Relapsed or Refractory Neuroblastoma

As with newly diagnosed neuroblastoma, the symptoms of relapsed neuroblastoma can vary greatly, depending on the size and location of the tumor and whether or not the tumor has spread.

While neuroblastoma usually begins in the abdomen, especially in the tissues of the adrenal glands, it may also begin in nerve tissues in the neck, chest or pelvis. These tumors often spread (metastasize) to other areas of the body, including the lymph nodes, liver, bones and bone marrow.

The symptoms of relapsed neuroblastoma can include:

• an abdominal mass, either felt during an examination or seen as a swollen abdomen
• enlarged lymph nodes in the neck
• swelling and bruising of the area around the eyes
• unexplained fevers, bone pain or limping caused by bone or bone marrow involvement
• weakness or paralysis caused by compression of the spinal cord by tumor
• weight loss or poor appetite
• uncontrolled eye or leg movements caused by an autoimmune response to the tumor can be asymptomatic and be picked up by scans done as a routine check

To make a diagnosis of relapsed neuroblastoma, your doctor may order a variety of tests, including:

• imaging studies, such as a computerized tomography (CT or CAT) scan, magnetic resonance imaging (MRI) scan or bone scan, to evaluate the tumor and determine the extent and location of metastases
• a metaiodobenzylguanidine (MIBG) scan, which uses a radioactive chemical that is absorbed by most neuroblastomas, and a specialized scanner to locate the presence of the neuroblastoma
• bone marrow biopsy and/or aspiration, to determine whether neuroblastoma cells have spread to the bone marrow
• urine test to measure specific chemicals made by neuroblastoma cells
• blood tests, including a complete blood count, blood chemistries, and kidney and liver function tests

In some cases, your doctor may also order a tumor biopsy, in which surgeons or interventional radiologists remove either a piece of the tumor or the whole tumor, depending on tumor location and size. Pediatric pathologists will analyze the tumor, and other important tests will be done to determine the tumor biology, such as genetic studies to look for genes that may be targeted using new drugs.

After all tests are completed, doctors will be able to outline the best treatment options.

There is no standard treatment for relapsed neuroblastoma. Rather, our treatment approach is personalized for each patient depending on several factors, including:

• extent of relapse
• length of time from prior treatment
• type of prior treatment

Treatment options for relapsed neuroblastoma include:

• MIBG therapy, which uses a radioactive isotope that is readily absorbed by most neuroblastomas and can be used to detect neuroblastoma in the body or to deliver radiation in order to kill the neuroblastoma cells
• chemotherapy, generally using combinations of chemotherapy agents not used to treat newly diagnosed neuroblastoma
• immunotherapy, generally given in combination with chemotherapy, using Unituxin (dinutuximab), an antibody that binds to the surface of neuroblastoma cells

We also offer innovative clinical trials of experimental agents (Phase 1 or 2) for children with relapsed or recurrent neuroblastoma. Some of these were launched by our own physicians, while others are available through our participation in collaborative groups such as the New Approaches to Neuroblastoma Therapy (NANT) consortium, the Children's Oncology Group (COG) and the Pediatric Oncology Experimental Therapeutics Investigators' Consortium (POETIC).

Should you have questions or need advice on whether a particular trial would be appropriate for your child, email our clinical trials team at clinicaltrials@danafarberbostonchildrens.org. We can help you navigate your options.

At present, it is very difficult to cure relapsed high-risk neuroblastoma. For some patients, it can be managed as a chronic disease.

Research is a top priority at Dana-Farber/Boston Children's, and our physicians work continuously to translate laboratory findings into clinical therapies.

It’s possible that your child will be eligible to participate in one of the Neuroblastoma Program’s current clinical trials. In addition to launching our own clinical trials, we also offer the most Phase I studies in New England for children whose disease has recurred through the Children's Oncology Group and the New Approaches to Neuroblastoma Therapy (NANT) consortium.

Our current research efforts focus on improving established therapies for newly diagnosed and relapsed or recurrent neuroblastoma, studying the genetic causes of the disease and developing novel therapies. For instance, recent laboratory and animal studies by researchers at Dana-Farber/Boston Children's have focused on ways to counter MYCN amplification, one of the most common genetic features of aggressive neuroblastomas.

Our researchers are also teasing apart the relationship between neuroblastoma and a gene called ALK. We are working on therapies that target this gene and may improve treatment for newly diagnosed and relapsed neuroblastoma.