Recommendations for the standardization of bone marrow disease assessment and reporting in children with neuroblastoma on behalf of the International Neuroblastoma Response Criteria Bone Marrow Working Group

Abstract

BACKGROUND The current study was conducted to expedite international standardized reporting of bone marrow disease in children with neuroblastoma and to improve equivalence of care. METHODS A multidisciplinary International Neuroblastoma Response Criteria Bone Marrow Working Group was convened by the US National Cancer Institute in January 2012 with representation from Europe, North America, and Australia. Practical transferable recommendations to standardize the reporting of bone marrow disease were developed. RESULTS To the authors' knowledge, the current study is the first to comprehensively present consensus criteria for the collection, analysis, and reporting of the percentage area of bone marrow parenchyma occupied by tumor cells in trephine‐biopsies. The quantitative analysis of neuroblastoma content in bone marrow aspirates by immunocytology and reverse transcriptase‐quantitative polymerase chain reaction are revised. The inclusion of paired‐like homeobox 2b (PHOX2B) for immunohistochemistry and reverse transcriptase‐quantitative polymerase chain reaction is recommended. Recommendations for recording bone marrow response are provided. The authors endorse the quantitative assessment of neuroblastoma cell content in bilateral core needle biopsies‐trephines and aspirates in all children with neuroblastoma, with the exception of infants, in whom the evaluation of aspirates alone is advised. It is interesting to note that 5% disease is accepted as an internationally achievable level for disease assessment. CONCLUSIONS The quantitative assessment of neuroblastoma cells is recommended to provide data from which evidence‐based numerical criteria for the reporting of bone marrow response can be realized. This is particularly important in the minimal disease setting and when neuroblastoma detection in bone marrow is intermittent, where clinical impact has yet to be validated. The wide adoption of these harmonized criteria will enhance the ability to compare outcomes from different trials and facilitate collaborative trial design. Cancer 2017;123:1095–1105. © 2016 American Cancer Society.

Event‐free survival of infants and toddlers enrolled in the HR‐NBL‐1/SIOPEN trial is associated with the level of neuroblastoma mRNAs at diagnosis

“…This suggests that the analysis of both PB and BM for NB mRNAs may predict outcome most comprehensively. We also demonstrate that the highest level of NB mRNAs in one of the two BM aspirates is a stronger predictor of outcome than the average level, supporting recent recommendations for analysis of BM aspirates, and advocating separate investigations of right and left BM aspirates …”

Neuroblastoma cells undergo transcriptomic alterations upon dissemination into the bone marrow and subsequent tumor progression

“…As the BM is a common homing organ for disseminated neuroblastoma cells, it is widely used for MRD testing during or after cytotoxic treatment . Besides the standardized immunocytological detection of MRD, real‐time quantitative polymerase chain reaction approaches are also used for MRD detection . Our three‐fold enrichment of BM‐derived DTCs and their separation from the corresponding BM‐derived MNCs enabled us to characterize their gene expression profiles and to extend the variety of potential marker for MRD detection in stage M neuroblastoma.…”

“…Detection of DTCs in the BM of patients who are older than 18 months is of high prognostic importance, as these patients frequently suffer from disease recurrence and poor outcome . Importantly, BM can be used for the molecular quantification of minimal residual disease (MRD) and outcome prediction …”

Prospective investigation of applicability and the prognostic significance of bone marrow involvement in patients with neuroblastoma detected by quantitative reverse transcription PCR

“…Bone marrow (BM) is one of the most frequently affected metastatic sites in patients with neuroblastoma and is also well suited to be studied by biopsies . Detection of BM involvement is performed by conventional cytological and histological examination of BM biopsies, with an analytical sensitivity of less than (1 × 10 −3 ) . So for precise detection of tumor cells in the BM, more sensitive technologies are required, such as immunocytological investigation of BM slides, reverse transcriptase PCR or flow cytometry, with an analytical sensitivity up to (1 × 10 −4 )–(1 × 10 −5 ) .…”