Prognostic Factors in Patients With Recurrent Neuroblastoma

A comprehensive analysis of the patterns of relapse was conducted using the International Neuroblastoma Risk Group (INRG) database on patients diagnosed/enrolled between 1989 and 2017.[14][Level of evidence C1]

The INRG database was used to examine clinical and biological features that are prognostic of survival after relapse or progression of INRG Staging System (INRGSS) stage MS pattern neuroblastoma. Of the 1,511 patients diagnosed between 1984 and 2021 who met the eligibility criteria, 209 patients were identified as having an event. Eligibility criteria included patients younger than 365 days at initial diagnosis with INRGSS stage MS disease or with International Neuroblastoma Staging System (INSS) stage 4S, or patients aged 365 to 546 days with INSS stage 4 disease and metastasis limited to the liver, skin, and/or bone marrow.[15][Level of evidence C1]

The International Neuroblastoma Risk Group Project performed a survival-tree analysis of clinical and biological characteristics (defined at diagnosis) associated with survival after relapse in 2,266 patients with neuroblastoma entered in large clinical trials in well-established clinical trials groups around the world.[8] The survival-tree analysis revealed the following:

Significant prognostic factors determined at diagnosis for postrelapse survival include the following:[8]

The Children’s Oncology Group (COG) experience with recurrence in patients with low-risk and intermediate-risk neuroblastoma showed that most patients can be salvaged. The COG reported a 3-year event free survival (EFS) rate of 88% and an OS rate of 96% in intermediate-risk patients and a 5-year EFS rate of 89% and OS rate of 97% in low-risk patients.[16,17] Moreover, 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 observation alone, surgery alone, or with moderate-dose chemotherapy, without myeloablative therapy and stem cell transplant.

The OS after recurrence in children presenting with high-risk neuroblastoma is generally extremely poor. However, such patients at first relapse after complete remission or minimal residual disease (MRD) in whom relapse was a single site of soft tissue mass (a few children also had bone marrow or bone disease at relapse) had a 5-year OS rate of 35% in one single-institution study. All patients underwent surgical resection of the soft tissue disease. MYCN amplification and multifocal soft tissue disease were associated with a worse postprogression survival.[18] Older children with local recurrence, with either unfavorable International Neuroblastoma Pathology Classification at diagnosis or MYCN gene amplification, have a poor prognosis and may be treated with surgery or aggressive combination chemotherapy, or they may be offered entry into a clinical trial.

Table 7 summarizes the treatment options for recurrent neuroblastoma by INSS-based risk group.