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Three-Dimensional In Vitro Biomimetic Model of Neuroblastoma Using Collagen-Based Scaffolds
Published on: July 9, 2021
Biologic factors determine prognosis in infants with stage IV neuroblastoma: A prospective Children's Cancer Group
M L Schmidt1, J N Lukens, R C Seeger
1Department of Pediatrics, University of Illinois at Chicago College of Medicine, Chicago, IL, USA. mls3@uic.edu
Insights
MYCN amplification in infant neuroblastoma (NBL) significantly impacts survival. Tumors without MYCN amplification show a 93% event-free survival, while amplified MYCN indicates a poor prognosis, guiding treatment intensity for stage IV NBL.
Area of Science:
- Pediatric Oncology
- Molecular Biology
- Cancer Genetics
Background:
- Stage IV neuroblastoma (NBL) in infants presents a significant challenge in pediatric oncology.
- Accurate prognostic markers are crucial for tailoring treatment intensity in high-risk infant NBL.
Purpose of the Study:
- To evaluate biologic features for improved prognosis prediction in infants with stage IV neuroblastoma.
- To identify subgroups of infants requiring different treatment intensities based on biologic markers.
Main Methods:
- A prospective study (CCG-3881) involving 134 infants with stage IV NBL.
- Analysis of tumor MYCN copy number, Shimada classification, serum ferritin, and bone marrow immunocytology.
- Standard chemotherapy (4 drugs for 9 months) with surgery and radiation; MYCN-amplified cases received intensified therapy.
Main Results:
- Overall 3-year event-free survival (EFS) was 63%.
- Tumors without MYCN amplification had a 93% 3-year EFS, versus 10% EFS for tumors with MYCN amplification (P <.0001).
- MYCN copy number was the primary prognostic factor, overshadowing other biologic features.
Conclusions:
- Infants under 1 year with stage IV NBL have a better outcome than older children.
- Nonamplified MYCN identifies a favorable prognostic group with high EFS.
- Amplified MYCN in infant NBL predicts poor survival despite intensive treatment, necessitating risk-adapted strategies.
Purpose:
A prospective Children's Cancer Group study, CCG-3881, has been completed to determine if a more accurate prediction of prognosis by biologic features can identify subgroups of infants with stage IV neuroblastoma (NBL) who require differing intensities of treatment.
Patients And Methods:
One hundred thirty-four infants were registered from June 1989 to August 1995, with a median follow-up of 47.1 months (range, 0 to 88 months). The biologic factors examined were tumor MYCN copy number, Shimada histopathologic classification, serum ferritin, and bone marrow immunocytology (sensitivity, one tumor cell per 10(5) bone marrow cells). Patients treated on CCG-3881 (n = 116) received four-drug chemotherapy for 9 months (cisplatin, cyclophosphamide, doxorubicin, and etoposide), with surgery and local radiation to residual disease. After January 1991, all subsequent infants with tumor MYCN amplification (n = 18) were transferred after one cycle of therapy to the high-risk CCG-3891 protocol (open January 1991 to April 1996) for more intensive treatment.
Results:
The 3-year event-free survival (EFS) and overall survival (mean +/- SD) for the 134 infants were 63% +/- 5% and 71% +/- 5%, respectively. Patients whose tumors were without MYCN amplification had a 93% +/- 4% 3-year EFS, whereas those with amplified MYCN had a 10% +/- 7% 3-year EFS (P <. 0001). Each of the other biologic features studied had prognostic significance in univariate analysis but not after stratifying by MYCN copy number.
Conclusion:
Infants less than 1 year of age at diagnosis with stage IV NBL have a much improved outcome compared with children >/= 1 year of age. Nonamplified MYCN tumors identify a group of infants with a 93% +/- 4% EFS, whereas amplified MYCN copy number clearly identifies patients who are unlikely to survive despite intensive chemotherapy.
