Volume of preclinical xenograft tumors is more accurately assessed by ultrasound imaging than manual caliper measurements.
Volume of preclinical xenograft tumors is more accurately assessed by ultrasound imaging than manual caliper measurements.
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DOI：
10.7863/jum.2010.29.6.891
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发表时间：
2010-06
期刊：
影响因子：
--
通讯作者：
Manning HC
中科院分区：
文献类型：
--
作者：
Ayers GD;McKinley ET;Zhao P;Fritz JM;Metry RE;Deal BC;Adlerz KM;Coffey RJ;Manning HC
皮下异种移植肿瘤的体积是临床前药物开发中疾病进展和治疗反应的重要指标。适用于测量异种移植物体积的非侵入性成像技术越来越多，但常规使用的手动卡尺容易出现不准确和偏差。本研究的目的是通过卡尺测量和超声成像来量化和比较异种移植肿瘤体积评估的准确性、精密度和评估者间变异性。在无胸腺裸鼠中产生源自人结直肠癌细胞系（DLD1、SW620）的皮下异种移植肿瘤。经验丰富的独立评审员分割三维超声数据集并收集手动卡尺测量结果得出肿瘤体积。将成像和测径器得出的体积与切除后确定的肿瘤质量（金标准）进行比较。评估者对每只小鼠的偏差、精确度和评估者间差异进行了估计。 Bootstrapping 用于估计方差分量的均值和置信区间、组内相关系数 (ICC) 以及每个变异源的置信区间。与卡尺体积相比，超声体积与真实体积的平均偏差和评估者间差异显着较低。超声和卡尺测量的评审者 ICC 同样低 (1%)，但卡尺体积方差比超声高 1.3 倍。超声成像比卡尺测量更准确、精确且可重复地反映异种移植肿瘤体积。这些数据表明，与利用卡尺测量的类似研究相比，利用异种移植负荷作为超声成像测量的替代终点的临床前研究需要减少多达 30% 的动物才能达到统计显着性。
Volume of subcutaneous xenograft tumors is an important metric of disease progression and response to therapy in preclinical drug development. Non-invasive imaging technologies suitable for measuring xenograft volume are increasingly available, yet manual calipers, which are susceptible to inaccuracy and bias, are routinely employed. The goal of this study was to quantify and compare the accuracy, precision, and inter-rater variability of xenograft tumor volume assessment by caliper measurements and ultrasound imaging. Subcutaneous xenograft tumors derived from human colorectal cancer cell lines (DLD1, SW620) were generated in athymic nude mice. Experienced independent reviewers segmented three-dimensional ultrasound data sets and collected manual caliper measurements resulting in tumor volumes. Imaging- and caliper-derived volumes were compared to tumor mass, the gold standard, determined following resection. Bias, precision and inter-rater differences were estimated for each mouse among reviewers. Bootstrapping was used to estimate mean and confidence intervals of variance components, intra-class correlation coefficients (ICC’s) and confidence intervals for each source of variation. Average deviation from true volume and inter-rater differences were significantly lower for ultrasound volumes compared to caliper volumes. Reviewer ICC’s for ultrasound and caliper measurements were similarly low (1%), yet caliper volume variance was 1.3-fold higher than ultrasound. Ultrasound imaging more accurately, precisely, and reproducibly reflects xenograft tumor volume than caliper measurements. These data suggest that preclinical studies utilizing xenograft burden as a surrogate endpoint measured by ultrasound imaging require up to 30% fewer animals to reach statistical significance compared to analogous studies utilizing caliper measurements.
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DOI：
10.1158/1078-0432.ccr-08-0239
发表时间：
2008-11-15
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Manning HC;Merchant NB;Foutch AC;Virostko JM;Wyatt SK;Shah C;McKinley ET;Xie J;Mutic NJ;Washington MK;LaFleur B;Tantawy MN;Peterson TE;Ansari MS;Baldwin RM;Rothenberg ML;Bornhop DJ;Gore JC;Coffey RJ
通讯作者：
Coffey RJ
影响因子：
2.9
作者：
Cheung, AMY;Brown, AS;Foster, FS
通讯作者：
Foster, FS
影响因子：
3
作者：
TOMAYKO, MM;REYNOLDS, CP
通讯作者：
REYNOLDS, CP
影响因子：
2.9
作者：
He, ZQ;Evelhoch, JL;Sarkar, FH
通讯作者：
Sarkar, FH
影响因子：
11.2
作者：
Graham, KC;Wirtzfeld, LA;Chambers, AF
通讯作者：
Chambers, AF