Outcome of children with neuroblastoma after progression or relapse. A retrospective study of the Italian neuroblastoma registry

Garaventa, Alberto; Parodi, Stefano; Bernardi, Bruno; Dau, D; Manzitti, Carla; Conte, Massimo; Casale, Fiorina; Viscardi, Elisabetta; Bianchi, Maurizio; D’Angelo, Paolo; Zanazzo, Giulio Andrea; Luksch, Roberto; Favre, Claudio; Tamburini, Angela; Haupt, Riccardo

doi:10.1016/j.ejca.2009.06.010

Cited by 112 publications

(120 citation statements)

References 23 publications

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“…This figure was derived from the widely held view that relapse of HR-NB was "uniformly fatal," 10 although only a single large study with supportive data was available: The European NB Study Group found a 2-year OS (which is always better than PFS) of 8% from the date of relapse for patients aged >1 year with Stage 3-4 NB diagnosed from 1982-1992. 9 Subsequent reports presented confirmatory data about the dismal prognosis post-relapse: 5-year OS rates after relapse were 0% and 11%, respectively, in 2 single institutional studies of HR-NB patients treated in the 1990s to early 2000s; 11,12 5% and 8%, respectively, for Stage 4 disease (no age cut-off) in the Italian experience 13 Kingdom (1990Kingdom ( -2010. 17 In the large INRG experience, 14 patients with MYCN-amplified stage 4 at any age and MYCN-non-amplified stage 4 at age >18 months were not considered to be "salvageable after relapse.…”

Section: Discussionmentioning

confidence: 67%

“…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.…”

Section: Introductionmentioning

confidence: 99%

“…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.…”

Section: Introductionmentioning

confidence: 99%

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Prolonged progression-free survival after consolidating second or later remissions of neuroblastoma with Anti-G_D2immunotherapy and isotretinoin: a prospective Phase II study

et al. 2015

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Relapse of high-risk neuroblastoma (HR-NB) is deemed invariably fatal yet increasing numbers of HR-NB patients achieve a second complete/very good partial remission (CR/VGPR), hence the urgency to find a successful consolidative therapy. Identifying efficacy in patients without assessable disease, however, is problematic. We report the first study providing outcome data for this group of patients with poor prognosis. To prevent another relapse, HR-NB patients in second or later CR/VGPR received the anti-G D2 murine antibody 3F8 plus granulocyte-macrophage colony-stimulating factor plus isotretinoin in a Phase II trial. Upon meeting the target aim for progression-free survival (PFS) in the initial cohort of 33 patients, the trial was amended to allow patients who developed human anti-mouse antibody (HAMA) to receive rituximab to ablate HAMA with or without low-dose maintenance chemotherapy until immunotherapy could resume. For the total of 101 study patients, 5-year PFS and overall survival (OS) rates were 33% § 5% and 48% § 5%, respectively. Among the 33 long-term progression-free survivors, 19 had MYCN amplification, 19 had previously received anti-G D2 immunotherapy plus isotretinoin (as first-line therapy), and 15 never received maintenance chemotherapy. In a multivariate analysis of prognostic factors, only absence of minimal residual disease in bone marrow after 2 cycles of immunotherapy and before initiation of isotretinoin or anti-HAMA therapy was significantly favorable for both PFS and OS. Therefore, long-term PFS is possible for HR-NB patients who achieve at least a second CR/VGPR and receive consolidation that includes anti-G D2 immunotherapy plus isotretinoin, even if the patients received these biological treatments before relapse. Results from this prospective study will aid in the development of future Phase II studies for this growing ultra high-risk patient population.

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Section: Discussionmentioning

confidence: 67%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Prolonged progression-free survival after consolidating second or later remissions of neuroblastoma with Anti-G_D2immunotherapy and isotretinoin: a prospective Phase II study

et al. 2015

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“…The reported 5-year OS rate for patients after the first relapse of neuroblastoma is 20% [94], with outcomes dependent on the time of relapse and the initial patient tumor stage [94][95][96]. A recently published meta-analysis of three phase II clinical trials run through the SIOPEN group in Europe reported median progression free survival rates of 12.5% and 5.7% for patients with refractory and relapsed disease, respectively, while median OS rates were 27.9 months for patients with refractory disease versus 11.0 months for patients with relapsed disease, confirming the poor outcomes in both cohorts of patients [97].…”

Section: Treatment -Relapsed and Refractory Neuroblastomamentioning

confidence: 99%

Overview and recent advances in the treatment of neuroblastoma

Whittle

Smith

Doherty

et al. 2017

Expert Review of Anticancer Therapy

325

258

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Introduction: Children with neuroblastoma have widely divergent outcomes, ranging from cure in >90% of patients with low risk disease to <50% for those with high risk disease. Recent research has shed light on the biology of neuroblastoma, allowing for more accurate risk stratification and treatment reduction in many cases, although newer treatment strategies for children with high-risk and relapsed neuroblastoma are needed to improve outcomes. Areas covered: Neuroblastoma epidemiology, diagnosis, risk stratification, and recent advances in treatment of both newly diagnosed and relapsed neuroblastoma. Expert commentary: The identification of newer tumor targets and of novel cell-mediated immunotherapy agents may lead to novel therapeutic approaches, and clinical trials for regimens designed to target individual genetic aberrations in tumors are underway. A combination of therapeutic modalities will likely be required to improve survival and cure rates for patients with high-risk neuroblastoma.ARTICLE HISTORY

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“…Despite current therapeutic advances and basic mechanism investigations, neuroblastoma remains a complex medical challenge with the unpredictable clinical course and dismal overall outcome for advanced-stage disease (3)(4)(5).…”

Section: Introductionmentioning

confidence: 99%

RACK1 downregulation suppresses migration and proliferation of neuroblastoma cell lines

Fan

Zhang²,

Wu³

et al. 2012

Oncol Rep

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Abstract. Neuroblastoma is the most common extracranial solid tumor in childhood, whose molecular mechanism on clinically heterogeneous behavior is still unclear. Receptor for activated C-kinase 1 (RACK1) has been shown to be involved in the regulation of growth and migration in many types of cells. Two types of human neuroblastoma cell lines, SK-N-SH and SK-N-BE (2), were used to explore the role of RACK1 in neuroblastoma cell migration and proliferation. Cell migration and proliferation were detected by a transwell system and colorimetric bromodeoxyuridine (BrdU) ELISA, respectively. The expressions of RACK1, N-Myc, phospho-Src(Tyr416), phospho-Src(Tyr527), phospho-Akt, phospho-ERK1/2 and phospho-p38 were analyzed by Western blotting. The expression of RACK1 was then repressed by target RNA interference (RNAi) in both types of neuroblastoma cells, and the expression of signaling molecules, migration and proliferation of cells was analyzed. Compared with SK-N-SH, the migration and proliferation of SK-N-BE(2) cells was remarkably higher which was accompanied by higher expression of RACK1 and phospho-Src(Tyr416). RACK1 RNAi repressed cell migration and proliferation, and decreased the expression of phosphoSrc(Tyr416) in both cell lines. In summary, RACK1 was expressed in the neuroblastoma cells and positively regulated cell migration and proliferation probably via modulating the activation of Src on Tyr416 residue. IntroductionNeuroblastoma, a neoplasm of peripheral neural crest origin, is the most common extracranial solid tumor in childhood and the most frequently diagnosed neoplasm during infancy (1,2). Despite current therapeutic advances and basic mechanism investigations, neuroblastoma remains a complex medical challenge with the unpredictable clinical course and dismal overall outcome for advanced-stage disease (3-5).Extraordinary migration and proliferation plays an important role in invasive and malignant of neuroblastoma cells (6,7). It is proposed that finding key point proteins or signaling molecules that participated in the invasive potential, such as migration and proliferation, of neuroblastoma cells, might be a potential therapeutic targets and might be a way to overcome current clinical dilemma of neuroblastoma treatments (8).Receptors for activated C-kinases (RACK1) is the founding member of the family of intracellular receptors of activated protein kinase C (PKC) (9,10). The human RACK1 gene (Gene Bank accession no. GNB2L1) is highly conserved, includes eight exons and seven introns and is located on chromosome 5 (5q35.3). The gene product is a 36-kDa cytosolic protein that contains seven tryptophan-aspartate repeats, a domain involved in protein-protein interactions. RACK1 is widely expressed in the nervous system (11). Several studies suggested that RACK1 are involved in numerous key cellular functions, such as cellular apoptosis (9) and migration (12). It had been reported that the expressions of RACK1 mRNA and protein were upregulated in damaging and repairing process (13) and during angiog...

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Outcome of children with neuroblastoma after progression or relapse. A retrospective study of the Italian neuroblastoma registry

Cited by 112 publications

References 23 publications

Prolonged progression-free survival after consolidating second or later remissions of neuroblastoma with Anti-G_D2immunotherapy and isotretinoin: a prospective Phase II study

Prolonged progression-free survival after consolidating second or later remissions of neuroblastoma with Anti-G_D2immunotherapy and isotretinoin: a prospective Phase II study

Overview and recent advances in the treatment of neuroblastoma

RACK1 downregulation suppresses migration and proliferation of neuroblastoma cell lines

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Outcome of children with neuroblastoma after progression or relapse. A retrospective study of the Italian neuroblastoma registry

Cited by 112 publications

References 23 publications

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

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

Overview and recent advances in the treatment of neuroblastoma

RACK1 downregulation suppresses migration and proliferation of neuroblastoma cell lines

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Product

Resources

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Prolonged progression-free survival after consolidating second or later remissions of neuroblastoma with Anti-G_D2immunotherapy and isotretinoin: a prospective Phase II study

Prolonged progression-free survival after consolidating second or later remissions of neuroblastoma with Anti-G_D2immunotherapy and isotretinoin: a prospective Phase II study