Treatment of INSS Stage 4S and INRG Stage MS Neuroblastoma

International Neuroblastoma Staging System (INSS) stage 4S patients are younger than 12 months and have an INSS stage 1 or stage 2 primary tumor. International Neuroblastoma Risk Group (INRG) stage MS patients are younger than 18 months with any stage of primary tumor. Both staging systems have the same definition of limited pattern of metastases.

The decision by the INRG Task Force to replace the category of 4S disease with that of the new MS definition was based on reports in which small numbers of infants with L2 primary tumors and 4S metastatic patterns, including patients aged 12 to 18 months, had favorable outcomes.[1,2] A subsequent study of the actual INRG data found that a number of biological characteristics predicted poor outcome of patients aged 12 to 18 months with stage MS disease, and that only those infants with favorable biology had long-term outcomes similar to those with the traditional 4S diagnosis.[2]

Infants with INRG stage MS disease have more favorable biology and superior outcomes despite receiving less aggressive therapy. The 5-year event-free survival (EFS) rate was 86%, and the overall survival (OS) rate was 95%. For patients with MYCN-amplified tumors, the 5-year EFS rate was 60%, and the OS rate was 65%.[3]

Many patients with stage 4S/MS neuroblastoma do not require therapy. However, tumors with unfavorable biology or patients who are symptomatic because of evolving hepatomegaly and organ compromise are at increased risk of death and are treated with low-dose to moderate-dose chemotherapy. Eight percent to 10% of these patients will have MYCN amplification and are treated with high-risk treatment regimens.[4]

For more information about the Children's Oncology Group (COG) classification schema for stage 4S/MS neuroblastoma, see Table 3.