Understanding Neuroblastoma
Neuroblastoma is a solid tumor cancer that arises from immature nerve cells, often developing before a child is born. These tumors most commonly form in the abdomen, specifically in the adrenal glands located on top of the kidneys, but can also be found in nerve tissue in the chest, neck, or pelvis. It is the most prevalent solid tumor diagnosed in infancy and is typically found in children under the age of five.
To design an effective treatment strategy, oncologists first assess several factors to create a complete picture of the disease. This process involves staging the cancer to map its location and spread, and classifying it into a risk group to predict its behavior.
- Staging: Doctors determine the cancer's stage to understand how far it has spread from its original site. A Stage I tumor, for instance, is confined to one area and may be removable with surgery alone. In contrast, a Stage IV tumor has metastasized to distant parts of the body, such as the bones or liver, necessitating more intensive, body-wide treatments. A unique category, Stage 4S, applies only to infants under one year old and often has a better prognosis despite widespread disease.
- Risk Classification: Beyond staging, neuroblastoma is categorized into low, intermediate, or high-risk groups. This classification is critical for guiding the intensity of therapy. It is determined by the child's age, the tumor's stage, and specific biological markers within the cancer cells. A child with low-risk disease may only require surgery or even just careful observation, whereas a child with high-risk neuroblastoma will need an aggressive, multi-step treatment plan to address its aggressive nature.
Primary Treatment Approaches
The treatment for neuroblastoma is tailored to each child's specific risk group. A team of pediatric cancer specialists collaborates to create a plan that aims to cure the cancer while minimizing long-term side effects.
Surgery
Surgery is a cornerstone of neuroblastoma treatment, but its role and timing depend on the tumor's risk classification and location.
For low-risk, localized tumors, upfront surgery is often the primary treatment. If a surgeon can remove the tumor completely in a single operation (a complete resection), it may be the only therapy needed. This allows the child to avoid the side effects of chemotherapy and radiation.
In intermediate- and high-risk cases, tumors are often too large or dangerously wrapped around vital organs and blood vessels to be removed safely at diagnosis. Here, surgery is typically performed after an initial course of chemotherapy. The chemotherapy shrinks the tumor, pulling it away from critical structures and making the operation safer and more likely to succeed.
In some situations, the first procedure is a biopsy, where a surgeon removes a small piece of the tumor. This tissue sample is essential for confirming the diagnosis and allows pathologists to analyze its genetic makeup, providing crucial information for risk classification and treatment planning.
Chemotherapy
Chemotherapy uses powerful drugs that circulate through the body to kill cancer cells. It is a vital component of treatment for any neuroblastoma that has spread or is classified as intermediate- or high-risk. These medications can be used to shrink tumors before surgery, eliminate cancer cells that remain after an operation, or treat metastatic disease in the bone marrow, liver, or other distant sites.
Radiation Therapy
This therapy uses high-energy beams to destroy cancer cells in a targeted area. For high-risk neuroblastoma, radiation is often used after surgery to eliminate any microscopic tumor cells left behind, reducing the risk of the cancer returning at the original site. It can also be used palliatively to relieve symptoms, such as shrinking a tumor that is compressing the spinal cord.
High-Dose Chemotherapy and Stem Cell Transplant
This intensive procedure is a standard part of treatment for high-risk neuroblastoma. After the initial rounds of therapy have reduced the amount of cancer in the body, the patient receives very high doses of chemotherapy to wipe out any remaining, resistant cancer cells. Because this process also destroys the body’s healthy bone marrow, the child’s own blood-forming stem cells are collected beforehand. After the high-dose chemotherapy is complete, these stored stem cells are returned to the body through an infusion, where they restore the bone marrow and immune system.
Immunotherapy
Immunotherapy harnesses the body’s own immune system to identify and attack cancer cells. For high-risk neuroblastoma, a drug called dinutuximab is often given after a stem cell transplant. It attaches to neuroblastoma cells, flagging them for destruction by immune cells. This treatment has significantly improved survival rates by helping to eliminate residual disease and prevent relapse.
Treating Relapsed and Refractory Neuroblastoma
When neuroblastoma returns after treatment (relapsed) or stops responding to it (refractory), it presents a formidable challenge. The surviving cancer cells are often more aggressive and resistant, requiring a shift from standard protocols to more innovative and personalized strategies.
Overcoming Treatment Resistance
Cancer cells that survive initial therapy have often developed mechanisms to evade the drugs used. This means that simply repeating the first treatment plan is unlikely to be effective. Oncologists must turn to different combinations of chemotherapy or explore newer classes of drugs that the cancer has not yet been exposed to. Because of this, there is no single standard of care for relapsed disease; treatment must be highly individualized.
Identifying New Therapeutic Targets
A relapsed tumor may not be biologically identical to the original one. It can evolve and develop new genetic mutations. To understand these changes, doctors often perform another biopsy to analyze the tumor's current genetic profile. This analysis can reveal new vulnerabilities, such as a mutation in the ALK gene, which can be attacked with specific targeted therapies, often available through clinical trials.
Balancing Treatment and Quality of Life
A child who has already undergone intensive therapy is more vulnerable to the toxicities of further treatment. Doctors must carefully balance the need for aggressive therapy against the impact on the child’s overall health and quality of life. This requires constant monitoring and robust supportive care to manage symptoms like pain, fatigue, and nausea that arise from both the disease and its treatment.
Emerging Therapies and Clinical Trials
Research is constantly advancing the fight against neuroblastoma, with clinical trials offering patients access to the most promising new treatments. These studies explore innovative ways to attack cancer cells more effectively and with fewer side effects.
Early Integration of Immunotherapy
A key area of investigation is combining immunotherapy with chemotherapy from the very beginning of treatment for high-risk patients. Rather than waiting until after a stem cell transplant, major clinical trials are testing whether adding drugs like dinutuximab to the initial chemotherapy cycles can eliminate more cancer cells upfront and improve long-term outcomes.
New Combinations for Relapsed Disease
For neuroblastoma that has returned, researchers are actively studying new and more powerful drug combinations. This includes pairing standard chemotherapy agents with immunotherapy or adding novel agents that block specific pathways that cancer cells use to grow and spread.
Advancing Targeted and Post-Transplant Therapies
The development of drugs that target specific genetic mutations represents a move toward personalized medicine. For tumors with an ALK gene mutation, newer drugs like lorlatinib are being tested to shut down the cancer's growth signals. At the same time, other trials are focused on strengthening the post-transplant phase of treatment by adding low-dose chemotherapy or other immune-boosting drugs to standard immunotherapy, aiming to prevent the cancer from ever returning.
