Rhabdomyosarcoma

What is Rhabdomyosarcoma?

Rhabdomyosarcoma (RMS) is a form of cancer that starts in the soft tissues of the body. It’s believed to begin in early forms of cells that usually turn into skeletal tissues like your muscles. However, these tumors can also grow in other tissues and anywhere in the body. RMS is the most common type of soft tissue cancer found in children; it is very rare in adults. The causes and risk factors of RMS are largely unknown. Most of the time, RMS occurs randomly; but in some cases, it can be linked to certain inherited syndromes.

RMS comes in different types: embryonal, alveolar, pleomorphic, spindle, and mixed-type. The embryonal type is the most common and usually has the best chance of recovery. When it comes to treating RMS, the plan is personalized according to a patient’s level of risk. There are two systems doctors use to decide the risk level: one is the Clinical Group and the other is the Stage. Each system uses different considerations to classify patients according to risk. In general, doctors use both systems to decide the best treatment plan. Nowadays, treatment usually involves a combination of surgery (if possible) to remove the main tumor, and chemotherapy (medication treatment) to control the spread of the disease. This is the case even if there are no signs of the disease spreading elsewhere on the images taken by the doctors, because studies have found that most patients often have small, undetected spread of the disease. Radiotherapy (treatment using radiation) is used for most patients who are at high and intermediate risk too.

Thanks to teamwork in healthcare, survival rates for RMS patients have increased with improved ways of diagnosing and treating the disease. Healthcare professionals should continuously improve their knowledge, skills, and strategies in diagnosing RMS in a timely manner and providing effective treatments to improve patient outcomes and reduce health-related problems.

What Causes Rhabdomyosarcoma?

The exact cause of rhabdomyosarcoma, a type of cancer, is still largely unknown. However, it’s believed that it might be partly due to genetic factors. This is because RMS tumors often have a certain chromosome change, and the condition has been linked to several inherited cancer syndromes, like Noonan, Li-Fraumeni, Beckwith-Wiedemann, and Costello syndromes.

There are also certain risk factors that can increase the chances of developing this type of cancer. These include:

• Exposure to radiation while in the womb
• Parental use of certain drugs
• Having a close family member itself with RMS
• Being born prematurely
• Use of fertility drugs
• Having a history of birth defects

Risk Factors and Frequency for Rhabdomyosarcoma

Rhabdomyosarcoma (RMS) is a rare type of cancer that mostly affects children, making up 3% of all pediatric cancers. It’s also the most common soft tissue sarcoma seen in the under 20 age group and accounts for 50% of these cases. The annual new cases of RMS in the U.S. stand at about 350. The disease is more common in males. In adults, it’s very rare and represents about 1% of solid cancers.

RMS can develop anywhere in the body, but it varies according to subtype. The most common subtype, known as embryonal, mostly affects the head and neck. The alveolar subtype, on the other hand, commonly appears on the limbs. The alveolar and the pleomorphic subtypes, though, are more likely to spread to other parts of the body (a process called metastasis), which results in a worse prognosis. Common sites where these subtypes metastasize include lungs, bone marrow, and lymph nodes.

• Rhabdomyosarcoma (RMS) is a rare type of cancer mostly affecting children.
• It makes up 50% of soft tissue sarcomas in people under 20 years old.
• Each year in the U.S., about 350 new RMS cases are diagnosed.
• RMS is more common in males.
• In adults, RMS is extremely rare, making up just 1% of solid cancer cases.
• The most common type of RMS affects the head and neck.
• The alveolar subtype of RMS often affects the limbs.
• The alveolar and pleomorphic subtypes have a higher risk of spreading to other parts of the body, making them more dangerous.
• These dangerous subtypes often spread to the lungs, bone marrow, and lymph nodes.

Signs and Symptoms of Rhabdomyosarcoma

Rhabdomyosarcoma (RMS) is a type of cancer that may not show symptoms at first. However, depending on where the tumor is located, its size, and whether it has spread, different symptoms may occur. The most common places for RMS tumors are the head, neck, and urinary and reproductive areas.

• People with tumors in the head and neck (like around the eyes or in the nasal area) may experience symptoms like a stuffy nose with mucus, eye bulging, dizziness, nausea, or headaches.
• If the tumor is located in the urinary or reproductive area, it can cause symptoms such as unusual vaginal bleeding, pelvic pain, difficulty or pain when urinating, blood in the urine, and the need to urinate often.
• For those with RMS tumors in the limbs, they usually don’t experience any pain. However, for a specific type of RMS called pleiomorphic RMS, rapidly growing, and painful growths can occur.

The physical signs doctors may observe during an examination can also vary. They may see things like impaired facial expressions due to nerve damage in the head, swollen reproductive organs, visible tumors in the vagina, and enlarged lymph nodes.

Testing for Rhabdomyosarcoma

If you are showing signs of musculoskeletal tumor, doctors usually start by evaluating your symptoms. The next step then is to identify the root cause of your symptoms or visible lump. This typically involves a series of tests like image scans and tissue samples analysis. The results from these tests can help confirm if you have a tumor and how far it has spread. These are important details needed for predicting outcome of the disease.

When it comes to imaging studies, your doctor will most likely order an MRI scan. MRI scans are preferred because they provide a clearer view of the tumor in comparison to CT scans. In some cases, extra image scans like CT and PET scans may be required depending on the possible areas the tumor could have spread to. While ultrasound can be useful for observing tumors that are just beneath the skin, MRI and CT scans are typically better for giving a detailed image of soft tissue tumors. Image scans are very important for checking tumor response to treatment and also potential recurrence. Before performing a biopsy, an image scan of the tumor is usually taken so that doctors can guide the biopsy. Therefore, a team involving radiologists, surgeons, and oncologists really need to work closely together for effective treatment of the patient.

Image scans can provide information on characteristics of the tumor such as size, whether lymph nodes are affected, and if the disease has spread to distant parts of the body. Having a clear understanding of what areas are involved is crucial for surgeons. This information assists them to thoroughly remove the tumor and reduce chances of the disease recurring.

For the molecular analysis, tissue samples of the tumor are often taken and analyzed under a microscope. This can help identify the disease. Sometimes, a biopsy may also be required for more detailed information if the tissue sample shows malignancy, or cancerous growths. Although a less invasive procedure, fine needle biopsy is not typically recommended because it may not provide enough tissue for adequate testing. Genetic tests can also be performed on the tissue sample to confirm the diagnosis and identify specific tumor types because some tumors show similar attributes under a microscope.

It has been found that certain forms of rhabdomyosarcoma (RMS) are linked to particular genetic changes, including aneuploidies of the RAS and TP53 genes. This condition can also be related to a few specific chromosomal translocations. Thus, molecular analysis can help provide a more accurate diagnosis of RMS. Additionally, knowing the specific subtype of RMS can help doctors predict the prognosis or outcome. For example, spindle cell and sclerosing types generally have a positive prognosis, whereas some mutations of this type, as well as all pleomorphic types, have a less positive outlook.

Treatment Options for Rhabdomyosarcoma

In the US, the approach to managing Rhabdomyosarcoma (RMS), a type of muscle tumor, is personalized to the patient’s level of risk. To identify this risk, doctors utilize two systems: the Clinical Group and the Stage. These systems help to determine the best course of treatment by breaking down different factors, such as the tumor’s characteristics (size, how far it’s spread, where it’s located), if lymph nodes are involved, if the disease has spread elsewhere, and how successful initial surgery was.

Patients are sorted into low, moderate, or high-risk groups depending on these factors. Europe uses a slightly different method for identifying risk levels.

The treatment for RMS generally includes a combination of surgery (where possible) to remove the primary tumor, and chemotherapy to control the spread of the disease, even if imaging doesn’t show it’s spread, as most patients are found to have tiny, spread-out tumors during studies. Radiotherapy, also known as radiation therapy, which uses high-energy beams to kill cancer cells, is also used to treat high and moderate-risk patients.

The type of chemotherapy used for RMS in the US usually includes three medicines (vincristine, actinomycin D, and cyclophosphamide) given every three weeks, whereas in Europe, the regimen includes ifosfamide, vincristine, and actinomycin D. Research shows that both regimens have similar outcomes.

For patients with moderate to high risk, chemotherapy typically lasts 6 to 9 months. For low-risk patients, chemotherapy lasts around 24 months, and the dosages may also be reduced. Some doctors suggest doing repeat imaging after 3 cycles of chemotherapy to track how the tumor is responding to the treatment.

Monitoring patients post-treatment for recurring disease is done differently between Europe and the US. European guidelines suggest imaging every 4 months for 2 years. In the US, there are no set guidelines, but most doctors follow current Children’s Oncology Group recommendations for imaging every 4 months for 4 years. Given the known side effects from radiation exposure, especially in children, many experts have recently suggested that US doctors adopt the European monitoring method, as both methods have similar outcomes.

The way we manage patients with RMS is continually changing as more research emerges from clinical trials and treatment advancements.

What else can Rhabdomyosarcoma be?

When a patient presents with symptoms suggesting a musculoskeletal tumor, a physician will exclude a number of other conditions to reach an accurate diagnosis. These include:

• Ewing sarcoma
• Li-Fraumeni syndrome
• Lipomas
• Liposarcoma
• Lymphadenopathy
• Lymphoproliferative disorders
• Neurofibromatosis type 1
• Osteosarcoma
• Wilms tumor

Surgical Treatment of Rhabdomyosarcoma

Rhabdomyosarcoma, known in short as RMS, is a disease often treated through a combination of surgery, chemotherapy, and radiation. Surgery is primarily used for diagnosing the disease and assessing its risk level. By removing the entire tumour, doctors can better understand the severity of your case. However, not all RMS tumours can be safely removed because doing so could harm vital surrounding tissue. Respecting and preserving your long-term bodily functions is always a priority in these surgical procedures.

For those patients where complete removal of the tumour is not immediately possible, doctors often use an approach called ‘delayed primary excision’. This involves giving you several cycles of chemotherapy first, to reduce the size of the tumour. After this, they will surgically remove what remains of the tumour, minimizing the amount of surgery required, and therefore the risk of disfigurement or loss of function.

A key goal of surgery is to remove the tumour, leaving a 5mm ring of healthy tissue untouched around the tumour. This is known as creating ‘clear margins’. Patients who end up with clear margins after their tumour is removed tend to have better survival rates than those where some of the tumour is left behind. However, for RMS cases involving the head and neck, the main treatment involves chemotherapy, with surgery only used to take tissue samples (biopsies) or to treat recurrent disease.

RMS can also occur in other parts of the body like the limbs or the testicles. In such scenarios, the doctors try their best to preserve limb function while ensuring complete tumour removal. If complete removal is not feasible, the tumour is first shrunk using chemotherapy and then excised. In cases where the cancer is found in the testicles, the standard treatment involves removing through an orchiectomy, which involves removing the entire spermatic cord. Testicular preservation is not recommended in such cases.

When RMS occurs in the bladder, prostate, or female reproductive organs, it’s generally treated by confirming the diagnosis through a biopsy, followed by chemotherapy to reduce tumour size, and finally, surgical excision. In some patients, internal radiation therapy, known as brachytherapy, could be beneficial as well.

It should be noted that about 20% of children diagnosed with RMS are found to have metastatic disease, which means the cancer has spread to other parts of the body like the lungs, bones, and bone marrow. Unfortunately, the overall survival rate for patients with metastatic disease is quite low and treatments targeted specifically at these distant sites where the cancer has spread are usually not beneficial. However, some studies suggest an improved survival rate by combining surgical removal and radiation therapy of the primary tumor even if the cancer has already spread.

Second-look surgeries are a somewhat disputed practice that is used to check how the tumour has responded to treatment and to judge the patient’s suitability for reduced dose radiation. Even though these surgeries haven’t shown a direct increase in overall survival rates, they may help improve outcomes by allowing doctors to adjust the radiotherapy plan to the patient’s specific condition. Therefore, these decisions are usually made after thorough consultation and collaboration among the medical team.

What to expect with Rhabdomyosarcoma

The prognosis or the outlook for Rhabdomyosarcoma (RMS), a type of cancer affecting soft tissues, depends on several factors. These include clinical factors, such as the patient’s health status, and histopathologic characteristics, which relate to the microscopic structure of the tumor. When the disease is localized or restricted to a favorable site, the five-year survival rate is approximately 90%, implying that nine out of 10 patients are expected to live for at least five years after diagnosis.

However, for patients with metastatic RMS, a condition where the cancer has spread to other parts of the body, the five-year survival rate is reported to be less than 20%. Additionally, adults tend to have a lower five-year survival rate when compared to children (27% versus 61%). Moreover, RMS occurring in the areas near the meninges (membranes covering the brain and spinal cord) or extremities like arms or legs tends to have a poorer prognosis compared to other sites.

Recurrent RMS, where the cancer comes back after treatment, has a very poor prognosis, and the best treatment options are still under study. As with an initial diagnosis, the overall survival rate with recurrent RMS depends on various factors, including the original tumor stage, the site of tumor recurrence, and its microscopic structure.

Possible Complications When Diagnosed with Rhabdomyosarcoma

There hasn’t been much research into the quality of life people experience after being successfully treated for RMS (Rhabdomyosarcoma). What research there is suggests that individuals who have survived RMS, especially the kind that affects the urinary system, might experience ongoing problems. These can include involuntarily urine leakage, needing to go to the bathroom often, and trouble maintaining an erection.

Chemotherapy and radiotherapy for RMS, especially for children, can result in complications at the treatment sites. Doctors and caregivers should be aware of potential issues such as:

• Mental and cognitive problems
• Facial changes, such as underdeveloped facial bones
• Hormonal issues, like growth hormone deficiency, diabetes, central hypothyroidism (impaired thyroid function), and ACTH deficiency (which can lead to lack of certain hormones)
• Eye-related problems including cataracts, lazy eye, retinopathy (damage to the retina), and reduced visual clarity

There could also be complications affecting the nose and mouth such as pain when swallowing, chronic sinusitis, nosebleeds, inflammation of the mucous membrane, and late teeth eruption. Other potential issues include skin inflammation, bowel obstruction, chronic ear inflammation and hearing loss, urinary frequency and incontinence, narrowing of the vagina, erectile dysfunction, stiffness and reduced mobility in joints, impaired skeletal growth and pathologic bone fractures, and a risk of developing a secondary cancer.

Preventing Rhabdomyosarcoma

The exact cause of RMS, a type of cancer, is largely unknown, which means it’s challenging to create the best prevention strategies. Nevertheless, studies have shown that RMS is often associated with certain cancer syndromes. Therefore, some experts suggest that lab tests and imaging studies can be used to observe people afflicted with cancers associated with RMS (for instance, Li-Fraumeni syndrome) in an effort to detect RMS at an earlier stage.