When using calipers there is dependency in the measured data of the positioning by the operator of the tool on the xenograft. & Moon, R.C. After sacrificing mice, tumors were removed, and their mass was measured. NCI CPTC Antibody Characterization Program. Bousquet, P.F. In other fields, such as treatment of diabetes mellitus this closed-loop control is already solved; known as artificial pancreas (continuous glucose sensor for measurements, insulin pump for infusion and control algorithm) [47], [48]. The size of maximum tumor volumes observed in our study fulfills the requirements of Hungarian animal experimental research protocol. For ultrasonography measurements, we calculated tumor volume . https://doi.org/10.1371/journal.pone.0142190.g004. The other eight tumors exhibit forms that cannot be compared to a perfect ellipsoid. Investigating the results of Phase III/3 one can observe that the two-dimensional mathematical model has good estimation property when the tumor width and length values are small; however, for large tumor diameter values the estimation could result in significant error, the estimated value is greater than the measured one (outliers are E8, C2). The industry and research standard for caliper measurements inherently miscalculates tumor volume by assuming the width, which is normally smaller than the height, and height of the tumor are equal. The tumor shown has a dip in its form, which means that its volume will be less than that of a tumor without a dip. A caliper measurement would only take into account the components for length and width and therefore ignore this dip measured by the values for height, which would, in turn, inaccurately measure the tumors volume. Google Scholar. <> stream Yes In this way, the targeted therapy can be used in a much more individualized form. In addition, studies using CT scans concluded that CT yielded tumor volume values 11 to 12% less (an underestimate) than those which were measured by calipers, and that CT-based measurements yielded more accurate and consistent values than caliper-based measurements[6, 7]. The last step is to find the f constant of the two-dimensional mathematical model for tumor growth without therapy (Phase I). Combining Mechanisms of Growth Arrest in Solid Tumours: A Mathematical Investigation, Dramatic increase in volume versus length of invasive ductal carcinoma mimicking intramammary lymph node in a small nodular lesion, Alteration in Inflammasome Cytokine Profile and Functional Plasticity of Macrophage Phenotype in Arsenic(0) Nanoparticle Treated Murine Fibrosarcoma, Tumoral CD105 promotes immunosuppression, metastasis, and angiogenesis in renal cell carcinoma, Cancel In this case, tumor volume has to be calculated in the following way: Competing interests: The authors have the following interests: Coauthors PK and DG are employed by Gedeon Richter Ltd. Avastin (bevacizumab) is manufactured by Genentech, Inc., South San Francisco, California, USA; EU patent expiry in 2019 in the US and 2022 in EU. Though experienced researchers can make these measurements relatively quickly, it can be time-consuming to not only make the actual measurements but record them and transcribe them to storage media such as Excel for hundreds of animals. Med. Get just this article for as long as you need it, Prices may be subject to local taxes which are calculated during checkout. r>12TzPn 4x PUj50"pJ{{>y{.mn|Cvz{PP5x kH:5:YM.gn?c[J8oQWkR_!X/C@6P@WT=gO5Sn>om}&SI cyT>E"TnkhSju>~yVOm^C~0__ww@ y[xQr33?6O~hZcR{{u]=O5T. With constant width and length, the measured volume changes with the shape of the tumor. Figure 4. Get the most important science stories of the day, free in your inbox. 1st Department of Pathology and Experimental Cancer Research, Semmelweis University, Budapest, Hungary. Predicting tumor volume in radical prostatectomy specimens from patients with prostate cancer. broad scope, and wide readership a perfect fit for your research every time. Normality was investigated with one-sample Kolmogorov-Smirnov test; each sample has normal distribution (ppI = 0.883, ppIII/3_case = 0.716, ppIII/3_control = 0.869). One can see that the two-dimensional mathematical model fits to the MRI-measured values, while the protocol-based values present totally different curve. Cancer Inst. Consequences are manifold. For this dataset, linear curve fitting was carried out (fitted linear curve) to find the mathematical relationship between MRI-measured tumor volume and tumor mass. During the scan, a mouse should be held in a relaxed manner without stretching its skin to cause unwanted deformation of the tumor body. Figure 1. This site needs JavaScript to work properly. We are sorry, but there is no personal subscription option available for your country. The means of the samples are mpIV_control = 0.65, mpIV_case1 = 0.70, mpIV_case2 = 0.46. Preclinical Imaging Center, Gedeon Richter Plc., Budapest, Hungary, Affiliation We also compared the tumor volumes measured by calipers to compare them with the scanner measurements. The 1st Department of Pathology and Experimental Cancer Research of the Semmelweis University (Budapest, Hungary) and the Physiological Controls Group of the Obuda University (Budapest, Hungary) began collaborating on antiangiogenic therapy research in 2012including the current experimental investigations. Monaco performed the dose calculation of the VMAT treatment plans with the dose calculation grid of 3.0 mm by utilizing the Monte Carlo algorithm. The explanation of the effectiveness of low dose VEGF therapy is the following ([3944]). Tumor Volume Formula for Caliper Measurements, 3. Usage of this formula to calculate tumor volume from length and width values resulted in much more precise approximation of the MRI-measured tumor volume than protocol-based calculation. 2 0 obj Figure 15. Tumor Volume Measurement Accessibility Measure the three dimensions of peanut M&M's, serving as our similar-sized tumor surrogates, using vernier calipers. A tumor expands in width rather than height as it grows. How the device is positioned over the tumor will not influence the result. Radiology 254, 110118 (2010). Tumor volume (and the third diameter) has to be approximated, assuming a certain shape for the tumor. (4). Verma, R. et al. To obtain These images also provide extra morphological information about the tumor growth and the effect of the compounds on tumor behavior. and JavaScript. HHS Vulnerability Disclosure, Help Google Scholar. Internet J. Surg. Kobayashy, T. et al. & Robinson, S.P. Comparison of volume measurement results between four users. A caliper only digitizes the length and width of the tumor. Department of Control Engineering and Information Technology, Budapest University of Technology and Economics, Budapest, Hungary, Affiliation & Russo, I.H. Importantly, these measured size differences are real; they are not due to a miscalculation by the algorithm but due to the pressing of the tumor mass into the body. J. Ultrasound Med. Pritt, B., Ashikaga, T., Oppenheimer, R.G. & Lin, C.A. Ultrasound Med. Westerlind, K.C. Cell Rep Med. Lab Anim 42, 217224 (2013). Ultrasonographic, thermographic and histologic evaluation of MNU-induced mammary tumors in female Sprague-Dawley rats. Treat. Both methods cannot avoid variability introduced by the manipulation of the animal. Article Caliper instructions are provided as well as an introduction to ellipsoids. Med. Faustino-Rocha, A., Oliveira, P., Pinho-Oliveira, J. et al. calipers and Water Displacement methods Tumor mimicking objects Vol. Levenes test showed that the sample variances are equal (p = 0.108). Med. No, Is the Subject Area "Breast cancer" applicable to this article? & Weaver, D.L. B){00)Y$Ixlr{dYe}#@ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ ,^X_zN5:EZN]zM^k /Wu^ZZi#Ju.!L!z@u*kUim|+aZmjth-}z5'^|= 4L1_]qVZV*h@! Open Access This can happen if the mouse is pressed into the mask or if the body is stretched when held. We have found that there is significant difference between the means of the samples (p = 0.002, using 0.05 level of significance). 1.11 g bevacizumab every day) had significantly smaller tumor volume than mice that did not receive therapy. Thus, caliper-based measurements are less accurate the more the height of the stack deviates from its width. Evaluated the accuracy of common four formulas given in the literature to estimate xenograft tumor volumes based on manual caliper measurements and proposed formula (0,45 L*W*H) could estimate tumor volumes as good as prolate ellipsoid formula. In order to estimate tumor volume by external caliper, the greatest longitudinal diameter (length) and the greatest transverse diameter (width) were determined while mice were scruffed and conscious. Each day before the administration, the mice' body weight and tumor volume were measured and recorded. Keller M, Rohlf K, Glotzbach A, Leonhardt G, Lke S, Derksen K, Demirci , Gener D, AlWahsh M, Lambert J, Lindskog C, Schmidt M, Brenner W, Baumann M, Zent E, Zischinsky ML, Hellwig B, Madjar K, Rahnenfhrer J, Overbeck N, Reinders J, Cadenas C, Hengstler JG, Edlund K, Marchan R. J Exp Clin Cancer Res. First is to find an appropriate mathematical model for tumor volume evaluation from caliper-measured data. Mammary tumors seemed to take on an oblate spheroid geometry. Frozen samples were used to create 15 m frozen cuts. Better results can be obtained by proper handling of the mice. In Phase I, Phase II and Phase III, a piece of C38 colon adenocarcinoma was transplanted subcutaneously in the recipient animal on the 1st day of the experiment (approximately 2106 cells were transplanted into each mouse). From the abovementioned methods, the consequence is that the promising new direction in tumor volume evaluation is the dimension reduction, namely to find a statistical constant which can replace the need of measuring the tumor height. A possible solution for height approximation [23] is: Mammary tumors seemed to take on an oblate spheroid geometry. et al. Figure 16. depicts the results from a study attended by Biopticon in which ten subcutaneous tumors in mice were measured by scanner and caliper by four operators. In Phase I, 12 mice were implanted with C38 colon adenocarcinoma. Yes Autopsy revealed large metastasis in the lung, this is the suspected cause of the death. Mammary tumors seemed to take on an oblate spheroid geometry. Intrinsic susceptibility MR imaging of chemically induced rat mammary tumors: relationship to histologic assessment of hypoxia and fibrosis. Sport. This results in the loss of information about its real growth.. With constant width and length, the measured volume does not change with the tumor shape. The R2 value for the scanner is 0.99, as opposed to that for the caliper being 0.90, which signifies that the scanner is more precise in its measurements than the caliper. However mice which were treated with a quasi-continuous therapy (one-tenth dose of control dose spread over 18 days, i.e. Thank you for visiting nature.com. It then segments the tumor boundary (red area surrounded by the yellow boundary in Figure 12.) Measurement by Caliper In order to estimate tumor volume by external caliper, the greatest longitudinal diameter (length) and the Without prior training of users, this effect can lead to greater variability in intra and inter-user measurements. Unable to load your collection due to an error, Unable to load your delegates due to an error. Using the mathematical model, different dosage algorithms can be designed for antiangiogenic cancer therapy [1619]. J Clin Oncol. For both one has to have the ease of hand and get used to manipulation of the instrument. 35, 18341840 (2003). In Phase IV, the first measurement occurred when the tumors have reached an average volume of 5060 mm3 (according to the xenograft protocol [20]). Based on the experimental data, model identification can be carried out which describes the mathematical model of the investigated biological process. Animals were carried out in the most humane and environmentally sensitive manner possible; in addition the 3Rs principle (replacement, refinement, reduction) was adequately implemented according to the Directive 2010/63/EU of the European Parliament. Conceived and designed the experiments: ZS JS. 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