Welcome to the Science Spotlight, where we highlight the scientific advancements made possible by our consortia and data commons.
In this Science Spotlight, INRG profiles two recent neuroblastoma publications, how they used INRG data from the PCDC, and how they might impact future research and patient care.
Nomogram for identifying high-risk patients at highest risk of disease progression/death
Spotlight by Dr. Lucas Moreno, on behalf of the INRG Executive Committee
The paper
Moreno L, Guo D, Irwin MS, Berthold F, Hogarty M, Kamijo T, Morgenstern D, Pasqualini C, Ash S, Potschger U, Ladenstein R, Valteau-Couanet D, Cohn SL, Pearson ADJ, London WB. A nomogram of clinical and biologic factors to predict survival in children newly diagnosed with high-risk neuroblastoma: An International Neuroblastoma Risk Group project. Pediatr Blood Cancer. 2021 Mar;68(3):e28794. doi: 10.1002/pbc.28794. Epub2020 Nov 18.PMID: 33205902
The research
The objectives of this study were to (a) identify prognostic biomarkers and apply them in a nomogram to identify the subgroup of ultra-high-risk patients at highest risk of disease progression/death and (b) validate the nomogram in an independent cohort. A nomogram was created using data from over 1800 high-risk patients (≥18 months old with metastatic neuroblastoma), in the International Neuroblastoma Risk Groups (INRG) Data Commons, which is part of the Pediatric Cancer Data Commons (PCDC). External validation was performed using the SIOPEN HR-NBL1 trial cohort (n = 521). We show the nomogram, including MYCN status (P < 0.0001), lactate dehydrogenase (LDH) (P = 0.0007), and presence of bone marrow metastases (P = 0.004), had robust performance and was validated.
Why it matters
Primary endpoints in clinical trials for patients with soft tissue sarcoma are based on imaging response definitions (either response or progression). These response assessments are subject to several efforts to integrate more recently discovered genomic and biologic prognostic factors into the INRG data commons are ongoing. We anticipate these biomarkers will lead to further refinement in risk classification and improved treatment decisions. This study would not have been possible without the large INRG Data Commons patient cohort. We are pleased to have created this nomogram that is now available to the international neuroblastoma community.
Relapse of Rare Category of Neuroblastoma
Spotlight by Dr. Steven DuBois, on behalf of the INRG Executive Committee
The paper
Campbell K, Kao PC, Naranjo A, Kamijo T, Ramanujachar R, London WB, DuBois SG. Clinical and biological features prognostic of survival after relapse or progression of INRGSS stage MS pattern neuroblastoma: A report from the International Neuroblastoma Risk Group (INRG) project. Pediatr Blood Cancer. 2023 Feb;70(2):e30054. doi: 10.1002/pbc.30054. Epub 2022 Oct 31.PMID: 36316811
The research
Stage MS neuroblastoma is a specific subtype of this disease characterized by young age, specific metastatic pattern, and potential to spontaneously regress. Very little is known about outcomes after relapse from stage MS neuroblastoma. In order to address this knowledge gap, an international team of investigators turned to the International Neuroblastoma Risk Group (INRG) Data Commons, the largest available collection of patients with neuroblastoma. They identified 209 patients with relapsed stage MS
neuroblastoma. Most patients with recurrent disease relapsed in metastatic sites. Outcomes were generally poor, with an overall survival rate of only 53% by 5 years after relapse, though patients treated in more recent years had superior outcomes. The group evaluated factors associated with less favorable outcomes and showed that non-white race, the presence of MYCN amplification, or diploid DNA content were each independent adverse prognostic factors.
Why it matters
These findings will enable clinicians to better counsel and treat these rare patients with relapsed stage MS disease and provide an important example of leveraging the INRG Data Commons, a Pediatric Cancer Data Commons (PCDC) resource, to evaluate a rare clinical scenario.