Pluimakers V G, van Waas M, Looman C W N, de Maat M P, de Jonge R, Delhanty P, Huisman M, Mattace-Raso F U S, van den Heuvel-Eibrink M M, Neggers S J C M M
Princess Máxima Centre for Paediatric Oncology, Utrecht, The Netherlands.
Department of Paediatric Oncology/Haematology, Erasmus MC-Sophia Children's Hospital, Rotterdam, The Netherlands.
Endocr Connect. 2020 Jul;9(7):676-686. doi: 10.1530/EC-20-0144.
Augmented survival of childhood nephroblastoma and neuroblastoma has increased long-term side effects such as metabolic syndrome (MetS). Risk stratification is difficult after abdominal radiation because waist circumference underestimates adiposity. We aimed to develop a strategy for determining MetS in irradiated survivors using an integrated biomarker profile and vascular ultrasonography.
The NCEP-ATPIII MetS-components, 14 additional serum biomarkers and 9 vascular measurements were assessed in a single-centre cohort of childhood nephroblastoma (n = 67) and neuroblastoma (n = 36) survivors and controls (n = 61). Multivariable regression models were used to study treatment effects. Principal component analysis (PCA) was used to study all biomarkers in a combined analysis, to identify patterns and correlations.
After 27.5 years of follow-up, MetS occurred more often in survivors (14%) than controls (3%). Abdominal radiotherapy and nephrectomy, to a lesser extent, were associated with MetS and separate components and with several biomarker abnormalities. PCA of biomarkers revealed a pattern on PC1 from favourable lipid markers (HDL-cholesterol, adiponectin) towards unfavourable markers (triglycerides, LDL-cholesterol, apoB, uric acid). Abdominal radiotherapy was associated with the unfavourable biomarker profile (β = 1.45, P = 0.001). Vascular measurements were not of added diagnostic value.
Long-term childhood nephro- and neuroblastoma survivors frequently develop MetS. Additional assessment of biomarkers identified in PCA - adiponectin, LDL, apoB, and uric acid - may be used especially in abdominally irradiated survivors, to classify MetS as alternative for waist circumference. Vascular ultrasonography was not of added value.
儿童肾母细胞瘤和神经母细胞瘤生存率的提高增加了代谢综合征（MetS）等长期副作用。腹部放疗后风险分层较为困难，因为腰围会低估肥胖程度。我们旨在制定一种策略，通过综合生物标志物谱和血管超声检查来确定接受过放疗的幸存者是否患有MetS。
在一个单中心队列中，对67例儿童肾母细胞瘤幸存者、36例儿童神经母细胞瘤幸存者以及61例对照者进行了美国国家胆固醇教育计划成人治疗组第三次报告（NCEP-ATPIII）的MetS组分、另外14种血清生物标志物和9项血管测量评估。使用多变量回归模型研究治疗效果。主成分分析（PCA）用于在综合分析中研究所有生物标志物，以识别模式和相关性。
经过27.5年的随访，幸存者中MetS的发生率（14%）高于对照组（3%）。腹部放疗以及程度较轻的肾切除术与MetS及其各个组分以及几种生物标志物异常有关。生物标志物的PCA显示，在主成分1（PC1）上存在一种模式，从有利的脂质标志物（高密度脂蛋白胆固醇、脂联素）向不利的标志物（甘油三酯、低密度脂蛋白胆固醇、载脂蛋白B、尿酸）转变。腹部放疗与不利的生物标志物谱相关（β = 1.45，P = 0.001）。血管测量没有额外的诊断价值。
儿童肾母细胞瘤和神经母细胞瘤的长期幸存者经常发生MetS。对PCA中确定的生物标志物——脂联素、低密度脂蛋白、载脂蛋白B和尿酸——进行额外评估，可能特别适用于接受腹部放疗的幸存者，以将MetS分类，作为腰围测量的替代方法。血管超声检查没有额外价值。
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