Neuroblastoma Treatment (PDQ®): Treatment - Health Professional Information [NCI] - Treatment of High-Risk Neuroblastoma
Refer to the Treatment Option Overview section of this summary for more information.
In North America, the Children's Oncology Group (COG) investigated a risk-based neuroblastoma treatment plan that assigned all patients to a low-, intermediate-, or high-risk group based on age, International Neuroblastoma Staging System (INSS) stage, and tumor biology (i.e., MYCN gene amplification, International Neuroblastoma Pathology Classification [INPC] system, and DNA ploidy) (COG-P9641 and COG-A3961). (Low-, intermediate- and high-risk groups are defined in Table 1 in the Stage Information section of this summary.)
There is no defined staging system for childhood central nervous system atypical teratoid/rhabdoid tumor (AT/RT). Patients are classified as having newly diagnosed or recurrent disease with or without neuraxis dissemination.
For children with high-risk neuroblastoma, long-term survival with current treatments is about 30%. Children with aggressively treated, high-risk neuroblastoma may develop late recurrences, some more than 5 years after completion of therapy.[1,2] A randomized study was performed comparing high-dose therapy with purged autologous hematopoietic stem cell transplantation (HSCT) versus three cycles of intensive consolidation chemotherapy. The 3-year event-free survival (EFS) was significantly better in the HSCT arm (34%) compared with the consolidation chemotherapy arm (18%). Superiority of myeloablative chemotherapy over maintenance therapy was confirmed in another study. In addition, patients on this study were subsequently randomized to stop therapy or to receive 6 months of 13-cis-retinoic acid. Patients who received 13-cis -retinoic acid had significantly better 3-year EFS than patients who received no maintenance therapy. This was true for all patient subgroups. The 5-year EFS and overall survival (OS) for patients treated with both HSCT and retinoic acid is 50% and 59%, respectively. The 10-year OS remains greater than 50%. However, these patients were selected for having completed HSCT without developing progressive disease. Based on these results, clinical trials have built upon autologous HSCT and 13-cis -retinoic acid for high-risk neuroblastoma. Compared to retinoic acid alone, the addition of chimeric anti-GD2 antibody ch14.18 combined with granulocyte macrophage-colony stimulating factor and interleukin-2 improves EFS for high-risk neuroblastoma patients in remission after stem cell transplant (SCT) (COG-ANBL0032 and COG-ANBL0931).
The potential benefit of aggressive surgical approaches in high-risk patients with metastatic disease to achieve complete tumor resection, either at the time of diagnosis or following chemotherapy, has not been unequivocally demonstrated. Several studies have reported that complete resection of the primary tumor at diagnosis improved survival; however, the outcome in these patients may be more dependent on the biology of the tumor, which itself may determine resectability, than on the extent of surgical resection.[7,8,9,10,11] The use of radiation therapy to consolidate local control after surgical resection is recommended.; [Level of evidence: 3iiA]
Assessment of risk for low-stage MYCN-amplified neuroblastoma is controversial because it is so rare. A study of 87 INSS stage 1 and 2 patients pooled from several clinical trial groups demonstrated no effect of age, stage, or initial treatment on outcome. The EFS and OS were 53% and 72%, respectively. Survival was superior in patients whose tumors were hyperdiploid rather than diploid (EFS 82% ± 20% vs. 37% ± 21%; OS 94% ± 11% vs. 54% ± 15%). The overall EFS and OS for infants with stage 4 and 4S disease and MYCN-amplification was only 30% at 2 to 5 years post-treatment in a European study.