Response to treatment

Response to treatment has been associated with outcome. In patients with intermediate-risk disease who had a poor response to initial therapy in the COG ANBL0531 (NCT00499616) study, 6 of 20 patients subsequently developed progressive or recurrent disease, and one patient died.[102]

In patients with high-risk disease, the persistence of neuroblastoma cells in bone marrow after induction chemotherapy is associated with a poor prognosis. Sensitive techniques that detect minimal residual disease may be used to assess prognosis.[108-110] For example, detection of RNA transcripts expressed by neuroblastoma cells (in the bone marrow) after initial induction chemotherapy in children with high-risk neuroblastoma has been associated with significantly inferior EFS and OS.[111]

Similarly, the persistence of MIBG-avid tumor, measured as Curie score greater than 2 after completion of induction therapy, predicts a poor prognosis for patients with MYCN-nonamplified high-risk tumors. A Curie score greater than 0 after induction therapy is associated with a worse outcome for high-risk patients with MYCN-amplified disease.[112,113] An analysis of North American patients who went on to receive tandem transplants showed that patients with Curie scores greater than 0 at the end of induction therapy had inferior EFS rates.[114] For more information about Curie scoring, see the Curie and SIOPEN scoring methods section.

In an analysis of patients from four consecutive COG high-risk trials, an end-induction response of partial response (PR) or better, according to the 1993 International Neuroblastoma Response Criteria,[64] was significantly associated with higher EFS and OS. On multivariable analysis (n = 407), the absence of 11q loss of heterozygosity (LOH) was the only factor that remained significantly associated with PR or better (OR, 1.962 vs. 11q LOH; 95% CI, 1.104–3.487; P = .0216).[115]

A treatment-associated decrease in mitosis and an increase in histological differentiation of the primary tumor are also prognostic of response.[116]

The accuracy of prognostication based on decrease in primary tumor size is less clear. In a study conducted by seven large international centers, 229 high-risk patients were treated in a variety of ways. Treatment included chemotherapy, surgical removal of the primary tumor, radiation to the tumor bed, high-dose myeloablative therapy plus stem cell transplant, and, in most cases, isotretinoin and anti-GD2 antibody immunotherapy enhanced by cytokines. Primary tumor response was measured after induction chemotherapy in three ways: as 30% or greater reduction in the longest dimension, 50% or greater reduction in tumor volume, or 65% or greater reduction in tumor volume (calculated from three tumor dimensions, a conventional radiological technique). The measurements were performed at diagnosis and after induction chemotherapy before primary tumor resection. None of the methods of measuring primary tumor response at end of induction chemotherapy predicted survival.[117]