Relapsed or Refractory Neuroblastoma

Relapsed neuroblastoma refers to the return of neuroblastoma in patients who have already undergone treatment for the disease. Approximately half of children who are treated for high-risk neuroblastoma and achieve an initial remission will have the disease come back.

In addition, in approximately 15 percent of children with high-risk neuroblastoma, the tumor does not respond to initial treatment. These children are said to have refractory neuroblastoma. The treatment approach for children with refractory neuroblastoma is similar to that for children with relapsed 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 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
• Enlarged lymph nodes in the neck
• Swelling and bruising of the area around the eyes
• Unexplained fevers, bone pain, or limping
• Weakness or paralysis
• Weight loss or poor appetite
• Uncontrolled eye or leg movements

It is important to understand that tumors often emerge with no known cause. Many may result from the combined effects of genetic and environmental factors, but some cancers are caused by inherited conditions. Conditions associated with pheochromocytomas include neurofibromatosis, von Hippel-Lindau disease, multiple endocrine neoplasia (MEN) syndromes, tuberous sclerosis, Sturge-Weber syndrome, and ataxia-telangiectasia.

Adrenocortical carcinomas are often linked to genetic conditions, most often Li-Fraumeni syndrome. About 50 to 80 percent of pediatric ACC patients have this syndrome. Other related conditions include MEN1, Lynch syndrome, Beckwith-Wiedemann syndrome, and hemihypertrophy.

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

• Computerized tomography (CT or CAT) scan
• Magnetic resonance imaging (MRI) scan
• Bone scan
• Metaiodobenzylguanidine (MIBG) scan
• Bone marrow biopsy and/or aspiration
• Urine tests
• Blood 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. It may also include chemotherapy using combinations of chemotherapy agents not used to treat newly diagnosed neuroblastoma, or immunotherapy generally given in combination with chemotherapy.

We also offer innovative clinical trials of experimental agents (Phase 1 or 2) for children with relapsed or recurrent neuroblastoma.

Children and adolescents with relapsed or refractory neuroblastoma are treated at Dana-Farber/Boston Children’s Cancer and Blood Disorders Center through the Neuroblastoma Program, one of the largest and most experienced pediatric neuroblastoma programs in the world.

Our neuroblastoma specialists are known for treating children with the most complex cases, as well as for their expertise in delivering specialized treatments. We are one of only about 10 centers in the country, and the first and only center in New England, to offer MIBG therapy, an advanced treatment option for neuroblastoma that delivers targeted radiation to kill neuroblastoma cells.

Research is a top priority at Dana-Farber/Boston Children's Cancer and Blood Disorders, 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.