Dose‐escalation is needed for gross disease in high‐risk neuroblastoma

Casey, Dana L.; Kushner, Brian H.; Cheung, Nai‐Kong V.; Modak, Shakeel; LaQuaglia, Michael P.; Wolden, Suzanne L.

doi:10.1002/pbc.27009

Cited by 20 publications

(7 citation statements)

References 17 publications

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“…There has been speculation whether the presence of gross disease after surgery can be controlled by a higher dose of radiation (36 Gy) as employed in the NB97 trial . A recent publication reviewed the published locoregional control rates after standard dose radiation (21–24 Gy) versus higher dose radiation (30–36 Gy); in children with STR, local failure was found in 17% to 43% of patients receiving standard and 0% in those receiving higher dose RT . We did not find a difference in locoregional control, progression‐free, or OS according to the degree of resection.…”

Section: Discussionmentioning

confidence: 55%

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: Discussionmentioning

confidence: 55%

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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“…In Europe, there is a debate, if, after subtotal resection a dose increase with 36 Gy may be advantageous. A retrospective study from the Memorial Sloan Kettering Cancer Centre showed that patients with residual tumor who had received a dose of more than 30 Gy remained free of local failure (100%), while 30% of those who were irradiated with a dose below 30 Gy experienced local failure (44). Simon et al had comparable results for patients with residual tumor who received a dose of 36-40 Gy.…”

Section: Discussionmentioning

confidence: 99%

Proton Beam Therapy for Children With Neuroblastoma: Experiences From the Prospective KiProReg Registry

et al. 2021

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ObjectiveRadiotherapy (RT) is an integral part of the interdisciplinary treatment of patients with high-risk neuroblastoma (NB). With the continuous improvements of outcome, the interest in local treatment strategies that reduce treatment-related side effects while achieving optimal oncological results is growing. Proton beam therapy (PBT) represents a promising alternative to conventional photon irradiation with regard to the reduction of treatment burden.MethodRetrospective analysis of children with high or intermediate risk NB receiving PBT of the primary tumor site during first-line therapy between 2015 and 2020 was performed. Data from the prospective in-house registry Standard Protonentherapie WPE – Kinder- (KiProReg) with respect to tumor control and treatment toxicity were analyzed. Adverse events were classified according to CTCAE Version 4 (V4.0) before, during, and after PBT.ResultsIn total, 44 patients (24 male, 20 female) with high (n = 39) or intermediate risk NB (n = 5) were included in the analysis. Median age was 3.4 years (range, 1.4–9.9 years). PBT doses ranged from 21.0 to 39.6 Gray (Gy) (median 36.0 Gy). Five patients received PBT to the MIBG-avid residual at the primary tumor site at time of PBT according to the NB-2004 protocol. In 39 patients radiation was given to the pre-operative tumor bed with or without an additional boost in case of residual tumor. After a median follow-up (FU) of 27.6 months, eight patients developed progression, either local recurrence (n = 1) or distant metastases (n = 7). Four patients died due to tumor progression. At three years, the estimated local control, distant metastatic free survival, progression free survival, and overall survival was 97.7, 84.1, 81.8, and 90.9%, respectively. During radiation, seven patients experienced higher-grade (CTCAE ≥ °3) hematologic toxicity. No other higher grade acute toxicity occurred. After PBT, one patient developed transient myelitis while receiving immunotherapy. No higher grade long-term toxicity was observed up to date.ConclusionPBT was a well tolerated and effective local treatment in children with high and intermediate risk NB. The role of RT in an intensive multidisciplinary treatment regimen remains to be studied in the future in order to better define timing, doses, target volumes, and general need for RT in a particularly sensitive cohort of patients.

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“…Although some studies reported that a higher dose is needed to control gross residual tumor after incomplete surgery [17,18], the optimal dose of RT is still unclear. In this study, 2 patients received boost RT for gross residual tumor with a total radiation dose of 27 and 36 Gy, respectively.…”

Section: Discussionmentioning

confidence: 99%

Patterns of recurrence after radiation therapy for high-risk neuroblastoma

Ahn

Koh

et al. 2019

Radiat Oncol J

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PurposeTo investigate the patterns of recurrence in patients with neuroblastoma treated with radiation therapy to the primary tumor site.Materials and MethodsWe retrospectively analyzed patients with high-risk neuroblastoma managed with definitive treatment with radiation therapy to the primary tumor site between January 2003 and June 2017. These patients underwent three-dimensional conformal radiation therapy or intensity-modulated radiation therapy. A total of 14–36 Gy was delivered to the planning target volume, which included the primary tumor bed and the selected metastatic site. The disease stage was determined according to the International Neuroblastoma Staging System (INSS). We evaluated the recurrence pattern (i.e., local or systemic), progression-free survival, and overall survival.ResultsA total of 40 patients with high-risk neuroblastoma were included in this study. The median patient age was 4 years (range, 1 to 11 years). Thirty patients (75%) had INSS stage 4 neuroblastoma. At the median follow-up of 58 months, there were 6 cases of local recurrence and 10 cases of systemic recurrence. Among the 6 local failure cases, 4 relapsed adjacent to the radiation field. The other 2 relapsed in the radiation field (i.e., para-aortic and retroperitoneal areas). The main sites of distant metastasis were the bone, lymph nodes, and bone marrow. The 5-year progression-free survival was 70.9% and the 5-year overall survival was 74.3%.ConclusionRadiation therapy directed at the primary tumor site provides good local control. It seems to be adequate for disease control in patients with high-risk neuroblastoma after chemotherapy and surgical resection.

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Dose‐escalation is needed for gross disease in high‐risk neuroblastoma

Abstract: After subtotal resection, patients who received less than 30 Gy had poor local control. Doses of 30-36 Gy are likely needed for optimal control of gross residual disease at the time of consolidative RT in high-risk neuroblastoma.

Cited by 20 publications

References 17 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

Proton Beam Therapy for Children With Neuroblastoma: Experiences From the Prospective KiProReg Registry

Patterns of recurrence after radiation therapy for high-risk neuroblastoma

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