Current and Future Strategies for Relapsed Neuroblastoma

Abstract

More than half of the patients with high-risk neuroblastoma (NB) will relapse despite intensive multimodal therapy, with an additional 10% to 20% refractory to induction chemotherapy. Management of these patients is challenging, given disease heterogeneity, resistance, and organ toxicity including poor hematological reserve. This review will discuss the current treatment options and consider novel therapies on the horizon. Cytotoxic chemotherapy regimens for relapse and refractory NB typically center on the use of the camptothecins, topotecan and irinotecan, in combination with agents such as cyclophosphamide and temozolomide, with objective responses but poor long-term survival. I-meta-iodobenzylguanidine therapy is also effective for relapsed patients with meta-iodobenzylguanidine-avid disease, with objective responses in a third of cases. Immunotherapy with anti-GD2 has recently been incorporated into upfront therapy, but its role in the relapse setting remains uncertain, especially for patients with bulky disease. Future cell-based immunotherapies and other approaches may be able to overcome this limitation. Finally, many novel molecularly targeted agents are in development, some of which show specific promise for NB. Successful incorporation of these agents will require combinations with conventional cytotoxic chemotherapies, as well as the development of predictive biomarkers, to ultimately personalize approaches to patients with "targetable" molecular abnormalities.

Prolonged progression-free survival after consolidating second or later remissions of neuroblastoma with Anti-GD2immunotherapy and isotretinoin: a prospective Phase II study

“…7 The randomized study of the Children's Oncology Group showed significantly better outcome in patients treated post-ASCT with the anti-G D2 chimeric mAb ch14.18 plus granulocyte-macrophage colony-stimulating factor (GM-CSF) plus interleukin-2. 8 Nevertheless, relapse remains common and carries a dismal prognosis, [9][10][11][12][13][14][15][16][17] and has been deemed to be "invariably fatal" in a recent review. 1 Adverse prognostic factors for duration of survival post relapse include short time to first relapse and MYCN amplification.…”

“…1 Adverse prognostic factors for duration of survival post relapse include short time to first relapse and MYCN amplification. 11,[13][14][15][16][17] The murine IgG3 anti-G D2 mAb 3F8 localizes selectively to NB. 18 In Phase II studies [19][20][21] and in the adjuvant setting, 22,23 3F8 caused pain and urticaria without delayed toxicities.…”

10-Hydroxycamptothecin induces apoptosis in human neuroblastoma SMS-KCNR cells through p53, cytochrome c and caspase 3 pathways

“…NB is highly malignant and rapidly progressive, and is typically diagnosed at a late stage in the majority of cases [1]. Due to the greater chemoresistance of high-risk NB patients to first-line treatment drugs, the long-term survival rates of these patients remain extremely low [2]. This has become the greatest impediment for the improvement of survival in children with NB, and novel effective drugs are urgently required for high-risk patients.…”

Differential Diagnosis of CT Images in Children with Neuroblastomas and Ganglioneuroblastomas

“…With higher malignancy than nephroblastoma and hepatoblastoma, it can be easily misdiagnosed due to non-specific symptoms (Heczey et al, 2013;Morgenstern et al, 2013). As a sort of rare mixedtype malignant tumor, ganglioneuroblastoma originates from sympathetic ganglionic cells of neural crest, and its differentiated degree is between benign ganglion cells and malignant neural mother cells (Angelini et al, 2014).…”