Almost 90% of the establishments that make tumor volume measurements using calipers use a modified version of the ellipsoid formula, under the incorrect assumption that a tumor is always a perfect ellipsoid. 41, 16901694 (1981). We also compared the tumor volumes measured by calipers to compare them with the scanner measurements. Copyright 2023 ISSN 1548-4475 (online) Biol. To obtain Bookshelf The other eight tumors exhibit forms that cannot be compared to a perfect ellipsoid. Consequently, when tumor mass data is unavailable (during the experiment), tumor volume value can be validated with MRI; in that way outlier data points (which were calculated using the two-dimensional mathematical model) can be filtered out. Autopsy revealed large metastasis in the lung, this is the suspected cause of the death. Radiology 254, 110118 (2010). where v is tumor volume [mm3] and m is tumor mass [g]. Designed by In the case of HT-29 adenocarcinoma, the daily treatment with one-twelfth total dose resulted in significantly smaller tumors than the protocol-based treatment (p = 0.038). https://doi.org/10.1038/laban.254. . Using an extremely low dosage (as in our study), there is a high probability that these adverse effects can be minimized. 105, 2023 (1983). This means that continuous, low dose antiangiogenic factor (VEGF) administration is needed. Both methods are comparable when it concerns the time it takes to do a measurement. Ultrasound Med. We have investigated the relationship between MRI-measured tumor volume and vascularization area (Phase III/3 case and control groups, 23rd (final) day of the experiment) but no significant correlation was found (same results were published in the case of Phase I [26] and Phase III/2 [23]). An official website of the United States government. Figure 18. In addition, we have found that the quasi-continuous administration of bevacizumab is effective against tumor growth of C38 colon adenocarcinoma, in contrast . Breast cancer measurements with magnetic resonance imaging, ultrasonography, and mammography. 1st Department of Pathology and Experimental Cancer Research, Semmelweis University, Budapest, Hungary. When the tumors became palpable, measurements of tumor volume were performed (with calipers) once per week. McCormick, D.L., Adamowski, C.B., Fiks, A. Oncol. According to the Xenograft tumor model protocol [20], tumor volume has to be calculated using the following formula: Hoffman-Goetz, L. et al. In another, 7,286 tumors were measured and 99.97% of those exhibited smaller heights than widths. Catheter was placed in the tail vein for injectionaccording to the mouse tail vein injection protocol [30]to investigate drug effect. https://doi.org/10.1371/journal.pone.0142190.g001. First of all, our hypothesis according to the importance of administration is proved. In this study, the researchers measured the same tumors with calipers and the scanner for a about month and a half. In a study done in England, the researchers at the end of their experiment, dissected tumors and measured their weight with a precise balance, and used these weight values of the tumors to compare results of the caliper and the scanner measurements. Homogeneity of variance was examined with Levenes test; the sample variances are equal (p = 0.052). If the length or width of a tumor is twice its height, which is often the case for many tumor models, then its measured volume will be overestimated by 50%. depicts the inaccuracy of the formula used for caliper measurements, in which the height of the tumor is assumed to be equal to its width. % Denis, F., Paon, L. & Tranquart, F. Radiosensitivity of rat mammary tumors correlates with early vessel changes assessed by Power Doppler sonography. and calculates an interpolated surface under the tumor boundary based on the healthy surface around the tumor (navy blue line in Figure 12.). Effects of holding an animal on tumor volume while scanning. The manipulation of the handheld tool is at least as easy as holding a measurement caliper. Epub 2013 Jul 11. 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]. here. . 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. Current standard technique for volume determination of subcutaneously xenografted tumors in vivo is by external caliper where tumor volume is calculated by use of the modified ellipsoid formula 1/2(Length Width 2)[1,2]. Figure 18. shows the results of an experiment in which mice were given different doses of a drug and their tumors were measured both with a caliper or TumorImager scanner. The advantage of this model is that there is no need to approximate tumor height (which could result in error). BMC Medical . Kubatka, P. et al. They then used different formulas to calculate tumor volume from these tumor measurements and compared the calculated tumor volumes with the real tumor volume to identify the formulas that gave the most accurate volume calculations. Applying the two-dimensional mathematical model (described in Eq 5) the goal is to find the f constant which belongs to the C38 colon adenocarcinoma and the treatment type. This saves money, as mice, drugs, and calipers can be costly for researchers. Results from an experiment that measures tumor volume and varies drug dose and measuring methods. Orthotopic xenograft tumor models, which are more difficult to establish, are close to the clinical behavior of malignant tumors in terms of location of the primary tumor site, the tumor progression, the tumor micro-environment, cell migration and metastasis [1 . Based on the experimental data, model identification can be carried out which describes the mathematical model of the investigated biological process. In the case2 group, one mouse died on the 8th day, before the therapy (bevacizumab administration) started. in The Laboratory Mouse (eds. In order to assess interobserver variation, each . 12 immunocompetent mice were transplanted subcutaneously with C38 colon adenocarcinoma, and 11 immunocompetent mice were injected intramuscularly with B16 melanoma. In Phase IV, case2 group members received 1.11 g bevacizumab (with 45 l 0.9% NaCl solution) every day form the 8th day for 15 days. Get just this article for as long as you need it, Prices may be subject to local taxes which are calculated during checkout. This process slightly stretches the body and deforms the tumor. In vivo measurements of tumor metabolism and growth after administration of enzastaurin using small animal FDG positron emission tomography. Substituting tumor mass values which were measured on the 24th day of Phase I to the equation of the resulted curve, the corresponding tumor volume values can be evaluated (evaluated data). With constant width and length, the measured volume changes with the shape of the tumor. 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. In this study, the authors measured dimensions of rat mammary tumors using a caliper and using real-time . 2 0 obj For example, one of the main reasons why the US FDA revoked the approval of Avastin for treating advanced breast cancer is the high rate of side-effects when bevacizumab was applied [46]. 37, 331337 (2011). https://doi.org/10.1371/journal.pone.0142190.t003. https://doi.org/10.1371/journal.pone.0142190.g002. Determining tumor volume is a useful and quantitative way to monitor tumor progression. For ultrasonography measurements, we calculated tumor volume . Analyzed the data: JS ZS PK DG DAD LK. Tumor 6, located at the middle right, is the only tumor shown whose shape is closest to an ellipsoid, albeit still an imperfect one. Would you like email updates of new search results? Figure 7. [45] have found that the combination of low-dose cyclophosphamide and ginsenoside Rg3 therapy can be more effective than the normal administration. The .gov means its official. 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. Tumor volumes measured with a Plethysmometer (VPleth) independent of caliper and scanner measurements (VC, VS) vs. VC and VS. Table 1. Bousquet, P.F. Mice were humanely sacrificed using cervical dislocation. 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. In the concept of model-based treatment, a continuous and precise tumor volume monitoring is needed concerning which, may be possible in the near future by nanotechnology [38]. Sci Rep. 2022 Dec 26;12(1):22336. doi: 10.1038/s41598-022-25258-3. & Deshayes, J.L. Pathology of tumours in laboratory animals. Secondly, the aspect of side-effects are not inconsiderable. J. 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. A caliper only digitizes the length and width of the tumor. Inhibiting the glycerophosphodiesterase EDI3 in ER-HER2+ breast cancer cells resistant to HER2-targeted therapy reduces viability and tumour growth. The first measurement in Phase I occurred on the 5th day; in Phase III/3, it occurred on the 4th day. 35, 18341840 (2003). Figure 10. As it was discussed above, the handling of animals by calipers measurements also suffers such deformations of the animal body during the measurements. 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. Later in a study, when a tumor grows into larger masses, the shape of the tumor can differ greatly from an ellipsoid, as shown in Figure 7. (9). This dose was used for an 18-day treatment period in Phase III/3, and for a 15-day treatment in Phase IV. Carlsson, G., Gullberg, B. This device measures the volume displacement of the water due to any object dipped into a measuring cylinder. We compared tumor volumes estimated in vivo by BLI and FLI, to those calculated by caliper measurements and found a good correlation between these two techniques (Figure 4). 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. Enter your measurements into the Tumor Volume Calculator to determine the volume of the tumor. Similarly, we may have the possibility to a) measure the tumor volume using nanotechnology, b) create a pump for drug administration and c) design control algorithms for specific tumor types. In addition, even though there is about a 20% difference between the low-dose treatment group for the scanner measurements, the caliper-based measurements do not show any effect for this dose. Phase I and Phase III/3 control groups are not significantly different (p = 0.572), while Phase I and Phase III/3 control groups are significantly different (p = 0.002). and JavaScript. J Clin Oncol. No, Is the Subject Area "Breast cancer" applicable to this article? If one measures the volume of a penny using calipers and uses the widely accepted formula, repeating the measurement each time another penny is added to the stack, the stack will yield the same volume each time, regardless of how many pennies are stacked. []. 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. J. Oncol. Cancer Inst. Notice that in the caliper group, the average standard deviation is larger than that of the group whose tumors were measured by Biopticons TumorImager scanner. M}{Gt{zj|&cXx[k?CZ ~AjTxMr0 '~ix$mj/)9?$ t-o6MkVXs's}^E6-^_Yrv#w&r7w@WsQs]#G g$Cn. This effect is illustrated in the included video. In Phase IV, control group members received no bevacizumab. 37, 19 (1996). Measurement by Caliper In order to estimate tumor volume by external caliper, the greatest longitudinal diameter (length) and the Accessibility Fornage, B.D., Toubas, O. Med. Compute the volume assuming perfect ellipsoids. 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. Harris, R.E., Alshafie, G.A., Abou-Issa, H. & Seibert, K. Chemopreventive of breast cancer in rats by celecoxib, a ciclooxygenase 2 inhibitor. Calculate the correct dose of STELFONTA once you have the volume of the tumor in cm 3, using the Dose Calculator. Kobayashy, T. et al. Generally, to make caliper measurements, the measurer first traps the tail of the mouse under her fingers, then, grabs the neck of the mouse, and aligns the mouse in her hand in a way to expose the tumor for length and width measurements. Mammary tumors seemed to take on an oblate spheroid geometry. Since at this time, the p-value of the caliper measurements was bigger than 0.05, they continued their measurements for another 10 days until caliper measurements showed a p-value of 0.0484 as shown in Figure 17. Physical activity cancer preventionmechanisms. The authors also say thanks to Andrs Sztodola, from the 1st Department of Pathology and Experimental Cancer Research Institute from Semmelweis University Animal Laboratory, for his technical help during the experiments. Imaging 16, 816 (2008). 8600 Rockville Pike Better results can be obtained by proper handling of the mice. Levenes test showed that the sample variances are equal (p = 0.108). PASW Statistics 18 (SPSS Statistics, IBM, USA) and Matlab R2009b (MathWorks, USA) were used for statistical analysis. Internet Explorer). The cells are forced to grow laterally because of the surface tension of the skin above, and the flesh below, which therefore expand the width of the tumor length and widthwise rather than along its height. No, Is the Subject Area "Cancer treatment" applicable to this article? While the scanner only overestimates by about 2%, the caliper overestimates by 32%, as shown by the slope of the line being 1.32. The caliper mean-percent-error is 10.6%, nearly twice that of the scanners mean-percent-error of 4.6%. Is the Subject Area "Cancers and neoplasms" applicable to this article? These model-based protocols can be more effective than the current ones, since they provide individual treatment for the patients. A direct 3d measurement tool such as the TM900 does not induce such method sensitivity but cannot exclude operator dependency of the obtained values. The TM900 also stores an optical image in the measurement data base. In the light of the above mentioned, linear curve fitting was carried out to find the mathematical relationship between MRI-measured tumor volume and tumor mass (Phase III/3 case and control groups). calculate an average volume based on two extreme segmentations; one including most of the border, and one excluding it. Breathing was monitored with piezoelectric transducer; temperature of the body was measured by rectal thermometer. Mammary tumors similar to those observed in women can be induced in rats by intraperitoneal administration of N-methyl-N-nitrosourea. Small MRI measurements were done in the Preclinical Imaging Center of Gedeon Richter Plc. The widely accepted method for calculating the volume of subcutaneous tumors is to measure the length and width of the tumor with a caliper, and, while assuming that the tumor is the shape of an ellipsoid and that the height of the tumor is equal to its width, use the formula for the volume of an ellipsoid. The scanner-based measurements yield a higher correlation in this sense than caliper-based measurements. (4). @0u !7oyc5/Ck To compare the effectiveness of the different investigated treatment methods, statistical analysis was used. Frozen samples were used to create 15 m frozen cuts. Effects of different applied voltages of irreversible electroporation on prostate cancer in a mouse model. 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). Google Scholar. & trukelj, B. N-methylnitrosourea induced breast cancer in rat, the histopathology of the resulting tumours and its drawbacks as a model. Wrote the paper: JS ZS PK LK. broad scope, and wide readership a perfect fit for your research every time. Tumor volumes ranged from 0.5 cc to 187.9 cc, with a median of 21.8 cc. Open Access Internet J. Surg. The first group did not receive therapy, the second group received one 200 g bevacizumab dose for a treatment period (protocol-based therapy), and the third group received 1.1 g bevacizumab every day (quasi-continuous therapy). Tievsky AL, Ziegler RB, Salhus MR, Weisskoff R. Comparison of diameter and perimeter methods for tumor volume calculation. Firstly, since the tumor is assumed to be an ellipsoid shape, and the tumors morphology often deviates significantly from this as it grows, this method will produce errors as big as 18.4%. Mice were killed after 38 days. Measured data is the MRI-measured tumor volumetumor mass pairs on the 23rd day of Phase III/3 (case and control group). 29 September 2022, Bulletin of Mathematical Biology In this phase, three groups were created. How the device is positioned over the tumor will not influence the result. Materials and methods: The murine CaNT subcutaneous xenograft model was used. The study was carried out in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. An average penny has a diameter of 19 mm and a height of 1.27 mm, yielding a volume of 360.1 mm3. Mice in Phase I and Phase IV control group received no bevacizumab. Res. 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