Treat. Clipboard, Search History, and several other advanced features are temporarily unavailable. 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). The first measurement in Phase I occurred on the 5th day; in Phase III/3, it occurred on the 4th day. CAS 19, 6170 (1989). 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. 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.). A direct 3d measurement tool such as the TM900 does not induce such method sensitivity but cannot exclude operator dependency of the obtained values. Powered by WordPress 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]. Caliper Measurement. One can see that the two-dimensional mathematical model fits to the MRI-measured values, while the protocol-based values present totally different curve. (Budapest, Hungary). The caliper mean-percent-error is 10.6%, nearly twice that of the scanners mean-percent-error of 4.6%. Figure 14. endobj Homogeneity of variance was examined with Levenes test; the sample variances are equal (p = 0.052). The figure shows the results of a mouse (C4) from control group (first row), and a mouse (E9) from case group (second row). First way is the caliper measurement; in that case tumor diameters (width, length) are measured with digital caliper. 37, 19 (1996). In Phase I, 12 mice were implanted with C38 colon adenocarcinoma. Radiology 254, 110118 (2010). Frozen samples were used to create 15 m frozen cuts. Hoffman-Goetz, L. et al. Figure 2. Effects of holding an animal on tumor volume while scanning. (6) (7). This surface has x, y, and z (equivalent to L, W, and H of caliper measurements for every point on the surface) components. Even the same operator, with different trials or at different moments in time does not always hold the animal in exactly the same way. After sacrificing mice, tumors were removed, and their mass was measured. Yes Get just this article for as long as you need it, Prices may be subject to local taxes which are calculated during checkout. 01 July 2022. Google Scholar. J Clin Oncol. Mice were monitored daily. Due to the collaboration between medical doctors and biomedical engineers, model-based treatment protocols can be created. Faustino-Rocha AI, Gama A, Oliveira PA, Vanderperren K, Saunders JH, Pires MJ, Ferreira R, Ginja M. Life Sci. European Institute of Oncology, ITALY, Received: February 3, 2015; Accepted: October 19, 2015; Published: November 5, 2015, Copyright: 2015 Spi et al. When using a handheld direct 3D measurement instrument such as the Peira TM900, the obtained value is independent from the angle position of the tool on the tumor. The significant difference between quasi-continuous therapy (Phase III/3 case group) and tumor growth without treatment (Phase I) was proved with statistical analysis as well. In vivo measurements of tumor metabolism and growth after administration of enzastaurin using small animal FDG positron emission tomography. NCI CPTC Antibody Characterization Program. The first group did not receive therapy, the second group received one 200 g bevacizumab dose for a treatment period (protocol-based therapy), and the third group received 1.1 g bevacizumab every day (quasi-continuous therapy). Ultrasonography as the Gold Standard for In Vivo Volumetric Determination of Chemically-induced Mammary Tumors. Scientific Reports On the bottom left graph in Fig. & Pisani, P. Global cancer statistics, 2002. Figure 6. depicts three components used to measure the volume of a tumor: its length, represented by blue arrows, its width by green, and its height by yellow. Although the low dose bevacizumab therapy is well known in the literature, we found no article (in the English literature) regarding very low dose and quasi-continuous bevacizumab therapy, as used in our study. et al. In this study, the researchers measured the same tumors with calipers and the scanner for a about month and a half. Importantly, these measured size differences are real; they are not due to a miscalculation by the algorithm but due to the pressing of the tumor mass into the body. Mice were monitored daily by personnel experienced in recognizing signs of morbidity (illness, injury, or abnormal behavior) also in weekends and holidays. mum tumor volume of 0.6 mL was reached. 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]. Int. Tumor morphology was investigated using standard Haematoxylin Eosin staining on the samples stored in formalin. Yes Comp. In Phase III/3, MRI-measured tumor volume values are available which can be used as reference values for caliper-measured data. In Phase IV, eleven weeks old male SCID mice with implanted HT-29 human colorectal adenocarcinoma was used. A study[4]on caliper measurements, shoved the very poor accuracy of the formula used for caliper measurements. Measured data is the MRI-measured tumor volumetumor mass pairs on the 23rd day of Phase III/3 (case and control group). A possible solution for height approximation [23] is: In the case of Phase III/3 and Phase IV, period of time was specified according to the previous phases (Phase I and Phase III/1); mice were sacrificed on the 23rd day of the experiment. A two-dimensional mathematical model was created from the experimental results of BALB/c mice with KHJJ tumor line [25]: Results from a vaccine trial from AstraZeneca. No, Is the Subject Area "Magnetic resonance imaging" applicable to this article? To reduce the time of analysis one could e.g. 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. Our results provide a theoretical background for a much more effective bevacizumab treatment using optimized administration. In each case the reference value is the MRI-measured tumor volume. []. Using the above mentioned iterative method, the resulted equation is 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 scan images obtained are only for the external surface of the tumor. 47, 510 (2001). Yes The software captures data hands-free via the use of electronic calipers, balances, and an optional foot pedal. 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. calculate an average volume based on two extreme segmentations; one including most of the border, and one excluding it. All surgery and sacrifice were performed under sodium pentobarbital anaesthesia (Nembutal, 70 mg/kg), and all efforts were made to minimize suffering. Table 1. 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. 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. Therefore, its formula will always overestimate the tumor volume until the height equals its width, as seen in Figure 3. The size of maximum tumor volumes observed in our study fulfills the requirements of Hungarian animal experimental research protocol. 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 . In order to understand inter-operator differences between operators making both caliper and scanner measurements, we conducted experiments in which multiple numbers of operators measured several tumors both with caliper and scanner. Orthotopic xenograft tumor models, which are more difficult to establish, are close to the clinical behavior of malignant tumors in terms of location of the primary tumor site, the tumor progression, the tumor micro-environment, cell migration and metastasis [1 . https://doi.org/10.1371/journal.pone.0142190.g004. Secondly, the aspect of side-effects are not inconsiderable. Cell Rep Med. The mathematical relationship between MRI-measured tumor volume and mass was investigated to estimate accurate tumor volume using caliper-measured data. PubMed Tumor measurement by TumorImager-2TM. https://doi.org/10.1371/journal.pone.0142190.g001. Pathol. 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. In one trial, 208 tumors were measured, and 98.94% of those tumors exhibited much smaller heights than widths. {(Q~J9}=ow[5nkW"C; >tDve+7K,}g?A Pairwise comparison was done by Tukeys honest significant difference test to find those samples, which have significantly different means. CAS Unauthorized use of these marks is strictly prohibited. In Phase I, 10 mice were sacrificed at the 24th day of the experiment. Tumor volume was measured with digital caliper. An average penny has a diameter of 19 mm and a height of 1.27 mm, yielding a volume of 360.1 mm3. Phase III contained three subphases, in every subphases two groups were created; control group received bevacizumab in one dose according to the protocol, while case group received substantially lower doses every day. This is a preview of subscription content, access via your institution. To obtain 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. Modulation of mammary tumor vascularization by mast cells: Ultrasonographic and histopathological approaches. In Phase IV, the caliper measurement days were the 10th, 12th, 17th, 19th, 22nd and 23rd days. Cancer 60, 765771 (1987). For the TM900 one has to push the acquisition button and almost immediately the images are stored and values calculated. Mice were humanely sacrificed using cervical dislocation. Cells should be suspended in a volume so that 300 l contains required number of cells per injection. In the case of HT-29 adenocarcinoma, the daily treatment with one-twelfth total dose resulted in significantly smaller tumors than the protocol-based treatment (p = 0.038). A typical comparison of tumor volume measurements by TumorImager-2TM with calipers. Kobayashy, T. et al. Careers. <> Generally, to make caliper measurements, the measurer first traps the tail of the mouse under her fingers, then, grabs the neck of the mouse, and aligns the mouse in her hand in a way to expose the tumor for length and width measurements. Table 1 shows the results for tumor volume measure- ments on seven A431 tumors, indicating next to both gold standard volumes (V w , V L ) the caliper/formula derived volume V E and the ARTIDA . Mammary tumors similar to those observed in women can be induced in rats by intraperitoneal administration of N-methyl-N-nitrosourea. As the height values of the tumors deviate from those of the width, the caliper-based volume values of those tumors begin to mirror real-life measurements less closely. https://doi.org/10.1038/laban.254. 2015 Feb;43(2):145-70. doi: 10.1177/0192623314532036. No, Is the Subject Area "Cancer treatment" applicable to this article? . The majority of debate over Avastin is about breast cancer because, in 2011, the US Food and Drug Administration (FDA) revoked the approval of Avastin for breast cancer treatment in the absence of decisive therapeutic benefit; however, several clinical trials suggested that Avastin can be effective in breast cancer treatment [6, 7]. In this phase, three groups were created. Using a caliper, growth of the tumor in height is not measured as only width and length changes will affect the calculated volume. CA Cancer J. Clin. Tumors should also be placed so that the tumor peak is near the center of the mask and is not highly inclined. Disclaimer. Therefor it allows a direct 3D capture of the volume. However, most serious questions are: for how long and continuous or not? 2017 May 1;176:35-41. doi: 10.1016/j.lfs.2017.03.013. Ultrasonographic, thermographic and histologic evaluation of MNU-induced mammary tumors in female Sprague-Dawley rats. Figure 16. Enter your measurements into the Tumor Volume Calculator to determine the volume of the tumor. The system includes database, data management and processing software and can be complemented with a weight . The TumorImagerTM line of scanners by Biopticon Corporation fixes these problems by keeping the animals relaxed during measuring and yielding measurements closer to actual values than caliper-based measurements. In Phase IV, control group members received no bevacizumab. This means that the daily treatment with one-twelfth total dose resulted in significantly smaller tumors than the protocol-based treatment. In our study, we applied a two-dimensional mathematical model and determined the corresponding tumor- and therapy-specific constants in the three investigated cases (C38 colon adenocarcinoma growth without therapy, C38 colon adenocarcinoma growth with protocol-based bevacizumab therapy and C38 colon adenocarcinoma growth with quasi-continuous bevacizumab therapy). & Lin, C.A. Accessibility 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. & Deshayes, J.L. A structured light-based system for scanning subcutaneous tumors in laboratory animals. The specific roles of these authors are articulated in the author contributions section. 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. 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. 16 (2008). In the control group, one mouse died on the 20th day due to tumor toxicity. tumor height has to be approximated. In the first four measurement times 30 slices were done from each mouse; in the last two measurement times 40 slices were done from each mouse due to the larger tumor volume. Internet J. Surg. Hence, the first step has to be the vasculature normalization with the reconstruction of the balance of pro- and antiangiogenic factors. The explanation of the effectiveness of low dose VEGF therapy is the following ([3944]). Healthy tissues have efficient vasculature and effective blood supply due to the balance of proangiogenic and antiangiogenic factors. The most recent ESMO (European Society for Medical Oncology) consensus guidelines suggest that treatment discontinuation or maintenance are feasible options after 46 months of full-dose first-line therapy to treat colon and rectal adenocarcinoma [37]. 39, 16 (1996). Typical side-effects and adverse events are arterial and venous thromboembolic events, bleeding, hypertension, febrile neutropenia, infections, proteinuria, mucositis, and hand-foot syndrome. In the case of C38 adenocarcinoma, protocol-based treatment did not result in significantly smaller tumor volume compared to the no treatment group; however, there was a significant difference between untreated mice and mice who received quasi-continuous therapy (p = 0.002). Effects of different applied voltages of irreversible electroporation on prostate cancer in a mouse model. B){00)Y$Ixlr{dYe}#@ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ ,^X_zN5:EZN]zM^k /Wu^ZZi#Ju.!L!z@u*kUim|+aZmjth-}z5'^|= 4L1_]qVZV*h@! . In caliper measurements, two values, for length and width, must be recorded for one tumor in each animal; this means that for every 100 animals studied, at least 200 measurements must be made and recorded. Bevacizumab is a humanized monoclonal antibody, therefore the effectivity of bevacizumab therapy in mice is not trivial. . Tumor volume was measured in two different ways. In Phase II, the toxicology investigation of the applied angiogenic inhibitor (bevacizumab) was performed; there was no tumor implantation into mice in this phase. 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. 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