Favorable Prognosis for Patients 12 to 18 Months of Age With Stage 4 Nonamplified <i>MYCN</i> Neuroblastoma: A Children's Cancer Group Study

Schmidt, Mary Lou; Lal, Ashutosh; Seeger, Robert C.; Maris, John M.; Shimada, Hiroyuki; O’Leary, Maura; Gerbing, Robert B.; Matthay, Katherine K.

doi:10.1200/jco.2005.05.183

Cited by 135 publications

(80 citation statements)

References 19 publications

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“…Moreover, high expression levels of DEIN were found to be associated with age at diagnosis <1 year even after exclusion of stage IVS tumors. In light of the beneficial outcome of infants in comparison with patients >12 to 18 months (23,24), expression of DEIN may represent a molecular correlate of the distinct biology of these tumors in comparison with neuroblastoma developing in older children. However, the biological role of DEIN in neuroblastoma and normal development has yet to be determined by functional analyses.…”

Section: Discussionmentioning

confidence: 99%

Identification of DEIN, a Novel Gene with High Expression Levels in Stage IVS Neuroblastoma

Voth

Oberthuer²,

Simon³

et al. 2007

Molecular Cancer Research

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Neuroblastoma at stage IVS, defined by dissemination to specific tissues and age <1 year at diagnosis, regularly follows spontaneous regression without cytotoxic treatment. To uncover the molecular characteristics of this subtype, Serial Analysis of Gene Expression (SAGE) profiles from stage IVS and fatal stage IV tumors were compared. A SAGE tag (GCAACTTAAC) was detected that was overrepresented in stage IVS disease and that had no reliable match in current National Center for Biotechnology Information databases of SAGE profiles, thus pointing to a novel gene. The corresponding gene, which maps to chromosome 4q33-34, was identified using a modified 3 ¶-and 5 ¶-rapid amplification of cDNA ends PCR and was designated as DEIN (differentially expressed in neuroblastoma). The gene comprises five transcript variants and its sequence overlaps with expressed sequences of the yet uncharacterized UniGene cluster Hs.61435. DEIN exhibits nucleotide sequence conservation over a broad range of species with an overall homology of 65% between human and mouse. As none of the predicted amino acid sequences is homologous to known proteins, it remains to be determined whether DEIN represents a coding or noncoding RNA. Northern blot analysis and semiquantitative reverse transcription-PCR showed high DEIN expression in neuroblastoma, whereas expression was absent or weak in most normal adult tissues. Analysis of 121 primary neuroblastomas by real-time reverse transcription-PCR revealed a strong association with age at diagnosis <1 year and particularly with stage IVS disease (both P < 0.001). The characteristic expression pattern of DEIN suggests a specific role of this gene in the unique biology of stage IVS tumors and may help to molecularly define this special subtype of neuroblastoma. (Mol Cancer Res 2007;5(12):1276 -84)

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Section: Discussionmentioning

confidence: 99%

Identification of DEIN, a Novel Gene with High Expression Levels in Stage IVS Neuroblastoma

Voth

Oberthuer²,

Simon³

et al. 2007

Molecular Cancer Research

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“…27 More recently, a very good outcome has been described in children aged 12-18 months with stage 4 NBL, suggesting that 365 days might not be the best cutoff for risk stratification. [28][29][30] Consequently, the new International Neuroblastoma Risk Group Staging System extended the age group for stage 4s to patients aged o18 months. 31 In our population, we did not identify a better prognosis in patients aged from 12 to 17 months compared with those aged from 18 to 24 months, but these results might be related to the low number of patients in these two groups.…”

Section: Discussionmentioning

confidence: 99%

Busulfan–melphalan in high-risk neuroblastoma: the 30-year experience of a single institution

Pasqualini

Blanchard

et al. 2016

Bone Marrow Transplant

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High-dose chemotherapy (HDC) was investigated in high-risk neuroblastoma (HR-NBL) to reduce the risk of relapse. We report the results of the 30-year experience of a cohort of patients with HR-NBL treated with high-dose (HD) busulfan (Bu)-containing regimens. From 1980From to 2009 patients aged 41 year with stage 4 NBL were treated with HD Bu-containing regimens at Gustave Roussy. These data were prospectively recorded in the Pediatric Transplantation Database. The median age at diagnosis was 40 months (12-218 months). All patients had a stage 4 neuroblastoma. NMYC amplification was displayed in 24% of the tumors. The hematopoietic support consisted of bone marrow or PBSCs in 46% and 49% of patients, respectively. The 5-year eventfree survival and overall survival rates of the whole cohort were 35.1% and 40%, respectively. Age at diagnosis, bone marrow involvement and tumor response after induction chemotherapy were significant prognostic factors. Toxicity was manageable and decreased over time, owing to both PBSC administration and better supportive care. Based on this experience, HD Bu-melphalan (Mel) has been implemented in Europe and compared with Carboplatin-Etoposide-Mel in the European SIOP Neuroblastoma (SIOPEN)/HR-NBL randomized protocol. It has now become the standard HDC in the SIOPEN HR strategy. INTRODUCTIONThe improved survival rates of patients with high-risk (HR) neuroblastoma (NBL) observed during the past decades are related to the intensification of induction therapy, high-dose chemotherapy (HDC) and better supportive care. 1 In the HR-NBL population, a correlation between survival and dose intensity has been reported, and three randomized studies showed that HDC followed by autologous stem cell transplantation (ASCT) or autologous bone marrow transplantation (ABMT) improved survival rates. [2][3][4] As NBL is notoriously radiosensitive, hyperfractionated TBI was incorporated into the conditioning regimen and has yielded encouraging results. 5 Alkylating agents were demonstrated to produce a log-linear dose response against tumor cells in vitro. 6 Since the mid-1980s, HDC with alkylating agents and ASCT has been the treatment strategy used at Gustave Roussy. HD busulfan (Bu) was selected because of its specific cytotoxicity against quiescent cells, 7 as an alternative to TBI in HR-NBL patients to avoid its side-effects, 8 especially in this very young population, and to achieve better survival rates.We report here the results of our 30-year experience on patients with HR-NBL treated with HD Bu-containing regimens. Bu was combined with melphalan (Mel) or Mel plus cyclophosphamide, and HDC was followed by stem cell (SC) or bone marrow (BM) transplantation. These results provided the rationale to widely implement the use of HD Bu-Mel, which was then compared with Carboplatin-Etoposide-Mel (CEM) in the European SIOP Neuroblastoma (SIOPEN)/HR-NBL randomized trial. HD Bu-Mel has now become the standard HD regimen in the SIOPEN HR strategy.

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“…Patients with neuroblastoma are risk stratified based on presenting factors including age, stage and location of disease, and specific biologic molecular markers of the tumor, including NMYC status and ploidy [1][2][3]. Treatment given is tailored to whether a patient has low, intermediate or high-risk disease.…”

Section: Introductionmentioning

confidence: 99%

Novel Therapeutic Approaches for Neuroblastoma

Joshi¹,

Singh²,

Hartman³

et al. 2013

Neuroblastoma

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Favorable Prognosis for Patients 12 to 18 Months of Age With Stage 4 Nonamplified MYCN Neuroblastoma: A Children's Cancer Group Study

Cited by 135 publications

References 19 publications

Identification of DEIN, a Novel Gene with High Expression Levels in Stage IVS Neuroblastoma

Identification of DEIN, a Novel Gene with High Expression Levels in Stage IVS Neuroblastoma

Busulfan–melphalan in high-risk neuroblastoma: the 30-year experience of a single institution

Novel Therapeutic Approaches for Neuroblastoma

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