Aggressive surgical therapy and radiotherapy for patients with high-risk neuroblastoma treated with rapid sequence tandem transplant

Allmen, Daniel von; Grupp, Stephan A.; Diller, Lisa; Marcus, Karen J.; Ecklund, Kirsten; Meyer, James S.; Shamberger, Robert C.

doi:10.1016/j.jpedsurg.2005.03.008

Cited by 47 publications

(43 citation statements)

References 19 publications

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“…We found that only 38% of children evaluated at our HSCT center for treatment of NB had undergone a GTR of their primary tumor. Although a limited number of studies suggest a possible advantage of GTR [11,12], our findings do not demonstrate an association between GTR and improved outcomes in high-risk NB, consistent with much of the current literature [9,[13][14][15][16].…”

Section: Discussionsupporting

confidence: 87%

“…Examining the results of several studies suggests that resection >90% may be a more appropriate cut-off than GTR to achieve optimal survival [9,15,18]. In a recent meta-analysis comparing >90% resection to <90% resection, an overall benefit of >90% resection was demonstrated, although few individual studies were able to achieve statistical significance [18].…”

Section: Discussionmentioning

confidence: 99%

“…Gross total resection (GTR) was defined as no visible or palpable disease at the end of operation. Less than GTR included those patients undergoing no surgery, biopsy only, partial resection (50-90%), or near-gross total resection (>90% but with palpable or visible tumor remaining) [12,15]. Other variables of interest included: age, gender, tumor location, INSS stage, radiographic results, MYCN amplification status, Shimada classification, lactate dehydrogenase (LDH), neo-adjuvant therapies, and radiographic response to neoadjuvant therapy (complete response, very good partial response, and partial response vs. mixed response, no response, Background.…”

Section: Methodsmentioning

confidence: 99%

“…The optimal role of surgical therapy for high-risk NB is poorly defined and the value of gross total resection (GTR) for highrisk NB remains intensely debated [9][10][11][12][13][14][15][16][17][18]. Surgeons are often challenged with determining the aggressiveness with which to pursue GTR, particularly in the setting of bulky or extensive intraabdominal involvement.…”

Section: Introductionmentioning

confidence: 99%

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Value of surgical resection in children with high‐risk neuroblastoma

Englum

Rialon

Speicher

et al. 2015

Pediatric Blood & Cancer

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BackgroundThe value of gross total resection (GTR) for children with high‐risk neuroblastoma (NB) is controversial. We hypothesized that patients undergoing GTR would demonstrate improved overall survival (OS) compared those having <GTR.MethodsUsing a single institutional database, we reviewed the medical records of all children with high‐risk NB undergoing hematopoietic stem cell transplantation (HSCT) as part of multimodality therapy from 1990 to 2012. Children had received surgical care at multiple institutions (n = 14) prior to HSCT and were divided into two groups based on extent of surgical resection: GTR (no visible or palpable disease at end of operation) and <GTR (no surgery, biopsy only, or subtotal resection). Kaplan–Meier curves and Cox hazards models evaluated differences in overall survival (OS).ResultsOne hundred four children underwent HSCT, and 87 (83.6%) had adequate data for analysis. Thirty eight percent had GTR while 62% had <GTR prior to HSCT. There was no significant difference in OS in patients undergoing GTR compared to <GTR (Log rank test: P = 0.49). Post‐hoc analysis demonstrated a survival advantage for patients undergoing >90% resection compared to <90% resection (P = 0.008). Multivariable Cox models confirmed these findings with improved survival in children undergoing >90% vs. <90% resection but no difference in GTR vs. <GTR.ConclusionGross total resection prior to HSCT in high‐risk NB patients is not associated with improved OS compared to <GTR; however, these results suggest that >90% resection is associated with improved OS compared to less than 90% resection. Pediatr Blood Cancer 2015;62:1529–1535. © 2015 Wiley Periodicals, Inc.

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Section: Discussionsupporting

confidence: 87%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Value of surgical resection in children with high‐risk neuroblastoma

Englum

Rialon

Speicher

et al. 2015

Pediatric Blood & Cancer

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“…Standard therapy for advanced disease includes chemotherapy, surgery, and radiation. Patients who do not respond to these modalities may undergo highdose chemoradiation followed by bone marrow transplant (1,2), which seems to provide some control of disease progression but is complicated by significant morbidity and mortality. Neuroblastoma has been described as a highly angiogenic tumor with poor prognosis linked to vascular index (3), suggesting that this tumor type may respond to antiangiogenic treatment.…”

Section: Introductionmentioning

confidence: 99%

Potent antitumor effects of ZD6474 on neuroblastoma via dual targeting of tumor cells and tumor endothelium

Beaudry

Nilsson²,

Rioth

et al. 2008

Molecular Cancer Therapeutics

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Among children with relapsed or refractory neuroblastoma, the prognosis is poor and novel therapeutic strategies are needed to improve long-term survival. As with other solid tumors, high vascular density within neuroblastoma is associated with advanced disease, and therapeutic regimens directed against the tumor vasculature may provide clinical benefit. The receptor tyrosine kinase RET is widely expressed in neuroblastoma and is known to activate key signal transduction pathways involved in tumor cell survival and progression including Ras/mitogenactivated protein kinase and phosphatidylinositol 3-kinase/ Akt. We investigated the effect of dual targeting of tumor cells and tumor endothelium with ZD6474, a smallmolecule tyrosine kinase inhibitor of vascular endothelial growth factor (VEGF) receptor 2, epidermal growth factor receptor, and RET. ZD6474 inhibited the phosphorylation of RET in neuroblastoma cells and had a direct effect on tumor cell viability in seven neuroblastoma cell lines. In a human neuroblastoma xenograft model, ZD6474 inhibited tumor growth by 85% compared with treatment with vehicle alone. In contrast, no significant inhibition of tumor growth was observed after treatment with bevacizumab,

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Neuroblastoma: A 20‐year experience in a UK regional centre

Salim

Mullassery

Pizer

et al. 2011

Pediatric Blood & Cancer

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While complete tumour resection may be desirable in advanced neuroblastoma (stage 3-4) these findings suggest that the radicality of operation is not significantly associated with better overall survival/relapse. Improving outcomes in the 1995-2005 era for patients with stage 3-4 tumours complements the introduction of new high dose-intensive chemotherapy regimens and other adjuvant therapies for this enigmatic disease.

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Aggressive surgical therapy and radiotherapy for patients with high-risk neuroblastoma treated with rapid sequence tandem transplant

Cited by 47 publications

References 19 publications

Value of surgical resection in children with high‐risk neuroblastoma

Value of surgical resection in children with high‐risk neuroblastoma

Potent antitumor effects of ZD6474 on neuroblastoma via dual targeting of tumor cells and tumor endothelium

Neuroblastoma: A 20‐year experience in a UK regional centre

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