McCormick, D.L., Adamowski, C.B., Fiks, A. Finding the mathematical relationship between MRI-measured tumor volume and tumor mass creates the possibility to estimate tumor volume from caliper-measured data. Even though, now, the formula is calculated in an Excel spreadsheet where can be defined as a function, pi(), almost in all cases, in the volume formula is defined as 3.0. recurrent glioblastoma (rGBM) [36]) as a first or second line treatment, usually in combination with chemo- or immunotherapy. M}{Gt{zj|&cXx[k?CZ ~AjTxMr0 '~ix$mj/)9?$ t-o6MkVXs's}^E6-^_Yrv#w&r7w@WsQs]#G g$Cn. YH29407 with anti-PD-1 ameliorates anti-tumor effects. We have examined C38 mouse colon adenocarcinoma and HT-29 human colorectal adenocarcinoma. Bethesda, MD 20894, Web Policies 20, the red dots that represent scanner-based measurements are closer to the black dotted (objective) line than the blue squares that represent caliper-based measurements. Mammary tumors similar to those observed in women can be induced in rats by intraperitoneal administration of N-methyl-N-nitrosourea. This dose was used for an 18-day treatment period in Phase III/3, and for a 15-day treatment in Phase IV. Yes Modulation of mammary tumor vascularization by mast cells: Ultrasonographic and histopathological approaches. In the case2 group, one mouse died on the 8th day, before the therapy (bevacizumab administration) started. In this study, the authors measured dimensions of rat mammary tumors using a caliper and using real-time compound B-mode ultrasonography. & trukelj, B. N-methylnitrosourea induced breast cancer in rat, the histopathology of the resulting tumours and its drawbacks as a model. Federal government websites often end in .gov or .mil. Epub 2014 May 28. To obtain This saves money, as mice, drugs, and calipers can be costly for researchers. 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. 2 0 obj https://doi.org/10.1371/journal.pone.0142190.g008. For more information about PLOS Subject Areas, click Predicting tumor volume in radical prostatectomy specimens from patients with prostate cancer. Tumor area was determined with flood fill algorithm [31] from the slides; by knowing the volume of a voxel, tumor volume was calculated from these two values. 55, 74108 (2005). This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. 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]. https://doi.org/10.1371/journal.pone.0142190, Editor: Francesco Bertolini, Traditionally, caliper measurements are used to calculate tumor volume. The other eight tumors exhibit forms that cannot be compared to a perfect ellipsoid. The scanner-based measurements yield a higher correlation in this sense than caliper-based measurements. []. Almost 90% of the establishments that make tumor volume measurements using calipers use a modified version of the ellipsoid formula, under the incorrect assumption that a tumor is always a perfect ellipsoid. 35, 18341840 (2003). Mice were killed after 38 days. 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). Cancer 83, 621628 (1998). Pere, M., Cerar, A. 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. Value of prostate volume measurement using transabdominal ultrasonography for the improvement of prostate-specific antigen-based cancer detection. Our results provide a theoretical background for a much more effective bevacizumab treatment using optimized administration. All surgery and sacrifice were performed under sodium pentobarbital anaesthesia (Nembutal, 70 mg/kg). PLoS ONE 10(11): & Pisani, P. Global cancer statistics, 2002. PMC Article Tumor growth was investigated without therapy and with antiangiogenic therapy (using bevacizumab [15]). Tumor size was measured every 3 days using a digital caliper and computed according to the ellipsoidal calculation formula: V . Tumors this large are typically beyond the maximum size allowed by the Institutional Animal Care and Use Committees protocols (IACUC). J. Natl. Can the Kuznetsov Model Replicate and Predict Cancer Growth in Humans? produced by the TumorImager-2TM so that the animal is aligned under the mask each time similarly to the previous scan. One of them died on the 18th day, and another one on the 23rd day. r>12TzPn 4x PUj50"pJ{{>y{.mn|Cvz{PP5x kH:5:YM.gn?c[J8oQWkR_!X/C@6P@WT=gO5Sn>om}&SI cyT>E"TnkhSju>~yVOm^C~0__ww@ y[xQr33?6O~hZcR{{u]=O5T. 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. mum tumor volume of 0.6 mL was reached. A standard deviation of 0% is almost impossible in real life, but a smaller standard deviation is generally favorable. When the tumor has a symmetrical, solid closed shape (typically without treatment), volume can be evaluated accurately from caliper-measured data with the applied two-dimensional mathematical model. and JavaScript. 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. In this phase, three groups were created. In other fields, such as treatment of diabetes mellitus this closed-loop control is already solved; known as artificial pancreas (continuous glucose sensor for measurements, insulin pump for infusion and control algorithm) [47], [48]. Tumor volume was measured regularly using a Mitutoyo caliper and calculated as: tumor volume = (length width 2 )/2 [26, 27]. In Phase IV, approximately 2.9106 cells were injected subcutaneously into each SCID mouse. {(Q~J9}=ow[5nkW"C; >tDve+7K,}g?A Even though all the three diameters can be measured, the estimation of the volume has quite a large error. Cell Rep Med. Quantity of the optimal solvent administration was also examined in this subphase. The explanation of the effectiveness of low dose VEGF therapy is the following ([3944]). obtained using vernier calipers (c.c) Vol. Cancer Res. the tumor volume are made using digital calipers, and bio logical activity is quantified via the assessment of changes in tumor volume between treated and control mice. Unmeasured part of the tumor for caliper, Figure 11. Correlation was investigated with Pearsons rank correlation test (Pearsons R) and coefficient of determination (R2). contracts here. Thus, caliper-based measurements are less accurate the more the height of the stack deviates from its width. Cells should be suspended in a volume so that 300 l contains required number of cells per injection. Weber, W.A. 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. The other way to measure tumor volume is the usage of small animal MRI, a non-invasive in vivo technology giving the possibility of a more precise volume measurement [29]. Description of Lesions. J. Oncol. 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. 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. where V m is the measurement threshold that represents the smallest measurable tumor volume using a caliper. Thank you for visiting nature.com. In Phase III/3, control group members received 200 g bevacizumab (with 455 l 0.9% NaCl solution) in one dose intraperitoneally on the 3rd day and on the 21st day. https://doi.org/10.1371/journal.pone.0142190.g007. Figure 4. The closer the value is to 1, the more precise the data. In addition, we have found that the quasi-continuous administration of bevacizumab is effective against tumor growth of C38 colon adenocarcinoma, in contrast . Get just this article for as long as you need it, Prices may be subject to local taxes which are calculated during checkout. A direct 3d measurement tool such as the TM900 does not induce such method sensitivity but cannot exclude operator dependency of the obtained values. After sacrificing mice, tumors were removed, and their mass was measured. Clinical aspects which have to be considered to determine when animals should be euthanized are body weight, physical appearance, measurable clinical signs, unprovoked behavior and response to external stimuli. Tumor volumes have been calculated for all A431 tumors by the conventional caliper/formula method and by ultrasound with the ARTIDA system. Tumor volume measurement cannot happen right after tumor implantation. A smaller standard deviation in a set of measurements suggests a lesser possibility of error. . An average penny has a diameter of 19 mm and a height of 1.27 mm, yielding a volume of 360.1 mm3. Figure 12. MeSH The protocol was approved by the Hungarian Animal Experimental Research Ethics Council (llatksrleti Tudomnyos Etikai Tancs, ATET), Permit Number: 22.1/1159/3/2010. Figure 2. Tumor cells form and expand subcutaneously in the cavity they are injected, into between the layers of the skin. Bookshelf Calculate the correct dose of STELFONTA once you have the volume of the tumor in cm 3, using the Dose Calculator. In this study, the authors measured dimensions of rat mammary tumors using a caliper and using real-time compound B-mode ultrasonography. This concept can easily be understood by a simple thought experiment: the volume of a stack of pennies (Figure 4.). 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. (8) J. Ultrasound Med. To compare more than two samples, ANOVA test was applied. Using an extremely low dosage (as in our study), there is a high probability that these adverse effects can be minimized. () and were used with the parameters displayed in Table 1Parameters for Gompertz growth were taken from Benzekry et al. 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. Estimation of rat mammary tumor volume using caliper and ultrasonography measurements. Pathology of tumours in laboratory animals. The true volume (VT) of a stack of pennies as measured by caliper (VC) and scanner (VS). . Funding: This work was supported by Hungarian Scientific Research Fund (OTKA), http://www.otka.hu/en, No: K-112993 (Jnos) and Bolyai Research Scholarship of the Hungarian Academy of Sciences, http://mta.hu/cikkek/?node_id=26057, No: 425_12. 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]. Tumor Volume Measurement & Morel, M. Clinical, mammographic, and sonographic determination of preoperative breast cancer size. 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. 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. Analysis of Variance (ANOVA) test was used to compare more than two samples, while pairwise comparison was done by Tukeys honest significant difference (HSD) test. Davis, P.L. Finally, it finds the volume between these two surfaces and sets this to be the volume of the tumor (shaded red region in Figure 11, red region in Figure 14 below). The manipulation of the handheld tool is at least as easy as holding a measurement caliper. 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]). Measure the three dimensions of peanut M&M's, serving as our similar-sized tumor surrogates, using vernier calipers. 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. For both one has to have the ease of hand and get used to manipulation of the instrument. Sci Rep. 2022 Dec 26;12(1):22336. doi: 10.1038/s41598-022-25258-3. We found the same result for human colorectal adenocarcinoma (HT-29) xenografts. 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. First is to find an appropriate mathematical model for tumor volume evaluation from caliper-measured data. The results presented here were provided by them. Res. & Deshayes, J.L. Make sure you get accurate measurements for length, width and height. 15, 115121 (2009). One can find datasets in the last column of Table 2. The effectiveness of bevacizumab administration was examined by statistical analysis. Click through the PLOS taxonomy to find articles in your field. (Fig 2). Breast cancer measurements with magnetic resonance imaging, ultrasonography, and mammography. by water displace ment (c.c) Vol. Controller-based therapy has the obvious advantage against e.g. Performed the experiments: JS ZS PK DG. Article (5) Get the most important science stories of the day, free in your inbox. As is the case with caliper measurements, if the tumor appears visibly flattened and is hard to see by eye then the mouse should be repositioned. 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. Cancer Inst. 2022 Dec 5;10:998013. doi: 10.3389/fchem.2022.998013. & Wieder, H. Monitoring chemotherapy and radiotherapy of solid tumors. 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