Treatment Option Overview
The treatments described in this summary are based on the Children's Oncology Group (COG) group assignment, which is described in the Stage Information section of this summary. Treatment information is presented in this format because most children with neuroblastoma in North America are treated according to the COG schema. The prior COG risk-based neuroblastoma studies established the standard of care. They assigned each patient to a low-, intermediate-, or high-risk group and the basis of the assignment is described in Table 1. The current COG study of intermediate-risk neuroblastoma is evaluating whether the duration of chemotherapy can safely be reduced and assigns low- and intermediate-risk patients to four different treatment groups and is described in Table 2 in the Treatment of Low-Risk Neuroblastoma section of the summary. To define the risk groups, the risk of progression of the tumor causing morbidity and mortality is gauged based on the stage of the tumor, the age of the child at diagnosis, and tumor biology. The biological features considered are the International Neuroblastoma Pathology Classification (INPC) system, amplification of the MYCN gene, and the number of chromosomes in tumor cells (measured as the DNA index by flow cytometry).
In patients without metastatic disease, the standard of care is to perform an initial surgery to establish the diagnosis, to resect as much of the primary tumor as is safely possible, to accurately stage disease through sampling of regional lymph nodes that are not adherent to the tumor, and to obtain adequate tissue for biological studies. Accurate determination of biological characteristics, such as INPC system, usually requires an open biopsy. The accuracy of diagnosis and staging is increased by performing a metaiodobenzylguanidine (MIBG) scan.[1] Urinary excretion of the catecholamine metabolites vanillylmandelic acid (VMA) and homovanillic acid (HVA) per mg of excreted creatinine should be measured prior to therapy. If elevated, these markers can be used to determine the persistence of disease.
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There is controversy about the need for immediate diagnostic biopsy in infants aged 3 months and younger with suspected neuroblastoma tumors that are likely to spontaneously regress. Biopsy is not required for infants entered into a COG study of expectant observation of adrenal masses in neonates. In a German clinical trial, 25 infants aged 3 months and younger with presumed neuroblastoma were observed without biopsy for periods of 1 to 18 months prior to biopsy or resection. There were no apparent ill effects of the delay.[2] In the current COG trial (COG-ANBL0531), infants with severely symptomatic apparent stage 4S neuroblastoma may be entered on trial and treated without diagnostic biopsy.
There is also controversy about the need for attempted resection, whether at the time of diagnosis or later, in asymptomatic infants aged 12 months or younger with apparent stage 2B and 3 MYCN-nonamplified disease. In a German clinical trial, some of these patients were observed after biopsy or partial resection without chemotherapy or radiation, and many did not progress locally and never received additional resection.[2]
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