Symptoms of neuroblastoma

Signs and symptoms depend on where the cancer is located. They may include:

• Lump or mass in the neck, chest, or abdomen
• Bulging eyes or dark circles around the eyes
• Stomach pain
• Irritability
• Less appetite
• Constipation
• Feeling tired
• Leg weakness

Other symptoms may include:

• Diarrhea
• Change in eye movement
• High blood pressure
• Headache
• Cough
• Trouble breathing
• Fever
• Bruising
• Horner syndrome

Neuroblastoma has often spread to other parts of the body before it is diagnosed.

 

What is Horner syndrome?

Some neuroblastoma patients develop Horner syndrome, or nerve damage around the eye. Symptoms may include:

• A drooping eyelid 
• Small pupil  
• Loss of the ability to sweat on one side of the face 

 

Tumor Location	Symptoms
Eye	Bulging eye, dark circles, bruising, blindness
Neck	Lump or swelling, Horner syndrome
Abdomen	Lump, loss of appetite, vomiting, constipation, pain
Pelvis	Change in toilet behavior; bowel or bladder problems
Spine	Weakness, paralysis
Bone	Pain
Bone marrow	Pain, fatigue, burning
Chest	Horner syndrome

 

Risk factors and causes of neuroblastoma

Neuroblastoma is most common in young children. It happens slightly more often in males than females.

A small number of patients (1–2%) have hereditary neuroblastoma. This can be passed down in families. It is often caused by a change in the ALK or PHOX2B genes. But other gene mutations have also been linked to hereditary neuroblastoma. 

Diagnosis of neuroblastoma

Doctors use several types of tests when diagnosing neuroblastoma. Tests may include: 

• A physical exam and health history
• Blood tests to check blood counts, kidney and liver function 
• Urine tests to look for vanillylmandelic acid (VMA) and homovanillic acid (HVA). VMA and HVA are produced by the breakdown of catecholamines, which are hormones produced by neuroblasts. Children with neuroblastoma often have high levels of VMA and HVA. These substances may help monitor response to treatment.
• A neurological exam to measure brain and nerve function including memory, vision, hearing, muscle strength, balance, coordination, and reflexes 
• Imaging tests to learn about the size and location of the tumor(s)
• X-ray 
• Ultrasound 
• Computed tomography (CT or CAT scan) 
• Magnetic resonance imaging (MRI)

• Bone marrow aspiration and biopsy 
• A biopsy of the tumor 

Tumor features and neuroblastoma prognosis

Biology and tumor histology affect neuroblastoma risk and prognosis.

Certain genetic features of the tumor are linked to higher risk. These include:

• MYCN status – MYCN is a gene present in cells. Neuroblastoma cells can have many copies of this gene. This is called MYCN amplification. It means that the tumor cells are:
• Much harder to treat
• More likely to spread
• More likely to come back after treatment

Stages of neuroblastoma

Neuroblastoma is staged using the International Neuroblastoma Risk Group Staging System (INRGSS). Staging is based on these factors:

• Tumor location  
• Effect on nearby organs   
• Spread of disease 

Stage	Spread of disease
Stage L1 Localized	The tumor has not spread from where it began. It does not affect important nearby body organs. It is limited to one body area such as the neck, chest, abdomen, or pelvis.
Stage L2 Localized	The tumor has not spread to parts of the body that are far away from the tumor. But tests show the tumor is acting more aggressive to nearby areas and organs. These are " image-defined risk factors." The tumor also may have spread nearby.
Stage M Metastatic	The tumor has spread to distant parts of the body. This includes all metastatic disease except Stage MS tumors.
Stage MS Metastatic	For children under 18 months old: Cancer spread is limited to the skin, liver, or less than 10% of bone marrow.

 

Neuroblastoma risk groups

Doctors use risk groups to classify neuroblastoma and plan treatments. There are 3 risk groups:

• Low risk
• Intermediate risk
• High risk

High-risk neuroblastoma means that the cancer is hard to remove and more likely to come back. Children with high-risk neuroblastoma need intense therapy.

 Risk groups are based on factors that include:

• Patient age
• Stage of disease
• Tumor characteristics

Treatment of neuroblastoma

Treatment depends on the assigned risk group. Treatment options may include:

• Observation (no treatment)
• Surgery
• Chemotherapy
• High-dose chemotherapy with stem cell rescue
• Immunotherapy
• Radiation therapy

Very young, low-risk patients may be followed with observation instead of active treatment. Sometimes neuroblastoma goes away on its own (regression). But this is rare. Patients are watched closely for tumor progression.

Neuroblastoma treatments are planned based on risk groups:

Risk category	% of new patients	Main treatments	Prognosis
Low Risk	40%	Observation Surgery	About 98% survival
Intermediate Risk	15%	Surgery Chemotherapy	About 95% survival
High Risk	45–50%	Surgery Chemotherapy High-dose chemotherapy with stem cell rescue Radiation therapy Isotretinoin	Less than 60% survival

Support for neuroblastoma patients

Monitoring for relapse

Patients need follow-up care to watch for recurrence after treatment ends. The medical team will suggest specific tests and their schedule.

In patients who do not have high-risk disease, the chance of relapse is 5–15%. In high-risk patients, the risk of relapse is about 50%. Relapse is most common in the first 2 years after treatment. Relapse is rare when there is no sign of cancer 5 years after completing treatment.

Health after cancer 

Survivors treated with chemotherapy or radiation should be monitored for long-term and late effects of therapy. Problems due to treatment could include hearing loss, heart problems, thyroid problems, decreased growth, decreased bone density, and kidney damage.

About 25% of survivors have serious chronic health conditions 25 years after diagnosis 

Regular medical checkups by a primary health care provider are important to watch for health problems that can develop years after therapy.  

Your child's care team should give you a survivorship care plan after treatment has ended. This report will include needed tests and tips for a healthful lifestyle. 

 

Diagnostics of Neuroblastoma

The program includes:

• Initial presentation in the clinic
• clinical history taking
• review of medical records
• physical examination
• laboratory tests:

• complete blood count
• biochemical analysis of blood
• inflammation markers (CRP, ESR)
• indicators of blood coagulation
• tumor markers

• CT/MRI local
• Bilateral BMA& B
• Renal scan
• Bone Scan
• Audiometry
• PET-CT
• Echocardiography
• biopsy with histological and immunohistochemical study 
• nursing services
• consultation of related specialists
• treatment by chief physician and all leading experts
• explanation of individual treatment plan (the cost of medicines is not included)

Required documents

• Medical records
• MRI/CT scan (not older than 3 months)
• Biopsy results (if available)

Type of program : Outpatient

Expected duration of the program: 15 days 

  

Chemotherapy of Neuroblastoma 

The program includes:

• Initial presentation in the clinic
• clinical history taking
• review of medical records
• physical examination
• laboratory tests:

• complete blood count
• general urine analysis
• biochemical analysis of blood
• TSH-basal, fT3, fT4
• tumor markers
• inflammation indicators
• indicators of blood coagulation

• courses of chemotherapy
• nursing services
• consultations of related specialists
• treatment by head doctor and leading experts
• explanation of individual treatment plan

How program is carried out

During the first visit, the doctor will conduct a clinical examination and go through the results of previous laboratory tests and instrumental examinations. After that, you will undergo an additional examination, including laboratory assessment of liver and kidney function, ultrasound scan. Based on the received results, the doctor will elaborate the chemotherapy regimen. If necessary, related medical specialists will be involved in the elaboration of a treatment regimen (tumor board).

Chemotherapy is carried out as the inpatient procedure, with mandatory admission to the hospital. After the placement of a venous catheter, you will stay in a comfortable ward. An infusion system will be connected to the catheter, through which the required drug or a drug combination will be administered. All drugs are administered by intravenous drip, slowly, so the total duration of the infusion can be up to several hours. All this time, doctors and nurses will monitor your health condition closely.

After the course of chemotherapy, you will stay under medical supervision in the ward for a few more hours. After the completion of the chemotherapy course you will receive the medical report with detailed recommendations regarding further treatment. In the future, you will be able to have a distant consultation with your attending physician and schedule the next course of chemotherapy, if necessary.

Required documents

• Medical records
• MRI/CT scan (not older than 3 months)
• Biopsy results (if available)

Type of program : Inpatient

Duration: 7 days

Surgical intervention 

 

The program includes:

• Initial presentation in the clinic
• clinical history taking
• physical examination
• review of medical records
• laboratory tests:

• complete blood count
• general urine analysis
• biochemical analysis of blood
• tumor markers
• indicators of inflammation
• indicators blood coagulation

• CT/MRI scan of the local tumor
• CT Chest with contrast
• preoperative care
• tumor resection
• histologically and immunohistochemically examination
  of the remote tissues
• symptomatic treatment
• control examinations
• the cost of essential medicines and materials
• nursing services
• full hospital accommodation
• explanation of future recommendations

Required documents

• Medical records
• MRI/CT scan (not older than 3 months)
• Biopsy results (if available)

Type of program: Inpatient

Expected duration of the program: 10 days

 

Radiotherapy 

The program includes:

• Initial presentation in the clinic
• clinical history taking
• review of medical records
• physical examination
• laboratory tests:

• complete blood count
• general urine analysis
• biochemical analysis of blood
• tumor markers

• CT / MRI of local tumor
• full curse of radiotherapy
• nursing services
• consultations of related specialists
• explanation of individual treatment plan

How program is carried out

During the first visit, the doctor will conduct a clinical examination and go through the results of previous laboratory tests and instrumental examinations. After that, you will undergo an additional examination, including complete blood count, laboratory assessment of liver and kidney function. Based on the received results, the physician will conduct radiotherapy planning with the help of CT or MRI, make the permanent tattoo marks on the skin and conduct CT simulation in order to assess the accuracy of the rays and the radiation dose. If necessary, related medical specialists will be involved in the elaboration of a treatment regimen (tumor board).

Radiation therapy is carried out as the day hospital procedure, without mandatory admission to the hospital. At each visit, the physician will assess your general condition and the marks on the skin. After that, you will be placed in a shielded radiation therapy room, on a special table.

Each radiation therapy session lasts less than half an hour (including preparation). All this time, doctors and nurses are monitoring your condition, you can communicate with them through a loudspeaker. The procedure is completely painless. Depending on the planned course of treatment, you will visit the hospital from 1 to 3-5 times a week.

After the completion of the radiation therapy course, you will undergo control examinations aimed at assessing your condition and efficacy of treatment. After that you will receive the medical report with detailed recommendations regarding further follow-up and treatment. In the future, you will be able to have a distant consultation with your attending physician and schedule the next course of treatment, if necessary.

Required documents

• Medical records
• MRI/CT scan (not older than 3 months)
• Biopsy results (if available)

Type of program : Outpatient