Advances in Risk Classification and Treatment Strategies for Neuroblastoma

Abstract

Risk-based treatment approaches for neuroblastoma have been ongoing for decades. However, the criteria used to define risk in various institutional and cooperative groups were disparate, limiting the ability to compare clinical trial results. To mitigate this problem and enhance collaborative research, homogenous pretreatment patient cohorts have been defined by the International Neuroblastoma Risk Group classification system. During the past 30 years, increasingly intensive, multimodality approaches have been developed to treat patients who are classified as high risk, whereas patients with low- or intermediate-risk neuroblastoma have received reduced therapy. This treatment approach has resulted in improved outcome, although survival for high-risk patients remains poor, emphasizing the need for more effective treatments. Increased knowledge regarding the biology and genetic basis of neuroblastoma has led to the discovery of druggable targets and promising, new therapeutic approaches. Collaborative efforts of institutions and international cooperative groups have led to advances in our understanding of neuroblastoma biology, refinements in risk classification, and stratified treatment strategies, resulting in improved outcome. International collaboration will be even more critical when evaluating therapies designed to treat small cohorts of patients with rare actionable mutations.

Documentation of Our Neuroblastoma Cases ( 49 Cases, Retrospective Study)

“…Bunun içinde 5 adet perkutan iğne biyopsisi yeterli gelmektedir (7) . Nöroblastom prognozunda önemli olan diferansiasyon, MKİ ve n-myc amplifikasyonu birbiri ile iliş-kilidir (1,3,8) . N-myc amplifikasyonu ile fazla miktarda üretilen myc-n proteini, daha fazla myc-max protein kompleksi oluşmasına neden olur.…”

“…Bu kompleks ise hücre çekirdeğinde, hücrenin diferansiasyonunu azaltır ve hücre proliferasyonunu uyarır. Bu nedenle N-myc amplifiye eden tümörlerin diferansiyasyonu kötü ve proliferasyon indeksi yüksektir (1,6,8) . Bazı ailesel nöroblastom olgularında PHOX2B ve ALK gen mutasyonları tanımlanmıştır (9,10,11) .…”

Seltene Tumordispositionssyndrome mit Manifestation im Kindesalter

“…[12] möglicher Metastasen (zum Beispiel in Lymphknoten, Knochen, Knochenmark, Haut, Leber und andere), (iii) die Histologie sowie (iv) charakteristische somatische genetische Veränderungen. Diese Marker finden Berücksichtigung in dem "international neuroblastoma risk group pretreatment classification" Schema und erlauben die Einteilung in 16 Risikogruppen, sodass der Behandlungsumfang dem Risiko entsprechend angepasst werden kann [25].…”

“…Sie bilden die Grundlage verbesserter Risikoklassifikationen sowie neuer Therapiestrategien [20,24,25].…”

CD4+CD25hiCD127− Treg and CD4+CD45R0+CD49b+LAG3+ Tr1 cells in bone marrow and peripheral blood samples from children with neuroblastoma

“…3 The clinical course of patients with NB is heterogeneous, ranging from spontaneous remission to progressive metastatic disease, with dissemination to multiple organs, including bone marrow (BM). 4 BM infiltration is indeed a predictor of poor clinical outcome. 5 NB patients are now classified in different risk classes following the International Neuroblastoma Risk Group staging system, 6 that consider genetic alterations, DNA ploidy, histological features, age, and stage as classification criteria.…”