests will continue to be done from time to time after treatment has ended. The results of these tests can show if your condition has changed or if the cancer has recurred (come back). These tests are sometimes called follow-up tests or check-ups.
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Treatment Options for Adult Soft Tissue Sarcoma
A link to a list of current clinical trials is included for each treatment section. For some types or stages of cancer, there may not be any trials listed. Check with your doctor for clinical trials that are not listed here but may be right for you.
Stage I Adult Soft Tissue Sarcoma
Treatment of stage I adult soft tissue sarcoma may include the following:
- Surgery (wide local excision or Mohs microsurgery).
- Radiation therapy before and/or after surgery.
If cancer is found in the head, neck, abdomen, or chest, treatment may include the following:
- Surgery.
- Radiation therapy before or after surgery.
- Fast neutron radiation therapy.
Check for U.S. clinical trials from NCI's PDQ Cancer Clinical Trials Registry that are now accepting patients with stage I adult soft tissue sarcoma. For more specific results, refine the search by using other search features, such as the location of the trial, the type of treatment, or the name of the drug. General information about clinical trials is available from the NCI Web site.
Stage II and III Adult Soft Tissue Sarcoma
Treatment of stage II and III adult soft tissue sarcoma may include the following:
- Surgery (wide local excision).
- Surgery (wide local excision) with radiation therapy, for large tumors.
- High-dose radiation therapy for tumors that cannot be removed by surgery.
- Radiation therapy or chemotherapy before limb-sparing surgery. Radiation therapy may also be given after surgery.
- A clinical trial of surgery followed by chemotherapy, for large tumors.
Check for U.S. clinical trials from NCI's PDQ Cancer Clinical Trials Registry that are now accepting patients with stage II adult soft tissue sarcoma and stage III adult soft tissue sarcoma. For more specific results, refine the search by using other search features, such as the location of the trial, the type of treatment, or the name of the drug. General information about clinical trials is available from the NCI Web site.
Stage IV Adult Soft Tissue Sarcoma
Treatment of stage IV adult soft tissue sarcoma that involves lymph nodes may include the following:
- Surgery (wide local excision) with or without lymphadenectomy. Radiation therapy may also be given after surgery.
- Radiation therapy before and after surgery.
- A clinical trial of surgery followed by chemotherapy.
- A clinical trial of targeted therapy (Gleevec) for gastrointestinal stromal tumors.
Treatment of stage IV adult soft tissue sarcoma that involves internal organs of the body may include the following:
- Surgery (wide local excision).
- Surgery to remove as much of the tumor as possible, followed by radiation therapy.
- High-dose radiation therapy, with or without chemotherapy, for tumors that cannot be removed by surgery.
- Chemotherapy with 1 or more anticancer drugs, before surgery or as palliative therapy to relieve symptoms and improve the quality of life.
- A clinical trial of chemotherapy with or without stem cell transplant.
- A clinical trial of chemotherapy following surgery to remove cancer that has spread to the lungs.
- A clinical trial of targeted therapy (Gleevec) for gastrointestinal stromal tumors.
These treatments may be followed by surgery to remove lesions on the lungs.
Check for U.S. clinical trials from NCI's PDQ Cancer Clinical Trials Registry that are now accepting patients with stage IV adult soft tissue sarcoma. For more specific results, refine the search by using other search features, such as the location of the trial, the type of treatment, or the name of the drug. General information about clinical trials is available from the NCI Web site.
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Treatment Options for Recurrent Adult Soft Tissue Sarcoma
Treatment of recurrent adult soft tissue sarcoma may include the following:
- Surgery (wide local excision) with radiation therapy before or after surgery.
- Surgery (amputation).
- Radiation therapy followed by limb-sparing surgery.
- Surgery to remove cancer that has recurred in the lungs.
- Chemotherapy with 1 or more anticancer drugs.
- A clinical trial of new anticancer drugs.
- A clinical trial of high-dose chemotherapy with or without stem cell transplant.
Check for U.S. clinical trials from NCI's PDQ Cancer Clinical Trials Registry that are now accepting patients with recurrent adult soft tissue sarcoma. For more specific results, refine the search by using other search features, such as the location of the trial, the type of treatment, or the name of the drug. General information about clinical trials is available from the NCI Web site.
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To Learn More About Adult Soft Tissue Sarcoma
For more information from the National Cancer Institute about adult soft tissue sarcoma, see the following:
For general cancer information and other resources from the National Cancer Institute, see the following:
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This information is provided by the National Cancer Institute.
This information was last updated on September 10, 2009.
Purpose of This PDQ Summary
This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about the treatment of adult soft tissue sarcoma. This summary is reviewed regularly and updated as necessary by the PDQ Adult Treatment Editorial Board.
Information about the following is included in this summary:
- Prognostic factors.
- Cellular classification.
- Staging.
- Treatment options by cancer stage.
This summary is intended as a resource to inform and assist clinicians who care for cancer patients. It does not provide formal guidelines or recommendations for making health care decisions.
Some of the reference citations in the summary are accompanied by a level-of-evidence designation. These designations are intended to help readers assess the strength of the evidence supporting the use of specific interventions or approaches. The PDQ Adult Treatment Editorial Board uses a formal evidence ranking system in developing its level-of-evidence designations. Based on the strength of the available evidence, treatment options are described as either “standard” or “under clinical evaluation.” These classifications should not be used as a basis for reimbursement determinations.
This summary is available in a patient version, written in less technical language, and in Spanish.
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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 2009: [1]
- New cases: 10,660.
- Deaths: 3,820.
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][4][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][13][14][15][16][17][18][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][24][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][31][32] Doxorubicin alone
or with dacarbazine is considered the best chemotherapeutic regimen for
advanced sarcoma.[33][34][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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Santoro A, Tursz T, Mouridsen H, et al.: Doxorubicin versus CYVADIC versus doxorubicin plus ifosfamide in first-line treatment of advanced soft tissue sarcomas: a randomized study of the European Organization for Research and Treatment of Cancer Soft Tissue and Bone Sarcoma Group. J Clin Oncol 13 (7): 1537-45, 1995.
Zalupski M, Metch B, Balcerzak S, et al.: Phase III comparison of doxorubicin and dacarbazine given by bolus versus infusion in patients with soft-tissue sarcomas: a Southwest Oncology Group study. J Natl Cancer Inst 83 (13): 926-32, 1991.
Borden EC, Amato DA, Rosenbaum C, et al.: Randomized comparison of three adriamycin regimens for metastatic soft tissue sarcomas. J Clin Oncol 5 (6): 840-50, 1987.
Antman K, Crowley J, Balcerzak SP, et al.: An intergroup phase III randomized study of doxorubicin and dacarbazine with or without ifosfamide and mesna in advanced soft tissue and bone sarcomas. J Clin Oncol 11 (7): 1276-85, 1993.
Heslin MJ, Lewis JJ, Nadler E, et al.: Prognostic factors associated with long-term survival for retroperitoneal sarcoma: implications for management. J Clin Oncol 15 (8): 2832-9, 1997.
Jaques DP, Coit DG, Hajdu SI, et al.: Management of primary and recurrent soft-tissue sarcoma of the retroperitoneum. Ann Surg 212 (1): 51-9, 1990.
Top
Cellular Classification
Soft tissue sarcomas are classified histologically according to the soft tissue
cell of origin, though the cell type is not part of the prognostic staging
system. Additional studies, including electron microscopy, histochemistry,
flow cytometry, cytogenetics, and tissue culture studies may allow
identification of particular subtypes within the major histologic categories.
The histologic grade reflects the metastatic potential of these tumors more
accurately than the classic cellular classification listed below.[1][2][3]
Overall, malignant fibrous histiocytoma is the most common histologic type (40%
of the total) followed by liposarcoma (25%); however, frequency of histologic
type is site-dependent. Pathologists assign grade based on the number of
mitoses per high-powered field, presence of necrosis, cellular and nuclear
morphology, and the degree of cellularity; discordance among expert
pathologists can reach 40% on prospective review.[3][4]
Soft tissue sarcomas include the following tumors:
- Alveolar soft-part sarcoma.[5]
- Angiosarcoma.[6][7][8]
- Dermatofibrosarcoma protuberans.[9]
- Epithelioid sarcoma.
- Extraskeletal chondrosarcoma.
- Extraskeletal osteosarcoma.
- Fibrosarcoma.
- Gastrointestinal stromal tumor (GIST).
- Leiomyosarcoma.
- Liposarcoma.
- Malignant fibrous histiocytoma.
- Malignant hemangiopericytoma.
- Malignant mesenchymoma.
- Malignant schwannoma.
- Malignant peripheral nerve sheath tumor.
- Peripheral neuroectodermal tumors.
- Rhabdomyosarcoma.
- Synovial sarcoma.
- Sarcoma, NOS (not otherwise specified).
GISTs are mesenchymal in origin and are
immunohistochemically distinct from leiomyosarcomas, schwannomas, and
fibrosarcomas with which they are often classified. They can be distinguished
by being CD34 positive and CD117 positive. These tumors express a growth
factor receptor with tyrosine kinase activity called c-kit (CD117). GISTs of
the stomach wall are considered malignant when they exceed 5 to 10 cm,
have a high mitotic index, or have metastasized. GISTs of the small bowel are
considered malignant if they have any mitoses or are larger than 2
cm. Current evidence suggests that c-kit mutations are more commonly
identified in malignant GISTs than in benign GISTs. Malignant GISTs are also usually CD34 positive.[10][11][12][13]
References:
Marcus SG, Merino MJ, Glatstein E, et al.: Long-term outcome in 87 patients with low-grade soft-tissue sarcoma. Arch Surg 128 (12): 1336-43, 1993.
Soft tissue sarcoma. In: American Joint Committee on Cancer.: AJCC Cancer Staging Manual. 6th ed. New York, NY: Springer, 2002, pp 193-7.
Gaynor JJ, Tan CC, Casper ES, et al.: Refinement of clinicopathologic staging for localized soft tissue sarcoma of the extremity: a study of 423 adults. J Clin Oncol 10 (8): 1317-29, 1992.
Alvegård TA, Berg NO: Histopathology peer review of high-grade soft tissue sarcoma: the Scandinavian Sarcoma Group experience. J Clin Oncol 7 (12): 1845-51, 1989.
van Ruth S, van Coevorden F, Peterse JL, et al.: Alveolar soft part sarcoma. a report of 15 cases. Eur J Cancer 38 (10): 1324-8, 2002.
Fury MG, Antonescu CR, Van Zee KJ, et al.: A 14-year retrospective review of angiosarcoma: clinical characteristics, prognostic factors, and treatment outcomes with surgery and chemotherapy. Cancer J 11 (3): 241-7, 2005 May-Jun.
Abraham JA, Hornicek FJ, Kaufman AM, et al.: Treatment and outcome of 82 patients with angiosarcoma. Ann Surg Oncol 14 (6): 1953-67, 2007.
Fayette J, Martin E, Piperno-Neumann S, et al.: Angiosarcomas, a heterogeneous group of sarcomas with specific behavior depending on primary site: a retrospective study of 161 cases. Ann Oncol 18 (12): 2030-6, 2007.
Mendenhall WM, Zlotecki RA, Scarborough MT: Dermatofibrosarcoma protuberans. Cancer 101 (11): 2503-8, 2004.
Pidhorecky I, Cheney RT, Kraybill WG, et al.: Gastrointestinal stromal tumors: current diagnosis, biologic behavior, and management. Ann Surg Oncol 7 (9): 705-12, 2000.
Wang L, Vargas H, French SW: Cellular origin of gastrointestinal stromal tumors: a study of 27 cases. Arch Pathol Lab Med 124 (10): 1471-5, 2000.
Nishida T, Hirota S: Biological and clinical review of stromal tumors in the gastrointestinal tract. Histol Histopathol 15 (4): 1293-301, 2000.
Miettinen M, Sarlomo-Rikala M, Lasota J: Gastrointestinal stromal tumors: recent advances in understanding of their biology. Hum Pathol 30 (10): 1213-20, 1999.
Top
Stage Information
Staging has an important role in determining the most effective treatment of
soft tissue sarcomas. The stage is determined by the size of the tumor, the
histologic grade, and whether it has spread to lymph nodes or distant sites.
Intracompartmental or extracompartmental extension of extremity sarcomas is
also important for surgical decision making. For complete staging, a thorough
physical examination, x-rays, laboratory studies, and careful review of all
biopsy specimens (including those from the primary tumor, lymph nodes, or other
suspicious lesions) are essential. Computed tomographic scan of the chest is
recommended for sarcomas larger than 5 cm (T2) or with moderate to
poor differentiation (grades 2–4). Nodal involvement is rare, occurring in
less than 3% of patients with sarcoma.[1]
The American Joint Committee on Cancer (AJCC) has designated staging by the
four criteria of tumor size, nodal status, grade, and metastasis (TNGM).[2]
Grade and TNM Definitions
Tumor grade (G)
- GX: Grade cannot be assessed
- G1: Well differentiated
- G2: Moderately differentiated
- G3: Poorly differentiated
- G4: Poorly differentiated or undifferentiated
Primary tumor (T)
- TX: Primary tumor cannot be assessed
- T0: No evidence of primary tumor
- T1: Tumor 5 cm or less in greatest dimension
- T1a: Superficial tumor
- T1b: Deep tumor
- T2: Tumor 5 cm or larger in greatest dimension
- T2a: Superficial tumor
- T2b: Deep tumor
Superficial tumor is located exclusively above the superficial fascia
without invasion of the fascia; deep tumor is located either exclusively
beneath the superficial fascia, or superficial to the fascia with invasion of
or through the fascia, or both superficial yet beneath the fascia. Retroperitoneal,
mediastinal, and pelvic sarcomas are classified as deep tumors.
Regional lymph nodes (N)
- NX: Regional lymph nodes cannot be assessed
- N0: No regional lymph node metastasis
- N1: Regional lymph node metastasis Presence of positive nodes (N1) is considered stage IV.
Distant metastasis (M)
- MX: Distant metastasis cannot be assessed
- M0: No distant metastasis
- M1: Distant metastasis
AJCC Stage Groupings
Stage I
Stage I tumor is defined as low-grade, superficial, and deep.
- G1, T1a, N0, M0
- G1, T1b, N0, M0
- G1, T2a, N0, M0
- G1, T2b, N0, M0
- G2, T1a, N0, M0
- G2, T1b, N0, M0
- G2, T2a, N0, M0
- G2, T2b, N0, M0
Stage II
Stage II tumor is defined as high-grade, superficial, and deep.
- G3, T1a, N0, M0
- G3, T1b, N0, M0
- G3, T2a, N0, M0
- G4, T1a, N0, M0
- G4, T1b, N0, M0
- G4, T2a, N0, M0
Stage III
Stage III tumor is defined as high-grade, large, and deep.
- G3, T2b, N0, M0
- G4, T2b, N0, M0
Stage IV
Stage IV is defined as any metastasis to lymph nodes or distant sites.
- Any G, any T, N1, M0
- Any G, any T, N0, M1
References:
Fong Y, Coit DG, Woodruff JM, et al.: Lymph node metastasis from soft tissue sarcoma in adults. Analysis of data from a prospective database of 1772 sarcoma patients. Ann Surg 217 (1): 72-7, 1993.
Soft tissue sarcoma. In: American Joint Committee on Cancer.: AJCC Cancer Staging Manual. 6th ed. New York, NY: Springer, 2002, pp 193-7.
Top
Stage I Adult Soft Tissue Sarcoma
Low-grade soft tissue sarcomas (grade 1 or 2) have little metastatic potential,
but they may recur locally if they are inadequately treated. Accordingly,
surgical excision with negative tissue margins of 2 cm or larger in all directions is the treatment of choice for patients with these early-stage
sarcomas.[1] 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][3]
Carefully executed high-dose radiation therapy using a shrinking
field technique may be beneficial for unresectable tumors or for resectable
tumors in which a high likelihood of residual disease is thought to be present,
when margins are known to be smaller than 2 cm, and when wider resection
would require either an amputation or the removal of a vital organ.[4] Because
of the low metastatic potential of these tumors, chemotherapy is usually not
given.[5]
Standard treatment options:
- Surgical excision with negative tissue margins of several centimeters in
all directions.
- Conservative surgical excision with preoperative or postoperative radiation
therapy.[6][7][8]
- If the tumor is unresectable, high-dose preoperative radiation therapy may
be used, followed by surgical resection and postoperative radiation
therapy.[4][9]
- For tumors of the retroperitoneum, trunk, and head and neck:
- Surgical resection with the option of postoperative radiation
therapy if negative margins cannot be obtained. Wide margins are unusual in these sites, and radiation therapy is usually
advocated for trunk and head and neck primary sites.[3]
- Preoperative radiation therapy followed by maximal surgical
resection. Radiation therapy is usually used to maximize local
control because of the inability to obtain wide surgical margins.
- Fast neutron therapy.[10]
Current Clinical Trials
Check for U.S. clinical trials from NCI's PDQ Cancer Clinical Trials Registry that are now accepting patients with
stage I adult soft tissue sarcoma. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.
General information about clinical trials is also available from the NCI Web site.
References:
Pearlstone DB, Pisters PW, Bold RJ, et al.: Patterns of recurrence in extremity liposarcoma: implications for staging and follow-up. Cancer 85 (1): 85-92, 1999.
Fish FS: Soft tissue sarcomas in dermatology. Dermatol Surg 22 (3): 268-73, 1996.
Brennan M, Singer S, Maki R, et al.: Sarcomas of the soft tissues and bone. In: DeVita VT Jr, Hellman S, Rosenberg SA, eds.: Cancer: Principles and Practice of Oncology. 7th ed. Philadelphia, Pa: Lippincott Williams & Wilkins, 2005, pp 1581-1631.
Temple WJ, Temple CL, Arthur K, et al.: Prospective cohort study of neoadjuvant treatment in conservative surgery of soft tissue sarcomas. Ann Surg Oncol 4 (7): 586-90, 1997 Oct-Nov.
Geer RJ, Woodruff J, Casper ES, et al.: Management of small soft-tissue sarcoma of the extremity in adults. Arch Surg 127 (11): 1285-9, 1992.
Tepper JE, Suit HD: Radiation therapy of soft tissue sarcomas. Cancer 55 (9 Suppl): 2273-7, 1985.
Yang JC, Chang AE, Baker AR, et al.: Randomized prospective study of the benefit of adjuvant radiation therapy in the treatment of soft tissue sarcomas of the extremity. J Clin Oncol 16 (1): 197-203, 1998.
Pisters PW, Pollock RE, Lewis VO, et al.: Long-term results of prospective trial of surgery alone with selective use of radiation for patients with T1 extremity and trunk soft tissue sarcomas. Ann Surg 246 (4): 675-81; discussion 681-2, 2007.
Schmidt RA, Conrad EU 3rd, Collins C, et al.: Measurement and prediction of the short-term response of soft tissue sarcomas to chemotherapy. Cancer 72 (9): 2593-601, 1993.
Schwartz DL, Einck J, Bellon J, et al.: Fast neutron radiotherapy for soft tissue and cartilaginous sarcomas at high risk for local recurrence. Int J Radiat Oncol Biol Phys 50 (2): 449-56, 2001 Jun 1.
Top
Stage II and III Adult Soft Tissue Sarcoma
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.)
High-grade localized soft tissue sarcomas have an increased potential for
metastatic spread. For sarcomas of the extremities, local control comparable
to that obtained with amputation may be achieved with limb-sparing surgery that
involves wide local excision in combination with preoperative or postoperative
radiation therapy and in some instances, chemotherapy.[1][2][3][4]
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.[5] Interstudy variability was wide
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.[6][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.
Complete surgical resection is often difficult for sarcomas of the
retroperitoneum because of their large size before detection and anatomical
location.[7][8] As opposed to soft tissue sarcomas of the extremities, local
recurrence is the most common cause of death in patients with retroperitoneal
soft tissue sarcomas. Complete surgical resection (i.e., removal of all gross tumor)
is the most important factor in preventing local recurrence and, in many
instances, requires resection of adjacent viscera. The role of adjuvant radiation therapy in the treatment of patients with retroperitoneal sarcoma has not been clearly defined. Prospective randomized
trials have not shown improved survival with preoperative or adjuvant
chemotherapy for this subgroup.[6][9]
Standard treatment options:
- Surgical excision with negative tissue margins of several centimeters in all
directions may be used.
- If the tumor is greater than 5 cm in diameter, surgical excision with negative tissue margins of several centimeters in all
directions followed by radiation therapy may be used.
- If the tumor is unresectable, high-dose radiation therapy may be used, but
poor local control is likely to result.
- In some situations, radiation therapy or chemotherapy
may be used prior to surgery to convert a marginally resectable tumor to one
that can be adequately resected with limb preservation; this treatment may be
followed by postoperative radiation therapy.
Current Clinical Trials
Check for U.S. clinical trials from NCI's PDQ Cancer Clinical Trials Registry that are now accepting patients with
stage II adult soft tissue sarcoma and stage III adult soft tissue sarcoma. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.
General information about clinical trials is also available from the NCI Web site.
References:
Schmidt RA, Conrad EU 3rd, Collins C, et al.: Measurement and prediction of the short-term response of soft tissue sarcomas to chemotherapy. Cancer 72 (9): 2593-601, 1993.
Temple WJ, Temple CL, Arthur K, et al.: Prospective cohort study of neoadjuvant treatment in conservative surgery of soft tissue sarcomas. Ann Surg Oncol 4 (7): 586-90, 1997 Oct-Nov.
Watson DI, Coventry BJ, Langlois SL, et al.: Soft-tissue sarcoma of the extremity. Experience with limb-sparing surgery. Med J Aust 160 (7): 412-6, 1994.
Cormier JN, Huang X, Xing Y, et al.: Cohort analysis of patients with localized, high-risk, extremity soft tissue sarcoma treated at two cancer centers: chemotherapy-associated outcomes. J Clin Oncol 22 (22): 4567-74, 2004.
O'Byrne K, Steward WP: The role of adjuvant chemotherapy in the treatment of adult soft tissue sarcomas. Crit Rev Oncol Hematol 27 (3): 221-7, 1998.
Adjuvant chemotherapy for localised resectable soft-tissue sarcoma of adults: meta-analysis of individual data. Sarcoma Meta-analysis Collaboration. Lancet 350 (9092): 1647-54, 1997.
Heslin MJ, Lewis JJ, Nadler E, et al.: Prognostic factors associated with long-term survival for retroperitoneal sarcoma: implications for management. J Clin Oncol 15 (8): 2832-9, 1997.
Jaques DP, Coit DG, Hajdu SI, et al.: Management of primary and recurrent soft-tissue sarcoma of the retroperitoneum. Ann Surg 212 (1): 51-9, 1990.
Eilber FC, Eilber FR, Eckardt J, et al.: The impact of chemotherapy on the survival of patients with high-grade primary extremity liposarcoma. Ann Surg 240 (4): 686-95; discussion 695-7, 2004.
Top
Stage IV Adult Soft Tissue Sarcoma
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.)
Nodal Disease
Stage IV sarcomas are tumors that have metastatic involvement of regional lymph
nodes or have spread to distant organs. Soft tissue sarcomas that more
commonly spread to lymph nodes include synovial cell sarcomas, epithelioid
sarcomas, and rhabdomyosarcomas. For stage IV sarcomas, local control of the
primary tumor is probably best obtained by resection with negative margins,
lymphadenectomy when appropriate, and postoperative external-beam radiation
therapy.[1] For gastrointestinal stromal tumors (GISTs), preliminary evidence
indicates that imatinib mesylate, a tyrosine kinase inhibitor,
induced sustained tumor response in patients with unresectable or metastatic
tumors.[2][3][4][5][6][Level of evidence: 3iiiDiv]
Standard treatment options:
- Surgical resection and lymphadenectomy for patients with clinically positive
lymph nodes with or without postoperative radiation to the primary site may be used.
- In some centers, radiation therapy may be used prior to and following
surgical extirpation.[7]
- Adjuvant chemotherapy may be considered for patients eligible for clinical
trials.[8][9][10][11]
Visceral Disease
With distant metastases, surgery with curative intent is possible
for patients with limited pulmonary metastases who are also undergoing or have
undergone complete resection of the primary tumor.[12][13][14] The role of adjuvant
therapy for pulmonary nodules is under clinical evaluation in trials such as the EORTC-62933 trial.
The value of
resection of hepatic metastases is unclear. Doxorubicin alone or with
dacarbazine is considered one of the most frequently used chemotherapeutic
regimens for advanced sarcoma.[15][16][17] When used as single agents, only
doxorubicin and ifosfamide show greater than 20% response rates; less active
drugs include dacarbazine, cisplatin, methotrexate, and vinorelbine.[18] 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 months vs. 4
months, P < .02) for doxorubicin, dacarbazine, ifosfamide, and mesna versus
doxorubicin and dacarbazine alone.[19][Level of evidence: 1iiDiii] For older
patients, sequential use of single agents with each recurrence is a better
strategy for palliation. High-dose chemotherapy (with or without
transplantation) has not influenced disease-free survival or overall survival in
published studies so far, but it remains under clinical evaluation for patients
with metastatic disease in first complete remission, after resection of
pulmonary nodules, or for inoperable large primaries.[20][Level of evidence: 3iiiDiv]
For GISTs, preliminary evidence indicates that imatinib mesylate,
a tyrosine kinase inhibitor, induced sustained tumor response
in patients with unresectable or metastatic tumors.[2][3][4][Level of evidence: 3iiiDiv]
Standard treatment options:
- Surgical resection of the primary tumor with radiation therapy. Resection
of pulmonary lesions may be performed following definitive therapy of the
primary tumor.[12][13][14]
- Surgical excision with negative tissue margins may be used.
- If the tumor is resectable but wide margins cannot be obtained,
radiation therapy may be added.
- If the tumor is unresectable, high-dose radiation therapy may be
used, often with chemotherapy.
- For tumors of the retroperitoneum, trunk, and head and neck,
surgical resection with preoperative and/or postoperative radiation
therapy, and sometimes chemotherapy, may be used.
- For palliation of patients with unresectable visceral disease, chemotherapy
with the following agents may be used:
- Doxorubicin.[15]
- Doxorubicin + dacarbazine.[15][16]
- Doxorubicin + ifosfamide.[21]
- Doxorubicin + dacarbazine + ifosfamide + mesna.[19][22]
- High-dose ifosfamide regimens.[23][24][25]
Current Clinical Trials
Check for U.S. clinical trials from NCI's PDQ Cancer Clinical Trials Registry that are now accepting patients with
stage IV adult soft tissue sarcoma. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.
General information about clinical trials is also available from the NCI Web site.
References:
Eilber FR, Eckhardt J, Morton DL: Advances in the treatment of sarcomas of the extremity. Current status of limb salvage. Cancer 54 (11 Suppl): 2695-701, 1984.
Joensuu H, Roberts PJ, Sarlomo-Rikala M, et al.: Effect of the tyrosine kinase inhibitor STI571 in a patient with a metastatic gastrointestinal stromal tumor. N Engl J Med 344 (14): 1052-6, 2001.
Blanke CD, von Mehren M, Joensuu H, et al.: Evaluation of the safety and efficacy of an oral molecularly-targeted therapy, STI157, in patients (pts) with unresectable or metastatic gastrointestinal stromal tumors (GISTs) expressing c-kit (CD117). [Abstract] Proceedings of the American Society of Clinical Oncology 20: A-1, 1a, 2001.
Van Oosterom AT, Judson I, Verweij J, et al.: STI 571, an active drug in metastatic gastro intestinal stromal tumors (GIST), an EORTC phase I study. [Abstract] Proceedings of the American Society of Clinical Oncology 20: A-2, 1a, 2001.
Debiec-Rychter M, Sciot R, Le Cesne A, et al.: KIT mutations and dose selection for imatinib in patients with advanced gastrointestinal stromal tumours. Eur J Cancer 42 (8): 1093-103, 2006.
Blanke CD, Rankin C, Demetri GD, et al.: Phase III randomized, intergroup trial assessing imatinib mesylate at two dose levels in patients with unresectable or metastatic gastrointestinal stromal tumors expressing the kit receptor tyrosine kinase: S0033. J Clin Oncol 26 (4): 626-32, 2008.
Schwartz DL, Einck J, Bellon J, et al.: Fast neutron radiotherapy for soft tissue and cartilaginous sarcomas at high risk for local recurrence. Int J Radiat Oncol Biol Phys 50 (2): 449-56, 2001 Jun 1.
Antman KH: Adjuvant therapy of sarcomas of soft tissue. Semin Oncol 24 (5): 556-60, 1997.
Adjuvant chemotherapy for localised resectable soft-tissue sarcoma of adults: meta-analysis of individual data. Sarcoma Meta-analysis Collaboration. Lancet 350 (9092): 1647-54, 1997.
Buesa JM, López-Pousa A, Martín J, et al.: Phase II trial of first-line high-dose ifosfamide in advanced soft tissue sarcomas of the adult: a study of the Spanish Group for Research on Sarcomas (GEIS) Ann Oncol 9 (8): 871-6, 1998.
Patel SR, Vadhan-Raj S, Burgess MA, et al.: Results of two consecutive trials of dose-intensive chemotherapy with doxorubicin and ifosfamide in patients with sarcomas. Am J Clin Oncol 21 (3): 317-21, 1998.
van Geel AN, Pastorino U, Jauch KW, et al.: Surgical treatment of lung metastases: The European Organization for Research and Treatment of Cancer-Soft Tissue and Bone Sarcoma Group study of 255 patients. Cancer 77 (4): 675-82, 1996.
Casson AG, Putnam JB, Natarajan G, et al.: Five-year survival after pulmonary metastasectomy for adult soft tissue sarcoma. Cancer 69 (3): 662-8, 1992.
Putnam JB Jr, Roth JA: Surgical treatment for pulmonary metastases from sarcoma. Hematol Oncol Clin North Am 9 (4): 869-87, 1995.
Santoro A, Tursz T, Mouridsen H, et al.: Doxorubicin versus CYVADIC versus doxorubicin plus ifosfamide in first-line treatment of advanced soft tissue sarcomas: a randomized study of the European Organization for Research and Treatment of Cancer Soft Tissue and Bone Sarcoma Group. J Clin Oncol 13 (7): 1537-45, 1995.
Zalupski M, Metch B, Balcerzak S, et al.: Phase III comparison of doxorubicin and dacarbazine given by bolus versus infusion in patients with soft-tissue sarcomas: a Southwest Oncology Group study. J Natl Cancer Inst 83 (13): 926-32, 1991.
Borden EC, Amato DA, Rosenbaum C, et al.: Randomized comparison of three adriamycin regimens for metastatic soft tissue sarcomas. J Clin Oncol 5 (6): 840-50, 1987.
Demetri GD, Elias AD: Results of single-agent and combination chemotherapy for advanced soft tissue sarcomas. Implications for decision making in the clinic. Hematol Oncol Clin North Am 9 (4): 765-85, 1995.
Antman K, Crowley J, Balcerzak SP, et al.: An intergroup phase III randomized study of doxorubicin and dacarbazine with or without ifosfamide and mesna in advanced soft tissue and bone sarcomas. J Clin Oncol 11 (7): 1276-85, 1993.
Elias AD: High-dose therapy for adult soft tissue sarcoma: dose response and survival. Semin Oncol 25 (2 Suppl 4): 19-23; discussion 45-8, 1998.
Edmonson JH, Ryan LM, Blum RH, et al.: Randomized comparison of doxorubicin alone versus ifosfamide plus doxorubicin or mitomycin, doxorubicin, and cisplatin against advanced soft tissue sarcomas. J Clin Oncol 11 (7): 1269-75, 1993.
Elias A, Ryan L, Sulkes A, et al.: Response to mesna, doxorubicin, ifosfamide, and dacarbazine in 108 patients with metastatic or unresectable sarcoma and no prior chemotherapy. J Clin Oncol 7 (9): 1208-16, 1989.
Patel SR, Vadhan-Raj S, Papadopolous N, et al.: High-dose ifosfamide in bone and soft tissue sarcomas: results of phase II and pilot studies--dose-response and schedule dependence. J Clin Oncol 15 (6): 2378-84, 1997.
Reichardt P, Tilgner J, Hohenberger P, et al.: Dose-intensive chemotherapy with ifosfamide, epirubicin, and filgrastim for adult patients with metastatic or locally advanced soft tissue sarcoma: a phase II study. J Clin Oncol 16 (4): 1438-43, 1998.
van Oosterom AT, Mouridsen HT, Nielsen OS, et al.: Results of randomised studies of the EORTC Soft Tissue and Bone Sarcoma Group (STBSG) with two different ifosfamide regimens in first- and second-line chemotherapy in advanced soft tissue sarcoma patients. Eur J Cancer 38 (18): 2397-406, 2002.
Top
Recurrent Adult Soft Tissue Sarcoma
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.)
Treatment of recurrent soft tissue sarcomas depends on the type of initial
presentation and treatment. Patients who develop a local recurrence often can
only be salvaged by aggressive local therapy: local excision plus radiation
therapy after previous minimal therapy or amputation after previous aggressive
treatment.[1][2] For selected patients who received radiation therapy,
preoperative radiation therapy and wide local excision may avoid the need for
amputation.[3][4][5] Metastases to the lung as first recurrence usually occur
within 2 to 3 years of initial diagnosis and should be treated as described
under treatment for stage IV disease.[6][7][8] A 30% survival rate at 3 years is
noted if limited pulmonary metastases are resectable.
Doxorubicin alone or with dacarbazine is one of the most frequently used
chemotherapeutic regimens for advanced sarcoma.[9][10][11] When used as single
agents, only doxorubicin and ifosfamide show response rates greater than 20%;
less active drugs include dacarbazine, cisplatin, methotrexate, and
vinorelbine.[12] In a small study, pegylated liposomal doxorubicin has shown similar activity to
doxorubicin, with fewer toxic effects.[13][Level of evidence: 3iiiDiv] 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
versus doxorubicin and dacarbazine alone.[14][Level of evidence: 1iiDiii]
Sequential use of doxorubicin followed by ifosfamide or other drugs with each
subsequent recurrence is frequently preferred. Clinical trials of phase I and
II agents should be considered for subsequent recurrences. High-dose
chemotherapy (with or without transplantation) has not influenced disease-free
survival or overall survival in published studies, but it remains under clinical
evaluation for patients with metastatic disease in first complete remission,
after resection of pulmonary metastases, or for inoperable large
primaries.[15][16][17]
Current Clinical Trials
Check for U.S. clinical trials from NCI's PDQ Cancer Clinical Trials Registry that are now accepting patients with
recurrent adult soft tissue sarcoma. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.
General information about clinical trials is also available from the NCI Web site.
References:
Brennan M, Singer S, Maki R, et al.: Sarcomas of the soft tissues and bone. In: DeVita VT Jr, Hellman S, Rosenberg SA, eds.: Cancer: Principles and Practice of Oncology. 7th ed. Philadelphia, Pa: Lippincott Williams & Wilkins, 2005, pp 1581-1631.
Midis GP, Pollock RE, Chen NP, et al.: Locally recurrent soft tissue sarcoma of the extremities. Surgery 123 (6): 666-71, 1998.
Essner R, Selch M, Eilber FR: Reirradiation for extremity soft tissue sarcomas. Local control and complications. Cancer 67 (11): 2813-7, 1991.
Singer S, Antman K, Corson JM, et al.: Long-term salvageability for patients with locally recurrent soft-tissue sarcomas. Arch Surg 127 (5): 548-53; discussion 553-4, 1992.
Lewis JJ, Leung D, Heslin M, et al.: Association of local recurrence with subsequent survival in extremity soft tissue sarcoma. J Clin Oncol 15 (2): 646-52, 1997.
van Geel AN, Pastorino U, Jauch KW, et al.: Surgical treatment of lung metastases: The European Organization for Research and Treatment of Cancer-Soft Tissue and Bone Sarcoma Group study of 255 patients. Cancer 77 (4): 675-82, 1996.
Casson AG, Putnam JB, Natarajan G, et al.: Five-year survival after pulmonary metastasectomy for adult soft tissue sarcoma. Cancer 69 (3): 662-8, 1992.
Putnam JB Jr, Roth JA: Surgical treatment for pulmonary metastases from sarcoma. Hematol Oncol Clin North Am 9 (4): 869-87, 1995.
Santoro A, Tursz T, Mouridsen H, et al.: Doxorubicin versus CYVADIC versus doxorubicin plus ifosfamide in first-line treatment of advanced soft tissue sarcomas: a randomized study of the European Organization for Research and Treatment of Cancer Soft Tissue and Bone Sarcoma Group. J Clin Oncol 13 (7): 1537-45, 1995.
Zalupski M, Metch B, Balcerzak S, et al.: Phase III comparison of doxorubicin and dacarbazine given by bolus versus infusion in patients with soft-tissue sarcomas: a Southwest Oncology Group study. J Natl Cancer Inst 83 (13): 926-32, 1991.
Borden EC, Amato DA, Rosenbaum C, et al.: Randomized comparison of three adriamycin regimens for metastatic soft tissue sarcomas. J Clin Oncol 5 (6): 840-50, 1987.
Demetri GD, Elias AD: Results of single-agent and combination chemotherapy for advanced soft tissue sarcomas. Implications for decision making in the clinic. Hematol Oncol Clin North Am 9 (4): 765-85, 1995.
Judson I, Radford JA, Harris M, et al.: Randomised phase II trial of pegylated liposomal doxorubicin (DOXIL/CAELYX) versus doxorubicin in the treatment of advanced or metastatic soft tissue sarcoma: a study by the EORTC Soft Tissue and Bone Sarcoma Group. Eur J Cancer 37 (7): 870-7, 2001.
Antman K, Crowley J, Balcerzak SP, et al.: An intergroup phase III randomized study of doxorubicin and dacarbazine with or without ifosfamide and mesna in advanced soft tissue and bone sarcomas. J Clin Oncol 11 (7): 1276-85, 1993.
Buesa JM, López-Pousa A, Martín J, et al.: Phase II trial of first-line high-dose ifosfamide in advanced soft tissue sarcomas of the adult: a study of the Spanish Group for Research on Sarcomas (GEIS) Ann Oncol 9 (8): 871-6, 1998.
Patel SR, Vadhan-Raj S, Burgess MA, et al.: Results of two consecutive trials of dose-intensive chemotherapy with doxorubicin and ifosfamide in patients with sarcomas. Am J Clin Oncol 21 (3): 317-21, 1998.
Elias AD: High-dose therapy for adult soft tissue sarcoma: dose response and survival. Semin Oncol 25 (2 Suppl 4): 19-23; discussion 45-8, 1998.
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This information is intended mainly for use by doctors and other health care professionals. If you have questions about this topic, you can ask your doctor, or call the Cancer Information Service at 1-800-4-CANCER (1-800-422-6237).
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This information is provided by the National Cancer Institute.
This information was last updated on May 15, 2009.