Soft Tissue Sarcoma

What is Rhabdomyosarcoma?

Risk Factors and Causes of Rhabdomyosarcoma

Certain factors may increase risk for rhabdomyosarcoma including age, gender, and ethnicity. 

• About 2/3 of rhabdomyosarcoma tumors are diagnosed in children under 10 years old. 
• Rhabdomyosarcoma occurs slightly more often in males than females.
• Caucasian children have a higher risk of rhabdomyosarcoma compared to African-American children.
• Certain inherited conditions can increase risk for rhabdomyosarcoma including Li Fraumeni syndrome (P53 mutations), DICER1 mutations, Neurofibromatosis type 1 (NF1), Costello syndrome, Beckwith Weidemann syndrome, and Noonan syndrome.

Signs and Symptoms of Rhabdomyosarcoma

Symptoms of rhabdomyosarcoma depend on where the tumor is located. Signs and symptoms of rhabdomyosarcoma include: 

• Swelling or a lump that does not go away, sometimes painful
• Headaches
• Bulging of the eye
• Bleeding in the nose, vagina, or rectum
• Constipation or difficulty urinating

Diagnosis of Rhabdomyosarcoma

Several types of procedures and tests are used to diagnose rhabdomyosarcoma. These include: 

• A health history, physical exam, and blood test to learn about symptoms, general health, past illnesses, and risk factors.
• Imaging tests including MRI, CT scan, and/or ultrasound to evaluate the primary tumor determine other tests that are needed. 
  • An MRI is used to evaluate the primary tumor.
  • A CT scan of the chest is used to see if rhabdomyosarcoma has spread to the lungs. If the tumor is in the lower part of the body, a CT scan of the abdomen and pelvis may be needed.
  • Full body imaging using bone scans or PET scans is used to look for cancer in bone and other areas of the body.
• Bone marrow aspiration and biopsy to see if cancer has spread. Doctors will obtain bone marrow sample by inserting a thin, hollow needle into the hipbone. A pathologist will view the bone marrow under a microscope to look for signs of cancer.
• A biopsy of the tumor to make a diagnosis. In a biopsy, the doctor removes a small amount of tissue from the tumor. The cells are then examined with a microscope to look for signs of cancer. An incisional biopsy or core needle biopsy may be used depending on tumor location.

Depending on the location of the tumor, additional tests may be needed including:

• Sentinel lymph node biopsy to examine spread of rhabdomyosarcoma to nearby lymph nodes. In this procedure, a special dye or radioactive substance is injected near the tumor. The dye travels through the lymph system to the first lymph nodes near the primary tumor. Those lymph nodes can be removed and evaluated for signs of cancer. This is important to determine stage of rhabdomyosarcoma and help in planning treatments.
• A lumbar puncture to look for cancer cells in the cerebrospinal fluid in the case of tumors that occur near the membranes of the brain and spinal cord (parameningeal).

Site-specific evaluations may be needed depending on tumor location. A multidisciplinary medical team is important to provide optimal care throughout treatment.

Staging of Rhabdomyosarcoma

In rhabdomyosarcoma, there are different ways the disease can be classified. This can help doctors better understand the disease and plan appropriate treatments.

Rhabdomyosarcoma is grouped based on tumor location, spread of disease, and result of surgery.

Rhabdomyosarcoma can also be staged using the TNM system. This system considers 3 factors:

1. Tumor (T) – Size and location of the primary tumor
2. Node (N) – Spread of disease to lymph nodes
3. Metastasis (M) – Spread of disease to other parts of the body

Using the TNM System, rhabdomyosarcoma can be divided into 4 stages.

If rhabdomyosarcoma has recurred, prognosis may be influenced by where in the body the cancer came back, how much time passed between the original cancer and recurrence, and what therapies were originally used to treat the cancer.

Children with localized rhabdomyosarcoma have greater than 70% chance of long term cure. About 20% of patients have metastatic disease at diagnosis. If the cancer has already spread at diagnosis (metastatic rhabdomyosarcoma), the chance of survival is less than 30%.

Approximately 30% of patients with rhabdomyosarcoma will have recurrence of cancer. Rhabdomyosarcoma may recur at the location of the initial tumor or in other sites. Recurrent rhabdomyosarcoma is difficult to treat, and the chance of cure is low.

Treatment of Rhabdomyosarcoma

Rhabdomyosarcoma requires a combination of treatments including chemotherapy, surgery, and/or radiation therapy. All children receive systemic chemotherapy as part of treatment for rhabdomyosarcoma. This is important to treat microscopic spread of disease that may not be detected. Tumors visible on imaging are also treated with surgery and/or radiation therapy. 

• Surgery is used to remove the cancer when possible. A small amount of tissue around the tumor and nearby lymph nodes are also removed. Because rhabdomyosarcoma can occur anywhere in the body, each surgery is different. Patients are treated with chemotherapy after surgery to kill any remaining cancer. 
• Chemotherapy (“chemo”) is uses powerful medicines to kill cancer cells or stop them from growing and making new cancer cells. Often, more than one type of medicine will be used to treat the cancer. Most chemotherapy is given through injections but some chemo may be given by mouth. Chemotherapy may be given before surgery to make the tumor smaller. Chemotherapy is given after surgery to kill any remaining cancer cells and to help keep the tumor from coming back.

The chemotherapy regimen for rhabdomyosarcoma includes vincristine, actinomycin D, and cyclophosphamide and irinotecan. A standard course of treatment is 14-16 cycles (period of treatment followed by period of rest).

• Radiation therapy may be used to treat rhabdomyosarcoma in combination with chemotherapy and/or surgery. Radiation uses high energy particles to kill or stop the growth of cancer cells. Radiation therapy is the main treatment for metastatic disease in rhabdomyosarcoma.

Other treatments include other chemotherapy drugs like doxorubicin and experimental agents such as targeted therapies, drugs that inhibit the cell cycle, and immunotherapy.

Many children are offered treatment for rhabdomyosarcoma as part of a clinical trial.

Risk Factors and Causes of NRSTS

NRSTS in children are most often seen in two age groups: infants and adolescents. They occur slightly more often in males. Previous treatment with radiation therapy can also increase risk for NRSTS. 

Certain inherited conditions can increase risk for rhabdomyosarcoma. These include Li-Fraumeni syndrome (P53 mutations), Neurofibromatosis type 1 (NF1), familial adenomatous polyposis (FAP), Werner syndrome, Retinoblastoma 1 (RB1) gene changes, and SMARCB1 (INI1) gene changes.

Signs and Symptoms of NRSTS

Symptoms of NRSTS depend on where the tumor is located. Often there are no symptoms in the early stages other than a painless lump. Problems such as pain or weakness may develop as the tumor grows and presses on other structures. More advanced disease can sometimes produce symptoms such as fever, sweating, or weight loss.

Diagnosis of NRSTS

Several types of procedures and tests are used to diagnose rhabdomyosarcoma. These include:

• A health history, physical exam, and blood tests to learn about symptoms, general health, past illnesses, and risk factors.
• Imaging tests including MRI or CT scan to evaluate the primary tumor.
• A biopsy of the tumor to make a diagnosis. In a biopsy, the doctor removes a small amount of tissue from the tumor. The cells are then examined with a microscope to look for signs of cancer. An incisional biopsy or core needle biopsy may be used depending on tumor location.
• If there are concerns about metastatic disease, a CT scan of the chest is used to see if sarcoma has spread to the lungs. Full body imaging using bone scans or PET scans is used to look for metastatic cancer in bone and other areas of the body. Imaging and biopsy of lymph nodes may also be performed.

Staging of NRSTS

Soft tissue sarcomas are classified by stage. Staging is based on features of the tumor such as size, whether it has spread, and grade of the tumor.

Soft tissue sarcomas can be grouped into four stages. The American Joint Committee on Cancer (AJCC) uses the following criteria:

Prognosis for NRSTS

The prognosis, or chance of recovery, from NRSTS depends on several factors:

• Type of tumor
• Where the tumor formed in the body
• Tumor grade and how the cells look under a microscope (histology); low grade tumors have a better prognosis
• Size of the tumor - larger tumors (greater than 5 centimeters) are harder to treat
• How deep the tumor is located below the skin
• Whether the cancer has spread to lymph nodes or other parts of the body (metastatic disease) 
• Whether surgery can completely remove the tumor
• Whether the tumor is new or has come back (recurrent) 
• Whether radiation has been used to treat the cancer

Patients with a favorable tumor that meets certain conditions have a better prognosis:

About 15% of patients have metastatic disease at diagnosis. The lung is the most common site for metastasis of NRSTS. Rarely, NRSTS may spread to bone or lymph nodes.

If the cancer has already spread at diagnosis (metastatic disease), the chance of long-term survival is less than 20%.

Recurrent NRSTS is difficult to treat, and the chance of cure is low.

Treatment of NRSTS

Surgery is used to remove as much of the cancer as possible. A small amount of tissue around the tumor and nearby lymph nodes are also removed to make sure that no cancer is left behind. Low risk patients may be treated with surgery alone if the tumor can be fully removed with no remaining cancer cells. 

Radiation therapy may be used to treat NRSTS that cannot be removed completely with surgery. In some cases, radiation may be used before surgery to make the tumor easier to remove. 

Chemotherapy (“chemo”) uses powerful medicines to kill cancer cells or stop them from growing and making new cancer cells. Chemotherapy is not as effective for NRSTS. It is most often used to treat high risk patients including those with metastatic disease or patients who cannot be treated with surgery.

Targeted therapies

Targeted therapies are being studied in the treatment of NRSTS. These drugs act on specific targets of cancer cells to stop them from growing. Certain therapies are specific for subtypes of NRSTS. Many of these treatments are being studied in clinical trials.