Current biologic and therapeutic implications in the surgery of neuroblastoma

Azizkhan, Richard G.; Haase, Gerald M.

doi:10.1002/ssu.2980090607

Cited by 15 publications

(7 citation statements)

References 49 publications

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“…However, resection of as much gross tumor as possible in patients who receive a stem cell transplant in combination with high-dose chemotherapy and total body irradiation (TBI) may be of some benefit. 38 Despite the uncertainty of the role of surgery, the COG high-risk protocol currently recommends attempting gross total resection of the primary tumor and locoregional disease in patients with high-risk neuroblastoma. Most children undergo delayed surgery after the completion of the fifth cycle of induction chemotherapy, even though tumor volume reduction plateaus after the second or third cycle of chemotherapy.…”

Section: Risk and Treatment Stratificationmentioning

confidence: 99%

Neuroblastoma

Davidoff

2012

Seminars in Pediatric Surgery

161

115

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Neuroblastoma is a heterogeneous disease; tumors can spontaneously regress or mature, or display an aggressive, therapy-resistant phenotype. Increasing evidence indicates that the biologic and molecular features of neuroblastoma significantly influence and are highly predictive of clinical behavior. Because of this, neuroblastoma has served as a paradigm for biological risk assessment and treatment assignment. Most current clinical studies of neuroblastoma base therapy and its intensity on a risk stratification that takes into account both clinical and biologic variables predictive of relapse. For example, surgery alone offers definitive therapy with excellent outcome for patients with low-risk disease, while patients at high-risk for disease relapse are treated with intensive multimodality therapy. In this review recent advances in the understanding of the molecular genetic events involved in neuroblastoma pathogenesis are discussed, and how they are impacting the current risk stratification and providing potential targets for new therapeutic approaches for children with neuroblastoma. In addition, the results of significant recent clinical trials for the treatment of neuroblastoma are reviewed.

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Section: Risk and Treatment Stratificationmentioning

confidence: 99%

Neuroblastoma

Davidoff

2012

Seminars in Pediatric Surgery

161

115

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“…Although significant progress has been made in the treatment of infants (younger than 1 yr old),1, 2 most older children have metastatic disease at the time of diagnosis and have a poor prognosis 3. Surgical resection is the treatment of choice for localized neuroblastoma,2–4 but the role and optimal timing of surgery have not been determined for older patients with advanced‐stage disease 5–37…”

mentioning

confidence: 99%

The impact of early resection of primary neuroblastoma on the survival of children older than 1 year of age with stage 4 disease

McGregor

Rao

Davidoff

et al. 2005

Cancer

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BACKGROUND It remains unclear whether primary tumor resection benefits patients with metastatic neuroblastoma. The authors assessed the impact of extent and timing of resection on outcome in these patients. METHODS The authors reviewed the records of 124 patients > 1 year of age at diagnosis of International Neuroblastoma Staging System Stage 4 neuroblastoma. The survival estimates of those who did and did not have a gross total resection (GTR) and of those who had initial versus delayed GTR were compared. Surgical complications were reviewed. RESULTS The 5‐year survival estimates were comparable for the 90 patients who had a GTR and the 17 who underwent surgery but did not have a GTR (29.9% ± 5.1% [standard error] vs. 29.4% ± 10.1%). The 7 patients who underwent GTR at the time of diagnosis had a higher 5‐year survival estimate than the 83 patients who had a GTR after induction chemotherapy (83.3% ± 13.9% vs. 25.2% ± 5.0%) (P = 0.001). Five‐year event‐free survival estimates were similarly higher in the initial‐GTR group (57.1% ± 18.7% vs. 14.5% ± 4.2%) (P = 0.002). These two groups did not differ significantly in age at diagnosis (P = 0.118), site of primary tumor (P = 0.34), MYCN amplification status (P = 1), serum lactate dehydrogenase activity at diagnosis (P = 0.34), or treatment protocol (P = 0.22). Twenty‐two (21%) patients had a surgical complication. CONCLUSIONS In this small cohort of patients with metastatic neuroblastoma, GTR at the time of diagnosis offered a survival benefit. Further prospective studies are warranted before this approach can be applied to all patients with metastatic neuroblastoma. Cancer 2005. © 2005 American Cancer Society.

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“…Despite such aggressive therapy, the vast majority of patients will succumb to their disease. Conventional approaches for patients with extensive locoregional disease (stage III) and metastatic disease (stage IV) fail to control tumor progression [6,7]. Progressive tumor growth in these patients suggests that the tumor escapes, whatever level of immune recognition exists.…”

Section: Introductionmentioning

confidence: 99%

Apoptosis Induced in T Cells by Human Neuroblastoma Cells: Role of Fas Ligand

Shurin

Gerein²,

Lotze³

et al. 1998

Nat Immun

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The CD95/CD95L (Fas/Fas ligand) receptor/ligand system plays an important role in regulation of cell survival and induction of a programmed cell death. It is also involved in regulation of effector phase of T and NK cell cytotoxicity, establishment of immune privilege sites, and tumor escape from immune recognition. In this study, we assessed expression of CD95L in tumors obtained from patients with neuroblastoma (NB) and in established NB cell lines. We measured the presence of intratumoral T cell infiltrates and T cell survival in tumor tissue samples. High levels of apoptosis were observed in tumor-associated lymphocytes as well as in Jurkat T cells cocultured with NB cells in vitro. T cell death was reduced after treatment of NB cells (in vitro) with antibody to FAS ligand (FasL). Overall, our data suggest that NB-induced apoptosis of Fas-sensitive Jurkat T cells is mediated by functional FasL expressed on NB and Fas/FasL interaction may be responsible for the elimination of T cells in the NB microenvironment.

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Current biologic and therapeutic implications in the surgery of neuroblastoma

Cited by 15 publications

References 49 publications

Neuroblastoma

Neuroblastoma

The impact of early resection of primary neuroblastoma on the survival of children older than 1 year of age with stage 4 disease

Apoptosis Induced in T Cells by Human Neuroblastoma Cells: Role of Fas Ligand

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