Likelihood of Bone Recurrence in Prior Sites of Metastasis in Patients With High-Risk Neuroblastoma

Polishchuk, Alexei L.; Li, Richard; Hill‐Kayser, Christine; Little, Anthony; Hawkins, Randall A.; Hamilton, Jeffrey; Lau, Michael; Tran, Hung C.; Strahlendorf, Caron; Lemons, Richard S.; Weinberg, Vivian; Matthay, Katherine K.; DuBois, Steven G.; Marcus, Karen J.; Bagatell, Rochelle; Haas‐Kogan, Daphne A.

doi:10.1016/j.ijrobp.2014.04.004

Cited by 32 publications

(35 citation statements)

References 21 publications

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“…Our study adds to the scant proton literature and is consistent with the existing proton and photon literature with longer follow‐up . The predominant site of failure is progression in post‐induction non‐MIBG‐avid distant sites, similar to previously published reports . Although proton therapy provides high rates of local control with acceptable toxicity for neuroblastoma, our results suggest that advances in systemic therapy are needed for improved control of systemic disease.…”

Section: Discussionsupporting

confidence: 88%

Efficacy of proton therapy in children with high‐risk and locally recurrent neuroblastoma

Bagley

Grosshans

Philip

et al. 2019

Pediatric Blood & Cancer

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Purpose Proton therapy is currently used in the management of pediatric tumors to decrease late toxicities. However, one of the criticisms of proton therapy is the limited data regarding efficacy on disease control. The purpose of this study was to examine local and distant control rates after proton therapy for neuroblastoma. Methods and materials Eighteen patients with high‐risk (n = 16) and locally recurrent neuroblastoma (n = 2) were treated with curative intent and received proton therapy to the primary site and up to three post‐induction MIBG‐avid metastatic sites. Primary sites (n = 18) were treated to 21–36 Gy (relative biological effectiveness [RBE]), and metastatic sites (n = 16) were treated to 21–24 Gy (RBE). Local control and survival rates were calculated using the Kaplan–Meier method. Results With a median follow‐up of 60.2 months, two‐ and five‐year local control rates at the irradiated primary site were 94% and 87%, respectively. No failures at irradiated distant metastatic sites were observed. The five‐year progression‐free survival (PFS) was 64%, and the five‐year overall survival (OS) was 94%. The extent of surgical resection was not associated with local control, PFS, or OS. No radiation‐related nephropathy or hepatopathy was reported. Conclusions Excellent local control was achieved using proton therapy to the primary and post‐induction MIBG‐positive distant sites. The predominant site of failure is progression in post‐induction non‐MIBG‐avid distant sites. Although proton therapy provides high rates of local control with acceptable toxicity for neuroblastoma, further advances in systemic therapy are needed for the improved control of systemic disease.

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Section: Discussionsupporting

confidence: 88%

Efficacy of proton therapy in children with high‐risk and locally recurrent neuroblastoma

Bagley

Grosshans

Philip

et al. 2019

Pediatric Blood & Cancer

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“…Treatment of NB is based on risk stratification and typically includes surgery, chemotherapy, radiation, and immunotherapy in high risk patients [8][9][10][11]. Prevention of tumor recurrence is particularly difficult in patients with high-risk NB, for whom the 5-year survival rate is less than 50% [12][13][14].…”

Section: Introductionmentioning

confidence: 99%

Increased plasma concentration of cell-free DNA precedes disease recurrence in children with high-risk neuroblastoma

Wang²,

Jiang

et al. 2020

BMC Cancer

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Background: Neuroblastoma is the most common extracranial solid tumor of childhood. The high rate of recurrence is associated with a low survival rate for patients with high-risk neuroblastoma. There is thus an urgent need to identify effective predictive biomarkers of disease recurrence. Methods: A total of 116 patients with high-risk neuroblastoma were recruited at Beijing Children's Hospital between February 2015 and December 2017. All patients received multidisciplinary treatment, were evaluated for the therapeutic response, and then initiated on maintenance treatment. Blood samples were collected at the beginning of maintenance treatment, every 3 months thereafter, and at the time of disease recurrence. Plasma levels of cell-free DNA (cfDNA) were quantified by qPCR. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the ability of plasma cfDNA concentration to predict recurrence. Results: Of the 116 patients, 36 (31.0%) developed recurrence during maintenance treatment. The median time to recurrence was 19.00, 9.00, and 8.00 months for patients who had achieved complete response (n = 6), partial response (n = 25), and stable disease (n = 5), respectively, after multidisciplinary treatment. The median plasma cfDNA concentration at the time of recurrence was significantly higher than the concentration in recurrence-free patients throughout maintenance treatment (29.34 ng/mL vs 10.32 ng/mL). Patients recorded a plasma cfDNA level ≥ 29 ng/mL an average of 0.55 months before diagnosis of disease recurrence. ROC analysis of the power of plasma cfDNA to distinguish between patients with or without recurrence yielded an area under the curve of 0.825, with optimal sensitivity and specificity of 80.6 and 71.3%, respectively, at a cfDNA level of 12.93 ng/mL. Conclusions: High plasma cfDNA concentration is a potential molecular marker to signal disease recurrence in patients with high-risk neuroblastoma.

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“…This survival rate is mainly due to tumor relapse or regrowth caused by the activation of chemoresistant minimal residual disease (MRD) . To evaluate the therapeutic response and disease status of NB patients, several MRD detection methods, including 131 I‐metaiodobenzylguanidine ( 131 I‐MIBG), have a high detection sensitivity in NB primary tumors and bone or bone marrow metastasis . However, 131 I‐MIBG detection is complicated and requires a long time.…”

Section: Introductionmentioning

confidence: 99%

“…1,[3][4][5] To evaluate the therapeutic response and disease status of NB patients, several MRD detection methods, including 131 I-metaiodobenzylguanidine ( 131 I-MIBG), have a high detection sensitivity in NB primary tumors and bone or bone marrow metastasis. 6,7 However, 131 I-MIBG detection is complicated and requires a long time. Therefore, the clinical evaluation of a precise diagnosis of MRD by molecular pathology in NB patients remains to be established.…”

Section: Introductionmentioning

confidence: 99%

Plasma cell‐free DNA quantification is highly correlated to tumor burden in children with neuroblastoma

Wang

Wang²,

et al. 2018

Cancer Medicine

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To evaluate plasma cell‐free DNA (cfDNA) as a promising biomarker for neuroblastoma (NB) tumor burden. Seventy‐nine eligible patients with newly diagnosed NB were recruited from Beijing Children's Hospital between April 2016 and April 2017. Additionally, from September 2011 to June 2017, 79 patients with stable NB were evaluated with a median follow‐up time of 21 months. Approximately 2 mL of peripheral blood was drawn upon enrollment, and plasma cfDNA levels were measured via quantitative polymerase chain reaction (qPCR). Total cfDNA analysis was performed using the long interspersed nuclear element 1 (LINE‐1) 79 bp fragment, and DNA integrity was calculated by the ratio of the LINE‐1 300 bp fragment to the LINE‐1 79 bp fragment. A total of 79 NB patients with a median age of 36 months comprised the group of newly diagnosed NB patients. The main primary tumor site was the retroperitoneal and adrenal region (81%). Three or more metastatic sites were found in 17.7% of patients. Stable NB patients older than 18 months comprised 98.7% of the stable NB patients. Neuron‐specific enolase (NSE), lactate dehydrogenase (LDH), and cfDNA levels were dramatically increased in the newly diagnosed NB patients and significantly different from those in the stable NB patients. Moreover, the concentration of cfDNA was much higher in patients with larger tumors. By analyzing the area under the receiver operator characteristic (ROC) curve (AUC), the areas of total cfDNA, NSE, and LDH levels were 0.953, 0.929, and 0.906, respectively. The sensitivity and specificity data clarified that the level of circulating cfDNA in plasma can be considered as a reliable biomarker for describing tumor load in NB. The plasma cfDNA concentration was as good as the levels of LDH and NSE to discriminate the tumor burden in children with NB.

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Likelihood of Bone Recurrence in Prior Sites of Metastasis in Patients With High-Risk Neuroblastoma

Cited by 32 publications

References 21 publications

Efficacy of proton therapy in children with high‐risk and locally recurrent neuroblastoma

Efficacy of proton therapy in children with high‐risk and locally recurrent neuroblastoma

Increased plasma concentration of cell-free DNA precedes disease recurrence in children with high-risk neuroblastoma

Plasma cell‐free DNA quantification is highly correlated to tumor burden in children with neuroblastoma

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