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%. They found that caliper and ultrasonography measurements were significantly correlated but that tumor volumes calculated using different formulas varied substantially. Pairwise comparison was done by Tukeys honest significant difference test to find those samples, which have significantly different means. and transmitted securely. A solution to these problems is the TumorImagerTM scanner. Figure 15. %PDF-1.4 Using an extremely low dosage (as in our study), there is a high probability that these adverse effects can be minimized. The last step is to find the f constant of the two-dimensional mathematical model for tumor growth without therapy (Phase I). 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. First way is the caliper measurement; in that case tumor diameters (width, length) are measured with digital caliper. 39, 720 (1996). During the scan, a mouse should be held in a relaxed manner without stretching its skin to cause unwanted deformation of the tumor body. 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 caliper-based findings can lead researchers to believe that the drug is less effective than it actually is because the change in tumor volume between the control and treatment groups is smaller. Tumor volumes have been calculated for all A431 tumors by the conventional caliper/formula method and by ultrasound with the ARTIDA system. where f is a constant which belongs to a certain tumor type. This process takes 45 days. Examining the relationship between MRI-measured tumor volume and tumor mass values, we have found a very strong linear correlation (R = 0.998, R2 = 0.996, p < 0.0001). A caliper only digitizes the length and width of the tumor. x|jY!==g'{oZ6-JiZ The figure shows the results of a mouse (C4) from control group (first row), and a mouse (E9) from case group (second row). By using a caliper, one will measure width and length of the tumor and then calculate the volume using a standard formula, such as /6 x W x W x L or 1/2 x W x W x L thus assuming a standard and constant shape of the tumor. It then segments the tumor boundary (red area surrounded by the yellow boundary in Figure 12.) A study[4]on caliper measurements, shoved the very poor accuracy of the formula used for caliper measurements. This estimation has the same disadvantage as ellipsoid estimation, i.e. Mice were monitored daily by personnel experienced in recognizing signs of morbidity (illness, injury, or abnormal behavior) also in weekends and holidays. In Phase IV, case1 group members received 200 g bevacizumab (with 200 l 0.9% NaCl solution) in one dose intraperitoneally on the 8th day. On the bottom left graph in Fig. The effectiveness of bevacizumab administration was examined by statistical analysis. Predicting tumor volume in radical prostatectomy specimens from patients with prostate cancer. 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). J Clin Oncol. A quiet and modestly T2-weighted spin-echo scan was acquired at 4.7T (TE = 15 msec, TR = 1100 msec, 0.5 mm isotropic . 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. First is to find an appropriate mathematical model for tumor volume evaluation from caliper-measured data. & Morel, M. Clinical, mammographic, and sonographic determination of preoperative breast cancer size. 2. (Budapest, Hungary). 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. Google Scholar. The authors say special thanks to Katalin Dezs MD. Bevacizumab is an exogenous inhibitor which inhibits the biological activity of human VEGF. Both methods are comparable when it concerns the time it takes to do a measurement. J. Nucl. The scan images obtained are only for the external surface of the tumor. The closer the value is to 1, the more precise the data. Biol. Fornage, B.D., Toubas, O. 41, 16901694 (1981). Tumor volume was measured with digital caliper. In order to assess interobserver variation, each . Correlation was investigated with Pearsons rank correlation test (Pearsons R) and coefficient of determination (R2). We are sorry, but there is no personal subscription option available for your country. 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. https://doi.org/10.1371/journal.pone.0142190.g002. Breast Cancer Res. . A two-dimensional mathematical model was created from the experimental results of BALB/c mice with KHJJ tumor line [25]: Ultrasonography as the Gold Standard for In Vivo Volumetric Determination of Chemically-induced Mammary Tumors. This concept can easily be understood by a simple thought experiment: the volume of a stack of pennies (Figure 4.). Yes Clipboard, Search History, and several other advanced features are temporarily unavailable. Verma, R. et al. Lab Animal 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. Typical side-effects and adverse events are arterial and venous thromboembolic events, bleeding, hypertension, febrile neutropenia, infections, proteinuria, mucositis, and hand-foot syndrome. The manipulation of the handheld tool is at least as easy as holding a measurement caliper. For the sake of convenience, establishments will simplify and H. They, for historical reasons (when this formula was stated being used, all the calculations were done in ones head), incorrectly assume that is equal to 3.0 and that the height of a tumor (H) is equal to its width (W). Most, if not all, tumors do not fit into this category; this discrepancy results in caliper-based volume measurements including sections that do not exist in the actual tumor, or an overestimation of tumor volume measurement. Based on the experimental data, model identification can be carried out which describes the mathematical model of the investigated biological process. Performed the experiments: JS ZS PK DG. Designed by The second subphase (Phase III/2) was similar to Phase III/1, mice received the same dosage of bevacizumab as in Phase III/1, however sample size was higher (6 immunocompetent mice in control group, 12 immunocompetent mice in case group), and bevacizumab administration started earlier, on the 3rd day of the experiment. Then we calculated the Coefficient of Variance between such measurements for both measurements to compare average inter-operator differences. 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. 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. Article Using the mathematical model, different dosage algorithms can be designed for antiangiogenic cancer therapy [1619]. In this way, the targeted therapy can be used in a much more individualized form. Enter your measurements into the Tumor Volume Calculator to determine the volume of the tumor. 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. Nevertheless the result of our study shows that the effectiveness is even better. 2023 Jan 12;9(1):5. doi: 10.1038/s41420-023-01300-9. However mice which were treated with a quasi-continuous therapy (one-tenth dose of control dose spread over 18 days, i.e. J. McPhail, L.D. Fornage, B.D., Toubas, O. CA Cancer J. Clin. Effects of different applied voltages of irreversible electroporation on prostate cancer in a mouse model. Notice that the caliper-based measurements have a larger standard deviation. here. Figure 1. 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. This site needs JavaScript to work properly. A smaller standard deviation in a set of measurements suggests a lesser possibility of error. Using the above mentioned iterative method, the resulted equation is Eur. Epub 2014 May 28. Get the most important science stories of the day, free in your inbox. Figure 16. A tumor image, its 3D shape and all geometrical data are automatically calculated and stored. 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. The tumor burden is evaluated by volume calculation using caliper measurement. Gullino, P.M., Pettigrew, H.M. & Grantham, F.H. 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. (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. PMID: 11208850. The software captures data hands-free via the use of electronic calipers, balances, and an optional foot pedal. Department of Control Engineering and Information Technology, Budapest University of Technology and Economics, Budapest, Hungary, Affiliation et al. HHS Vulnerability Disclosure, Help Open Access Materials and methods: The murine CaNT subcutaneous xenograft model 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. 2022 Dec 20;3(12):100852. doi: 10.1016/j.xcrm.2022.100852. calculate an average volume based on two extreme segmentations; one including most of the border, and one excluding it. 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. The tumor number, from one to ten, is shown against the percent error. Analyzed the data: JS ZS PK DG DAD LK. The parameters V m = 83 mm 3, = 0.84 and = 0.21 from the literature were used [].. For \( {y}_i^j \) eqs. For ultrasonography measurements, we calculated tumor volume . Figure 5. Estimation of rat mammary tumor volume using caliper and ultrasonography measurements. In addition, the mice were weighed . Make sure you get accurate measurements for length, width and height. Figure 14. Breathing was monitored with piezoelectric transducer; temperature of the body was measured by rectal thermometer. Measured data is the MRI-measured tumor volumetumor mass pairs on the 23rd day of Phase III/3 (case and control group). (6) (7). 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]. Figure 4. & Pisani, P. Global cancer statistics, 2002. Because the industrys caliper-based formula allows for these inclusions in nonexistent volumes more often than not, it yields inaccurate measurements, which can confuse. 2009, 18 (2009). Monitoring tumor volume through a direct 3D measurement will include changes in all three directions, height, width and length thus resulting in more accurate realistic data. Faustino-Rocha AI, Gama A, Oliveira PA, Vanderperren K, Saunders JH, Pires MJ, Ferreira R, Ginja M. Life Sci. In Phase I, tumor growth was investigated without antiangiogenic therapy for 24 days (mice were sacrificed when the tumor reached a lethal size). Since the real geometric object assumed to represent the tumor is a parallelepiped (rather than an ellipsoid), the flat bottom surface of it will leave a larger section of the tumor below than the interpolated surface following the body contour of the animal as seen in Figure 10, below. Folia Biol. Studies using other methods of imaging have exposed the problems that calipers pose. The problems with tumor volume measurements by calipers, 3.1 Tumor growth: Height is not equal to the width of the tumor, 3.3 Caliper measurements are time-consuming, 3.4 Caliper measurements ignore a larger volume, https://ugobasile.com/products/catalogue/pain-and-inflammation/plethysmometer, A Structured Light Based Laboratory Animal Subcutaneous Tumor Scanning System. 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. In the case of Phase I, no similar problem occurs; the two-dimensional mathematical model can handle great values as well (e.g. PubMed Central Tumours of the rat. CAS Copyright 2023 Recommended administration of bevacizumab is one 5 10 mg/kg dose for 23 weeks [1]. 1st Department of Pathology and Experimental Cancer Research, Semmelweis University, Budapest, Hungary. 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