Neuroblastoma Treatment in Delhi, India

Neuroblastoma is a type of cancer that forms in certain types of nerve tissue. It most often starts in the adrenal glands, which are located on top of the kidneys. However, it can also develop in nerve tissues in the neck, chest, abdomen, or spine. Neuroblastoma is the most common cancer in infants and young children, typically diagnosed before age 5. This cancer originates from neuroblasts, which are immature nerve cells found in the embryo or foetus that typically mature into nerve cells and fibres.

The exact cause of neuroblastoma is not well understood. However, it is believed to result from genetic mutations in neuroblasts that occur during foetal development. These mutations can cause the neuroblasts to continue growing and dividing uncontrollably, leading to the formation of a tumour. In most cases, these mutations occur sporadically and are not inherited. Also, a small percentage of neuroblastoma cases are linked to inherited genetic mutations.

Several factors can increase the risk of developing neuroblastoma, including:

• Age: Neuroblastoma is most commonly diagnosed in children under the age of 5. It is rare in older children and adults.
• Genetics: While most neuroblastomas are not inherited, a family history of neuroblastoma can increase the risk. Specific genetic mutations have been identified that are associated with a hereditary form of the disease.
• Congenital Conditions: Certain congenital disorders are associated with a higher risk of neuroblastoma. These include conditions like Hirschsprung disease and certain congenital abnormalities involving the nervous system.
• Environmental Factors: While the role of environmental factors in neuroblastoma is not clear, some studies suggest that exposure to certain chemicals or radiation might increase the risk, though more research is needed to confirm these links.
• Biological Factors: Factors such as the MYCN oncogene amplification and other specific genetic changes in the tumour cells themselves can influence the development and aggressiveness of neuroblastoma.

Understanding these risk factors and causes is essential for early detection and treatment of neuroblastoma.

Neuroblastoma symptoms can vary depending on the location of the tumour, its size, and whether it has spread to other parts of the body. Common symptoms of neuroblastoma may include:

• Swelling or a lump in the abdomen: This is often the most noticeable symptom, as neuroblastomas commonly originate in the adrenal glands, which are located in the abdomen.
• Abdominal pain: The presence of a tumour in the abdomen can cause discomfort or pain, which may worsen over time.
• Changes in bowel habits: Neuroblastomas in the abdomen can affect bowel function, leading to constipation, diarrhoea, or other changes in bowel habits.
• Weight loss: Unexplained weight loss, particularly in children, can be a sign of various underlying health conditions, including neuroblastoma.
• Fatigue: Children with neuroblastoma may appear more tired or lethargic than usual, even after getting enough rest.
• Bone pain: If the tumour has spread to the bones, it can cause bone pain or limping.
• Weakness or paralysis: In cases where the tumour presses on nerves or spinal cord, it may cause weakness, numbness, or paralysis in the affected area.
• Proptosis (bulging of the eye): Neuroblastomas that develop near the eyes or in the orbits can cause one or both eyes to bulge outwards.
• Fever: Occasionally, neuroblastomas can cause fever, although this is less common.

It's important to note that these symptoms can also be caused by other, less serious conditions. However, if your child experiences any of these symptoms, especially if they persist or worsen over time, it's essential to seek medical evaluation and diagnosis by a healthcare professional. Early detection and treatment of neuroblastoma can improve outcomes and increase the likelihood of successful treatment.

Diagnosing neuroblastoma involves a combination of medical history, physical examinations, imaging tests, laboratory tests, and biopsy procedures. Here’s a detailed overview of the diagnostic process:

Medical History and Physical Examination

The doctor will review the child's medical history and conduct a thorough physical examination to check for signs of neuroblastoma, such as lumps in the abdomen, neck, or chest, and other related symptoms.

Imaging Tests

• Ultrasound: Often the first imaging test used, especially for tumours in the abdomen.
• Computed Tomography (CT) Scan: Provides detailed cross-sectional images of the body, helping to locate the tumour and determine its size and spread.
• MRI (Magnetic Resonance Imaging): Offers detailed images of soft tissues, including the brain and spinal cord, and helps to assess the extent of the disease.
• MIBG (Metaiodobenzylguanidine) Scan: A special nuclear medicine scan that uses a radioactive substance absorbed by neuroblastoma cells, helping to identify the presence and spread of the disease.
• PET (Positron Emission Tomography) Scan: Uses a radioactive sugar to detect cancer cells, providing information about the tumour's metabolic activity.

Laboratory Tests

• Blood and Urine Tests: Neuroblastoma cells often produce certain chemicals called catecholamines. Elevated levels of these chemicals (or their metabolites, such as vanillylmandelic acid and homovanillic acid) in the blood or urine can indicate the presence of neuroblastoma.
• Complete Blood Count (CBC) and Other Blood Tests: To check overall health and function of organs.

Biopsy

• Surgical Biopsy: A sample of the tumour is removed surgically to examine under a microscope. This is the definitive way to diagnose neuroblastoma.
• Bone Marrow Biopsy and Aspiration: Since neuroblastoma can spread to the bone marrow, samples may be taken from the bone marrow to check for cancer cells.

Genetic and Molecular Testing

• MYCN Amplification: Testing for amplification of the MYCN gene, which is associated with more aggressive forms of neuroblastoma.
• Chromosomal and Other Genetic Abnormalities: Identifying specific genetic mutations and abnormalities can provide information about the prognosis and guide treatment options.

Treatment for neuroblastoma depends on several factors, including the child's age, the stage of the disease, the location of the tumour, and specific genetic characteristics of the cancer. Here are the main treatment options:

Surgery

Surgery can be the primary treatment for localised neuroblastoma, aiming to remove as much of the tumour as possible. In some cases, complete removal of the tumour may not be feasible due to its location near vital structures. Surgery is also used in combination with other treatments to remove residual tumour tissue. The extent of surgical resection often depends on the tumour's location and the child's overall health. Surgeons may perform a biopsy during the initial surgery to confirm the diagnosis and assess the tumour's characteristics.

Chemotherapy

Chemotherapy involves the use of powerful drugs to kill cancer cells. For neuroblastoma, chemotherapy can be administered before surgery (neoadjuvant chemotherapy) to shrink the tumour, making it easier to remove. After surgery, adjuvant chemotherapy is often given to kill any remaining cancer cells and reduce the risk of recurrence. In high-risk neuroblastoma cases, high-dose chemotherapy followed by autologous stem cell transplant (using the patient's own stem cells) is a common treatment regimen. Chemotherapy is typically administered in cycles, with periods of treatment followed by rest periods to allow the body to recover.

Radiation Therapy

Radiation therapy uses high-energy beams to target and kill cancer cells. External beam radiation is commonly used after surgery or chemotherapy, especially in high-risk cases where there is a need to ensure that any remaining cancer cells are destroyed. MIBG therapy, a form of targeted radiation therapy, involves using radioactive iodine attached to metaiodobenzylguanidine (MIBG), which selectively targets neuroblastoma cells. This therapy is particularly used for advanced or refractory cases of neuroblastoma. Radiation therapy may cause side effects, such as fatigue and skin irritation, which are typically managed with supportive care.

Immunotherapy

Immunotherapy aims to boost the body's immune system to fight cancer. One form of immunotherapy for neuroblastoma is the use of monoclonal antibodies, such as dinutuximab, which target GD2, a molecule found on neuroblastoma cells. This helps the immune system to recognize and destroy these cancer cells. Another approach involves immune checkpoint inhibitors, which enhance the body's immune response against cancer cells. These drugs are being studied in clinical trials for neuroblastoma and may offer new treatment options for patients, particularly those with high-risk or recurrent disease.

Targeted Therapy

Targeted therapy involves using drugs that specifically target genetic abnormalities or proteins that contribute to cancer growth. For example, ALK inhibitors are used for neuroblastomas with mutations in the ALK gene. Crizotinib is an ALK inhibitor that can be effective in targeting and inhibiting this specific genetic abnormality. Targeted therapies can provide a more personalised treatment approach, potentially leading to better outcomes and fewer side effects compared to traditional chemotherapy.

Retinoid Therapy

Retinoid therapy involves the use of 13-cis-retinoic acid (isotretinoin), which helps induce differentiation in neuroblastoma cells, making them more like normal cells. This therapy is typically used after the main treatment phases (surgery, chemotherapy, and radiation) to prevent recurrence. Retinoids are a form of vitamin A and can help stop the growth and spread of cancer cells by promoting their maturation and death. Retinoid therapy is usually administered in cycles over several months.

Bone Marrow Transplant (Stem Cell Transplant)

Bone marrow transplant, or stem cell transplant, is used in high-risk neuroblastoma cases where high-dose chemotherapy can destroy bone marrow. To restore bone marrow function, a stem cell transplant is performed using the patient’s own previously harvested stem cells (autologous transplant). This procedure allows for higher doses of chemotherapy to be used, which can be more effective in treating the cancer. After the high-dose chemotherapy, the harvested stem cells are infused back into the patient to help rebuild the bone marrow and produce new blood cells.

Neuroblastoma, a cancer that arises from immature nerve cells, can lead to various complications depending on the tumour's location, size, and stage at diagnosis. Some of the key complications include:

• Metastasis: Neuroblastoma can spread (metastasize) to other parts of the body, such as the liver, bones, bone marrow, and lymph nodes. Metastatic disease can complicate treatment and worsen the prognosis.
• Spinal Cord Compression: Tumours located near the spine can grow and press on the spinal cord, leading to pain, weakness, and paralysis. This requires immediate medical intervention to prevent permanent damage.
• Paraneoplastic Syndromes: Some neuroblastomas produce substances that affect other tissues and organs. For example, opsoclonus-myoclonus-ataxia syndrome (OMAS) is a rare paraneoplastic syndrome associated with neuroblastoma, characterised by rapid eye movements, muscle jerks, and balance issues.
• Organ Dysfunction: Large tumours or those that have spread to vital organs like the liver, lungs, or kidneys can cause organ dysfunction, leading to complications such as respiratory distress, jaundice, and renal impairment.
• Bone Marrow Suppression: Both the disease and its treatments, particularly chemotherapy, can suppress bone marrow function, leading to anaemia, increased risk of infection, and bleeding tendencies due to low blood cell counts.
• Growth and Developmental Delays: Treatments like chemotherapy and radiation can impact a child's growth and development, potentially leading to short stature, learning difficulties, and delayed puberty.
• Long-Term Health Issues: Survivors of neuroblastoma may face long-term health issues related to their treatment, such as secondary cancers, cardiac problems, hearing loss, and endocrine disorders.

Can neuroblastoma go away on its own?

Yes, in some cases, especially in very young children (under 18 months), neuroblastoma can regress spontaneously without treatment. This phenomenon is known as spontaneous regression and is more common in lower-risk neuroblastomas.

Is neuroblastoma curable?

Neuroblastoma can be curable, particularly in cases where the disease is diagnosed at an early stage and in younger patients. The prognosis varies significantly depending on factors such as the patient's age, the stage of the disease, and the tumour's genetic characteristics. High-risk neuroblastomas are more challenging to treat but advances in treatment have improved outcomes.

Are neuroblastomas hereditary?

Most neuroblastomas are not hereditary and occur sporadically. However, a small percentage (1-2%) of cases are linked to familial neuroblastoma, which is associated with genetic mutations passed down from parents to children. Genetic counselling and testing can help identify familial cases.

Can neuroblastoma occur in the brain?

Neuroblastoma typically originates in the adrenal glands or sympathetic nervous system. While it can metastasize to the brain, primary neuroblastoma in the brain is extremely rare. When it spreads to the brain, it usually indicates advanced disease.

Does neuroblastoma affect adults?

Neuroblastoma is predominantly a paediatric cancer, most commonly diagnosed in children under the age of 5. It is exceedingly rare in adults, where it may present differently and is often harder to treat due to a lack of standardised protocols for adult patients.

Can neuroblastoma be detected through blood tests?

Blood tests alone cannot diagnose neuroblastoma, but certain markers can be indicative of the disease. Elevated levels of catecholamines (like vanillylmandelic acid (VMA) and homovanillic acid (HVA)) in the urine or blood can suggest neuroblastoma. Complete blood tests are used in conjunction with imaging studies and biopsies to diagnose the disease.

How does neuroblastoma affect the body?

Neuroblastoma can affect the body in various ways depending on the tumour's location and the extent of spread. Symptoms may include abdominal pain, a palpable mass, bone pain, weakness, and fatigue. Metastasis can lead to more severe complications affecting organs such as the liver, bones, bone marrow, and sometimes the brain.

Is neuroblastoma a tumour?

Yes, neuroblastoma is a type of tumour that arises from immature nerve cells called neuroblasts, which are part of the sympathetic nervous system. These tumours most commonly form in the adrenal glands located above the kidneys but can also develop in nerve tissues along the spine, chest, abdomen, or pelvis.

When does neuroblastoma relapse or recur?

Neuroblastoma can relapse after initial treatment, particularly in high-risk cases. Relapse is most likely to occur within the first few years after treatment, but late relapses can also happen. Regular follow-up and monitoring are essential to detect and manage relapses early.

What factors determine the treatment approach for neuroblastoma?

The treatment approach for neuroblastoma is determined by several factors, including the patient’s age, the stage and location of the tumour, genetic and molecular characteristics of the tumour, and overall health of the patient. Risk stratification into low, intermediate, and high-risk categories helps tailor the treatment plan.

Is surgery always necessary for treating neuroblastoma?

Surgery is a common treatment for neuroblastoma, especially for localised tumours, but it is not always necessary for every case. In high-risk or metastatic neuroblastoma, chemotherapy, radiation therapy, and other treatments are often used in conjunction with or instead of surgery.

What is the success rate of neuroblastoma treatment?

The success rate of neuroblastoma treatment varies based on the risk category. Low-risk neuroblastoma has a high cure rate, often exceeding 90%. Intermediate-risk cases have a slightly lower success rate but still favourable outcomes. High-risk neuroblastoma is more challenging to treat, with success rates around 40-50%, but improving with advancements in therapy.

What are the potential side effects of neuroblastoma treatment?

Potential side effects of neuroblastoma treatment depend on the specific treatments used. Common side effects include nausea, vomiting, hair loss, fatigue, increased risk of infection, and organ toxicity. Long-term side effects can include growth and developmental delays, hearing loss, secondary cancers, and fertility issues.

How long does neuroblastoma treatment typically last?

The duration of neuroblastoma treatment depends on the risk category and the treatment regimen. Low-risk cases might require several months of treatment, while high-risk cases can involve intensive treatment over a year or more, including chemotherapy, surgery, radiation, and stem cell transplant.

Can complementary and alternative therapies help in neuroblastoma treatment?

Complementary and alternative therapies may help manage symptoms and improve quality of life but should not replace standard medical treatments. Therapies such as acupuncture, massage, and dietary supplements can be beneficial when used alongside conventional treatment, but it's crucial to discuss these with the healthcare team to ensure they are safe and appropriate.

Can neuroblastoma affect fertility or reproductive health?

Neuroblastoma and its treatment, particularly high-dose chemotherapy and radiation, can affect fertility and reproductive health. The risk is higher in high-risk cases requiring intensive therapy. Fertility preservation options, such as cryopreservation of eggs or sperm, should be discussed with the healthcare team before starting treatment.

Reviewed By Dr. Ramandeep Singh Arora Associate Director Cancer Care / Oncology on 23 Aug 2024.