Long-term outcomes in patients with stage IV neuroblastoma

Escobar, Mauricio A.; Grosfeld, Jay L.; Powell, Robert L.; West, Karen W.; Scherer, L.R.; Fallon, Robert J.; Rescorla, Frederick J.

doi:10.1016/j.jpedsurg.2005.11.032

Cited by 55 publications

(40 citation statements)

References 31 publications

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“…Neuroblastoma, the most common pediatric solid tumor, is derived from neural crest cells and is remarkable for its clinical heterogeneity (1,2). The prognosis of neuroblastoma is multifactorial and depends on an assortment of clinical and biological factors.…”

Section: Introductionmentioning

confidence: 99%

“…Nonetheless, many tumors are poorly controlled by radiation therapy due to radiation resistance. The invasive, metastatic and hypervascular nature of stage IV neuroblastoma is refractory to all conventional therapeutic modalities and is associated with a dismal prognosis (5). Studies have reported apparently improved local control rates with radiation therapy or increasing radiation doses to primary sites of disease (6).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Response of neuroblastoma cells to ionizing radiation: Modulation of in vitro invasiveness and angiogenesis of human microvascular endothelial cells

Jadhav

Mohanam²

2006

Int J Oncol

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Abstract.Neuroblastomas are the most common extra-cranial tumors of childhood and well known for their heterogeneous clinical behavior associated with certain genetic aberrations. Radiation therapy is an important modality for the treatment of high-risk neuroblastomas. In this study, we investigated whether ionizing irradiation modulate the migration and invasiveness of human neuroblastoma cells and expression of proangiogenic molecules known to be involved in tumor progression and metastasis. Irradiation of neuroblastoma cells resulted in increased migration and invasion as measured by spheroid migration and matrigel invasion assay respectively. Zymographic analysis revealed an increase in enzyme activity of MMP-9 and uPA in conditioned medium of irradiated neuroblastoma cells compared with non-irradiated cells. An increase in VEGF levels was also found in lysates of irradiated neuroblastoma cells. The up-regulation of uPA, MMP-9 and VEGF transcripts was also confirmed by RT-PCR analysis. Next, we examined the irradiated tumor cell-mediated modulation of endothelial cell behavior. Conditioned media from irradiated neuroblastoma cells enhanced capillary-like structure formation of microvascular endothelial cells. In a coculture system, irradiation of neuroblastoma cells enhanced endothelial cell invasiveness through Matrigel matrix. Endothelial cells treated with irradiated tumor cell conditioned medium were also analyzed for expression of uPA, MMP-9 and VEGF and compared to cells treated with non-irradiated tumor cell conditioned medium. These findings suggest that the irradiation effects of tumor cells could influence endothelial angiogenesis present in non-irradiated fields.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Response of neuroblastoma cells to ionizing radiation: Modulation of in vitro invasiveness and angiogenesis of human microvascular endothelial cells

Jadhav

Mohanam²

2006

Int J Oncol

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“…Especially in stage IV disease, tumor frequently recurs even after complete response to initial therapy [1, 9, 10]. Patients with classic stage IV neuroblastoma do, however, very rarely survive long term [2, 11]. Reports of survivals, remission intervals of more than 14 years [11], of refractory recurrent disease [12] and of progressive disease [13] do nonetheless exist.…”

Section: Discussionmentioning

confidence: 99%

“…However, cerebral recurrence more than 5 years after diagnosis is extremely rare [2, 3]. We herein present the case of a young woman diagnosed initially with a stage IV spinal neuroblastoma as an infant, suffering from a CNS tumor as well as hepatic and peritoneal metastases 22 years following complete remission achieved by myeloablative chemotherapy.…”

Section: Introductionmentioning

confidence: 99%

CNS Tumor 22 Years after Spinal Neuroblastoma IV: Diagnostic Dilemma between Recurrence and Secondary Malignancy

Gutenberg

Schulten²,

Gunawan³

et al. 2009

Pediatr Neurosurg

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We present the very unusual case of a young woman suffering from a brain tumor 22 years after a stage IV spinal neuroblastoma as an infant, demonstrating the difficulties of differentiating late neuroblastoma relapse from secondary supratentorial primitive neuroectodermal tumor (sPNET). Lacking specific immunohistochemical features, the first cerebral tumor at the age of 21 was regarded as sPNET, and we pursued a therapeutic approach consisting of neurosurgical resection as well as irradiation and high-dose alkylator-based chemotherapy according to the HIT2000 protocol. Two years later the patient suffered from a diffusely infiltrating local recurrence, changing its imaging appearance as well as its immunohistochemical characteristics, now revealing disseminated positivity for neuron-specific enolase and neural cell adhesion molecule. Moreover, the lack of PNET-specific translocations (EWS/FLI1 gene fusion) in both brain tumors as well as the development of hepatic metastases was more compatible with the diagnosis of a very late relapse 22 years after initial stage IV spinal neuroblastoma.

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“…Between 1985 and 1988 the overall 5-year survival for children with neuroblastoma was 58% (1). However, only 34% of children diagnosed with stage 4 neuroblastoma are long-term survivors (22). The biological mechanisms that contribute to the poor survival in children with advanced stage neuroblastoma are a subject of intense research.…”

Section: Epidemiologymentioning

confidence: 99%

The Role of Multi-Drug Resistance Associated Protein 4 and P-glycoprotein in Resistance of Neuroblastoma to Topotecan and Irinotecan

Turner¹

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Clinton Stewart for his guidance and support. I will always appreciate his patience, the numerous opportunities he has provided, and all of the time he has spent teaching me. iii Abstract High-risk neuroblastoma presents a significant therapeutic challenge because the 5-year survival rate remains less than 30% despite the use of surgery, multi-agent chemotherapy, radiation, and autologous bone marrow transplant. Novel therapeutic modalities are under development. The camptothecin analogs topotecan and irinotecan have been identified as successful cytotoxic agents. For topotecan, pharmacokinetically guided dosing to achieve a systemic exposure associated with preclinical anti-tumor activity in neuroblastoma xenograft models is feasible and has elicited favorable responses in children with high-risk neuroblastoma. However, some children with highrisk disease did not respond to the putatively effective topotecan systemic exposure.These children represent a subset of the disease intrinsically resistant to topotecan.Furthermore, mRNA expression of the adenosine triphosphate (ATP)-binding cassette (ABC) transporters P-glycoprotein (Pgp) and multidrug resistance associated protein 1 (MRP1), which efflux many drugs used in neuroblastoma therapy, has been implicated in poor outcome in neuroblastoma. Therefore, the purpose of our studies was to determine the role of ABC transport protein expression in neuroblastoma resistance to the camptothecin analogs topotecan and irinotecan. The results of the in vitro studies demonstrate that MRP4 and Pgp confer resistance to topotecan and SN-38. In the xenograft studies, MRP4 expression was associated with failure to respond to topotecan. However, this phenotype was not recapitulated in children treated with topotecan. These results may be confounded by small sample size and timing of sample acquisition. Further investigation of the role of ABC transporters in children with neuroblastoma who receive either topotecan or irinotecan may be warranted. In addition to the camptothecin analogs, patients will receive other drugs effluxed by the ABC transporters (e.g., doxorubicin, vincristine, etoposide, and cyclophosphamide). Therefore, analyzing ABC transporter expression by immunohistochemistry in diagnostic tumor specimens may help to select agents not subject to efflux by ABC transporters expressed in the tumor. However, eliminating drugs effluxed by ABC transporters from the treatment regimen creates a potential gap in therapy and may reduce drug intensity. Therefore, further rational design and development of drugs that evade ABC transporter-mediated efflux, and potentially other resistance mechanisms in neuroblastoma, is also warranted.

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Long-term outcomes in patients with stage IV neuroblastoma

Cited by 55 publications

References 31 publications

Response of neuroblastoma cells to ionizing radiation: Modulation of in vitro invasiveness and angiogenesis of human microvascular endothelial cells

Response of neuroblastoma cells to ionizing radiation: Modulation of in vitro invasiveness and angiogenesis of human microvascular endothelial cells

CNS Tumor 22 Years after Spinal Neuroblastoma IV: Diagnostic Dilemma between Recurrence and Secondary Malignancy

The Role of Multi-Drug Resistance Associated Protein 4 and P-glycoprotein in Resistance of Neuroblastoma to Topotecan and Irinotecan

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