Neuroblastoma is a malignant tumor that develops from immature nervous tissue of adrenal glands or other extra-adrenal sympathetic nerve structures, and therefore can be located in retroperitoneum, in chest cavity and in certain areas of neck. As a primary brain tumor, neuroblastoma is extremely rare.
Neuroblastoma is the most common type of cancer among young children. In approximately 90% of cases, this tumor is diagnosed in children under 5 years of age, with a peak incidence at the age of 1-2 years. Mostly neuroblastoma develop spontaneously (for no apparent reason), and only 1-2% of such tumors are hereditary.
In vast majority cases, neuroblastomas produce hormones – catecholamines, but patients do not experience a significant increase in blood pressure, since the tumor does not produce adrenaline.
In 65% of cases, neuroblastoma is localized in abdominal cavity, in 20% in chest cavity, 15% in other locations (neck, pelvis, brain). 50-60% of children with neuroblastoma at the time of diagnosis already have distant metastases (bone marrow, bones, lymph nodes, brain).
Neuroblastoma is a serious malignant disease with a serious prognosis, but with timely diagnostics and competent modern comprehensive treatment, it is completely curable. The main thing is to find a specialist who has experience in treating children with neuroblastomas. Pediatric Hematology Oncology Department of Tel Aviv Medical Clinic employs only highly qualified doctors who have excellent theoretical training and extensive practical experience, most of them have repeatedly trained at the best children’s oncology centers in the world.
In their practice, TAMC oncologists are guided by modern clinical recommendations and global treatment protocols, while the approach to each little patient is individual. This allows us to create the most effective personalized treatment regimen for each individual child.
Neuroblastoma causes
Unfortunately, the true causes of neuroblastoma development have not been established to date. It is only known that this neoplasm occurs mainly in children under 5 years of age; boys are affected slightly more often than girls.
In approximately 1-2% of cases with neuroblastoma in a child, the hereditary nature of the disease is observed. Genetically determined neuroblastoma is associated with mutations in ALK or PHOX2B gene. In patients with a hereditary type of the disease, transmitting probability the pathology to their children is 50%.
Symptoms of neuroblastoma in children
Clinical manifestations of neuroblastoma completely depend on tumor location, its size and stage.
With the most common tumor location (in abdominal cavity), most often there is abdominal pain, an increase in volume of abdomen, discomfort and a feeling of rapid satiety while eating, and pelvic organs disruption.
Some symptoms appear as a result of metastases development. These include bone pain, hemorrhages around eyes and proptosis due to retrobulbar metastases, abdominal distension and breathing problems associated with liver and lung metastases.
Tumors in neck or upper chest can cause:
- the Horner’s syndrome appearance;
- swelling of face, neck and arms, upper body;
- cough, difficulty swallowing;
- headache and dizziness.
Modern diagnostic methods
A feature of TAMC diagnostics is its speed, accuracy and complexity. All necessary examinations can be completed within 3-5 working days in one place.
At the first stage, patient is consulted by the leading oncologist of Pediatric Hematology Oncology Department. Specialist collects a detailed medical history, studies complaints, examines the child and forms a plan for further examination.
The initial examination also includes a detailed neurological examination to evaluate various aspects of brain and nervous system function, including memory, vision, hearing, muscle strength, balance, coordination and reflexes.
If neuroblastoma is suspected, the content of homovallic acid (HVA) and vanillylmandelic acid (VMA) in urine must be examined. These substances are formed during the breakdown of catecholamines (hormones of sympathetic nervous system), which are released in excess into the blood by neuroblastoma. In addition to confirm the diagnosis, this test can be used to monitor the response to tumor treatment.
A set of studies to visualize the tumor is mandatory. This is necessary to determine its position, size, stage of the disease, and to diagnose neuroblastoma metastases. Most often, children are prescribed digital radiography of chest organs, ultrasound of internal organs and soft tissues, CT, MSCT, MRI, PET-CT, PET-MRI.
Bone marrow puncture can be used in some patients with suspected central nervous system damage.
Scintigraphy with MIBG is a modern and accurate radioisotope diagnostic method for neuroblastoma. Allows us to determine the location in child’s body not only of the primary tumor, but also of all metastases, if present. MIBG is metaiodobenzylguanidine, a special protein that is actively taken up by neuroblastoma cells. Thus, a radioisotope labeled with MIBG is injected into the patient intravenously, then the whole body is scanned in a special camera. An image is displayed on screen that shows all the places where MIBG accumulates in the body, that is, the localization of neuroblastoma and its metastases.
A tumor biopsy is necessary to confirm the diagnosis and select the most effective treatment regimen. After biopsy, we send all materials for study to the best pathohistological laboratories in Israel, where they are examined by a qualified specialist. Thanks to such thorough checks, we are confident in diagnosis and subsequent treatment tactics. Also, after a biopsy, in some cases, innovative molecular genetic tests are performed to identify some features of malignant cells, which make it possible to select the most effective treatment regimen. One such modern test is Foundation One’s comprehensive genomic tumor tissue profiling.
Prognosis for neuroblastoma
In neuroblastoma, the prognosis is influenced by several factors:
- child’s age at the time of diagnosis – the younger the patient, the better prognosis;
- features of tumor itself – its histological variant, molecular genetic features, rate of growth and spread;
- location of tumor conglomerate;
- risk group for neuroblastoma (low, medium high risk);
- presence of regional or distant metastases;
- the possibility of complete tumor removal during surgery;
- response to treatment (complete, incomplete response, lack of response to complex therapy);
- primary disease or relapse.
There are three risk groups for neuroblastoma:
- Low – 5-year survival rate is 95%.
- Average – 5-year survival rate is 90%.
- High – 5-year survival rate is 60%.
Until recently, the survival rate among high-risk children was only 15%. But the application of intensive treatment protocols and innovative treatment methods (immunobiological therapy) by TAMC oncologists made it possible to increase this figure to 60%
Neuroblastoma modern treatment
Neuroblastoma treatment depends, first of all, on child’s age, tumor location, its stage and characteristics of tumor cells (histological and molecular genetic). The following methods of therapy can be used both in combination and alone:
- surveillance tactics;
- surgical intervention;
- polychemotherapy;
- high-dose chemotherapy followed by autologous hematopoietic stem cell transplantation;
- radiation therapy;
- immunobiological therapy;
- participation in clinical trials.
Surveillance tactics can only be used in the smallest patients with low-low progression of neuroblastoma. In some cases, tumor may regress on its own, but this happens very rarely. If a wait-and-see approach is chosen, child needs constant and careful monitoring of condition and tracking of possible tumor progression.
The main treatment for neuroblastoma is surgery. Removing a tumor, it is very important to adhere to the rule – excision of tumor conglomerate within healthy tissue. Unfortunately, this is not always possible, since the tumor is often located in “close proximity” to important anatomical structures.
In patients with a single tumor lesion that was completely removed during surgery, no further treatment is required. If the tumor has spread or cannot be completely removed during surgery, the child may be prescribed additional therapies. In each individual case, the decision is made individually by a team of specialists from Pediatric Hematology Oncology Department at TAMC.
Chemotherapy is the mainstay of treatment for intermediate – and high-risk neuroblastoma. Treatment may be given before surgery (neoadjuvant chemotherapy) to reduce the tumor size so that it can be completely removed. Chemotherapy may also be prescribed after surgery (adjuvant chemotherapy) to destroy every single malignant cell that could remain after surgery and prevent recurrence of the disease.
Chemotherapeutic medications used in neuroblastoma treatment protocols: carboplatin, cyclophosphamide, doxorubicin, etoposide, topotecan, cisplatin and vincristine.
Patients with metastatic neuroblastoma or high-risk disease may receive high-dose chemotherapy followed by an autologous hematopoietic stem cell transplantation (bone marrow transplantation). In such cases, as a rule, the child is prescribed an initial course of chemotherapy and surgery. After this, the patient’s own hematopoietic stem cells are collected. The next step is for the child to undergo high-dose (myeloablative) chemotherapy, which destroys all malignant cells and, unfortunately, healthy bone marrow stem cells. Next, in a special inpatient Bone Marrow Transplantation Department, doctors perform the procedure of transplanting the patient’s own pre-harvested stem cells. They settle back well and begin to function correctly.
Radiation therapy is also used in neuroblastoma complex treatment. As a rule, irradiation is used in treatment of children from 3 years of age. For neuroblastoma treatment, oncologists prescribe external radiation therapy. TAMC clinic is equipped with modern linear accelerators, which make the treatment process not only effective, but also safe. Radiation is prescribed after surgery to destroy any remaining malignant cells and prevent recurrence of the disease.
Retinoid drugs such as 13-cis-retinoic acid (isotretinoin) are used to treat neuroblastoma. They reduce recurrence risk after treatment in children with high-risk tumors. This is especially effective in cases where retinoids are prescribed in combination with immunotherapy. Application of 13-cis-retinoic acid in combination with various types of chemotherapy drugs, immunotherapies, namely monoclonal antibodies and targeted drugs, is being studied in a number of clinical studies. All our patients can participate in such trials. For some of them, this is the only chance to overcome the disease and return to a healthy life.
Immunotherapy and targeted therapy are being actively studied in neuroblastoma treatment. For example, experts are now testing immunotherapy drugs like crizotinib (Xalkori) and alisertib (MLN8237). The following targeted agents are also being tested: bortezomib, vorinostat, temsirolimus, bevacizumab, nifurtimox and DMFO. The monoclonal antibody dinutuximab (Unituxin) is used to treat children with aggressive neuroblastoma. This drug helps immune system cells to find and destroy cancer cells. CAR T-cell therapy is a promising, innovative way to fight with cancer by modifying a patient’s T cells in vitro so they can effectively find and destroy malignant cells. A new clinical trial has created a CAR-T to target GD2 neuroblastoma cells.
