Treatment of Recurrent or Refractory Neuroblastoma

Tumor growth resulting from maturation should be differentiated from tumor progression by performing a biopsy and reviewing histology. Patients may have persistent maturing disease with metaiodobenzylguanidine (MIBG) uptake that does not affect outcome, particularly patients with low-risk and intermediate-risk disease.[1] An analysis of 23 paired MIBG and positron emission tomography (PET) scans in 14 patients with refractory or recurrent high-risk neuroblastoma treated with iodine I 131-MIBG (131I-MIBG) found that the MIBG scan was more sensitive than fluorine F 18-fludeoxyglucose (18F-FDG) PET for detecting metastatic bone lesions, although there was a trend for 18F-FDG PET to be more sensitive for soft tissue lesions.[2]

Subclonal ALK variants or other MAPK pathway lesions may be present at diagnosis, with subsequent clonal expansion at relapse. Consequently, serial sampling of progressive tumors may lead to the identification of potentially actionable variants.[3,4] Modern comprehensive molecular analysis comparing primary and relapsed neuroblastoma from the same patients revealed extensive clonal enrichment and several newly discovered variants, with many tumors showing new or clonal-enriched variants in the RAS-MAPK pathway. This was true for patients with both high-risk and low-risk tumors at diagnosis.[5,6] For more information, see the Genomic and Biological Features of Neuroblastoma section.

Sequencing of recurrent and refractory neuroblastoma tumors from pediatric (n = 59) and young adult patients (n = 1) enrolled in the NCI-COG Pediatric MATCH trial revealed genomic alterations that were considered actionable for treatment in MATCH study arms in 27 of 60 tumors (45%).[7] Hotspot variants in ALK were most frequent, reported in 19 of 60 tumors (31.7%). MAPK pathway variants (NF1, NRAS) were detected in 4 of 60 tumors (6.7%), and FGFR1 variants were detected in 3 of 60 tumors (5%).

If neuroblastoma recurs in a child originally diagnosed with high-risk disease, the prognosis is usually poor despite additional intensive therapy.[8-11] However, it is often possible to gain many additional months of life for these patients with alternative chemotherapy regimens.[12,13] Clinical trials are appropriate for these patients and may be offered. Information about ongoing clinical trials is available from the NCI website.