Overview of Soft Tissue Sarcomas

Cancer Connect - Overview of Soft Tissue Sarcomas

Overview of Soft Tissue Sarcomas

Medically reviewed by Dr. C.H. Weaver M.D. Medical Editor 10/2018

Adult soft tissue sarcoma (STS) is a disease in which malignant (cancer) cells form in the soft tissues of the body. Soft tissues include the muscles, tendons, fat, blood and lymph vessels, nerves and tissues that the surround the nerves. Soft tissue sarcomas can form almost anywhere in the body, but are most common in the head, neck, arms, legs, trunk, and abdomen.

Soft tissue sarcomas are relatively uncommon and account for approximately one percent of all cancers. These cancers when detected early are usually treated with surgery and radiation therapy. Historically insensitive to chemotherapy, new precision cancer medicines are being developed that are more effective and can target the cancer directly.[1],[2],[3]

It is important to have accurate pre-treatment evaluation to determine the exact extent of tumor spread. Fully functional limb preservation without amputation is the main goal of treatment for STS involving the arms or legs.

Since soft tissue sarcomas are rare it is important that patients receive treatment in specialized centers with experience and treatment protocols. Treatment requires a multidisciplinary team approach with involvement of surgeons, radiation oncologists, medical oncologists, nurse specialists and rehabilitation experts.

Sarcoma Focused Treatment Centers

The cells of each type of STS look different under a microscope and each STS is named according to the tissue in which the cancer originated.

Types of Soft Tissue Sarcoma (Adult and Childhood)

  • Alveolar Soft-part Sarcoma
  • Angiosarcoma
  • Chondrosarcoma
  • Dermatofibrosarcoma Protuberans
  • Epithelioid Sarcoma
  • Fibrosarcoma
  • Leiomyosarcoma
  • Liposarcoma
  • Malignant Fibrous Histiocytoma
  • Malignant Hemangiopericytoma
  • Malignant Mesenchymoma, Malignant Schwannoma (Malignant Peripheral Nerve Sheath Tumor)
  • Non-Bone Osteosarcoma
  • Peripheral Neuroectodermal Tumors
  • Synovial Sarcoma
  • Unidentifiable Sarcoma

Diagnosis & Tests for Sarcomas

Doctors use many tests to find, or diagnose, cancer. The suspicion of a STS often first arises when a lump or swelling in soft tissue of the body is detected. In order to diagnose the cause of the lump a physician will perform a biopsy. A biopsy can be performed on an outpatient basis. During a biopsy, a physician removes the lump or some cells adjacent lymph nodes and other suspicious areas for examination by a laboratory pathologist to determine the presence and aggressiveness of cancer if it is present. Because STS can be hard to diagnose patients should ask to have tissue samples checked by a pathologist who has experience in diagnosing STS.

When cancer is identified in the biopsy specimen, several other tests may be performed on the specimen in order to further classify the cancer and determine the optimal treatment strategy. Based on the stage of the cancer and the results of these tests, treatment of STS is personalized for each individual. Treatment may involve surgery, radiation therapy, chemotherapy, or targeted therapy.

Genomic or Biomarker Testing-Precision Cancer Medicine: The purpose of precision cancer medicine is to define the genomic alterations in the cancers DNA that are driving that specific cancer. Precision cancer medicine utilizes molecular diagnostic & genomic testing, including DNA sequencing, to identify cancer-driving abnormalities in a cancer’s genome. Once a genetic abnormality is identified, a specific targeted therapy can be designed to attack a specific mutation or other cancer-related change in the DNA programming of the cancer cells. Precision cancer medicine uses targeted drugs and immunotherapies engineered to directly attack the cancer cells with specific abnormalities, leaving normal cells largely unharmed.

By testing a sarcoma for specific unique biomarkers doctors can offer the most personalized treatment approach utilizing precision medicines.

Staging the Sarcoma

When diagnosed with a sarcoma further tests are necessary to determine the extent of spread (stage) of the cancer. Cancer’s stage is a key factor in determining the best treatment. Of particular concern is the presence of cancer in lymph nodes, spread of cancer to distant sites or local extension of cancer into surrounding structures, which might make attempts to remove all cancer with surgical resection impossible. Unfortunately, in many cases the true extent of spread of cancer can only be determined by surgical resection. Frequently, more advanced cancer is found at surgery than was detected by clinical tests. In addition to a physical examination, the following tests are used to evaluate a sarcoma.

  • Computed Tomography (CT) Scan: A CT scan is a technique for imaging body tissues and organs, during which X-ray transmissions are converted to detailed images, using a computer to synthesize X-ray data. A CT scan is conducted with a large machine positioned outside the body that can rotate to capture detailed images of the organs and tissues inside the body.
  • Magnetic Resonance Imaging (MRI): MRI uses a magnetic field rather than X-rays, and can often distinguish more accurately between healthy and diseased tissue than a CT. An MRI gives a better picture of cancer located near bone than does CT, does not use radiation, and provides pictures from various angles that enable doctors to construct a three-dimensional image of the cancer.
  • Positron emission tomography (PET): Positron emission tomography scanning is an advanced technique for imaging body tissues and organs. One characteristic of living tissue is the metabolism of sugar. Prior to a PET scan, a substance containing a type of sugar attached to a radioactive isotope (a molecule that emits radiation) is injected into the patient’s vein. The cancer cells “take up” the sugar and attached isotope, which emits positively charged, low energy radiation (positrons) that create the production of gamma rays that can be detected by the PET machine to produce a picture. If no gamma rays are detected in the scanned area, it is unlikely that the mass in question contains living cancer cells.

Sarcoma Stages:

Stage I is divided into stages IA and IB:

  • Stage IA cancers are low grade, less than 5 centimeters in size and have not spread to adjacent lymph nodes.
  • Stage IB: Stage IA cancers are low grade, greater than 5 centimeters in size and have not spread to adjacent lymph nodes.

Stage II is divided into stages IIA and IIB:

  • Stage IIA cancers are mod or high grade, less than 5 centimeters in size and have not spread to adjacent lymph nodes.
  • Stage IIB: Stage IIB cancers are mid or high grade, greater than 5 centimeters in size and have not spread to adjacent lymph nodes.

Stage III soft tissue sarcomas are either high grade, larger than 5 or have spread to nearby lymph nodes. Stage III STS that have spread to lymph nodes are often called “advanced STS”

Stage IV The sarcoma has spread to distant locations in the body, which may include the liver, lungs, bones or other sites.

Recurrent/Relapsed: The cancer has progressed or returned (recurred/relapsed) following an initial treatment.

Stage I Soft Tissue Sarcoma

Limbs, Outer Trunk, Head or Neck

Patients diagnosed with stage I soft tissue sarcoma (STS) have a low grade or unknown grade cancer that can be superficial or deep and does not involve any lymph nodes. Stage I STS is further distinguished by the size of the tumor:

  • Stage IA primary tumor is 5cm or smaller
  • Stage IB primary tumor is larger than 5cm.

The majority of stage I STSs are curable with surgical removal of the sarcoma. Some patients with stage IA and many patients with stage IB should consider the risks and benefits of radiation following surgery to avoid a recurrence.

Surgery is the mainstay of treatment for stage I STS and the following surgical techniques may be utilized:

  • Wide Local Excision (WLE): WLE involves removal of the sarcoma with some surrounding normal tissue to ensure complete excision can be used to treat sarcomas of the trunk, abdomen, head, and neck.
  • Mohs microsurgery: This type of surgery is designed to remove as little normal tissue as possible and is typically used where a good cosmetic result is desired, such as the face or skin. The sarcoma is cut from the skin in thin layers, examining each layer under a microscope during the surgery until no more cancer cells are present.
  • Limb-sparing surgery: Arms and legs are common sites for STS and surgical procedures that avoid amputation are important. Radiation is often given prior to wide excision to avoid amputation.
  • Lymphadenectomy: Lymph nodes are often sampled or removed during surgery to ensure the sarcoma has not spread.

In appropriate individuals, radiation therapy may be given before surgery to shrink the cancer or after surgery to reduce the risk of cancer recurrence. Treatment given prior to surgery is called neoadjuvant therapy and after surgery is referred to as adjuvant therapy.Radiation therapy uses high-energy x-rays to kill cancer cells and is considered a local therapy. It can only kill cancer cells within the exact area it is delivered.

Stage II and III Soft Tissue Sarcoma

Limbs, Outer Trunk, Head or Neck

Patients diagnosed with stage II or III soft tissue sarcoma (STS) are treated differently depending on the size of the primary tumor, the tumor grade, and whether or not the sarcoma has spread to the local lymph nodes.

  • Stage IIA tumor are 5cm or smaller, have not spread to lymph nodes or more distant sites, and are either intermediate or high grade
  • Stage IIB tumors are larger than 5cm, have not spread to lymph nodes and are intermediate grade
  • Stage III tumors are larger than 5cm, have not spread to lymph nodes and are high grade or any size or grade and spread to lymph nodes.

Sarcomas are relatively uncommon cancers and individuals diagnosed with a STS should consider being evaluated by a doctor that specializes in the management of STS.

For individuals whose cancer has not spread to lymph nodes, surgery remains the cornerstone of treatment. For some individuals with limited stage IIA STS, surgery may be the only treatment required. For patients with stage II/III STS, radiation therapy may be used before surgery to shrink the cancer and/or after surgery to reduce the risk of recurrence. Surgical techniques used in STS may include the following:

  • Wide Local Excision (WLE): WLE involves removal of the sarcoma with some surrounding normal tissue to ensure complete excision can be used to treat sarcomas of the trunk, abdomen, head, and neck.
  • Mohs microsurgery: This type of surgery is designed to remove as little normal tissue as possible and is typically used where a good cosmetic result is desired such as the face or skin. The sarcoma is cut from the skin in thin layers, examining each layer under a microscope during the surgery until no more cancer cells are present.
  • Limb-sparing surgery: Arms and legs are common sites for STS and surgical procedures that avoid amputation are important. Radiation or chemotherapy is often given prior to wide excision to avoid amputation.
  • Lymphadenectomy: Lymph nodes are often sampled or removed during surgery to ensure the sarcoma has not spread.

Radiation therapy given prior to surgery is called neoadjuvant therapy and after surgery is referred to as adjuvant therapy. Radiation therapy uses high-energy x-rays to kill cancer cells and is considered a local therapy. It can only kill cancer cells within the exact area it is delivered.

Stage IIB or III STS patients may have adjuvant therapy with a combination of radiation therapy and/or chemotherapy, and in some cases for patients who have had neoadjuvant radiation therapy, adjuvant therapy in the form of a radiation therapy boost might also be a treatment option. Although some patients with stage IIB or III STS may receive chemotherapy, there is limited evidence at this time regarding the benefits of chemotherapy in this setting. Patients should also consider participation in a clinical trial evaluating new treatments as they become available.

For stage II/III STS patients who are not initially eligible for surgery, treatment options may include radiation therapy, chemoradiation, chemotherapy, or isolated limb chemotherapy with the hope of debulking their cancer, making surgery an option.

Stage IV and Recurrent Soft Tissue Sarcoma

Limbs, Outer Trunk, Head or Neck

Patients diagnosed with stage IV soft tissue sarcoma (STS) have a cancer of any size or grade that has spread to distant parts of the body such as the lungs. The primary treatment is systemic therapy with chemotherapy, precision cancer medicines or participation in a clinical trial.

Depending on the size of the cancer and whether the cancer is confined to one organ, local treatment might be an option. Local treatment could include a combination of surgery, radiation therapy, ablation, and/or embolization with or without chemotherapy. For patients with stage IV sarcoma whose cancer has spread to more than one organ, local or systemic therapy may be used to help control symptoms and improve quality of life.

Importance of Clinical Trials

Because research has not definitively demonstrated the best treatment for stage IV sarcomas, clinical trials are often considered a preferred strategy. It is important for patients to undergo genomic and biomarker testing to determine if they are eligible for treatment with precision cancer medicines. All patients should discuss the risks and benefits of participating in a clinical trial with their healthcare team.

Systemic Treatment

Chemotherapy: Chemotherapy is a systemic treatment, meaning it can treat cancer cells anywhere in the body. In 2015 the US Food and Drug Administration (FDA) approved two new chemotherapy drugs, Halaven® (eribulin mesylate) and Yondelis® (trabectedin), for the treatment of advanced STS. Votrient® (pazopanib) was approved by the FDA for the treatment of advanced STS in 2012. Clinical trials are ongoing in order to determine how best to use these drugs as well as evaluating new drugs.

Yondelis is a chemotherapy agent that works by blocking certain types of proteins (transcription factors) that are involved in the copying and sending of tumor cell DNA. Clinical trial results have demonstrated that Yondelis improves outcomes compared to the standard agent, dacarbazine, in patients with advanced liposarcoma or leiomyosarcoma that has recurred or progressed following prior therapies.[1]

Halaven is a chemotherapy agent that works by causing abnormalities in microtubule formation in cells in order to prevent cell replication. Halaven was approved by the FDA based on clinical trial results directly comparing it to dacarbazine in STS patients with advanced liposarcoma. Overall survival almost doubled to 15.6 months for patients treated with Halaven, compared to only 8.4 months for patients treated with dacarbazine.[2]

Votrient is an oral medication known as a multi-targeted tyrosine kinase inhibitor. The drug works by interfering with the growth of new blood vessels that sarcomas need to survive. Clinical trial results have demonstrated that Votrient delays the time to cancer progression and increases overall survival in patients with advanced STS.[3]

Strategies to Improve Soft Tissue Sarcoma Treatment

The development of more effective treatment for STS requires that new and innovative therapies be evaluated with cancer patients in clinical trials. Patients who are interested in participating in a clinical trial should discuss the risks and benefits of clinical trials with their physician.

Genetic Assessment. Li-Fraumeni syndrome is a hereditary cancer predisposition syndrome associated with soft tissue sarcoma. Genetic assessment may be suggested for some patients with STS.

Adjuvant or Neoadjuvant Therapy: In 2015 the US Food and Drug Administration (FDA) approved two new drugs, Halaven® (eribulin mesylate) and Yondelis® (trabectedin), for the treatment of advanced STS. Votrient® (pazopanib) was approved by the FDA for the treatment of advanced STS in 2012. Clinical trials are ongoing in order to determine how best to use these drugs, whether they can improve outcomes in the adjuvant/neoadjuvant setting, and whether combining them with other drugs can further improve patient outcomes.

Hyperthermia: Applying heat to the blood supply of an extremity affected by sarcoma has been utilized to increase the effectiveness of chemotherapy or radiation therapy. In this procedure, the blood supply to the affected limb is isolated and heated before returning it to the body. This treatment is usually accompanied by intra-arterial infusion of chemotherapy. The theory underlying this treatment is sound, and encouraging results have been reported. However, the technique is difficult to perform and there have been no randomized trials comparing the effectiveness of hyperthermia and chemotherapy to conventional chemotherapy treatment. Heat can also be applied directly to cancer with the use of microwaves, but the advantages of this approach are not clear.

Isolated Limb Perfusion: Isolated limb perfusion is a procedure that sends chemotherapy directly to an arm or leg in which the cancer has formed. The flow of blood to and from the limb is temporarily stopped with a tourniquet and chemotherapy drugs are put directly into the blood of the limb sending a high dose of the drug directly to the sarcoma.

References:

[1] Demetri G, von Mehren M, Jones R, et al. Efficacy and Safety of Trabectedin or Dacarbazine for Metastatic Liposarcoma or Leiomyosarcoma After Failure of Conventional Chemotherapy: Results of a Phase III Randomized Multicenter Clinical Trial. Journal of Clinical Oncology. 2015.62.4734.

[2] FDA approves Votrient for advanced soft tissue sarcoma [FDA News Release]. U.S. Food and Drug Administration website. Available at:

[3] United States Food and Drug Administration. FDA approves first drug to show survival benefit in liposarcoma. Available at: .

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