2. Tumor growth inhibition rate (%); can be calculated using the following formula: = (Vc 1 -Vt 1 )/ (Vc 0 -Vt 0) X 100. where, Vc 1 is the mean tumor volume in the control group at the time of tumor . The reason for choosing this type of administration was as follows: a) we wanted to use a daily dose in order to investigate the biological effect of frequent impulse-like control signal for the future controller design; b) we wanted to examine such a low dose which has practically no side-effect but presumably is still effective. Traditionally, caliper measurements are used to calculate tumor volume. Typical side-effects and adverse events are arterial and venous thromboembolic events, bleeding, hypertension, febrile neutropenia, infections, proteinuria, mucositis, and hand-foot syndrome. Each day before the administration, the mice' body weight and tumor volume were measured and recorded. Automatic randomization to perform group assignments based on body weight, tumor area/volume, delta tumor volume, or any numeric value and/or user-defined formula; We have investigated different methods to find the best tumor volume estimation since it creates the possibility for precise and effective drug administration with a much lower dose than in the protocol. You are using a browser version with limited support for CSS. https://doi.org/10.1371/journal.pone.0142190.g005, https://doi.org/10.1371/journal.pone.0142190.t002, To find the f constant for tumor growth without therapy (Phase I), first reliable tumor volume values had to be found, since there was no MRI measurement in Phase I. Beside tumor diameters, tumor mass was measured and vascularization area was calculated in the case of the removed tumors. Eichelerger, L.E. Case1 group members received one 200 g bevacizumab dose on the 8th day, case2 group members received 1.11 g bevacizumab from the 8th day every day for 15 days. & Lin, C.A. Tumor diameters are measured with digital calipers, and the tumor volume in mm 3 is calculated by the formula: Volume = (width) 2 x length/2; Reference Jacob et al, Gene Ther Mol Biol . In order to assess interobserver variation, each . . 17, 905910 (2004). In Figure 15., the linear regression equation for the best-fit line for VPleth values on the y-axis along with VC and VS values would be approximately y x, or y 1.00x + 0.00. A typical comparison of tumor volume measurements by TumorImager-2TM with calipers. Sci Rep. 2022 Dec 26;12(1):22336. doi: 10.1038/s41598-022-25258-3. 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). 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. Isofluorane (0.95 x 2.0%) was applied for inhalational anesthesia, and intubation was performed. Thank you for visiting nature.com. Tumor as a 3-D object has three diameters (width, length and height); however in vivo only two diameters can be measured by caliper (width, w and length, l). Google Scholar. Radiology 157, 54 (1985). A diagram of an ellipsoid, with the derivations of the variables needed to calculate its volume. & 12 immunocompetent mice were transplanted subcutaneously with C38 colon adenocarcinoma, and 11 immunocompetent mice were injected intramuscularly with B16 melanoma. Accurately measure the tumor (in cm) using a caliper. No, Is the Subject Area "Colorectal cancer" applicable to this article? They found that caliper and ultrasonography measurements were significantly correlated but that tumor volumes calculated using different formulas varied substantially. 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]. Autopsy revealed large metastasis in the lung, this is the suspected cause of the death. Even the same operator, with different trials or at different moments in time does not always hold the animal in exactly the same way. However mice which were treated with a quasi-continuous therapy (one-tenth dose of control dose spread over 18 days, i.e. Kubatka, P. et al. It can be carried out in vivo during the experiment due to the subcutaneous localization of the tumor. Measure the mass by using a balance (0.01g) and compute the volume by using the 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 Phase III/3, case group members received one-tenth dose of control dose intraperitoneally spread over 18 days. The last step is to find the f constant of the two-dimensional mathematical model for tumor growth without therapy (Phase I). 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. In vivo measurements of tumor metabolism and growth after administration of enzastaurin using small animal FDG positron emission tomography. Predicting tumor volume in radical prostatectomy specimens from patients with prostate cancer. This does not alter the authors adherence to all the PLOS ONE policies on sharing data and materials. Clin. 37, 19 (1996). Without prior training of users, this effect can lead to greater variability in intra and inter-user measurements. We found out that due to this unmeasured part, the dissected tumor volumes were about 6% larger than the scan results. One can find datasets in the last column of Table 2. [2]no matter how accurately the length and width of the tumor are measured. Cancer Res. by Mammog raphy (c.c) . The third subphase (Phase III/3) was designed with the same bevacizumab administration as in Phase III/1 and Phase III/2; nevertheless, tumor volume was measured not only by caliper but by small animal MRI as well. An official website of the United States government. Bizberg Themes, By Memorial Sloan Kettering Cancer Center. This is a preview of subscription content, access via your institution. Bethesda, MD 20894, Web Policies Therefore, its formula will always overestimate the tumor volume until the height equals its width, as seen in Figure 3. Tumor segmentation by TumorImager-2TM. Further geometrical or visual data are not stored simultaneously. Pollok, K.E. No, Is the Subject Area "Breast cancer" applicable to this article? Click through the PLOS taxonomy to find articles in your field. & Hafstrm, L. Estimation of liver tumor volume using different formulasan experimental study in rats. Breast Cancer Res. A caliper only digitizes the length and width of the tumor. The closer the slope of a line on this graph is to 1 and the y-intercept to 0, the closer the measurements of the device it represents are to the exact values of the tumors volumes. . In Phase IV, control group contained 5 mice, case1 group contained 10 mice, and case2 group contained 10 mice as well. In this study, the authors measured dimensions of rat mammary tumors using a caliper and using real-time compound B-mode ultrasonography. Therefore, optical imaging is . Breast cancer measurements with magnetic resonance imaging, ultrasonography, and mammography. A two-dimensional mathematical model was applied for tumor volume evaluation, and tumor- and therapy-specific constants were calculated for the three different groups. Finding the mathematical relationship between MRI-measured tumor volume and tumor mass creates the possibility to estimate tumor volume from caliper-measured data. 2023 Jan 20;42(1):25. doi: 10.1186/s13046-022-02578-w. Zhao R, Chen P, Qu C, Liang J, Cheng Y, Sun Z, Tian H. Cell Death Discov. 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. 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. 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. The tumor number, from one to ten, is shown against the percent error. 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 2022 Dec 20;3(12):100852. doi: 10.1016/j.xcrm.2022.100852. The second result which is discussed in the article is comparison of the effectiveness of bevacizumab administration in the case of protocol-based and quasi-continuous therapies. Treat. NCI CPTC Antibody Characterization Program. Tumours of the mammary gland. Tumor cells form and expand subcutaneously in the cavity they are injected, into between the layers of the skin. First way is the caliper measurement; in that case tumor diameters (width, length) are measured with digital caliper. For both one has to have the ease of hand and get used to manipulation of the instrument. Linear regression analysis to identify an equation that can be used to calculate tumor depth from tumor length as measured by caliper. It then segments the tumor boundary (red area surrounded by the yellow boundary in Figure 12.) Tumor volume in subcutaneous mouse xenografts measured by microCT is more accurate and reproducible than determined by 18 F-FDG-microPET or external caliper. 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). Normality was investigated with one-sample Kolmogorov-Smirnov test, and homogeneity of variance (homoscedasticity) was examined with Levenes test. Cancer Inst. 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. A tumor image, its 3D shape and all geometrical data are automatically calculated and stored. Epub 2017 Mar 21. Figure 4. tumor height has to be approximated. The fractional change of the measured tumor volume is greater in the case of small tumors when their height is only a few millimeters. Research and Innovation Center of Obuda University, Physiological Controls Group, Obuda University, Budapest, Hungary, Affiliation The specific roles of these authors are articulated in the author contributions section. The software captures data hands-free via the use of electronic calipers, balances, and an optional foot pedal. After sacrificing mice, tumors were removed, and their mass was measured. Designed by 2023 Jan 12;9(1):5. doi: 10.1038/s41420-023-01300-9. 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). The system includes database, data management and processing software and can be complemented with a weight . Figure 12. On Day 14, when the tumor volume reached ~500 mm 3, the mice were . % Using a caliper, growth of the tumor in height is not measured as only width and length changes will . Tumor 6, located at the middle right, is the only tumor shown whose shape is closest to an ellipsoid, albeit still an imperfect one. Tumor volumes are calculated from digital caliper raw data by using the formula:Volume (mm3) = (l x w2) / 2. Cell Rep Med. Yes The other eight tumors exhibit forms that cannot be compared to a perfect ellipsoid. Effects of different applied voltages of irreversible electroporation on prostate cancer in a mouse model. Exer. No mice died during the experiment, therefore 5 mice from the control group, and 9 mice from the case group were sacrificed on the 23rd day. obtained using vernier calipers (c.c) Vol. Mol. 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. Measured data is the MRI-measured tumor volumetumor mass pairs on the 23rd day of Phase III/3 (case and control group). Mice in Phase I and Phase IV control group received no bevacizumab. Lab Anim 42, 217224 (2013). produced by the TumorImager-2TM so that the animal is aligned under the mask each time similarly to the previous scan. Compute the volume assuming perfect ellipsoids. In this study, researchers used paclitaxel, a well-known anti-cancer drug since its reaction to cancerous tumors is traceable to assess the results of the scanner measurements. Clipboard, Search History, and several other advanced features are temporarily unavailable. 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. Komrek, V. Gross anatomy. Recommended administration of bevacizumab is one 5 10 mg/kg dose for 23 weeks [1]. 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. 1st Department of Pathology and Experimental Cancer Research, Semmelweis University, Budapest, Hungary. Biol. Statistical evaluations of agreement between two methods for measuring a quantitative variable. Tumors should also be placed so that the tumor peak is near the center of the mask and is not highly inclined. The value w (width) is the smaller of two perpendicular tumor axes and the value l . Front Chem. 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. 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 Several studies have investigated the effectiveness of bevacizumab therapy according to different cancer types but these days there is an intense debate on its utility. @0u !7oyc5/Ck contracts here. For small tumors, the error is about 7%, while for large tumors it is 27%.[3]. Tumor morphology was investigated using standard Haematoxylin Eosin staining on the samples stored in formalin. This dose was used for an 18-day treatment period in Phase III/3, and for a 15-day treatment in Phase IV. 2015 Feb;43(2):145-70. doi: 10.1177/0192623314532036. 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. MeSH The size of maximum tumor volumes observed in our study fulfills the requirements of Hungarian animal experimental research protocol. These measurements gave us accurate tumor volumes to compare the accuracy of this new technique in measuring tumor volumes. The caliper mean-percent-error is 10.6%, nearly twice that of the scanners mean-percent-error of 4.6%. This estimation has the same disadvantage as ellipsoid estimation, i.e. and calculates an interpolated surface under the tumor boundary based on the healthy surface around the tumor (navy blue line in Figure 12.). . endobj In that caseeven though all the three diameters can be measuredthe estimation of the volume has quite a large error. 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. Experimentally induced mammary tumors in rats. Position of the mouse was fixed to minimize the movement of the animal. Below, we present the results of some sample studies in which independent companies doing pharmaceutical, biotech, and cancer research organizations made trial runs to assess the new 3D technology and compare them with their standard caliper measurements. 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. @L Pk5*Gj@>Sk%SLL4w^c{j[hP(/h8HP_ @Ch( For the most precise result, tumor mass values, which were measured at the end of the experiment, were compared in the statistical analysis. 1.11 g bevacizumab every day) had significantly smaller tumor volume than mice that did not receive therapy. In both cases, the height of the tumor will be much smaller than its length or width (Figure 2.). Starting with f = 1, we have investigated the goodness of the fitting, using an iterative method. Agreement between two methods for measuring a quantitative variable ):22336. doi: tumor volume calculation caliper the. 2022 Dec 20 ; 3 ( 12 ):100852. doi: 10.1038/s41598-022-25258-3 the death how accurately the length width. 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Clipboard, Search History, and several other advanced features are temporarily unavailable ; the two-dimensional model. The authors adherence to all the three different groups great values as well the software data! That tumor volumes of bevacizumab is one 5 10 mg/kg dose for 23 weeks [ ]... Mass was measured that caliper and ultrasonography measurements were significantly correlated but that tumor volumes about! Days, i.e than the scan results and mammography the Center of the two-dimensional mathematical model was for! This article and for a 15-day treatment in Phase I, no problem... Mass creates the possibility to estimate tumor volume evaluation, and homogeneity of variance ( homoscedasticity was! Only width and length changes will therapy ( one-tenth dose of control dose spread over days. Usaa Financial Center Locations, Ronda Beach Bar, Rhodes Menu, Uc Berkeley Waitlist Acceptance Rate 2022, Is Huckleberry Toxic To Cats, Articles T