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Rhabdomyosarcoma

Disease Details

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Description: Rhabdomyosarcoma is a type of cancer that forms in the soft tissue, specifically skeletal muscle tissue, and is most commonly found in children.
Type: Rhabdomyosarcoma (RMS) is a type of cancer that arises from skeletal muscle tissue. The genetic transmission of rhabdomyosarcoma is typically sporadic, meaning it generally occurs by chance and is not inherited. However, there are rare instances where familial cases are seen, often associated with underlying genetic syndromes such as Li-Fraumeni syndrome, Beckwith-Wiedemann syndrome, or neurofibromatosis type 1.
Signs And Symptoms: RMS can occur in almost any soft-tissue site in the body; the most common primary sites are genitourinary (24%), parameningeal (16%), extremity (19%), orbit (9%), other head and neck (10%), and miscellaneous other sites (22%). RMS often presents as a mass, but signs and symptoms can vary widely depending on the site of the primary tumor. Genitourinary tumors may present with hematuria, urinary tract obstruction, and/or a scrotal or vaginal mass. Tumors that arise in the retroperitoneum and mediastinum can become quite large before producing signs and symptoms. Parameningeal tumors may present with cranial nerve dysfunction, symptoms of sinusitis, ear discharge, headaches, and facial pain. Orbital tumors often present with orbital swelling and proptosis. Extremity tumors generally present as a rapidly enlarging, firm mass in the relevant tissue. The cancer's prevalence in the head, face, and neck will often allow for earlier signs of the disease simply due to the obvious nature of tumors in these locations. Despite the varying presentation and typically aggressive nature of the disease, RMS has the potential to be diagnosed and treated early. The fourth IRSG study found that 23% of patients were diagnosed in time for a complete resection of their cancer, and 15% had resection with only minimal remnants of the diseased cells.
Prognosis: Rhabdomyosarcoma (RMS) prognosis depends on various factors, including the patient's age, the tumor's location and size, the extent of spread (metastasis), histologic subtype, and how well the tumor responds to treatment. Generally, pediatric patients tend to have a better prognosis compared to adults. For instance:

1. **Localized RMS:** When the cancer is detected early and localized, the 5-year survival rate is approximately 70-80%.
2. **Metastatic RMS:** If the cancer has spread to other parts of the body, the 5-year survival rate drops significantly to around 20-30%.
3. **Histologic subtype:** Patients with embryonal rhabdomyosarcoma (ERMS) generally have a better prognosis compared to those with alveolar rhabdomyosarcoma (ARMS).

Prognosis is also influenced by newer treatments and support care options, which have improved over recent years, giving hope for better outcomes.
Onset: Rhabdomyosarcoma typically presents in childhood, most commonly affecting children between the ages of 2 and 6, and then again in early adolescence around 15 to 19 years old.
Prevalence: Rhabdomyosarcoma (RMS) is a rare type of cancer that primarily affects children. The prevalence is not typically represented as a fixed number because it varies by region and is influenced by a variety of factors. However, it is estimated that RMS affects about 4.5 per 1 million children under the age of 15 in the United States. It accounts for approximately 3% of all childhood cancers.
Epidemiology: Rhabdomyosarcoma is the most common soft-tissue sarcoma in children as well as the third most common solid tumor in children. Recent estimates place the incidence of the disease at approximately 4.5 case per 1 million children/adolescents with approximately 250 new cases in the United States each year. With the vast majority of cases of RMS occurring in children or adolescents, two-thirds of reported cases occur in youths under the age of 10. RMS also occurs slightly more often in males than in females, with a ratio of approximately 1.3–1.5:1. In addition, slightly lower prevalence of the disease has been reported in black and Asian children relative to white children. In most cases, there are no clear predisposing risk factors for the development of RMS. It tends to occur sporadically with no obvious cause. However, RMS has been correlated with familial cancer syndromes and congenital abnormalities including neurofibromatosis type 1, Beckwith-Wiedemann syndrome, Li–Fraumeni syndrome, cardio-facio-cutaneous syndrome, and Costello syndrome. It has also been associated with parental use of cocaine and marijuana.
Intractability: Rhabdomyosarcoma can be challenging to treat, especially in advanced stages or when it has metastasized. While some cases respond well to a combination of surgery, chemotherapy, and radiation therapy, others may prove more resistant. The outcome often depends on various factors including the tumor's location, size, subtype, and the patient’s overall health.
Disease Severity: Rhabdomyosarcoma is a highly malignant (cancerous) tumor of the skeletal muscle tissue. Its severity depends on numerous factors including the tumor's size, location, histological subtype, and the extent of spread at the time of diagnosis. This type of cancer generally requires aggressive treatment, including surgery, chemotherapy, and sometimes radiation. Early diagnosis and prompt treatment are critical for improving outcomes.
Healthcare Professionals: Disease Ontology ID - DOID:3247
Pathophysiology: Rhabdomyosarcoma (RMS) is a malignant soft tissue tumor originating from skeletal muscle progenitors. The pathophysiology involves genetic mutations and alterations that drive uncontrolled cell growth and failure of normal differentiation. Common genetic abnormalities include mutations in genes like PAX3, PAX7, and the fusion gene PAX-FOXO1, resulting from chromosomal translocations such as t(2;13) or t(1;13). These genetic changes lead to the activation of pathways that promote cell proliferation, survival, and migration, contributing to tumor development and progression. RMS primarily affects children and can occur in various anatomical locations including the head, neck, genitourinary tract, and extremities.
Carrier Status: Rhabdomyosarcoma is a type of cancer that forms in soft tissue, particularly in skeletal muscle tissue or sometimes in hollow organs such as the bladder or uterus. Carrier status is not applicable to rhabdomyosarcoma, as it is not typically related to a single gene mutation that can be carried and passed on to offspring. Instead, this cancer usually arises from genetic mutations that occur after conception, during the individual's lifetime.
Mechanism: Rhabdomyosarcoma (RMS) is a malignant tumor derived from striated muscle tissue. It primarily affects children and adolescents but can also occur in adults. There are two major subtypes: embryonal rhabdomyosarcoma (ERMS) and alveolar rhabdomyosarcoma (ARMS), with distinct molecular mechanisms.

1. **Mechanism**:
- **Embryonal Rhabdomyosarcoma (ERMS)**: It generally involves genetic alterations that disrupt normal cellular processes, leading to uncontrolled cell proliferation.
- **Alveolar Rhabdomyosarcoma (ARMS)**: Characterized by specific chromosomal translocations resulting in the formation of oncogenic fusion proteins.

2. **Molecular Mechanisms**:
- **ERMS**:
- **P53 Pathway**: Mutations in the TP53 gene, which codes for a tumor suppressor protein, are sometimes present.
- **RAS Pathway**: Mutations in genes such as KRAS and NRAS can lead to aberrant signaling and cell growth.
- **Loss of Heterozygosity (LOH)**: Common in chromosomes 11p15 and 2q, potentially involving genes important for muscle differentiation and growth regulation.

- **ARMS**:
- **PAX-FOXO1 Fusion Genes**: The most common translocations are t(2;13)(q35;q14) and t(1;13)(p36;q14), resulting in the fusion of PAX3 or PAX7 genes with FOXO1. These fusion proteins act as aberrant transcription factors, driving oncogenesis.
- **Upregulation of MYC**: Often associated with the PAX-FOXO1 fusion proteins, leading to further promotion of cell proliferation and survival.
- **Dysregulation of Apoptosis and Differentiation Pathways**: Altered expression of genes involved in programmed cell death and muscle differentiation, such as MYOD1 and MYCN.

Understanding these molecular mechanisms offers insights into potential therapeutic targets and improved treatment strategies for rhabdomyosarcoma.
Treatment: Treatment of rhabdomyosarcoma is a multidisciplinary practice involving the use of surgery, chemotherapy, radiation, and possibly immunotherapy. Surgery is generally the first step in a combined therapeutic approach. Resectability varies depending on tumor site, and RMS often presents in sites that don't allow for full surgical resection without significant morbidity and loss of function. Less than 20% of RMS tumors are fully resected with negative margins. Rhabdomyosarcomas are highly chemosensitive, with approximately 80% of cases responding to chemotherapy. In fact, multi-agent chemotherapy is indicated for all patients with rhabdomyosarcoma. Before the use of adjuvant and neoadjuvant therapy involving chemotherapeutic agents, treatment solely by surgical means had a survival rate of <20%. Modern survival rates with adjuvant therapy are approximately 60–70%.There are two main methods of chemotherapy treatment for RMS. There is the VAC regimen, consisting of vincristine, actinomycin D, and cyclophosphamide, and the IVA regimen, consisting of ifosfamide, vincristine, and actinomycin D. These drugs are administered in 9–15 cycles depending on the staging of the disease and other therapies used. Other drug and therapy combinations may also show additional benefit. Addition of doxorubicin and cisplatin to the VAC regimen was shown to increase survival rates of patients with alveolar-type, early-stage RMS in IRS study III, and this same addition improved survival rates and doubled bladder salvage rates in patients with stage III RMS of the bladder. In children and young adults with stage IV metastatic rhabdomyoscarcoma, a Cochrane review has found no evidence to support the use of high-dose chemotherapy as a standard therapy.Radiation therapy, which kill cancer cells with focused doses of radiation, is often indicated in the treatment of rhabdomyosarcoma, and the exclusion of this treatment from disease management has been shown to increase recurrence rates. Radiation therapy is used when resecting the entirety of the tumor would involve disfigurement or loss of important organs (eye, bladder, etc.). Generally, in any case where a lack of complete resection is suspected, radiation therapy is indicated. Administration is usually following 6–12 weeks of chemotherapy if tumor cells are still present. The exception to this schedule is the presence of parameningeal tumors that have invaded the brain, spinal cord, or skull. In these cases radiation treatment is started immediately. In some cases, special radiation treatment may be required. Brachytherapy, or the placement of small, radioactive "seeds" directly inside the tumor or cancer site, is often indicated in children with tumors of sensitive areas such as the testicles, bladder, or vagina. This reduces scattering and the degree of late toxicity following dosing. Radiation therapy is more often indicated in higher stage classifications.
Immunotherapy is a more recent treatment modality that is still in development. This method involves recruiting and training the patient's immune system to target the cancer cells. This can be accomplished through administering small molecules designed to pull immune cells towards the tumors, taking immune cells pulled from the patient and training to attack tumors through presentation with tumor antigen, or other experimental methods. A specific example here would be presenting some of the patient's dendritic cells, which direct the immune system to foreign cells, with the PAX3-FKHR fusion protein in order to focus the patient's immune system to the malignant RMS cells. All cancers, including rhabdomyosarcoma, could potentially benefit from this new, immune-based approach.
Compassionate Use Treatment: Rhabdomyosarcoma, a rare and aggressive form of cancer that originates in muscle tissue, often requires aggressive treatment approaches. For cases where standard therapies are ineffective or not suitable, compassionate use treatments, off-label, or experimental therapies may be considered.

1. **Compassionate Use Treatments**: These are investigational treatments provided to patients outside of clinical trials when no comparable or satisfactory alternative therapy options are available.
- **Larotrectinib (Vitrakvi)** and **Entrectinib (Rozlytrek)**: These drugs may be available through compassionate use for tumors with specific genetic mutations (e.g., NTRK gene fusions).

2. **Off-label Treatments**: These involve the use of approved medications for indications not specifically listed in the prescribing information.
- **Cyclophosphamide**, **ifosfamide**, and **doxorubicin**: While standard parts of rhabdomyosarcoma treatment, they are sometimes used off-label in different combinations or schedules.
- **Pazopanib (Votrient)**: Primarily approved for treating kidney cancer, it has been used off-label for refractory or relapsed cases of rhabdomyosarcoma.

3. **Experimental Treatments**: These are typically offered within the context of clinical trials but might also be available through expanded access programs.
- **Immunotherapy**: Treatments such as pembrolizumab (Keytruda) or nivolumab (Opdivo) are being explored in clinical trials for their potential benefit in rhabdomyosarcoma.
- **Targeted Therapy**: Agents targeting specific molecular pathways or genetic abnormalities within the tumor cells are under investigation.
- **Gene Therapy**: Experimental approaches exploring the insertion, alteration, or removal of genetic material within the cancer cells to halt tumor growth.

It's essential to consult with a specialized oncologist to explore these options, understand the potential benefits and risks, and determine the best course of action based on the patient's specific condition.
Lifestyle Recommendations: For rhabdomyosarcoma, here are some general lifestyle recommendations:

1. **Nutritional Support**: Maintain a balanced diet rich in fruits, vegetables, whole grains, and lean proteins to support overall health and recovery.
2. **Physical Activity**: Engage in light, regular physical activity as tolerated, and as advised by healthcare providers, to boost energy levels and improve well-being.
3. **Rest and Sleep**: Ensure adequate rest and sleep to help the body recover from treatment and maintain strength.
4. **Emotional Support**: Seek emotional and psychological support through counseling or support groups to help cope with the stress and emotional burden of the disease.
5. **Follow Medical Advice**: Adhere strictly to treatment plans and follow-up appointments with healthcare providers to monitor and manage the condition effectively.

Note: Always consult with a healthcare professional for personalized lifestyle recommendations based on individual health needs and treatment plans.
Medication: Rhabdomyosarcoma is a malignant tumor of skeletal muscle origin. Treatment often involves a combination of therapies, including medication, surgery, and radiation. The key medications used are chemotherapy agents, which may include:

1. **Vincristine** – A plant alkaloid that disrupts cell division.
2. **Cyclophosphamide** – An alkylating agent that interferes with DNA replication.
3. **Dactinomycin** – An antibiotic that binds to DNA and hinders its synthesis.
4. **Ifosfamide** – An alkylating agent used alongside mesna to protect the bladder.
5. **Etoposide** – A topoisomerase inhibitor that prevents DNA unwinding.

These medications are typically administered in various combinations as part of a chemotherapy regimen.
Repurposable Drugs: Rhabdomyosarcoma is a type of cancer that forms in soft tissue, such as muscle. Repurposable drugs for rhabdomyosarcoma are being studied, and some have shown potential in preclinical or early clinical trials. These drugs include:

1. **Metformin**: Commonly used for diabetes, it has shown some anticancer properties.
2. **Celecoxib**: A nonsteroidal anti-inflammatory drug (NSAID) that may inhibit tumor growth.
3. **Valproic Acid**: An anticonvulsant that may have a role in disrupting cancer cell growth pathways.

Research is ongoing, and these drugs are not yet standard treatments for rhabdomyosarcoma but offer potential future options.
Metabolites: Rhabdomyosarcoma is a type of soft tissue sarcoma that arises from skeletal muscle progenitors. Regarding metabolites, research is ongoing to identify and understand specific metabolic pathways and metabolites associated with rhabdomyosarcoma. Some studies have highlighted altered levels of certain amino acids, lipids, and other small molecules involved in energy metabolism, which may influence tumor growth and progression. However, the specific metabolic profile can vary depending on the subtype and genetic mutations present in the tumor.
Nutraceuticals: For rhabdomyosarcoma, there is limited evidence supporting the use of nutraceuticals as a primary treatment. Rhabdomyosarcoma is an aggressive form of cancer that typically requires conventional treatments such as surgery, chemotherapy, and radiation therapy. Nutraceuticals, which include dietary supplements and functional foods, may be used to support overall health and well-being but should not replace standard cancer treatments. Always consult with a healthcare provider before using any supplementary products.
Peptides: Rhabdomyosarcoma is a type of soft tissue sarcoma that arises from skeletal muscle progenitors. It's most common in children and adolescents. Treatment often involves a combination of surgery, radiation therapy, and chemotherapy. Current research is investigating the use of peptides and nanotechnology in developing targeted therapies to improve treatment specificity and reduce side effects. Peptide therapies aim to deliver drugs precisely to cancer cells, while nanotechnology can be used to enhance drug delivery, improve imaging techniques, and facilitate novel therapeutic approaches.