Internet J. Surg. Cancer 83, 621628 (1998). Tukeys HSD test resuled in significant difference between case1 and case2 groups (p = 0.038). Mice were monitored daily. Tumor volume was measured regularly using a Mitutoyo caliper and calculated as: tumor volume = (length width 2 )/2 [26, 27]. Biol. Using an extremely low dosage (as in our study), there is a high probability that these adverse effects can be minimized. Figure 2. Tumor growth Tumor regression Number of Number of volume volume doublings Percentage additional halvings: Decrease in Percentage decrcase in increase Volume Area" Diameterb volume doubling number Volume Area" Diameterb Doubling of Halving of Volume 1 .o 100.0 58.7 26.0 Volume 1 .o 50.0 37.0 20.6 Unable to load your collection due to an error, Unable to load your delegates due to an error. et al. No, Is the Subject Area "Mouse models" applicable to this article? This means that the daily treatment with one-twelfth total dose resulted in significantly smaller tumors than the protocol-based treatment. Caliper instructions are provided as well as an introduction to ellipsoids. 2015 Feb;43(2):145-70. doi: 10.1177/0192623314532036. (3), Another relatively new but not widely used approach to estimate tumor volume is to assume hemi-ellipsoid shape [24]. J. Oncol. []. Anyone you share the following link with will be able to read this content: Sorry, a shareable link is not currently available for this article. . Since 2004, the target therapy of bevacizumab (Avastin) is widely used to treat colorectal [9], kidney [10], cervical [34], ovarian [35], non-small cell lung cancers [5], melanoma [14] and certain brain tumors (e.g. Cancer Res. Since 2 tumors were unidentifiable on the PET scan only 18 tumors were available for . @0u !7oyc5/Ck Research and Innovation Center of Obuda University, Physiological Controls Group, Obuda University, Budapest, Hungary, Affiliation Using a caliper, growth of the tumor in height is not measured as only width and length changes will affect the calculated volume. Yes Position of the mouse was fixed to minimize the movement of the animal. Normality was investigated with one-sample Kolmogorov-Smirnov test, and homogeneity of variance (homoscedasticity) was examined with Levenes test. 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. Starting with f = 1, we have investigated the goodness of the fitting, using an iterative method. This estimation has the same disadvantage as ellipsoid estimation, i.e. https://doi.org/10.1371/journal.pone.0142190.g002. Examination of tumor growth belongs not only to the basic medical research, but to the biomedical engineering field as well. Is the Subject Area "Cancers and neoplasms" applicable to this article? Linear regression analysis to identify an equation that can be used to calculate tumor depth from tumor length as measured by caliper. n5). https://doi.org/10.1038/laban.254. PLoS ONE 10(11): While the scanner only overestimates by about 2%, the caliper overestimates by 32%, as shown by the slope of the line being 1.32. 1.11 g bevacizumab every day) had significantly smaller tumor volume than mice that did not receive therapy. Copyright 2023 Hoffman-Goetz, L. et al. This paper reviews the standard technique for tumour volume assessment, calliper measurements, by conducting a statistical review of a large dataset consisting of 2,500 tumour volume measurements from 1,600 mice by multiple operators across 6 mouse strains and 20 tumour models. Clarys, J.P. & Marfell-Jones, M.J. Soft tissue segmentation of the body and fractionation of the upper and lower limbs. Tumor growth can take place under such conditions; however delivery of chemotherapeutic drugs is obstructed. Effects of tamoxifen and melatonin on mammary gland cancer induced by N-methyl-N-nitrosourea and by 7,12-dimethylbenz(a)anthracene, respectively, in female Sprague-Dawley rats. CAS BMC Med. <> stream & Robinson, S.P. Designed by In Phase III/3, MRI-measured tumor volume values are available which can be used as reference values for caliper-measured data. Measurements with small animal MRI were done on the 4th, 8th, 11th, 15th, 18th and 23rd days of the experiment in Phase III/3. A two-dimensional mathematical model was applied for tumor volume evaluation, and tumor- and therapy-specific constants were calculated for the three different groups. Carlsson, G., Gullberg, B. Cancer 60, 765771 (1987). 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. and calculates an interpolated surface under the tumor boundary based on the healthy surface around the tumor (navy blue line in Figure 12.). On Day 14, when the tumor volume reached ~500 mm 3, the mice were . This concept can easily be understood by a simple thought experiment: the volume of a stack of pennies (Figure 4.). HHS Vulnerability Disclosure, Help In Phase II, the toxicology investigation of the applied angiogenic inhibitor (bevacizumab) was performed; there was no tumor implantation into mice in this phase. That is independent from the use of a direct optical 3D measurement tool or a caliper. Yes 16 (2008). & Moon, R.C. Verma, R. et al. here. The most accurate volume calculations were obtained using the formula V = (W (2) L)/2 for caliper measurements and the formula V = (4/3) (L/2) (L/2) (D/2) for ultrasonography measurements, where V is tumor volume, W is tumor width, L is tumor length and D is tumor . Data Availability: All relevant data are within the paper. We found out that due to this unmeasured part, the dissected tumor volumes were about 6% larger than the scan results. calipers and Water Displacement methods Tumor mimicking objects Vol. Epub 2014 May 28. 26 December 2022, Bulletin of Mathematical Biology Sport. Mice were humanely sacrificed using cervical dislocation. 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. Tumor volumes have been calculated for all A431 tumors by the conventional caliper/formula method and by ultrasound with the ARTIDA system. Biol. In addition, we have found that the quasi-continuous administration of bevacizumab is effective against tumor growth of C38 colon adenocarcinoma, in contrast to protocol-based treatment. When using calipers there is dependency in the measured data of the positioning by the operator of the tool on the xenograft. Comput. For both one has to have the ease of hand and get used to manipulation of the instrument. J. Urol. Our results provide a theoretical background for a much more effective bevacizumab treatment using optimized administration. In Phase I, mice were sacrificed when the tumor reached a lethal size; it was on the 24th day of the experiment. It can be carried out in vivo during the experiment due to the subcutaneous localization of the tumor. Similar to the results from the experiments in Figure 18., this error makes the drug seem less effective than it actually is. 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. Hence, the first step has to be the vasculature normalization with the reconstruction of the balance of pro- and antiangiogenic factors. The parameters V m = 83 mm 3, = 0.84 and = 0.21 from the literature were used [].. For \( {y}_i^j \) eqs. Better results can be obtained by proper handling of the mice. Due to the collaboration between medical doctors and biomedical engineers, model-based treatment protocols can be created. The last step is to find the f constant of the two-dimensional mathematical model for tumor growth without therapy (Phase I). 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, A., Oliveira, P., Pinho-Oliveira, J. et al. endobj a) Haematoxylin Eosin (H&E) staining was applied to investigate tumor morphology. 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]. To evaluate tumor volume, first the shape of the tumor has to be assumed, and if it is necessary for volume calculation, the third diameter (height, h) has to be approximated. Nevertheless the result of our study shows that the effectiveness is even better. To validate our results which come from the experiments where mouse tumor vascularization was inhibited with humanized VEGF, we evaluated the results of Phase IV, where immunocompromized (SCID) mice were used with human colorectal adenocarcinoma (HT-29) xenografts. Our results for the case group (daily, quasi-continuous small amount administration) and the control group (one big dose according to the protocol) are The aim of this article is therefore to explain of the tumor volume formula and the problems associated with the caliper measurements. Effects of holding an animal on tumor volume while scanning. Thank you for visiting nature.com. Faustino-Rocha AI, Gama A, Oliveira PA, Vanderperren K, Saunders JH, Pires MJ, Ferreira R, Ginja M. Life Sci. 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. Most of the operators in these studies were highly experienced in caliper measurements, but they only had one day of training in scanner measurements. Comparison of volume measurement results between four users. 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]). Yes The most accurate volume calculations were obtained using the formula V = (W2 L)/2 for caliper measurements and the formula V = (4/3) (L/2) (L/2) (D/2) for ultrasonography measurements, where V is tumor volume, W is tumor width, L is tumor length and D is tumor depth. 12, 881885 (2005). 39, 720 (1996). 105, 2023 (1983). To reduce the time of analysis one could e.g. Girit, I.C., Jure-Kunkel, M. & McIntyre, K.W. Imaging 16, 816 (2008). broad scope, and wide readership a perfect fit for your research every time. Tumor Volume Measurement In the case of C38 colon adenocarcinoma, first, the subcutaneously transplanted piece of tumor has to disintegrate, and after that the new tumor colony (which needs to be measured) can begin to grow from the disintegrated tumor cells. A quiet and modestly T2-weighted spin-echo scan was acquired at 4.7T (TE = 15 msec, TR = 1100 msec, 0.5 mm isotropic . & Bullock, G.) 253257 (Elsevier Academic, Boston, 2004). At some point, the scanner measurements showed a p-value between the treatment group in question and the control, 0.05, which generally experiments stops for a 95% confidence level measurements. J. Clin. Cancer Res. Cancer Res. Eur. Based on the experimental data, model identification can be carried out which describes the mathematical model of the investigated biological process. In Phase I, 10 mice were sacrificed at the 24th day of the experiment. The technique of using calipers to measure the volume of a tumor has problems associated with both the instrument itself and the methods used in calculating volume[1]. Healthy tissues have efficient vasculature and effective blood supply due to the balance of proangiogenic and antiangiogenic factors.
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