Rhabdomyosarcoma

October 21, 2013

Disclaimer

The information provided in this review is intended for general informational purposes only. It is not intended to be a substitute for professional medical advice, diagnosis, or treatment.

Always seek the advice of your physician or other qualified healthcare provider with any questions you may have regarding a medical condition. Feel free to share this information page with them.

Childhood Cancer Name:

Rhabdomyosarcoma.

Cancer Localization:

Common sites of RMS include:

Soft tissue
The head and neck (such as near the eye, inside the nasal sinuses or throat, or near the spine in the neck)
Urinary and reproductive organs (bladder, prostate gland, or any of the female organs)
Arms and legs
Trunk (chest and abdomen)

Biology:

Sarcomas are cancers that develop from connective tissues in the body, which include muscles, fat, bones, the linings of joints, and blood vessels. Many different types of sarcomas exist.

Rhabdomyosarcoma (RMS) is a type of sarcoma made up of cells that normally develop into skeletal muscles, which are the muscles that we can control to voluntarily move parts of our body. RMS is classified by type according to the histology of the cells, which is how the cells appear under a microscope.

Before birth, cells called rhabdomyoblasts, which will eventually develop into skeletal muscle, begin to form. These cells have the potential to develop into RMS. Because RMS is a cancer that originates in early forms of muscle cells, it is much more common in children than adults. However, RMS can occur in adults.

Note: We might think of skeletal muscle as the muscles in our arms and legs, but RMS can start nearly anywhere in the body, even in some parts of the body that do not normally have skeletal muscle.

Characteristics:

RMS is a relatively rare tumor, making up about 3% of all childhood cancers. Most RMS cases are diagnosed in children and teens, with more than half in children 10 years or younger. Children aged 1 to 9 are believed to have a better rate of survival compared to older children or adults with RMS. The cause is unknown.

Main Types of RMS:

There are four main types of RMS:

Embryonal – The most common type, usually diagnosed in children younger than 15 years old and found in the head and neck region, and the genitourinary tract.
Botryoid – A subset of embryonal RMS that is rare, aggressive, and primarily targets the female genitourinary tract, including the vagina and urinary bladder.
Alveolar – A more aggressive tumor that usually involves the muscles of the extremities or trunk and is more common in adolescents.

Parent Tip: Alveolar RMS (ARMS) is a very aggressive and very violent type of cancer with the tendency to relapse. That’s why is crucial to defeating cancer on the first try. Do the best you can and be proactive early!

Pleomorphic – Rarely seen in children, these tumors arise in muscles of the extremities.

Common Mutations in RMS:

Several genetic mutations and molecular alterations are associated with ependymomas. Some of the common mutations include:

PAX-FOXO1 Fusion Genes – These fusion genes result from the pieces of two genes, PAX3 or PAX7 and FOXO1, breaking off and swapping places in a “translocation” event. This results in a new gene that creates a protein which helps the tumor grow. The PAX-FOXO1 fusion gene is characteristic of alveolar RMS and plays a role in its progression.
KRAS Mutations – KRAS is a gene involved in regulating cell growth. Mutations in the KRAS gene can lead to tumor growth and are most seen in embryonal RMS. RMS with mutations in the KRAS gene are typically associated with a poor prognosis.
IGF2 Mutations – IGF2 is a gene involved in growth and development. Overexpression of IGF2 in some RMS cases may contribute to tumor growth.

Pediatric RMS Noticeable Symptoms:

Note: Symptoms of RMS in children can vary depending on the tumor’s location, size, and type. The unique biology of the tumor can also influence the symptoms.

Common signs of RMS in children include:

A visible lump under the skin, can often be painless
Pain or swelling around the tumor, especially when near muscles or joints
Abdominal pain and/or bloating, urinary problems if the tumor is in the pelvic region
Headaches, bulging or drooping of the eye if the tumor is in the head or neck area

Childhood Cancer Diagnostic Methods:

CT (computed topography) scans, MRI (magnetic resonance imaging), biopsy analysis.

The diagnostic process often begins with a physical examination to look for any signs of RMS, namely lumps.
Imaging tests (MRIs, CT scans) are usually ordered to help determine how large the tumor is and if it has grown into nearby body areas, such as the lymph nodes.
If imaging reveals a tumor, a biopsy (removing a small amount of the tumor to be examined under a microscope) can be taken from the child to help determine whether a tumor is benign or malignant, and to inform what kind of treatment is needed

Note: ALWAYS get a second opinion on the biopsy and suggested treatment. Sarcomas can be hard to diagnose. Remember: Any good Oncologist would welcome second and third opinions.

Childhood Cancer Treatment:

Surgery, radiation therapy, and chemotherapy.

Surgery

Surgery is a critical component of pediatric RMS treatment. The main goal of surgery is to remove as much of the tumor as possible while preserving the surrounding healthy tissue, with complete tumor removal/resection being the best option.

Note: In most children with RMS, complete tumor removal is unlikely. RMS can form in different places and the surgery will be different depending on the tumor’s location.

If feasible, a wide local excision may be performed to completely remove the tumor as well as some of the surrounding tissue, including the lymph nodes.
More than one surgery may be necessary to complete remove the cancerous tissue.
Chemotherapy and/or radiation therapy may be given pre-surgery to shrink the tumor, or post-surgery to reduce the risk of the cancer returning, which is called adjuvant therapy.
Pediatric RMS patients who can successfully undergo complete tumor removal have a 5-year survival rate greater than 80% when combined with adjuvant therapy.

Radiation Therapy (RT)

RT is also critical in pediatric RMS treatment, especially when complete tumor resection is not possible. In these cases, it has been shown that incorporating radiation into the treatment plan significantly improves survival outcomes. A study of 56 pediatric head and neck RMS cases between 2013-2019 showed that children with radiation therapy as part of their initial treatment plan had a 5-year overall survival rate of 3% compared to 49.7% in those who did not initially receive radiation therapy.
External beam radiation targets RMS while minimizing radiation exposure to healthy tissue.
When radiation is omitted, there is a high risk of cancer recurrence, especially local recurrence.

Note: Proton therapy is particularly beneficial in pediatric RMS cases and is considered an excellent treatment option for younger children and for children with RMS located in the head and neck, genito-urinary (near the genital and urinary organs), pelvic, and paravertebral (along the spinal cord) areas.

Parent Tip: The radiation treatment is super important as the RMS reacts well to radiation. Therefore, make sure this part of the treatment is being done in the most professional way; You may want to consider traveling to a facility which specializes in RT in children.

Chemotherapy

Chemotherapy is an important tool in pediatric RMS treatment, and is often used in combination with surgery and RT.
For embryonal RMS, the VAC (vincristine, actinomycin D, and cyclophosphamide) chemotherapy regimen is highly effective, with survival rates of 70-80% in low-risk cases.
With alveolar RMS, more intense chemotherapy regimens are often needed due to the cancer’s tendency to spread. A recent study suggested that the chemotherapeutic drug vinorelbine is effective in high-risk and metastatic RMS, which is common with alveolar RMS.

Parent Tip: At Memorial Sloan-Kettering Cancer Center in NY, Dr. Leonard Wexler is conducting a relatively successful clinical trial with high-dose chemotherapy. If your child has RMS, we believe this is the best place to be.

Late Effects of the Treatment:

While treatments for pediatric RMS have significantly improved survival rates, they have the potential to cause lasting side effects. Long-term unwanted effects can vary based on the treatment used, the child’s age, and the tumor’s location. Make sure you discuss possible unwanted late effects of treatment which your child’s doctors.

Follow-up, Late Effects:

Follow-up visits are generally scheduled every 3 months during the first-year post-treatment. Further visits may occur every 4-6 months during the second and third years, every 6 months in the fourth and fifth years, and annually afterwards.Tests are often part of follow-up visits. Your child may have:
- blood tests to see how well the organs are working
- tests to measure growth
- CT scan or MRI of the area where the tumour started
- chest x-ray or CT scan of the chest to see if cancer has spread there
- echocardiogram (an ultrasound that checks to see how well the heart is working)
If the cancer has come back, you and the healthcare team will discuss a plan for your child’s treatment and care.

The Main Goals Include:

Preserve the patient’s life. Monitor for recurrence and manage any late effects of treatment.

Current Options for Clinical Trials:

UCSF Phase III trial for very low-risk RMS: Involves treatment with 24 weeks of vincristine and dactinomycin to maintain excellent outcomes in patients with very low-risk RMS while decreasing the burden of therapy.
Jude Children’s Research Hospital – RMS2021 Protocol https://www.stjude.org/care-treatment/clinical-trials/rms2021-rhabdomyosarcoma.html
Children’s Oncology Group – FaR-RMS Study: A multicenter clinical trial for children and adults with newly diagnosed and relapsed RMS. This trial evaluates multiple treatment strategies. More details can be found here: https://www.cancerresearchuk.org/about-cancer/find-a-clinical-trial/a-trial-of-treatment-for-children-and-adults-with-rhabdomyosarcoma-far-rms#undefined