Pencil Beam Scanning Proton Therapy for Paediatric Neuroblastoma with Motion Mitigation Strategy for Moving Target Volumes

AimsMore efforts are required to minimise late radiation side-effects for paediatric patients. Pencil beam scanning proton beam therapy (PBS-PT) allows increased sparing of normal tissues while maintaining conformality, but is prone to dose degradation from interplay effects due to respiratory motion. We report our clinical experience of motion mitigation with volumetric rescanning (vRSC) and outcomes of children with neuroblastoma.Materials and methodsNineteen patients with high-risk (n = 16) and intermediate-risk (n = 3) neuroblastoma received PBS-PT. The median age at PBS-PT was 3.5 years (range 1.2–8.6) and the median PBS-PT dose was 21 Gy (relative biological effectiveness). Most children (89%) were treated under general anaesthesia. Seven patients (37%) underwent four-dimensional computed tomography for motion assessment and were treated with vRSC for motion mitigation.ResultsThe mean result of maximum organ motion was 2.7 mm (cranial–caudal), 1.2 mm (left–right), 1.0 mm (anterior–posterior). Four anaesthetised children (21%) showing <5 mm motion had four-dimensional dose calculations (4DDC) to guide the number of vRSC. The mean deterioration or improvement to the planning target volume covered by 95% of the prescribed dose compared with static three-dimensional plans were: 4DDC no vRSC, –0.6%; 2 vRSC, +0.3%; 4 vRSC, +0.3%; and 8 vRSC, +0.1%. With a median follow-up of 14.9 months (range 2.7–49.0) there were no local recurrences. The 2-year overall survival was 94% and distant progression-free survival was 76%. Acute grade 2–4 toxicity was 11%. During the limited follow-up time, no late toxicities were observed.ConclusionsThe early outcomes of mainly high-risk patients with neuroblastoma treated with PBS-PT were excellent. With a subset of our cohort undergoing PBS-PT with vRSC we have shown that it is logistically feasible and safe. The clinical relevance of vRSC is debatable in anaesthetised children with small pre-PBS-PT motion of <5 mm.     

LRIG3基因过表达对人神经母细胞瘤细胞系SK-N-MC细胞生物学行为的影响

目的 探讨富含亮氨酸重复序列免疫球蛋白样蛋白3（LRIG3）基因过表达对人神经母细胞瘤细胞系SK-N-MC细胞生物学行为的影响。方法 体外培养人神经母细胞瘤细胞系SK-N-MC细胞，分成空白对照组（A组，不转染任何载体或质粒）、载体组（B组，转染载体）和LRIG3过表达组（C组，转染含LRIG3基因过表达质粒）。 荧光定量PCR和免疫印迹法检测LRIG3、Caspase-3和Caspase-9的mRNA和蛋白表达水平。Transwell试剂盒检测细胞侵袭能力，AV-PI试剂盒检测细胞凋亡水平，CCK-8试剂盒检测细胞增殖能力。结果 C组Caspase-3和Caspase-9的mRNA和蛋白表达水平以及细胞凋亡率明显高于A组和B组（P<0.05），细胞增殖率和细胞侵袭能力明显低于A组和B组（P<0.05），而A组和B组之间均无统计学差异（P>0.05）。结论 LRIG3过表达可以抑制人神经母细胞瘤细胞系SK-N-MC细胞增殖和侵袭，促进其凋亡，其机制可能与促进Caspase-3和Caspase-9表达有关     

Spontaneous regression of stage Ⅲ neuroblastoma: A case report

BACKGROUND Neuroblastoma(NB) is the most common type of extracranial solid tumour in children. The overall prognosis of NB is poor, but at the same time, NB shows significant clinical diversity. NB can demonstrate spontaneous regression or can differentiate into benign ganglioneuroma.CASE SUMMARY This study retrospectively analyzed the clinical data of a patient with spontaneous regression of stage Ⅲ NB who was admitted in May 2015. Studies of the spontaneous regression of NB published from October 1946 to September 2019 were retrieved through Pub Med. The clinical manifestations, diagnosis,treatment, and follow-up results were analysed.CONCLUSION Spontaneous regression of stage Ⅲ NB is rare in the clinic. The report of this case is an important supplement to the study of the spontaneous regression of NB.     

Vancomycin-related convulsion in a pediatric patient with neuroblastoma: A case report and review of the literature

BACKGROUNDVancomycin is often used as an anti-infective drug in patients receiving anti-tumor chemotherapy. There are concerns about its adverse drug reactions during treatment, such as nephrotoxicity, ototoxicity, hypersensitivity reactions, etc. However, potential convulsion related to high plasma concentrations of vancomycin in children receiving chemotherapy has not been reported.CASE SUMMARYA 3.9-year-old pediatric patient with neuroblastoma receiving vancomycin to treat post-chemotherapy infection developed an unexpected convulsion. No other potential disease conditions could explain the occurrence of the convulsion. The subsequently measured overly high plasma concentrations of vancomycin could possibly provide a clue to the occurrence of this convulsion. The peak and trough plasma concentrations of vancomycin were 59.5 mg/L and 38.6 mg/L, respectively, which were much higher than the safe range. Simulation with the Bayesian approach using MwPharm software showed that the area under the concentration-time curve over 24 h was 1086.6 mg· h/L. Therefore, vancomycin was immediately stopped and teicoplanin was administered instead combined with meropenem and fluconazole as the anti-infective treatment strategy.CONCLUSIONUnexpected convulsion occurring in a patient after chemotherapy is probably due to toxicity caused by abnormal pharmacokinetics of vancomycin. Overall evaluation and close therapeutic drug monitoring should be conducted to determine the underlying etiology and to take the necessary action as soon as possible.     

Neuroblastoma: a master of disguise and a challenge to cure

Neuroblastoma is one of the commonest childhood cancers and typically affects very young children. It is characterized by a very broad spectrum of clinical presentation and outcome, driven by the biology of the tumour. This ranges from ‘low risk’ tumours, most commonly found in infants, which may spontaneously regress and have an excellent prognosis with minimal or no treatment, to ‘high risk’ disease, which carries a poor prognosis despite intensive multi-modal treatment. Although particular presentations may be associated with favourable or unfavourable outcome, the clinical features may mask the underlying biology of the tumour and a full assessment of the clinical and biological features is required to determine appropriate treatment. The International Neuroblastoma Risk Group classification, based on the age of the patient and the stage, grade and genetics of the tumour, is used to stratify treatment according to risk factors. This review provides an overview of current neuroblastoma management, focusing on how classification is applied in practice, and how this is used to determine individual patient treatment. The challenges that remain in treating patients with high-risk disease are discussed.     

“活板门”手术切除儿童颈胸部神经母细胞瘤

目的：由于颈胸部神经母细胞瘤其独特的位置致手术空间局限,加上肿瘤常常包绕血管,使手术操作困难而具有挑战性。本研究探讨以“活板门”前开胸手术法切除颈胸神经母细胞瘤的方法。方法对10例以“活板门”前开胸手术处理的颈胸神经母细胞瘤患儿,经一期手术切除肿瘤组织,并对结果进行分析。结果10例中,男6例,女4例,手术时年龄4个月至7岁10个月（平均3岁8个月）。5例行左侧开胸手术。临床分期[国际神经母细胞瘤分期系统（INSS）]：Ⅰ期（2例）,Ⅱ期（1例）,Ⅲ期（1例）,Ⅳ期（5例）,ⅣS期（1例）。6例术前接受化疗,其中1例手术前接受局部放疗。一期肉眼完全切除率100％。术后并发症包括霍纳氏综合征10例,膈神经麻痹1例,无围手术期死亡病例。中位随访时间为4．3（0．1～7．4）年。结论通过“活板门”前开胸手术方法切除儿童颈胸神经母细胞瘤,能够显著提高一期手术完全切除率,且并发症少。