Neuroblastoma is a challenging childhood cancer that originates in developing nerve tissue, affecting primarily babies and young children under five years of age. While treatment approaches vary widely based on disease stage and individual characteristics, advances in therapy have significantly improved survival rates over recent decades. Today, physicians combine standard proven treatments with innovative experimental approaches to give every child the best chance of recovery.

Understanding Treatment Goals and Approaches

When a child is diagnosed with neuroblastoma, the medical team immediately begins planning a treatment strategy tailored to that specific child. The ultimate goal is not just to eliminate cancer cells, but also to preserve quality of life and minimize long-term complications. For some children with less aggressive forms of the disease, treatment may focus simply on observation and supportive care. For others facing high-risk neuroblastoma, the goal becomes preventing the cancer from returning after intensive therapy, since relapse carries a much poorer outlook.

Treatment decisions depend heavily on several factors. The child’s age at diagnosis plays a crucial role—infants and very young children often have better outcomes than older children with similar disease stages. The location of the primary tumor matters, as does whether the cancer has spread to distant parts of the body such as bones, bone marrow, liver, or lymph nodes. Biological features of the tumor cells themselves, including specific genetic changes, help doctors predict how aggressive the disease will be and how well it might respond to various therapies.

Medical societies and expert groups have developed detailed treatment guidelines based on decades of research and clinical experience. These recommendations classify neuroblastoma into risk categories—low, intermediate, and high—which then guide the selection of appropriate therapies. Low-risk patients may need minimal treatment or even just careful watching, while high-risk patients require the most intensive multi-phase approaches combining several different treatment methods.

Alongside established standard treatments, there is active ongoing research into new therapies. Clinical trials test innovative drugs, biological agents, and treatment combinations that may prove more effective or cause fewer side effects than current options. Many children with neuroblastoma, especially those with high-risk disease, are offered the opportunity to participate in these research studies as part of their care.

Standard Treatment Methods

The foundation of neuroblastoma treatment rests on three main pillars: surgery, chemotherapy, and radiation therapy. The specific combination and intensity of these approaches depends on the child’s risk classification and how the tumor responds to initial treatment.

Surgical Treatment

Surgery plays an important role in neuroblastoma management. For children with localized tumors that have not spread, surgical removal of the tumor may be the only treatment needed. The surgeon attempts to remove the entire tumor along with a margin of healthy tissue when possible. However, neuroblastoma tumors often grow near vital structures such as major blood vessels, the spinal cord, or important organs, which can make complete surgical removal difficult or dangerous.

In many cases, surgery is not the first step. Instead, children receive chemotherapy first to shrink the tumor, making it smaller and safer to remove. This approach, called neoadjuvant therapy, can transform an inoperable tumor into one that can be safely resected. After several cycles of chemotherapy, the surgeon performs what is called a delayed primary excision, attempting to remove as much remaining tumor as possible. Even if complete removal is not achievable, removing the bulk of the tumor—called debulking—can improve the effectiveness of other treatments.

After surgery, children typically stay in the hospital for about one to two weeks, depending on the extent of the operation and their recovery. They may initially require care in an intensive care unit with close monitoring. The surgical team watches carefully for complications such as bleeding, infection, or problems with nearby organs affected by the procedure.

Chemotherapy

Chemotherapy uses powerful medications to kill cancer cells or stop them from growing and dividing. For neuroblastoma, chemotherapy is delivered primarily through a central venous catheter—a thin tube inserted into a large vein that allows repeated medication administration without multiple needle sticks. Most chemotherapy for neuroblastoma is given in the hospital as an inpatient treatment, where medical staff can closely monitor the child and provide supportive care.

Several different chemotherapy drugs are used against neuroblastoma, often in combination. Common agents include cyclophosphamide, doxorubicin, etoposide, cisplatin, and carboplatin. Each drug works differently to attack cancer cells, and using multiple drugs together can be more effective than single agents. Treatment is given in cycles, with periods of medication administration followed by rest periods to allow the body to recover.

The duration of chemotherapy varies considerably. Children with low-risk neuroblastoma may receive only a few cycles over several months. Those with intermediate-risk disease typically undergo more intensive chemotherapy lasting four to eight months. High-risk patients face the longest treatment courses, often exceeding a year when all phases of therapy are included.

Chemotherapy affects rapidly dividing cells throughout the body, not just cancer cells, which leads to side effects. Common problems include nausea and vomiting, hair loss, decreased appetite, mouth sores, and increased risk of infection due to low white blood cell counts. Anemia from low red blood cell counts causes fatigue and weakness. Low platelet counts increase bleeding and bruising risk. Many of these side effects are temporary and resolve after treatment ends, though some children may experience lasting effects on hearing, kidney function, or fertility.

Radiation Therapy

Radiation therapy uses high-energy beams to damage cancer cell DNA, preventing them from growing and dividing. In neuroblastoma treatment, radiation may be used to treat the primary tumor site after surgery and chemotherapy, especially in high-risk patients. It can also be directed at areas where the cancer has spread, such as bones or other distant sites.

Modern radiation techniques allow doctors to target tumors precisely while minimizing exposure to surrounding healthy tissues. The total radiation dose is divided into multiple small daily treatments, typically given five days per week over several weeks. This approach, called fractionation, allows normal tissues time to repair between treatments while steadily damaging cancer cells.

Side effects from radiation depend on the area being treated and the dose given. Common acute effects during treatment include skin irritation in the treatment area, fatigue, and temporary changes in blood cell counts. If the abdomen is treated, children may experience nausea, diarrhea, or poor appetite. Long-term effects can include growth problems in treated bones, risk of secondary cancers years later, and damage to organs within the radiation field.

High-Dose Chemotherapy with Stem Cell Rescue

For children with high-risk neuroblastoma, standard chemotherapy doses may not be sufficient to cure the disease. In these cases, doctors may recommend high-dose chemotherapy followed by autologous stem cell transplantation, also called stem cell rescue. This intensive approach uses chemotherapy doses much higher than the body could normally tolerate, specifically targeting any remaining cancer cells after initial treatment.

Before receiving high-dose chemotherapy, the child undergoes a collection procedure where their own blood-forming stem cells are harvested from the bloodstream or bone marrow and frozen for storage. After the high-dose chemotherapy is given, which destroys the bone marrow along with cancer cells, the stored stem cells are returned to the child’s body through an intravenous infusion. These stem cells travel to the bone marrow and begin producing new blood cells, eventually restoring normal blood cell production.

This treatment phase requires several weeks of hospitalization in a specialized transplant unit. Children are at high risk for serious infections and other complications during the period when their immune system is severely weakened. They receive extensive supportive care including antibiotics, blood and platelet transfusions, nutritional support, and careful monitoring for complications.

Immunotherapy

A significant advance in neuroblastoma treatment has been the introduction of immunotherapy, particularly for high-risk disease. The most widely used immunotherapy for neuroblastoma is dinutuximab, a monoclonal antibody that recognizes and binds to a substance called GD2 found on the surface of neuroblastoma cells. When dinutuximab attaches to these cancer cells, it alerts the body’s immune system to attack and destroy them.

Dinutuximab is typically given along with immune-stimulating molecules called cytokines, specifically granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-2 (IL-2), which help activate immune cells. This combination therapy is usually administered after high-dose chemotherapy and stem cell transplant in high-risk patients, as part of what doctors call the post-consolidation or maintenance phase of treatment.

The treatment consists of multiple cycles spread over several months. Each cycle includes several days of antibody infusions, which must be given in the hospital because they can cause significant side effects. Pain is the most common and challenging side effect—many children experience severe nerve pain during the infusions, requiring strong pain medications including narcotics. Other side effects include allergic reactions, fever, low blood pressure, and fluid retention. Despite these difficulties, immunotherapy has been shown to improve survival rates for children with high-risk neuroblastoma.

Retinoid Therapy

After completing the intensive phases of treatment, many children receive a medication called isotretinoin, which is a form of vitamin A (also called 13-cis-retinoic acid or retinoid). Isotretinoin works differently from chemotherapy—instead of directly killing cancer cells, it encourages any remaining neuroblastoma cells to mature into more normal nerve cells, a process called differentiation. Differentiated cells behave more normally and are less likely to grow uncontrollably.

Isotretinoin is given orally as capsules, making it one of the few neuroblastoma treatments that can be taken at home. The typical course lasts six months, with medication taken for two weeks followed by two weeks off, repeating this cycle. Side effects are generally milder than those from chemotherapy but can include dry skin, chapped lips, sensitivity to sunlight, and temporary changes in liver function or blood fats. This treatment is particularly important for children with high-risk neuroblastoma as part of their long-term maintenance therapy.

Promising Treatments Under Investigation in Clinical Trials

While standard treatments have improved survival for many children with neuroblastoma, outcomes for high-risk patients remain challenging, and better therapies are urgently needed. Researchers around the world are testing innovative approaches in clinical trials, offering hope for more effective treatments with fewer long-term complications.

Targeted Molecular Therapies

Scientists have identified specific genetic abnormalities and molecular pathways that drive neuroblastoma growth. Drugs designed to target these specific abnormalities, called targeted therapies, aim to interfere with cancer cell growth while causing less damage to normal cells compared to traditional chemotherapy.

One important target is the ALK gene, which is mutated in about 15 percent of neuroblastoma cases. ALK mutations cause cells to produce an abnormal protein that constantly signals cells to grow and divide. Several drugs called ALK inhibitors have been developed to block this faulty signaling. Crizotinib was one of the first ALK inhibitors tested in children with neuroblastoma, and newer agents such as lorlatinib and ceritinib are being evaluated in clinical trials. These medications are taken as pills, and early studies suggest they can shrink tumors in children whose neuroblastoma has ALK mutations, particularly when the disease has relapsed after standard treatment.

Another molecular target receiving attention is the MYCN oncogene, which is amplified (present in many extra copies) in about 25 percent of neuroblastomas and is associated with very aggressive disease. While directly targeting MYCN has proven difficult, researchers are exploring drugs that interfere with proteins that work alongside MYCN. One approach involves inhibiting aurora kinase, an enzyme that helps cells divide. Aurora kinase inhibitors are being tested in Phase I and Phase II clinical trials, examining both their safety and whether they can slow neuroblastoma growth in children with relapsed or refractory disease.

Drugs targeting the mTOR pathway, which controls cell growth and metabolism, are also under investigation. mTOR inhibitors such as temsirolimus and everolimus have shown some activity against neuroblastoma in early-phase trials. These medications can potentially make tumors more sensitive to chemotherapy when used in combination.

Immunotherapy Innovations

Building on the success of dinutuximab, researchers are developing next-generation immunotherapies. One promising approach involves modifying a child’s own immune cells to better recognize and attack neuroblastoma. CAR T-cell therapy involves collecting a patient’s T-cells (a type of white blood cell), genetically engineering them in the laboratory to express special receptors that recognize neuroblastoma cells, then infusing these modified cells back into the patient. These engineered T-cells can then seek out and destroy cancer cells throughout the body.

Several CAR T-cell therapies targeting GD2 on neuroblastoma cells are being tested in early-phase clinical trials in the United States, Europe, and other locations. Initial results have shown that some children with relapsed or refractory neuroblastoma who failed other treatments experienced tumor shrinkage with CAR T-cell therapy. However, this approach is still experimental, and researchers are working to understand the best way to manufacture these cells, what dose to use, and how to manage side effects such as cytokine release syndrome, a potentially serious immune reaction.

Other immunotherapy approaches being investigated include checkpoint inhibitors, drugs that release the brakes on the immune system, allowing it to attack cancer more effectively. Medications such as nivolumab and pembrolizumab, which block a protein called PD-1, are being tested in combination with other therapies in neuroblastoma trials. These drugs have proven effective in some adult cancers and are now being carefully studied in children.

Researchers are also exploring bispecific antibodies, which are engineered molecules that can simultaneously bind to cancer cells and immune cells, bringing them together so the immune system can destroy the tumor. Several bispecific antibodies targeting GD2 are in early clinical testing and have shown encouraging preliminary activity.

Radioactive Therapies

An innovative treatment approach for neuroblastoma uses radioactive substances that specifically target tumor cells, delivering radiation directly to cancer sites while sparing most healthy tissue. One such therapy involves meta-iodobenzylguanidine (MIBG), a molecule that resembles a natural substance made by nerve cells. Neuroblastoma cells take up MIBG from the bloodstream. When MIBG is combined with radioactive iodine (I-131), it delivers radiation directly to tumor cells throughout the body.

MIBG therapy is given through an intravenous infusion over several hours. Because the child becomes temporarily radioactive after the infusion, they must stay in a special hospital room with lead shielding for several days until the radiation levels decrease to safe levels. This treatment is being studied in clinical trials for children with high-risk, relapsed, or refractory neuroblastoma, often in combination with chemotherapy or stem cell transplantation. Early results suggest that MIBG therapy can shrink tumors and improve outcomes for some children, though side effects can include bone marrow suppression requiring blood and platelet transfusions.

A newer approach uses radiolabeled antibodies, where radioactive particles are attached to antibodies that target neuroblastoma cells. This combines the targeting ability of immunotherapy with the cancer-killing power of radiation. Several versions are in early clinical testing at specialized cancer centers.

Chemotherapy Combinations and Novel Drugs

Researchers continue to investigate new chemotherapy drugs and novel combinations of existing medications. Clinical trials are testing whether adding newer agents to standard chemotherapy regimens can improve outcomes without significantly increasing toxicity.

One drug receiving attention is topotecan, which interferes with an enzyme cancer cells need to copy their DNA. When combined with cyclophosphamide, topotecan has shown activity against neuroblastoma in relapsed patients. Trials are exploring whether adding this combination to upfront treatment might benefit certain high-risk patients.

Another medication being studied is irinotecan, another drug that targets DNA replication in cancer cells. Various clinical trials are testing irinotecan in combination with other chemotherapy drugs, including temozolomide, a pill-form chemotherapy that crosses into the brain and may be useful if neuroblastoma has spread to the central nervous system.

DFMO (difluoromethylornithine), also called eflornithine, represents a unique approach. This oral medication blocks an enzyme called ornithine decarboxylase, which is important for cell growth and is particularly active in neuroblastoma cells, especially those with MYCN amplification. DFMO has shown promising results in a Phase II clinical trial where it appeared to reduce relapse risk when given as maintenance therapy after standard treatment for high-risk neuroblastoma. This led to a large Phase III trial testing whether DFMO combined with isotretinoin is more effective than isotretinoin alone in preventing relapse.

Trial Phases and Patient Eligibility

Clinical trials for neuroblastoma proceed through several phases, each designed to answer specific questions. Phase I trials primarily test the safety of a new treatment, determining what dose can be given safely and what side effects occur. These trials usually involve small numbers of patients, often children whose disease has not responded to standard treatment.

Phase II trials focus on determining whether the new treatment actually works against neuroblastoma—does it shrink tumors, prevent disease progression, or improve survival? These trials enroll more patients than Phase I studies and continue to monitor safety closely.

Phase III trials compare a promising new treatment directly against the current standard of care. These large studies, involving hundreds of children at multiple hospitals and sometimes multiple countries, provide the strongest evidence about whether a new approach truly improves outcomes. Only treatments that prove superior or equally effective with fewer side effects in Phase III trials become new standard treatments.

Eligibility for clinical trials depends on many factors. The child’s age, disease stage, genetic features of their tumor, and previous treatments all influence which trials might be appropriate. Some trials are specifically designed for newly diagnosed patients, testing whether a new drug or combination can improve initial treatment results. Others focus on relapsed or refractory neuroblastoma—disease that has come back after treatment or never fully responded to therapy.

Clinical trials for neuroblastoma are conducted at specialized pediatric cancer centers throughout the United States, Europe, and other regions worldwide. Major cooperative research groups such as the Children’s Oncology Group coordinate multi-center trials across dozens of hospitals. Families interested in clinical trials should discuss options with their child’s oncology team, who can identify relevant studies and help determine eligibility.

Most Common Treatment Methods

• Surgery
  • Complete or partial removal of the primary tumor
  • May be performed after chemotherapy to shrink the tumor first
  • Goal is to remove as much tumor as safely possible
  • Delayed primary excision after neoadjuvant therapy
  • Debulking surgery when complete removal is not possible
• Chemotherapy
  • Multiple drug combinations targeting cancer cells
  • Common agents include cyclophosphamide, doxorubicin, etoposide, cisplatin, and carboplatin
  • Given in cycles with rest periods between treatments
  • Delivered primarily through central venous catheters
  • Duration varies from months to over a year depending on risk category
  • Newer agents being tested include topotecan, irinotecan, and temozolomide
• Radiation Therapy
  • High-energy beams directed at tumor sites
  • Used to treat primary tumor bed and metastatic sites
  • Given in daily fractionated doses over several weeks
  • Modern techniques minimize exposure to healthy tissues
  • MIBG therapy delivers targeted radiation using radioactive iodine
• High-Dose Chemotherapy with Stem Cell Transplant
  • Intensive chemotherapy at doses higher than bone marrow can tolerate
  • Patient’s own stem cells collected before treatment and returned afterward
  • Autologous stem cell rescue allows bone marrow recovery
  • Requires extended hospitalization in specialized transplant units
  • Used primarily for high-risk neuroblastoma patients
• Immunotherapy
  • Dinutuximab antibody targets GD2 on neuroblastoma cells
  • Given with immune-stimulating cytokines GM-CSF and IL-2
  • Multiple cycles administered after stem cell transplant
  • CAR T-cell therapy under investigation in clinical trials
  • Checkpoint inhibitors such as nivolumab and pembrolizumab in trials
  • Bispecific antibodies being tested in early-phase studies
• Targeted Molecular Therapies
  • ALK inhibitors for tumors with ALK mutations, including crizotinib, lorlatinib, and ceritinib
  • Aurora kinase inhibitors interfering with cell division
  • mTOR inhibitors such as temsirolimus and everolimus
  • DFMO blocking ornithine decarboxylase enzyme
  • Drugs targeting MYCN-related pathways
• Retinoid Therapy
  • Isotretinoin (13-cis-retinoic acid) promotes cell differentiation
  • Oral capsules taken at home
  • Six-month course with two weeks on, two weeks off
  • Part of maintenance therapy for high-risk patients
• Observation and Monitoring
  • Some infants and very low-risk patients may not need immediate treatment
  • Tumors can spontaneously regress in some cases
  • Regular check-ups with imaging and urine tests
  • Treatment initiated if disease progresses