The INRG History

Modern treatment for neuroblastoma is stratified by risk-group assignment. However, the factors selected by various cooperative groups around the world to define risk are not uniform. In addition, increasing number of genetic features included in more recently developed clinical trials to guide therapy decisions complicates comparisons of clinical trials conducted in different regions of the globe. To develop a consensus approach to pre-treatment risk stratification, investigators from the major cooperative groups, the Children’s Oncology Group [COG] (North America and Australia), the German Gesellschaft für Pädiatrische Onkologie und Hämatologie [GPOH], the Japanese Advanced Neuroblastoma Study Group [JANB], the Japanese Infantile Neuroblastoma Co-operative Study Group [JINCS], the International Society of Paediatric Oncology European Neuroblastoma Research [SIOPEN] and China with expertise in neuroblastoma established an INRG Task Force.

The INRG task force is comprised of leaders of the cooperative groups with expertise in one or more of the following categories: clinical trials related to neuroblastoma, chemotherapy, surgery, pathology, biology, radiology, nuclear medicine and statistics. In addition, young investigators were invited, and 52 investigators were identified. Four committees were formed: Surgery, Chair – Tom Monclair; Statistics, Chair – Wendy B. London; Biology, Chair – Peter F. Ambros and Metastatic Disease, Chair – Katherine K. Matthay. The four Chairs of the committees and the co-Chairs of the INRG Task Force (Drs. Andrew Pearson and Susan Cohn) comprised the INRG Executive Committee.

To develop the INRG classification system, the Task Force analyzed the prognostic effect of 13 variables in an 8,800 patient cohort. In addition, a new pre-treatment staging system was designed for the INRG classification system. In the INRGSS, extent of locoregional disease is determined by the absence or presence of image defined risk factors (L1 and L2, respectively). Stage M will be used for disseminated disease, analogous to INSS stage 4. Similar to INSS stage 4S tumors, metastases are limited to skin, liver and bone marrow without cortical bone involvement in INRGSS MS disease. However, the definition of MS has been expanded to include toddlers aged 12-18 months and large “unresectable” primary tumors (L1or L2). The INRG classification system will ensure that children diagnosed with NB in any country are stratified into homogenous pre-treatment groups.