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Neuroblastoma Treatment (PDQ®)

Health Professional Version
Last Modified: 05/23/2014

Changes to this Summary (05/23/2014)

The PDQ cancer information summaries are reviewed regularly and updated as new information becomes available. This section describes the latest changes made to this summary as of the date above.

General Information About Neuroblastoma

Added Yang et al. as reference 43.

Revised text to state that International Neuroblastoma Pathology Classification (INPC) cannot be determined from tumor metastatic to bone marrow. Also added text to state that testing for MYCN amplification and 1p/11q loss of heterozygosity may be successfully performed on involved bone marrow if there is at least 30% to 40% tumor involvement.

Revised text to state that management recommendations are evolving with regard to the need for immediate diagnostic biopsy in infants aged 6 months and younger with suspected neuroblastoma tumors that are likely to spontaneously regress.

Revised text to state that some neuroblastomas cannot be differentiated morphologically, via conventional light microscopy with hematoxylin and eosin staining alone, from other small round blue cell tumors of childhood, such as lymphomas, primitive neuroectodermal tumors, and rhabdomyosarcomas. In such cases, immunohistochemical and cytogenetic analysis may be needed to diagnose a specific small round blue cell tumor.

Revised text to state that children younger than 18 months at diagnosis have a good chance of long-term survival, with outcome particularly dependent on MYCN amplification and tumor cell ploidy (cited Baker et al. as reference 62).

Added text to state that a Children’s Oncology Group (COG) study of children with stage 1 and stage 2 neuroblastoma without MYCN amplification and with favorable histologic features reported a 5-year event-free survival (EFS) of 90% to 94% and overall survival (OS) of 99% to 100%, while those with unfavorable histology had an EFS of 80% to 86% and an OS of 89% to 93% (cited Strother et al. as reference 68). Also added text to state that similar results were found in a European study.

Cellular Classification of Neuroblastic Tumors

Added text to state that most neuroblastomas with MYCN amplification in the INPC system also have unfavorable histology, but about 7% have favorable histology. Of those with MYCN amplification and favorable histology, most do not express MYCN, despite the gene being amplified, and have a more favorable prognosis than those who do express MYCN (cited Suganuma et al. as reference 7).

Stage Information for Neuroblastoma

Revised text to state that the extent of metastatic disease is assessed by metaiodobenzylguanidine (mIBG) scan, which is applicable to all sites of disease (including soft tissue, bone marrow, and cortical bone involvement). Cortical bone metastases are also evaluated by technetium-99 scan. If all sites of bone metastases are imaged by mIBG scan, then subsequent restaging for assessment of disease response may omit the technetium-99 bone scan.

Added text to state that the International Society of Paediatric Oncology European Neuroblastoma Group (SIOPEN) independently developed an mIBG scan scoring system that divided the body into 12 segments, rather than nine, and assigned six degrees, rather than four, of mIBG uptake in each segment

Revised text to state that this led to some variability in stage assignments in different countries because of regional differences in surgical strategy and potentially because of limitations in access to experienced pediatric surgeons. As a result of further advances in the understanding of neuroblastoma biology and genetics, a risk classification system was developed that incorporates clinical and biological factors in addition to INSS stage to facilitate risk group and treatment assignment for COG studies.

Revised text to state that the risk group assignment for INSS stage 4 neuroblastoma in patients aged 12 to 18 months changed in 2005 for those whose tumors had single copy MYCN and all favorable biological features; these patients had been previously classified as high risk, but data from both Pediatric Oncology Group and Children's Cancer Group studies suggested that this subgroup of patients could be successfully treated as intermediate risk.

Treatment Option Overview for Neuroblastoma

Added text to state that 5-year OS was 97% in a large COG study (cited Strother et al. as reference 9).

Revised text to state that for intermediate-risk tumors, chemotherapy is usually given before definitive resection, with the amount and duration based on clinical and tumor biological risk factors and response to therapy. The 3-year OS rate for intermediate-risk patients was about 96% in a large COG study, and thus, the current trend is to decrease chemotherapy to diminish side effects (cited Baker et al. as reference 10).

Revised text to state that for high-risk patients, treatment has intensified to include chemotherapy, surgery, radiation therapy, hematopoietic stem cell transplantation, differentiation therapy, and immunotherapy, resulting in survival rates of 40% to 50%.

Revised Table 5 to update the treatment options for all stages of neuroblastoma.

Added text to state that infants with stage 4 and 4S disease with MYCN amplification are considered high risk in the COG.

Added text about a series of 34 infants with symptomatic epidural spinal cord compression that showed that both surgery and chemotherapy provided unsatisfactory results once paraplegia had been established; this supports the need for greater awareness and timely intervention in these infants (cited De Bernardi et al. as reference 24).

Treatment of Low-Risk Neuroblastoma

Revised text to state that the treatment options for low-risk neuroblastoma include the following: (1) surgery followed by observation; (2) chemotherapy with or without surgery (for symptomatic disease or unresectable progressive disease after surgery); and (3) observation without biopsy (for perinatal neuroblastoma with small adrenal tumors); this is not considered standard treatment.

Added text to state that additional studies are necessary to confirm this finding before it can be considered standard treatment.

Treatment of Intermediate-Risk Neuroblastoma

Revised text to state that one treatment option for intermediate-risk neuroblastoma is chemotherapy with or without surgery.

Revised text to state that whether initial chemotherapy is indicated for all intermediate-risk infants with localized neuroblastoma requires further study.

Revised text about a study that investigated an overall reduction in treatment compared with prior treatment plans in patients with unresectable, localized, MYCN-nonamplified tumors and infants with stage 4 MYCN-nonamplified disease.

Added text to state that 3-year OS was excellent for infants receiving chemotherapy.

Added text about a prospective SIOPEN trial that treated children with stage 2 or stage 3 unresectable neuroblastoma and those aged 12 to 18 months, with favorable INPC (cited Kohler et al. as reference 7 and level of evidence 3iiD).

Treatment of High-Risk Neuroblastoma

Revised text to state that the consolidation phase of treatment includes hematopoietic stem cell rescue/transplantation (HSCT) and radiation therapy to the site of the primary tumor.

Added text to state that tandem consolidation using 131I-mIBG, vincristine, and irinotecan with autologous SCT followed by busulfan/melphalan with autologous SCT has been studied in refractory patients (cited French et al. as reference 13).

Revised text to state that radiation of metastatic disease sites is determined on an individual case basis or according to protocol guidelines for patients enrolled in studies.

Revised text to state that in a COG phase III trial after HSCT, patients were randomly assigned to receive anti-GD2 monoclonal antibody (ch14.18) administered with GM-CSF and interleukin-2 in conjunction with isotretinoin, versus isotretinoin alone.

Added text about the COG-ANBL09P1 trial to state that this pilot study will evaluate the tolerability and feasibility of an induction chemotherapy regimen containing five cycles of multiagent chemotherapy and a block of 131I-mIBG followed by a consolidation regimen of busulfan/melphalan with autologous stem cell rescue and external-beam radiation therapy. The study has been amended to omit vincristine and irinotecan as radiation sensitizers, and the period from transplant to the start of radiation was extended to 42 days because of toxicity.

Treatment of Stage 4S Neuroblastoma

Revised text to state that tumors with unfavorable biology or patients who are symptomatic due to evolving hepatomegaly and organ compromise are at increased risk of death and are treated with low-dose to moderate-dose chemotherapy.

Revised text to state that treatment options for stage 4S neuroblastoma include the following: (1) observation with supportive care (for asymptomatic patients with favorable tumor biology); and (2) chemotherapy (for symptomatic patients, very young infants, or those with unfavorable biology).

Added text to state that rarely, infants with massive hepatic 4S neuroblastoma develop cirrhosis from the chemotherapy and/or radiation therapy that is used to control the disease and may benefit from orthotopic liver transplantation (cited Steele et al. as reference 5).

Revised text to state that on COG-ANBL0531, the 2-year OS rate for INSS stage 4S patients was 81%, which is lower than reported on COG-P9641 and thought to reflect the expanded eligibility allowing enrollment of patients who were too ill to undergo diagnostic biopsy. These patients would have been excluded from prior COG trials.

Recurrent Neuroblastoma

Revised text to state that patients may have persistent maturing disease with mIBG uptake that does not affect outcome, particularly in patients with low-risk and intermediate-risk disease.

Revised text to state that in most patients originally diagnosed with low-risk or intermediate-risk disease, local recurrence or recurrence in the 4S pattern may be treated successfully with either surgery and/or with moderate-dose chemotherapy, without HSCT.

Revised text to state that treatment options for locoregional recurrent neuroblastoma initially classified as low risk include the following: (1) surgery followed by observation or chemotherapy; and (2) chemotherapy that may be followed by surgery.

Revised text to state that chemotherapy may consist of moderate doses of carboplatin, cyclophosphamide, doxorubicin, and etoposide, or cyclophosphamide and topotecan. Also revised text to state that older children with local recurrence with either unfavorable INPC at diagnosis or MYCN gene amplification have a poor prognosis and may be treated with surgery, aggressive combination chemotherapy, or offered entry into a clinical trial.

Revised text to state that treatment options for metastatic recurrent neuroblastoma initially classified as low risk include the following: (1) observation (if metastatic disease is in a 4S pattern in an infant); and (2) chemotherapy.

Revised text to state that any child initially categorized as low risk who is older than 1 year at the time of metastatic recurrent or progressive disease and whose recurrence is not in the stage 4S pattern usually has a poor prognosis and should be considered for high-risk therapy.

Revised text to state that treatment options for metastatic recurrent neuroblastoma initially classified as intermediate risk include the following: (1) high-risk therapy.

Added text to state that patients with metastatic recurrent neuroblastoma are treated like patients with newly diagnosed high-risk neuroblastoma.

Revised text to state that topotecan in combination with cyclophosphamide or etoposide is a chemotherapy treatment option for recurrent or refractory neuroblastoma in patients initially classified as high risk.

Revised text to state that for children with recurrent or refractory neuroblastoma, 131I-mIBG is an effective palliative agent and may be considered alone or in combination with chemotherapy (with stem cell rescue) in a clinical research trial (cited French et al. as reference 22 and level of evidence 3iiiA).

This summary is written and maintained by the PDQ Pediatric Treatment Editorial Board, which is editorially independent of NCI. The summary reflects an independent review of the literature and does not represent a policy statement of NCI or NIH. More information about summary policies and the role of the PDQ Editorial Boards in maintaining the PDQ summaries can be found on the About This PDQ Summary and PDQ NCI's Comprehensive Cancer Database pages.