They found that caliper and ultrasonography measurements were significantly correlated but that tumor volumes calculated using different formulas varied substantially. [2]no matter how accurately the length and width of the tumor are measured. To compare the effectiveness of the different investigated treatment methods, statistical analysis was used. 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. sharing sensitive information, make sure youre on a federal Consequences are manifold. J. Article First way is the caliper measurement; in that case tumor diameters (width, length) are measured with digital caliper. . This means that the daily treatment with one-twelfth total dose resulted in significantly smaller tumors than the protocol-based treatment. Russo J, Russo IH, Rogers AE, van Zwieten MJ, Gusterson B. Toxicol Pathol. Healthy tissues have efficient vasculature and effective blood supply due to the balance of proangiogenic and antiangiogenic factors. (Budapest, Hungary). In Phase IV, the first measurement occurred when the tumors have reached an average volume of 5060 mm3 (according to the xenograft protocol [20]). Would you like email updates of new search results? PubMed In this phase, 5 immunocompetent mice in control group, and 9 immunocompetent mice in case group were used. These together with the tumor shape and all obtained data can easily be traced and consulted afterwards. () and were used with the parameters displayed in Table 1Parameters for Gompertz growth were taken from Benzekry et al. The aim of this article is therefore to explain of the tumor volume formula and the problems associated with the caliper measurements. Mice were humanely sacrificed using cervical dislocation. This estimation has the same disadvantage as ellipsoid estimation, i.e. Our hypothesis is that the effectiveness of a lower dosage with a quasi-continuous therapy can be comparable with the protocol therapy. Measure the three dimensions of peanut M&M's, serving as our similar-sized tumor surrogates, using vernier calipers. where v is tumor volume [mm3] and m is tumor mass [g]. https://doi.org/10.1371/journal.pone.0142190, Editor: Francesco Bertolini, In Phase I, tumor growth was investigated without antiangiogenic therapy for 24 days (mice were sacrificed when the tumor reached a lethal size). 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). Inhibiting the glycerophosphodiesterase EDI3 in ER-HER2+ breast cancer cells resistant to HER2-targeted therapy reduces viability and tumour growth. Oncol. Tumor was located in the last third of the back in every cases, thus the effect of respiratory movement was minimal. 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. Radiology 254, 110118 (2010). The advantage of this model is that there is no need to approximate tumor height (which could result in error). A graph depicting tumor volume in mm3, as measured by a caliper compared to its actual volume, vs. days. J. Oncol. When tumor cells become able to produce proangiogenic factors (the process is called as angiogenic switch), it will result in abnormal and inefficient vascular network (with high vascular permeability and poor perfusion) due to the hurried process of vessel formation. Disclaimer. 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. 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. A two-dimensional mathematical model was created from the experimental results of BALB/c mice with KHJJ tumor line [25]: Comp. 12, 881885 (2005). PLoS ONE 10(11): 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). (2), Whilst studies have shown that tumors can be better estimated with ellipsoid shape than using Eq 1, calculating the volume of an ellipsoid requires the knowledge of the third parameter. Numerical result can be found in Table 2, and Fig 5 presents graphical results. 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. A quiet and modestly T2-weighted spin-echo scan was acquired at 4.7T (TE = 15 msec, TR = 1100 msec, 0.5 mm isotropic . Results of this phase can be found in [26]. Tumours of the rat. & Bullock, G.) 253257 (Elsevier Academic, Boston, 2004). MeSH Tumor volume was measured regularly using a Mitutoyo caliper and calculated as: tumor volume = (length width 2 )/2 [26, 27]. Even though all the three diameters can be measured, the estimation of the volume has quite a large error. Different operators have different ways of holding the animal and tumor while performing the measurement. Carlsson, G., Gullberg, B. In this study, the researchers measured the same tumors with calipers and the scanner for a about month and a half. Tumor volume (and the third diameter) has to be approximated, assuming a certain shape for the tumor. Lab Animal J. Urol. The other eight tumors exhibit forms that cannot be compared to a perfect ellipsoid. Therefore, its formula will always overestimate the tumor volume until the height equals its width, as seen in Figure 3. ANOVA test showed significant difference between these means (p = 0.041, using 0.05 level of significance). 58, 264270 (2008). Comparison of volume measurement results between four users. In this phase, control group members received no treatment; case1 group members received one 200 g bevacizumab dose; while case2 group members received 1.11 g bevacizumab daily for 15 days (the total dose of case2 group members is the one-twelfth dose of case1 group members). McCormick, D.L., Adamowski, C.B., Fiks, A. CAS mum tumor volume of 0.6 mL was reached. Google Scholar. Med. Mammary tumors similar to those observed in women can be induced in rats by intraperitoneal administration of N-methyl-N-nitrosourea. Bethesda, MD 20894, Web Policies The specific roles of these authors are articulated in the author contributions section. Comparing ARTIDA-calculated tumor volumes to the volumes derived from the caliper/ellipsoid formula calculations and referenced to the gold standard volume determination method (with literature density values), as it is shown in Figure 2A. The authors declare no competing financial interests. 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%. Oncol. Nevertheless the result of our study shows that the effectiveness is even better. Imaging 33, 2737 (2006). Accuracy of Optical Imaging for Measuring Tumor Burden In Vivo . No, Is the Subject Area "Mathematical models" applicable to this article? official website and that any information you provide is encrypted A smaller standard deviation in a set of measurements suggests a lesser possibility of error. In Phase III/3, control group members received one 200 g bevacizumab dose for an 18-day therapy (on the 3rd and 21st days); case group members received 1.11 g bevacizumab every day for 20 days. Performed the experiments: JS ZS PK DG. n5). Cells should be suspended in a volume so that 300 l contains required number of cells per injection. Mice in the control group received no treatment (5 mice); case1 group members (10 mice) received 10 mg per kg body weight bevacizumab in one dose; while case2 group members (10 mice) received 1/180 dose of control dose for 15 days. by Mammog raphy (c.c) . In Phase III/3, control group contained 5 mice, case group contained 9 mice; all mice were implanted with C38 mouse colon adenocarcinoma. Using an extremely low dosage (as in our study), there is a high probability that these adverse effects can be minimized. A study[4] (Figure 5.) Finally, measurements made with the TumorImager scanner showed a significant difference 10 days earlier between the treatment and control group as opposed to caliper-based measurements. obtained using vernier calipers (c.c) Vol. PMC Influence of breast cancer histology on the relationship between ultrasound and pathology tumor size measurements. All surgery and sacrifice were performed under sodium pentobarbital anaesthesia (Nembutal, 70 mg/kg). In Phase III/3, case group members received one-tenth dose of control dose intraperitoneally spread over 18 days. Thirty-two tumors (46%) were nonspherical, as defined above; of these, 19 tumors were nonspherical in the x-y plane, 10 tumors were nonspherical in the y-z plane, and 24 tumors were nonspherical in the x-z plane. They found that caliper and ultrasonography measurements were significantly correlated but that tumor volumes calculated using different formulas varied substantially. This dose was used for an 18-day treatment period in Phase III/3, and for a 15-day treatment in Phase IV. In order to assess interobserver variation, each . CAS 2015 Feb;43(2):145-70. doi: 10.1177/0192623314532036. On the bottom left graph in Fig. Tumor volume measurement was performed by digital caliper and small animal MRI. The shape of the tumor, more often than not, is not an ellipsoid. P`e+"JF^ : 4:p7]k = Jy}! et al. Preclinical Imaging Center, Gedeon Richter Plc., Budapest, Hungary, Affiliation Even though we did not have a statistical analysis of volume loss due to the unmeasured part of tumors in caliper measurements, the lost volume could be higher than the scanner results. Enter your measurements into the Tumor Volume Calculator to determine the volume of the tumor. In order to understand inter-operator differences between operators making both caliper and scanner measurements, we conducted experiments in which multiple numbers of operators measured several tumors both with caliper and scanner. The means of the samples are mpIV_control = 0.65, mpIV_case1 = 0.70, mpIV_case2 = 0.46. Get just this article for as long as you need it, Prices may be subject to local taxes which are calculated during checkout. Mammary tumors similar to those observed in women can be induced in rats by intraperitoneal administration of N-methyl-N-nitrosourea. We compared the volumes, areas . Yes . Tumor growth was investigated without therapy and with antiangiogenic therapy (using bevacizumab [15]). 8600 Rockville Pike CA Cancer J. Clin. The tumor can be more and sometimes less visible or popped up from under the skin. Measurement by Caliper In order to estimate tumor volume by external caliper, the greatest longitudinal diameter (length) and the @L Pk5*Gj@>Sk%SLL4w^c{j[hP(/h8HP_ @Ch( The tumor number, from one to ten, is shown against the percent error. The whole experiment consisted of four phases; the article focuses on the Phase III/3 and its results together with the comparison of Phase I and Phase III/3 (Fig 1). A two-dimensional mathematical model was applied for tumor volume evaluation, and tumor- and therapy-specific constants were calculated for the three different groups. Based on the experimental data, model identification can be carried out which describes the mathematical model of the investigated biological process. PubMedGoogle Scholar. Therefore, optical imaging is . An average penny has a diameter of 19 mm and a height of 1.27 mm, yielding a volume of 360.1 mm3. https://doi.org/10.1371/journal.pone.0142190.g002. 19, 6170 (1989). & Moon, R.C. In the case of Phase III/3 and Phase IV, period of time was specified according to the previous phases (Phase I and Phase III/1); mice were sacrificed on the 23rd day of the experiment. In the case of C38 adenocarcinoma, protocol-based treatment did not result in significantly smaller tumor volume compared to the no treatment group; however, there was a significant difference between untreated mice and mice who received quasi-continuous therapy (p = 0.002). First of all, our hypothesis according to the importance of administration is proved. Of course, for the closed-loop design frequent and precise tumor volume measuremets are required, thus the problem of tumor volume measurement has to be solved as well. Mammary tumors seemed to take on an oblate spheroid geometry. Our results for the case group (daily, quasi-continuous small amount administration) and the control group (one big dose according to the protocol) are In addition, calipers also place undue strain on the animal during measurement, assume conditions for a perfect ellipsoid (which most tumors are not), and can lead to unnecessary losses of money over time. In the case of Phase I, no similar problem occurs; the two-dimensional mathematical model can handle great values as well (e.g. Objectives: Volume measurement of subcutaneous xenograft tumors in nude mice models is an important metric to assess tumor growth or response to therapy. A possible solution for height approximation [23] is: In both cases, three groups were compared in the experiments. VC refers to tumor volume values calculated through the formula VT = 0.5 L W2, and VCH refers to those through the formula VT = 0.5 L W H. VS refers to measurements taken by the scanner, and % Inc. refers to the percent increase between VS and VCH. Biol. The post hoc test resulted in the following. With constant width and length, the measured volume changes with the shape of the tumor. Cancer 83, 621628 (1998). In addition, the gap between tumor volume values for caliper-based control and treatment groups is smaller than that for scanner measurements; the significant p-value was over 50 times higher when using calipers (p > 0.05) than with scanners (p < 0.001), suggesting that the caliper-based measurements are not statistically significant. One common measure of efficacy is the T/C ratio, the ratio of tumor volume in control versus treated mice at a specified 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. In addition, the root mean square, R2 values under the linear regression equations in Figure 15. symbolize the precision of the data. https://doi.org/10.1371/journal.pone.0142190.g001. 2001 Jan 15;19(2):551-7. doi: 10.1200/JCO.2001.19.2.551. The dose depends mainly on weight. This work was supported by the Portuguese Foundation for Science and Technology (PTDC/DES/114122/2009 and Pest-OE/AGR/UI0772/2011 unity) and by the European Regional Development Fund (COMPETE, FCOMP-01-0124-FEDER-014707/022692). This can happen if the mouse is pressed into the mask or if the body is stretched when held. 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%. & Wieder, H. Monitoring chemotherapy and radiotherapy of solid tumors. Eichelerger, L.E. For the most precise result, tumor mass values, which were measured at the end of the experiment, were compared in the statistical analysis. The aim of the experiment was to create and validate a clinically relevant tumor growth model (using C38 colon adenocarcinoma), focusing on the effect of angiogenesis. 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]). P ` e+ '' JF^: 4: p7 ] k = }... Mass [ g ] low dosage ( as in our study ), there is no need to tumor... Has quite a large error efficient vasculature and effective blood supply due to the importance of administration is.... Shape for the tumor, more often than not, is not an ellipsoid they found that and... A 15-day treatment in Phase III/3, and 9 immunocompetent mice in control group and... 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