Open Access 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. Front Chem. Possible mechanisms mediating an association between physical activity and breast cancer. Results of this phase can be found in [26]. Oncol. calipers and Water Displacement methods Tumor mimicking objects Vol. Comparison of clinical assessment, mammography and ultrasound in pre-operative estimation of primary breast-cancer size: a practical approach. Contrast agents improve the visibility, but it is an extra strain to the organism, which can be lethal to animals which are in the final stage of cancer. Timing wise both methods perform the same. Hence, the first step has to be the vasculature normalization with the reconstruction of the balance of pro- and antiangiogenic factors. A study[4] (Figure 5.) The .gov means its official. This estimation has the same disadvantage as ellipsoid estimation, i.e. Bevacizumab administration was started on the 7th day in both cases. In one trial, 208 tumors were measured, and 98.94% of those tumors exhibited much smaller heights than widths. This means that the daily treatment with one-twelfth total dose resulted in significantly smaller tumors than the protocol-based treatment. Clarke, R. Animal models of breast cancer: their diversity and role in biomedical research. The shape of the tumor, more often than not, is not an ellipsoid. A patented algorithm running in the TumorManagerTM program calculates the tumor volume by creating a 3D surface map of the tumor (red-colored surface in Figure 12.). Faustino-Rocha AI, Gama A, Oliveira PA, Vanderperren K, Saunders JH, Pires MJ, Ferreira R, Ginja M. Life Sci. HHS Vulnerability Disclosure, Help A solution to these problems is the TumorImagerTM scanner. Figure 4. Tumors were cut into two pieces for sample processing: one piece was stored in formalin, and the other piece was frozen using liquid nitrogen. Isofluorane (0.95 x 2.0%) was applied for inhalational anesthesia, and intubation was performed. A tumor image, its 3D shape and all geometrical data are automatically calculated and stored. Russo J, Russo IH, Rogers AE, van Zwieten MJ, Gusterson B. Toxicol Pathol. J. Nucl. Recommended administration of bevacizumab is one 5 10 mg/kg dose for 23 weeks [1]. Pursuant to one-sample Kolmogorov-Smirnov test, each sample has normal distribution (ppIV_control = 0.981, ppIV_case1 = 0.998, ppIV_case2 = 0.854). 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. To compare the effectiveness of the different investigated treatment methods, statistical analysis was used. Estimation of rat mammary tumor volume using caliper and ultrasonography measurements. The post hoc test resulted in the following. For this dataset, linear curve fitting was carried out (fitted linear curve) to find the mathematical relationship between MRI-measured tumor volume and tumor mass. a) Haematoxylin Eosin (H&E) staining was applied to investigate tumor morphology. 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. ANOVA test showed significant difference between these means (p = 0.041, using 0.05 level of significance). Would you like email updates of new search results? European Institute of Oncology, ITALY, Received: February 3, 2015; Accepted: October 19, 2015; Published: November 5, 2015, Copyright: 2015 Spi et al. No, PLOS is a nonprofit 501(c)(3) corporation, #C2354500, based in San Francisco, California, US, Corrections, Expressions of Concern, and Retractions, https://doi.org/10.1371/journal.pone.0142190, http://www.gene.com/download/pdf/avastin_prescribing.pdf, http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Scientific_Discussion/human/000582/WC500029262.pdf, http://www.protocol-online.org/prot/Protocols/Xenograft-Tumor-Model-Protocol-3810.html, http://www.targeson.com/sites/default/files/content/pages/pdfs/tail_vein_protocol_2012_0.pdf. & Hafstrm, L. Estimation of liver tumor volume using different formulasan experimental study in rats. In the case of Phase I, no similar problem occurs; the two-dimensional mathematical model can handle great values as well (e.g. A structured light-based system for scanning subcutaneous tumors in laboratory animals. 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. CAS and JavaScript. The obtained data include height and topography changes. This helps to calculate accurate tumor volume from caliper measured data which will be useful for further animal experiments and as a consequence no small MRI measurements will be needed. Pritt, B., Ashikaga, T., Oppenheimer, R.G. No animals were sacrificed before the experimental endpoint. For both one has to have the ease of hand and get used to manipulation of the instrument. Measurements with small animal MRI were done on the 4th, 8th, 11th, 15th, 18th and 23rd days of the experiment in Phase III/3. Thus, caliper-based measurements are less accurate the more the height of the stack deviates from its width. One can see that the two-dimensional mathematical model fits to the MRI-measured values, while the protocol-based values present totally different curve. We compared the volumes, areas . Bevacizumab is a humanized monoclonal antibody, therefore the effectivity of bevacizumab therapy in mice is not trivial. %PDF-1.4 Even though all the three diameters can be measured, the estimation of the volume has quite a large error. Department of Control Engineering and Information Technology, Budapest University of Technology and Economics, Budapest, Hungary, Affiliation First of all, our hypothesis according to the importance of administration is proved. Each dot, in addition to signifying a real-life tumors width and height, also signifies through the right y-axis what percentage of a caliper-based measurement with the same width it is. Treat. Biol. 35, 18341840 (2003). 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. BMC Medical . After fixing in methanol, rat anti-mouse CD31 antibody (1:50, 550274 BD PHARMINGEN) was applied as primer antibody, and FITC conjugated anti-rat CD31 antibody (1:100, Jackson Immunoresearch, 712-095-150) was applied on the slides as secondary antibody. However mice which were treated with a quasi-continuous therapy (one-tenth dose of control dose spread over 18 days, i.e. Different operators have different ways of holding the animal and tumor while performing the measurement. After staining, fluorescence pictures were done from the slides using confocal microscope (BIO-RAD MRC-1024). Measure the mass by using a balance (0.01g) and compute the volume by using the Care should be taken not to stretch the mouse whether using one or two hands to hold the mouse during a scan. This site needs JavaScript to work properly. In a 2001 study utilizing MRI, it was concluded that 85% of tumors needed a measurement other than length and the width to yield an accurate volume[5]; caliper-based values do not provide this other measurement. here. (Budapest, Hungary). Affiliation 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. The produced images were converted to NIfTI (Neuroimaging Informatics Technology Initiative) format, which is suitable for image processing. Yes Cancer Res. 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. An average penny has a diameter of 19 mm and a height of 1.27 mm, yielding a volume of 360.1 mm3. Davis, P.L. 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). Both methods are comparable when it concerns the time it takes to do a measurement. 47, 510 (2001). & Deshayes, J.L. @L Pk5*Gj@>Sk%SLL4w^c{j[hP(/h8HP_ @Ch( Mice were killed after 38 days. In this study, the authors measured dimensions of rat mammary tumors using a caliper and using real-time . Therefor it allows a direct 3D capture of the volume. (4). 2009, 18 (2009). Both methods cannot avoid variability introduced by the manipulation of the animal. 41, 16901694 (1981). First is to find an appropriate mathematical model for tumor volume evaluation from caliper-measured data. This means that continuous, low dose antiangiogenic factor (VEGF) administration is needed. Sci. 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. Tievsky AL, Ziegler RB, Salhus MR, Weisskoff R. Comparison of diameter and perimeter methods for tumor volume calculation. <> stream M}{Gt{zj|&cXx[k?CZ
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t-o6MkVXs's}^E6-^_Yrv#w&r7w@WsQs]#G g$Cn. Westerlind, K.C. This creates the possibility of further efficient therapeutic agent use (if any) or assists the more effective direct antitumoral effect of bevacizumab. Tumor volume was measured regularly using a Mitutoyo caliper and calculated as: tumor volume = (length width 2 )/2 [26, 27]. (6) (7).
Tumor volumes ranged from 0.5 cc to 187.9 cc, with a median of 21.8 cc. Figure 16. depicts the results from a study attended by Biopticon in which ten subcutaneous tumors in mice were measured by scanner and caliper by four operators. In Phase III/3, case group members received one-tenth dose of control dose intraperitoneally spread over 18 days. The value w (width) is the smaller of two perpendicular tumor axes and the value l . [2]no matter how accurately the length and width of the tumor are measured. Preclinical evaluation of LU 79553: a novel bis-naphthalimide with potent antitumor activity. For ultrasonography measurements, we calculated tumor volume . 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. McCormick, D.L., Adamowski, C.B., Fiks, A. Tumor measurement by TumorImager-2TM. Lee, J., Koh, D. & Ong, C.N. Figure 7. Cancer 60, 765771 (1987). 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. Sign up for the Nature Briefing newsletter what matters in science, free to your inbox daily. A tumor expands in width rather than height as it grows. Measured data is the MRI-measured tumor volumetumor mass pairs on the 23rd day of Phase III/3 (case and control group). For small tumors, the error is about 7%, while for large tumors it is 27%.[3]. The variables for the volume of a tumor, as measured by a caliper, are determined by a, b, and c in Figure 1, where length L is 2a, width W is 2b, and height H is c. VT, the volume of a tumor is determined by. Better results can be obtained by proper handling of the mice. In addition, the root mean square, R2 values under the linear regression equations in Figure 15. symbolize the precision of the data. In this phase, 5 immunocompetent mice in control group, and 9 immunocompetent mice in case group were used. Competing interests: The authors have the following interests: Coauthors PK and DG are employed by Gedeon Richter Ltd. Avastin (bevacizumab) is manufactured by Genentech, Inc., South San Francisco, California, USA; EU patent expiry in 2019 in the US and 2022 in EU. With a caliper measurement, the angle at which the tool is held over the tumor will affect the obtained value, thus inducing an extra operator and manipulation sensitivity in the final results. 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. 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