A diagnosis of relapsed neuroblastoma signifies the cancer’s return after a period where it was undetectable following initial treatment. This is distinct from refractory neuroblastoma, where the cancer did not adequately respond to the first round of therapies. For families, this news marks a shift from the hope of remission to the challenge of confronting the disease again. The path forward involves a new phase of evaluation and treatment, tailored to the specifics of the relapsed disease by a medical team.
Understanding Why Neuroblastoma Returns
Neuroblastoma returns primarily because of minimal residual disease (MRD), a term for a small number of cancer cells that survive the initial treatment regimen. These cells can remain dormant and undetected by standard medical imaging for months or even years. Eventually, these resilient cells can begin to multiply again, leading to a relapse, which is more common in children originally diagnosed with high-risk neuroblastoma.
The biological characteristics of the original tumor play a part in its potential to return. Some neuroblastoma cells have specific genetic features that make them more aggressive and resistant to chemotherapy. These surviving cells may also undergo further genetic changes, making the relapsed disease different from the initial cancer. This cellular evolution is a reason why treatments that worked the first time may not be as effective for a relapse.
When neuroblastoma comes back, it often appears in specific parts of the body. The most common sites for relapse are the bone marrow, bones, and distant lymph nodes. It can also recur in the location of the original tumor or, less commonly, in the central nervous system, including the brain and spinal cord. The location and extent of the relapse are important factors that doctors consider when planning treatment.
Diagnostic Process for Relapsed Disease
When a relapse is suspected, comprehensive tests are performed to confirm the cancer’s presence and determine its extent in a process called “re-staging.” Imaging studies are the first step, including a meta-iodobenzylguanidine (MIBG) scan, which uses a radioactive tracer that accumulates in neuroblastoma cells to detect tumors throughout the body. Other imaging techniques like computed tomography (CT) or magnetic resonance imaging (MRI) scans provide detailed images to assess tumor size and location, while a positron emission tomography (PET) scan can identify metabolically active cancer cells.
To confirm the diagnosis at a cellular level, more invasive procedures are required. A bone marrow aspirate and biopsy are performed to check for cancer cells in the bone marrow. A biopsy of a suspicious tumor identified on a scan may also be necessary. Pathologists analyze these tissue samples to confirm the relapse and study the tumor’s genetic makeup, looking for mutations that could be targeted with specific drugs.
Advanced Treatment Strategies
There is no single standard treatment for relapsed neuroblastoma; instead, care is highly personalized. The choice of therapy depends on factors like the time to relapse, the location of new tumors, and the treatments previously used. Combination chemotherapy often forms the foundation of the new treatment plan, using different agents than those used initially, such as irinotecan with temozolomide or cyclophosphamide with topotecan.
Immunotherapy is a component of treating relapsed neuroblastoma, often used alongside chemotherapy. Drugs like dinutuximab are monoclonal antibodies that recognize a specific molecule on the surface of neuroblastoma cells. This antibody attaches to the cancer cells, flagging them for destruction by the patient’s own immune system. This approach helps the body’s natural defenses identify and attack the cancer.
For some patients, targeted radiation offers another option. MIBG therapy involves attaching a high dose of radioactive iodine to the MIBG molecule, which neuroblastoma cells readily absorb. This technique delivers radiation directly to the cancer cells throughout the body, minimizing damage to surrounding healthy tissues. It is a systemic treatment that can be effective when the disease has spread to multiple locations.
Newer targeted therapies are designed to attack specific vulnerabilities within the cancer cells. Some neuroblastoma tumors have a mutation in a gene called ALK, which drives cell growth. For these patients, ALK inhibitor drugs can block the signals that tell cancer cells to divide. Accessing these advanced treatments often involves participation in clinical trials, which are important for developing better therapies for children with relapsed neuroblastoma.
Prognosis and Factors of Influence
The prognosis for a child with relapsed neuroblastoma is highly individual and is influenced by several distinct factors. One of the most significant is the timing of the relapse. A relapse that occurs later, more than 18 months after the initial diagnosis, indicates a more favorable outlook compared to an early relapse, as a longer remission period suggests the cancer is less aggressive.
The location and extent of the disease at the time of relapse also play a large role in determining the prognosis. A relapse confined to a single, localized spot is easier to manage than widespread disease that has spread to multiple sites like the bones and bone marrow.
The biological features of the relapsed tumor are another consideration. Genetic analysis of the tumor cells can reveal new mutations or changes from the original cancer. The presence of an ALK gene mutation, for instance, may open the door to targeted therapies that can improve the prognosis. Finally, the cancer’s response to previous treatments is evaluated to help predict how it might behave with subsequent therapies.