The problems with tumor volume measurements by calipers 3.1 Tumor growth: Height is not equal to the width of the tumor . Watch our 2-minute video overview. Secondly, the aspect of side-effects are not inconsiderable. 47, 510 (2001). mum tumor volume of 0.6 mL was reached. A study[4] (Figure 5.) The produced images were converted to NIfTI (Neuroimaging Informatics Technology Initiative) format, which is suitable for image processing. It means that a mouse of the case group received 1.11 g bevacizumab (with 45 l 0.9% NaCl solution) every day from the 3rd day for 20 days. The authors say special thanks to Katalin Dezs MD. An average penny has a diameter of 19 mm and a height of 1.27 mm, yielding a volume of 360.1 mm3. Open Access Catheter was placed in the tail vein for injectionaccording to the mouse tail vein injection protocol [30]to investigate drug effect. Tumor volumes measured with a Plethysmometer (VPleth) independent of caliper and scanner measurements (VC, VS) vs. VC and VS. Table 1. Figure 6. & The last step is to find the f constant of the two-dimensional mathematical model for tumor growth without therapy (Phase I). National Library of Medicine Caliper measurements, rather than measuring the actual volume of a tumor, measure the volume of a parallelepiped that surrounds it. One common measure of efficacy is the T/C ratio, the ratio of tumor volume in control versus treated mice at a specified A two-dimensional mathematical model was created from the experimental results of BALB/c mice with KHJJ tumor line [25]: In the experiment 9.4 Tesla field strength Varian small-animal MRI was used. 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]. In Phase I, 10 mice were sacrificed at the 24th day of the experiment. Fj^P;7? Contrast agents improve the visibility, but it is an extra strain to the organism, which can be lethal to animals which are in the final stage of cancer. Results from an experiment that measures tumor volume and varies drug dose and measuring methods. In Phase IV, control group members received no bevacizumab. & Wieder, H. Monitoring chemotherapy and radiotherapy of solid tumors. 58, 264270 (2008). Article the tumor volume are made using digital calipers, and bio logical activity is quantified via the assessment of changes in tumor volume between treated and control mice. Comp. As the height values of the tumors deviate from those of the width, the caliper-based volume values of those tumors begin to mirror real-life measurements less closely. Figure 18. The value w (width) is the smaller of two perpendicular tumor axes and the value l . Diagnostic accuracy of mammography, clinical examination, US, and MR imaging in preoperative assessment of breast cancer. . Tumor size was measured every 3 days using a digital caliper and computed according to the ellipsoidal calculation formula: V . J. Clin. 2022 Dec 20;3(12):100852. doi: 10.1016/j.xcrm.2022.100852. In one trial, 208 tumors were measured, and 98.94% of those tumors exhibited much smaller heights than widths. Effects of different applied voltages of irreversible electroporation on prostate cancer in a mouse model. 35, 18341840 (2003). Can the Kuznetsov Model Replicate and Predict Cancer Growth in Humans? Jensen, M.M., Jrgensen, J.T., Binderup, T. & Kjr, A. Tumor volume in subcutaneous mouse xenografts measured by microCT is more accurate and reproducible than determined by 18F-FDG-microPET or external caliper. Hence, the first step has to be the vasculature normalization with the reconstruction of the balance of pro- and antiangiogenic factors. Tumor volumes are calculated from digital caliper raw data by using the formula:Volume (mm3) = (l x w2) / 2. We have found that there is significant difference between the means of the samples (p = 0.002, using 0.05 level of significance). Results from a vaccine trial from AstraZeneca. CAS Correlation was investigated with Pearsons rank correlation test (Pearsons R) and coefficient of determination (R2). et al. Med. It means that knowing the tumor mass, tumor volume can be estimated with suitable accuracy; hence the lack of MRI measurement can be replaced in the case of Phase I. Measurements with small animal MRI were done on the 4th, 8th, 11th, 15th, 18th and 23rd days of the experiment in Phase III/3. Disclaimer. The explanation of the effectiveness of low dose VEGF therapy is the following ([3944]). Sport. In the case2 group, one mouse died on the 8th day, before the therapy (bevacizumab administration) started. . For more information about PLOS Subject Areas, click Komrek, V. Gross anatomy. Mice were killed after 38 days. Mammary tumors seemed to take on an oblate spheroid geometry. https://doi.org/10.1371/journal.pone.0142190.g001. The most recent ESMO (European Society for Medical Oncology) consensus guidelines suggest that treatment discontinuation or maintenance are feasible options after 46 months of full-dose first-line therapy to treat colon and rectal adenocarcinoma [37]. This creates the possibility of further efficient therapeutic agent use (if any) or assists the more effective direct antitumoral effect of bevacizumab. For the most precise result, tumor mass values, which were measured at the end of the experiment, were compared in the statistical analysis. Faustino-Rocha AI, Gama A, Oliveira PA, Alvarado A, Fidalgo-Gonalves L, Ferreira R, Ginja M. Faustino-Rocha AI, Silva A, Gabriel J, Teixeira-Guedes CI, Lopes C, Gil da Costa R, Gama A, Ferreira R, Oliveira PA, Ginja M. Biomed Pharmacother. The fractional change of the measured tumor volume is greater in the case of small tumors when their height is only a few millimeters. Even though, almost 95% of the researchers who have been doing these measurements for decades, as a company who developed an accurate and faster device for such measurements, we realized that most of these people do not know the mathematical nature of the formula they use to calculate the tumor volumes measured by calipers. official website and that any information you provide is encrypted The variables for the volume of a tumor, as measured by a caliper, are determined by a, b, and c in Figure 1, where length L is 2a, width W is 2b, and height H is c. VT, the volume of a tumor is determined by. Measured data is the MRI-measured tumor volumetumor mass pairs on the 23rd day of Phase III/3 (case and control group). A tumor image, its 3D shape and all geometrical data are automatically calculated and stored. Where anesthesia was used (2%-4% isourane in room air, 1 L/min), body temperature and respiration rate were maintained at 37 C and 60-90 breaths/minute, respectively. Bizberg Themes, By Memorial Sloan Kettering Cancer Center. Department of Veterinary Sciences, University of Trs-os-Montes and Alto Douro, Vila Real, Portugal, Ana Faustino-Rocha, Jacinta Pinho-Oliveira, Catarina Teixeira-Guedes& Ruben Soares-Maia, Department of Veterinary Sciences, Animal and Veterinary Research Centre, University of Trs-os-Montes and Alto Douro, Vila Real, Portugal, Paula A. Oliveira, Bruno Colao, Maria Joo Pires& Jorge Colao, Laboratory for Process, Environmental and Energy Engineering, Faculty of Engineering, University of Porto, Porto, Portugal, Faculty of Veterinary Medicine of Lusophone University of Humanities and Technologies, Lisboa, Portugal, Department of Chemistry, Organic Chemistry of Natural Products and Agrifood, Mass Spectrometry Center, University of Aveiro, Aveiro, Portugal, Department of Veterinary Sciences, Centre for Research and Technology of Agro-Environment and Biological Sciences, University of Trs-os-Montes and Alto Douro, Vila Real, Portugal, You can also search for this author in Before The results of the three investigated cases using C38 mouse colon adenocarcinoma (Phase I, Phase III/3 control group, and Phase III/3 case group) were compared using tumor volume values from MRI measurements (Phase III/3 control and case groups, 23rd day) and evaluated data (Phase I MRI tumor volume calculated from linear curve fit, 24th day). sharing sensitive information, make sure youre on a federal @0u !7oyc5/Ck Consequences are manifold. by Mammog raphy (c.c) . In another, 7,286 tumors were measured and 99.97% of those exhibited smaller heights than widths. Unable to load your collection due to an error, Unable to load your delegates due to an error. Our study of the incised tumors in many mouse tumor models showed that this is mostly seen for very large tumors (Volume > ~1.5 cm3) where the tumors start bulging inward toward the flesh. Open Access https://doi.org/10.1038/laban.254. As is the case with caliper measurements, if the tumor appears visibly flattened and is hard to see by eye then the mouse should be repositioned. 19, 6170 (1989). Traditionally their volume growth has been monitored by using a mechanical caliper. A caliper was used to calculate the tumor volume every-three days, and the volume was calculated according to the formula: V = ab 2 /2, where a represents major axis length and b represents minor axis length. In Phase III/3, MRI-measured tumor volume values are available which can be used as reference values for caliper-measured data. % A study[4]on caliper measurements, shoved the very poor accuracy of the formula used for caliper measurements. Performed the experiments: JS ZS PK DG. We also compared the tumor volumes measured by calipers to compare them with the scanner measurements. Therefor it allows a direct 3D capture of the volume. The effectiveness strongly depends on the administration, and a drug which is effective on a molecular level can be applied in a less effective way because of the incorrectly chosen administration. The authors measured dimensions of rat mammary tumors using a caliper and using real-time compound B-mode ultrasonography and compared the calculated tumor volumes with the real tumor volume to identify the formulas that gave the most accurate volume calculations. Cancer 83, 621628 (1998). To compare more than two samples, ANOVA test was applied. Role of real-time sonography in assessment of breast diseases: a review of 200 cases (Abstr). One can see from Table 2 that the goodness of the fit is different in the case of Phase I (tumor growth without therapy) and in the case of Phase III/3 (tumor growth with antiangiogenic therapy). Tumor measurement by TumorImager-2TM. 105, 2023 (1983). Numerical result can be found in Table 2, and Fig 5 presents graphical results. 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. The other eight tumors exhibit forms that cannot be compared to a perfect ellipsoid. 37, 19 (1996). 3.4. Possible mechanisms mediating an association between physical activity and breast cancer. We have examined C38 mouse colon adenocarcinoma and HT-29 human colorectal adenocarcinoma. & Robinson, S.P. Additionally, this technique is plagued by the inconsistent selection of tumor axes at subsequent examinations. In this phase, three groups were created. Cancer Res. Since, the assumptions made to measure a 3D object with 2D measurements, the error due to the geometrical assumption are larger than the errors due to handling of the animal causing deformation of the tumor, and this aspect, in general, is ignored. The width of a fully formed tumor will be much larger than its height. Girit, I.C., Jure-Kunkel, M. & McIntyre, K.W. Fornage, B.D., Toubas, O. To compare the effectiveness of the different investigated treatment methods, statistical analysis was used. In clinical practice, the determination of the tumor size (volume) is done by MRI and/or CT, but this is for the purpose of validating the effectiveness of the treatment, and therefore it is not a continuous monitoring. In each case the reference value is the MRI-measured tumor volume. et al. Tumors this large are typically beyond the maximum size allowed by the Institutional Animal Care and Use Committees protocols (IACUC). The lines on the graphs have a slope of 1, signifying that it represents caliper-based measurements in which height equals width. In the case1 group, one mouse died on the 17th day. In order to assess interobserver variation, each . They found that caliper and ultrasonography measurements were significantly correlated but that tumor volumes calculated using different formulas varied substantially. In Phase III/3, case group members received one-tenth dose of control dose intraperitoneally spread over 18 days. Yes Kim DK, Synn CB, Yang SM, Kang S, Baek S, Oh SW, Lee GJ, Kang HW, Lee YS, Park JS, Kim JH, Byeon Y, Kim YS, Lee DJ, Kim HW, Park JD, Lee SS, Lee JY, Lee JB, Kim CG, Hong MH, Lim SM, Kim HR, Pyo KH, Cho BC. calipers and Water Displacement methods Tumor mimicking objects Vol. 54, 401414 (1975). 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