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Neuroblastoma Treatment (PDQ®): Treatment - Health Professional Information [NCI] - Treatment of High-Risk Neuroblastoma

Table 8. Children's Oncology Group (COG) Neuroblastoma High-Risk Group Assignment Schema Used for COG-P9641 and COG-A3961 Studiesa continued...

Preliminary outcomes for proton radiation therapy of high-risk neuroblastoma primary tumors have been published.[13]

Maintenance phase

Differentiation therapy is used to treat potential minimal residual disease following HSCT.[14] After recovery from myeloablative chemotherapy and stem cell rescue, patients are treated with the differentiating agent oral 13-cis -retinoic acid for 6 months. Immunotherapy is given along with differentiated therapy in the post-HSCT differentiation therapy regimen. Antibodies developed to target GD2, present on the surface of neuroblastoma cells, are used. For high risk-patients in remission following HSCT, chimeric anti-GD2 antibody ch14.18 combined with GM-CSF and interleukin-2 are given in concert with retinoic acid and have been shown to improve EFS.[15,16]

Evidence (all treatments):

  1. A randomized study was performed comparing high-dose therapy with purged autologous bone marrow transplant (ABMT) versus three cycles of intensive consolidation chemotherapy. In addition, patients on this study were subsequently randomly assigned to stop therapy or to receive 6 months of 13-cis-retinoic acid.[8]; [14][Level of evidence: 1iiA]
    • The 5-year EFS was significantly better in the ABMT arm (30%), compared with the consolidation chemotherapy arm (19%; P = .04). There was no significant difference in 5-year OS (39% vs. 30%; P = .39). However, in patients who survived more than 3 years, a significant benefit is seen in OS with ABMT.[14]
    • Patients who received 13-cis -retinoic acid had a higher 5-year EFS than patients who received no maintenance therapy (42% vs. 31%), although the difference was not significant. For patients who participated in both random assignments, the 5-year OS from the time of the second randomization for patients assigned ABMT and cis -retinoic acid was 59% and 41% for patients assigned to ABMT without cis -retinoic acid. Patients assigned to consolidation chemotherapy and cis -retinoic acid showed a 5-year survival of 38% and 36% for patients receiving consolidation chemotherapy and no cis -retinoic acid.[14] However, these patients were selected for having completed ABMT without developing progressive disease.
  2. In a separate study, there was no advantage to purging harvested stem cells of neuroblastoma cells before transplantation.[17]
  3. In a COG phase III trial following HSCT, patients were randomly assigned to receive anti-GD2 monoclonal antibody (ch14.18) administered with GM-CSF and interleukin-2.[15]
    • Immunotherapy together with cis -retinoic acid (EFS, 66%) was superior to standard cis -retinoic acid maintenance therapy (EFS, 46%). As a result, immunotherapy post-HSCT is considered the standard of care in COG trials for high-risk disease.
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