Treatment planning for children with neuroblastoma requires accurate assessment of prognosis. The most recent Children's Oncology Group (COG) risk classification system used tumor stage as defined by ...the International Neuroblastoma Staging System. Here, we validate a revised classifier using the International Neuroblastoma Risk Group Staging System (INRGSS) and incorporate segmental chromosome aberrations (SCA) as an additional genomic biomarker.
Newly diagnosed patients enrolled on the COG neuroblastoma biology study ANBL00B1 between 2007 and 2017 with known age, International Neuroblastoma Staging System, and INRGSS stage were identified (N = 4,832). Tumor
status, ploidy, SCA status (1p and 11q), and International Neuroblastoma Pathology Classification histology were determined centrally. Survival analyses were performed for combinations of prognostic factors used in COG risk classification according to the prior version 1, and to validate a revised algorithm (version 2).
Most patients with locoregional tumors had excellent outcomes except for those with image-defined risk factors (INRGSS L2) with
amplification (5-year event-free survival and overall survival: 76.3% ± 5.8% and 79.9% ± 5.5%, respectively) or patients age ≥ 18 months with L2
nonamplified tumors with unfavorable International Neuroblastoma Pathology Classification histology (72.7% ± 5.4% and 82.4% ± 4.6%), which includes the majority of L2 patients with SCA. For patients with stage M (metastatic) and MS (metastatic, special) disease, genomic biomarkers affected risk group assignment for those < 12 months (
) or 12-18 months (
, histology, ploidy, and SCA) of age. In a retrospective analysis of patient outcome, the 5-year event-free survival and overall survival using COG version 1 were low-risk: 89.4% ± 1.1% and 97.9% ± 0.5%; intermediate-risk: 86.1% ± 1.3% and 94.9% ± 0.8%; high-risk: 50.8% ± 1.4% and 61.9% ± 1.3%; and using COG version 2 were low-risk: 90.7% ± 1.1% and 97.9% ± 0.5%; intermediate-risk: 85.1% ± 1.4% and 95.8% ± 0.8%; high-risk: 51.2% ± 1.4% and 62.5% ± 1.3%, respectively.
A revised 2021 COG neuroblastoma risk classifier (version 2) that uses the INRGSS and incorporates SCAs has been adopted to prospectively define COG clinical trial eligibility and treatment assignment.
Abstract Neuroblastoma is an embryonic cancer of neural crest cell lineage, accounting for up to 10% of all pediatric cancer. The clinical course is heterogeneous ranging from spontaneous regression ...in neonates to life-threatening metastatic disease in older children. Much of this clinical variance is thought to result from distinct pathologic characteristics that predict patient outcomes. Consequently, many research efforts have been focused on identifying the underlying biologic and genetic features of neuroblastoma tumors in order to more clearly define prognostic subgroups for treatment stratification. Recent technological advances have placed emphasis on the integration of genetic alterations and predictive biologic variables into targeted treatment approaches to improve patient survival outcomes. This review will focus on these recent advances and the implications they have on the diagnostic, staging, and treatment approaches in modern neuroblastoma clinical management.
The International Neuroblastoma Risk Group (INRG) classification system was developed to establish a consensus approach for pretreatment risk stratification. Because the International Neuroblastoma ...Staging System (INSS) is a postsurgical staging system, a new clinical staging system was required for the INRG pretreatment risk classification system.
To stage patients before any treatment, the INRG Task Force, consisting of neuroblastoma experts from Australia/New Zealand, China, Europe, Japan, and North America, developed a new INRG staging system (INRGSS) based on clinical criteria and image-defined risk factors (IDRFs). To investigate the impact of IDRFs on outcome, survival analyses were performed on 661 European patients with INSS stages 1, 2, or 3 disease for whom IDRFs were known.
In the INGRSS, locoregional tumors are staged L1 or L2 based on the absence or presence of one or more of 20 IDRFs, respectively. Metastatic tumors are defined as stage M, except for stage MS, in which metastases are confined to the skin, liver, and/or bone marrow in children younger than 18 months of age. Within the 661-patient cohort, IDRFs were present (ie, stage L2) in 21% of patients with stage 1, 45% of patients with stage 2, and 94% of patients with stage 3 disease. Patients with INRGSS stage L2 disease had significantly lower 5-year event-free survival than those with INRGSS stage L1 disease (78% +/- 4% v 90% +/- 3%; P = .0010).
Use of the new staging (INRGSS) and risk classification (INRG) of neuroblastoma will greatly facilitate the comparison of risk-based clinical trials conducted in different regions of the world.
Background Parathyroid carcinoma (PC) is a rare malignancy with a moderate prognosis. The staging system, prognostic indicators, and optimal surgical management are still under debate. This large ...cohort explores prognostic factors for PC. Methods 1,022 cases of PC in the 1998–2011 National Cancer Data Base that underwent surgery were examined for predictors of lower overall survival (OS) and relative risk (RR) of death at 5 years. Results The 5-year OS was 81.1% in 528 patients with ≥60 months of follow-up. The overall cohort was mainly non-Hispanic (96.5%), white (77.4%), and insured (94.3%), with a median age of 57 years. Mean OS was lower and RR of death greater in older ( P < .001), black ( P = .007) patients with a secondary malignancy ( P = .015) and ≥2 comorbidities ( P = .005), whose surgical specimen had positive surgical margins ( P = .026) or positive lymph nodes ( P < .001). Multivariate cox regression demonstrated that positive lymph nodes (hazard ratio HR, 6.47; 95% CI, 1.81–23.11) and older age (HR, 2.35; 95% CI, 1.25–4.43) were associated with lower OS. Conclusion PC is a rare malignancy with a 5-year OS of 81.1%. Positive lymph nodes and older age predict lower OS and an increased risk of death.
The X-linked BCL-6 co-repressor (BCOR) gene encodes a key constituent of a variant polycomb repressive complex (PRC) that is mutated or translocated in human cancers. Here we report on the ...identification of somatic internal tandem duplications (ITDs) clustering in the C terminus of BCOR in 23 of 27 (85%) pediatric clear cell sarcomas of the kidney (CCSK) from two independent cohorts. We profile CCSK tumours using a combination of whole-exome, transcriptome and targeted sequencing. Identical ITD mutations are found in primary and relapsed tumour pairs but not in adjacent normal kidney or blood. Mutant BCOR transcripts and proteins are markedly upregulated in ITD-positive tumours. Transcriptome analysis of ITD-positive CCSKs reveals enrichment for PRC2-regulated genes and similarity to undifferentiated sarcomas harbouring BCOR-CCNB3 fusions. The discovery of recurrent BCOR ITDs defines a major oncogenic event in this childhood sarcoma with significant implications for diagnostic and therapeutic approaches to this tumour.
Global Disparities in Wilms Tumor Cunningham, Megan E.; Klug, Theodore D.; Nuchtern, Jed G. ...
The Journal of surgical research,
March 2020, 2020-Mar, 2020-03-00, 20200301, Letnik:
247
Journal Article
Recenzirano
Wilms tumor accounts for more than 90% of all malignant kidney neoplasms in children. Survival after diagnosis and treatment is excellent in most high-income countries. Low- and middle-income ...countries (LMICs) continue to struggle with Wilms tumor detection and treatment. The purpose of this study was to compare the global incidence and outcomes of Wilms tumor.
Wilms tumor incidence data from the World Health Organization (WHO), International Incidence of Childhood Cancer, Volume III, was analyzed according to world region and country socioeconomic status using descriptive statistics and independent-sample Kruskal–Wallis Test. A literature review was also performed to assess outcomes and identify common themes.
Wilms tumor was most common in children aged 0-4 y (median incidence 15.1 IQR 11.8-18.7 ASR/million). High-income countries reported significantly higher median incidence than middle-income countries (8.6 7.4–9.3 versus 6.1 4.9–8.7 ASR/million; P < 0.01), although low-income countries reported the highest median incidence overall (9.8 6.2–16.4 ASR/million). Low-income countries had the fewest countries with registries (n = 6). Overall survival ranged from 70% to 97% in high-income countries, 61%–94% in upper-middle-income countries, 0%–85% in lower-middle-income countries, and 25%–53% in low-income countries. Delay in diagnosis, lack of available treatment, and inadequate follow up contributed to the large variations in outcomes.
Reported Wilms tumor incidence is highest in low-income countries, and these are also the countries that have the lowest survival. Lack of significance may reflect incomplete and absent data reporting from lower income countries. Accurate and comprehensive registries are the first steps to appropriate resource allocation in order to improve outcomes for this highly curable childhood malignancy.
•Comprehensive, longitudinal curricula could enhance global surgery training.•Curricula should incorporate essential clinical and non-clinical elements aimed at capacity building.•Professional ...development, research, capacity, building, collaboration are essential components for global surgery training.
Background Well-differentiated thyroid cancer is the most common endocrine malignancy in children. Adult literature has demonstrated socioeconomic disparities in patients undergoing thyroidectomy, ...but the effects of socioeconomic status on the management of pediatric well-differentiated thyroid cancer remains poorly understood. Methods Patients ≤21 years of age with well-differentiated thyroid cancer remains were reviewed from the National Cancer Data Base. Three socioeconomic surrogate variables were identified: insurance type, median income, and educational quartile. Tumor characteristics, diagnostic intervals, and clinical outcomes were compared within each socioeconomic surrogate variable. Results A total of 9,585 children with well-differentiated thyroid cancer remains were reviewed. In multivariate analysis, lower income, lower educational quartile, and insurance status were associated with higher stage at diagnosis. Furthermore, lower income quartile was associated with a longer time from diagnosis to treatment ( P < .002). Similarly, uninsured children had a longer time from diagnosis to treatment (28 days) compared with those with government (19 days) or private (18 days) insurance ( P < .001). Despite being diagnosed at a higher stage and having a longer time interval between diagnosis and treatment, there was no significant difference in either overall survival or rates of unplanned readmissions based on any of the socioeconomic surrogate variables. Conclusion Children from lower income families and those lacking insurance experienced a longer period from diagnosis to treatment of their well-differentiated thyroid cancer remains. These patients also presented with higher stage disease. These data suggest a delay in care for children from low-income families. Although these findings did not translate into worse outcomes for well-differentiated thyroid cancer remains, future efforts should focus on reducing these differences.
OBJECTIVE:To create the first structured surgical report form for NBL with international consensus, to permit standardized documentation of all NBL-related surgical procedures and their outcomes.
...SUMMARY OF BACKGROUND DATA:NBL, the most common extracranial solid malignant tumor in children, covers a wide spectrum of tumors with significant differences in anatomical localization, organ or vessel involvement, and tumor biology. Complete surgical resection of the primary tumor is an important part of NBL treatment, but maybe hazardous, prone to complications and its role in high-risk disease remains debated. Various surgical guidelines exist within the protocols of the different cooperative groups, although there is no standardized operative report form to document the surgical treatment of NBL.
METHODS:After analyzing the treatment protocols of the SIOP Europe International Neuroblastoma Study Group, Childrenʼs Oncology Group, and Gesellschaft fuer Paediatrische Onkologie und Haematologie – German Association of Pediatric Oncology and Haematology pediatric cooperative groups, important variables were defined to completely describe surgical biopsy and resection of NBL and their outcomes. All variables were discussed within the Surgical Committees of SIOP Europe International Neuroblastoma Study Group, Childrenʼs Oncology Group, and Gesellschaft fuer Paediatrische Onkologie und Haematologie – German Association of Pediatric Oncology and Haematology. Thereafter, joint meetings were organized to obtain intercontinental consensus.
RESULTS:The “International Neuroblastoma Surgical Report Form” provides a structured reporting tool for all NBL surgery, in every anatomical region, documenting all Image Defined Risk Factors and structures involved, with obligatory reporting of intraoperative and 30 day-postoperative complications.
CONCLUSION:The International Neuroblastoma Surgical Report Form is the first universal form for the structured and uniform reporting of NBL-related surgical procedures and their outcomes, aiming to facilitate the postoperative communication, treatment planning and analysis of surgical treatment of NBL.
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