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Chordoma

Disease Details

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Description: Chordoma is a rare type of cancer that occurs in the bones of the skull base and spine.
Type: Chordoma is a type of primary bone cancer that usually occurs along the spine and at the base of the skull. The genetic transmission of chordoma is typically sporadic, meaning it occurs randomly rather than being inherited. However, there are rare familial cases where changes in the T gene (brachyury) are implicated, suggesting a genetic predisposition in those instances.
Signs And Symptoms: Signs and symptoms of chordoma, a rare type of bone cancer that usually occurs in the spine, can vary based on the tumor's location. Common signs and symptoms include:

1. Pain (localized to the tumor site, commonly in the lower back or neck)
2. Neurological symptoms (due to spinal cord or nerve compression)
3. Weakness
4. Numbness or tingling
5. Bowel or bladder dysfunction
6. Difficulty swallowing or breathing, if the tumor is located near the skull base
7. Changes in vision or double vision (with skull base tumors)
8. A palpable mass (in some cases)

These symptoms often develop slowly and can be mistaken for more common conditions, leading to delayed diagnosis.
Prognosis: In one study, the 10-year tumor free survival rate for sacral chordoma was 46%. Chondroid chordomas appear to have a more indolent clinical course.
Onset: Chordoma typically has an insidious onset, often presenting in adults between the ages of 40 and 70. Symptoms usually develop gradually due to the slow-growing nature of the tumor and its effects on surrounding structures, depending on its location along the spine or skull base.
Prevalence: Chordoma is a rare type of cancer that occurs in the bones of the skull base and spine. Its prevalence is estimated to be approximately 1 in 1,000,000 individuals.
Epidemiology: In the United States, the annual incidence of chordoma is approximately 1 in one million (300 new patients each year).Sacral chordomas make up 2 to 4% of all primary bone tumours and 44% of all primary sacral tumours, thus making it the most common malignant sacral tumour. About 50 to 60% of chordomas are located in the sacrococcygeal region. Males aged between 40 and 50 years are twice as likely as women to get sacral chordoma.There are currently no known environmental risk factors for chordoma. As noted above germline duplication of brachyury has been identified as a major susceptibility mechanism in several chordoma families.While most people with chordoma have no other family members with the disease, rare occurrences of multiple cases within families have been documented. This suggests that some people may be genetically predisposed to develop chordoma. Because genetic or hereditary risk factors for chordoma may exist, scientists at the National Cancer Institute are conducting a Familial Chordoma Study to search for genes involved in the development of this tumor.
Intractability: Chordoma, a rare type of bone cancer that typically occurs in the spine and skull base, can be considered intractable due to several factors. These tumors are often slow-growing but locally aggressive, making complete surgical removal challenging. Additionally, chordomas exhibit resistance to conventional radiation and chemotherapy. The complex anatomic locations where they occur further complicate treatment, often necessitating highly specialized surgical techniques and postoperative care. While recent advances in targeted therapies and proton beam radiation offer some hope, managing chordomas remains difficult, and recurrence is common.
Disease Severity: Chordoma is a rare type of cancer that occurs in the bones of the skull base and spine. The severity of chordoma can vary depending on the location, size, and extent of the tumor, but it is generally considered a serious and potentially life-threatening condition. It tends to grow slowly but can be aggressive and locally invasive. Treatment is often challenging due to the tumor's proximity to critical structures. Early diagnosis and comprehensive treatment are essential for improving outcomes.
Healthcare Professionals: Disease Ontology ID - DOID:3302
Pathophysiology: Chordoma is a rare type of cancer that occurs in the bones of the skull base and spine.

Pathophysiology:
1. Origin: Chordomas arise from remnants of the notochord, a structure present during embryonic development that usually disappears before birth but can persist abnormally in some individuals.
2. Location: They most commonly develop at the clivus at the skull base or the sacrococcygeal region of the spine.
3. Growth: Chordomas are generally slow-growing but can be locally aggressive and infiltrate adjacent bone and soft tissues.
4. Cellular Characteristics: Microscopically, chordoma cells typically have large, vacuolated, physaliferous (bubble-like) cytoplasm. These tumors often express brachyury, a protein commonly used as a diagnostic marker.
5. Molecular Pathology: Genetic mutations in the T (brachyury) gene and other signaling pathways can play a role in chordoma development.
6. Spread: Though primarily localized, chordomas can metastasize to distant organs, including the lungs, liver, and lymph nodes.

Understanding the pathophysiology helps in diagnosis, treatment planning, and research into targeted therapies for chordoma.
Carrier Status: Chordoma is a rare type of cancer that occurs in the bones of the skull base and spine. It typically does not have a carrier status, as it is not inherited in a traditional Mendelian pattern. Instead, it generally occurs sporadically, though there may be some genetic predispositions that increase the risk. The exact causes are not well understood, and there is no well-defined carrier state for this disease.
Mechanism: mTOR signaling is hyperactive in sporadic sacral chordomas: in one study 10 out of 10 sacral chordomas exhibited phosphorylation of Ribosomal protein s6 and EIF4EBP1 by immunohistochemistry
Partial or complete PTEN (gene) deficiency is observed in nearly all sacral chordomas
In a study of 49 chordomas Akt, TSC2, and EIF4EBP1 were phosphorylated in 92%, 96% and 98% of cases, respectively.
In a tissue microarray containing 21 chordomas Platelet-derived growth factor receptor-beta (PDGFR-b), epidermal growth factor receptor (EGFR), KIT (CD117) and HER2 were detected in 100%, 67%, 33% and 0% of cases, respectively.
The CDKN2A (p16) and CDKN2B (p15) loci on chromosome 9p21 are frequently deleted in chordomas Another study found CDKN2A immunoreactivity in just 4% of cases.
62% of chordomas express the High Molecular Weight Melanoma Associated Antigen, also known as Chondroitin sulfate proteoglycan 4 (CSPG4) which has been the target of immune therapy.
In 2009, scientists discovered that an inherited gene duplication is responsible for the familial form of this disorder. Familial chordoma are rare, with an estimated rate of 0.4% in all Chordomas.
Treatment: In most cases, complete surgical resection followed by radiation therapy offers the best chance of long-term control. Incomplete resection of the primary tumor makes controlling the disease more difficult and increases the odds of recurrence. The decision whether complete or incomplete surgery should be performed primarily depends on the anatomical location of the tumor and its proximity to vital parts of the central nervous system.Chordomas are relatively radioresistant, requiring high doses of radiation to be controlled. The proximity of chordomas to vital neurological structures such as the brain stem and nerves limits the dose of radiation that can safely be delivered. Therefore, highly focused radiation such as proton therapy and carbon ion therapy are more effective than conventional x-ray radiation.There are no drugs currently approved to treat chordoma; however, several have shown modest benefit in clinical trials, such as the following:

Pemetrexed: 14% objective response rate with median progression free survival of 10.5 months
Pembrolizumab: 12% objective response rate with median progression free survival of 6.1 months
Apatinib: 3% objective response rate with median progression free survival of 18 months
Imatinib: 2% objective response rate with median progression free survival of 9.2 months
Compassionate Use Treatment: For chordoma, which is a rare type of cancer that occurs in the bones of the skull base and spine, several treatments might be considered under compassionate use or as off-label/experimental approaches:

1. **Compassionate Use Treatments:**
- Compassionate use allows access to investigational drugs outside of clinical trials.
- Candidates must typically have no other treatment options and meet specific criteria set by regulatory agencies like the FDA or EMA.
- Examples may include targeted therapies, novel immunotherapies, or other investigational agents not yet fully approved.

2. **Off-Label Treatments:**
- Some drugs approved for other cancers might be used off-label for chordoma. Examples include:
- **Imatinib (Gleevec):** Originally approved for chronic myeloid leukemia but has shown efficacy in some chordoma cases due to shared molecular targets.
- **Erlotinib (Tarceva):** Typically used for non-small cell lung cancer; has been studied for chordoma.

3. **Experimental Treatments:**
- **Clinical Trials:** Participation in clinical trials offers access to cutting-edge therapies such as new targeted therapies, immune checkpoint inhibitors, and other novel modalities.
- **CAR-T Cell Therapy:** Experimental application in chordoma is under investigation for its potential to target cancer cells specifically.
- **Targeted Agents and Combination Therapies:** Ongoing studies are exploring inhibitors targeting specific mutations or pathways implicated in chordoma, often in combinations to enhance efficacy.

It's essential for patients to discuss these options with their healthcare team to evaluate suitability and potential benefits versus risks, and to consider enrolling in clinical trials where appropriate.
Lifestyle Recommendations: Lifestyle recommendations for someone with chordoma include:

1. **Regular Monitoring and Follow-up**: Adhering to scheduled appointments with healthcare providers for monitoring disease progression or recurrence.
2. **Healthy Diet**: Consuming a balanced diet rich in fruits, vegetables, lean proteins, and whole grains to support overall health and recovery.
3. **Exercise**: Engaging in gentle physical activity, as advised by a healthcare provider, to maintain physical function and improve quality of life.
4. **Pain Management**: Following prescribed pain management plans, which may include medications, physical therapy, and alternative treatments like acupuncture.
5. **Smoking Cessation**: Avoiding tobacco products, as smoking can impede healing and overall health.
6. **Adequate Rest**: Ensuring proper rest and sleep to aid the body's recovery and maintain energy levels.
7. **Support Networks**: Joining support groups or seeking counseling to navigate the emotional and psychological challenges associated with a chordoma diagnosis and treatment.

Medical advice should always be personalized, so it's important to work with healthcare professionals to tailor these recommendations to individual needs.
Medication: Chordoma is a rare type of cancer that occurs in the bones of the skull base and spine. Treatment typically involves surgery and radiation therapy, rather than medication alone. However, medications may be used for managing symptoms or following surgery and radiation to control the disease.

Some medications that may be used include:

1. **Imatinib (Gleevec)**: It targets specific molecules involved in tumor growth.
2. **Erlotinib (Tarceva)**: Another targeted therapy sometimes used in chordoma treatment.
3. **Chemotherapy**: While not standard, in certain cases, drugs such as doxorubicin or cisplatin may be used.

Always consult with a healthcare provider for the most appropriate treatment plan for chordoma.
Repurposable Drugs: Chordoma is a rare type of cancer that occurs in the bones of the skull base and spine. While treatment typically involves surgery and radiation, there is ongoing research into repurposing existing drugs to treat chordoma. Some drugs that have shown potential include:

1. **Imatinib (Gleevec)**: Originally used for chronic myeloid leukemia, it inhibits the PDGFR pathway, which can be active in chordomas.
2. **Erlotinib (Tarceva)**: A drug used for non-small cell lung cancer that targets the EGFR pathway, which may be relevant in some chordomas.
3. **Palbociclib (Ibrance)**: A CDK4/6 inhibitor used in breast cancer, which has shown promise in preclinical studies.
4. **Sirolimus (Rapamune)**: An mTOR inhibitor, sometimes used in combination with other therapies.

Clinical trials are essential for determining the effectiveness and safety of these drugs for chordoma patients. Always consult with a healthcare provider for personalized medical advice.
Metabolites: Chordoma is a rare type of cancer that occurs in the bones of the skull base and spine. Metabolite profiling in chordoma is not well-characterized, but research has identified certain metabolic pathways that may be altered. Commonly investigated metabolites in chordoma include lactate, glutamine, and various amino acids. Elevated levels of lactate may indicate altered glycolytic activity, while disturbance in glutamine metabolism suggests changes in nucleotide synthesis and energy production. Further study into the metabolome of chordoma could help identify biomarkers for diagnosis and targets for therapy.
Nutraceuticals: There currently isn't substantial evidence supporting the use of nutraceuticals (dietary supplements) specifically for chordoma, a rare type of cancer that occurs in the bones of the skull base and spine. Nutraceuticals like vitamins, minerals, and herbal supplements may be used to support general health, but they should not replace conventional treatments such as surgery, radiation, or pharmacological therapies. Always consult with a healthcare provider before starting any new supplement, particularly when dealing with serious conditions like chordoma. As for nanotechnology, research in this area is still emerging and focuses on developing targeted delivery systems for anticancer agents, potentially increasing the effectiveness and reducing the side effects of treatments for chordoma. However, these approaches are largely experimental at this stage.
Peptides: Chordoma is a rare type of cancer that occurs in the bones of the skull base and spine. Peptides have emerged as a potential therapeutic avenue in various cancers, including chordoma. Specific peptides are being researched for their ability to target and inhibit molecular pathways critical for chordoma cell growth and survival.

Nanotechnology is another promising area of research in chordoma treatment. Nanoparticles can be engineered to deliver drugs specifically to chordoma cells, potentially increasing the efficacy of treatment while minimizing side effects.

Both these approaches are still largely in the experimental stages, but they represent hopeful advancements in the treatment of chordoma.