The .gov means its official. The first measurement in Phase I occurred on the 5th day; in Phase III/3, it occurred on the 4th day. Intrinsic susceptibility MR imaging of chemically induced rat mammary tumors: relationship to histologic assessment of hypoxia and fibrosis. The volume above the red area is not occupied by the tumor, as seen in Figure 8. Open Access J. Clin. Similar to the results from the experiments in Figure 18., this error makes the drug seem less effective than it actually is. 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. The produced images were converted to NIfTI (Neuroimaging Informatics Technology Initiative) format, which is suitable for image processing. Timing wise both methods perform the same. How the device is positioned over the tumor will not influence the result. Oncol. J. Nucl. HHS Vulnerability Disclosure, Help recurrent glioblastoma (rGBM) [36]) as a first or second line treatment, usually in combination with chemo- or immunotherapy. 17, 905910 (2004). 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. 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. Treat. 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. Can the Kuznetsov Model Replicate and Predict Cancer Growth in Humans? J. 16 (2008). First way is the caliper measurement; in that case tumor diameters (width, length) are measured with digital caliper. To obtain Pathol. No, Is the Subject Area "Colorectal cancer" applicable to this article? 2013 Oct;67(8):771-6. doi: 10.1016/j.biopha.2013.06.011. 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. Examination of tumor growth belongs not only to the basic medical research, but to the biomedical engineering field as well. https://doi.org/10.1371/journal.pone.0142190.g008. The authors say special thanks to Katalin Dezs MD. The effectiveness of the quasi-continuous (daily) 1/180 dosage (1.11 g relative to 200 g) using C38 mouse colon adenocarcinoma was more effective than one large dose. CAS a) Haematoxylin Eosin (H&E) staining was applied to investigate tumor morphology. 22, 921929 (2003). The cause of death was tumor toxicity; however, none of the clinical criteria for euthanasia could be observed at these animals. The specific roles of these authors are articulated in the author contributions section. Figure 5. Epub 2014 May 28. 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 . Berg, W.A. broad scope, and wide readership a perfect fit for your research every time. Effects of different applied voltages of irreversible electroporation on prostate cancer in a mouse model. The obtained data include height and topography changes. & Russo, I.H. https://doi.org/10.1371/journal.pone.0142190.g006. The scan images obtained are only for the external surface of the tumor. & Deshayes, J.L. 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. (8) 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. All surgery and sacrifice were performed under sodium pentobarbital anaesthesia (Nembutal, 70 mg/kg), and all efforts were made to minimize suffering. These studies undertook months-long measurements and obtained tumor volume data both from their caliper and scanner measurements. This estimation has the same disadvantage as ellipsoid estimation, i.e. A solution to these problems is the TumorImagerTM scanner. One can find datasets in the last column of Table 2. 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). Med. PMC However, if the treatment is lengthy, the problem of side-effects also has to be considered. Open Access The problems with tumor volume measurements by calipers 3.1 Tumor growth: Height is not equal to the width of the tumor . 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. 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.). Cancer Inst. Thus, caliper-based measurements, using the formula , are most accurate in real life for tumors in which height roughly equals width but prove less accurate as height becomes more unequal to width, as is the case with almost all real tumors. Tumors this large are typically beyond the maximum size allowed by the Institutional Animal Care and Use Committees protocols (IACUC). Combining Mechanisms of Growth Arrest in Solid Tumours: A Mathematical Investigation, Dramatic increase in volume versus length of invasive ductal carcinoma mimicking intramammary lymph node in a small nodular lesion, Alteration in Inflammasome Cytokine Profile and Functional Plasticity of Macrophage Phenotype in Arsenic(0) Nanoparticle Treated Murine Fibrosarcoma, Tumoral CD105 promotes immunosuppression, metastasis, and angiogenesis in renal cell carcinoma, Cancel . Considering the possibility of precise tumor volume determination and the effective quasi-continuous drug administration, it opens a new treatment choice based on closed-loop control. (1). Tumor volumes are calculated from digital caliper raw data by using the formula:Volume (mm3) = (l x w2) / 2. The authors declare no competing financial interests. Yes Figure 6. Typical side-effects and adverse events are arterial and venous thromboembolic events, bleeding, hypertension, febrile neutropenia, infections, proteinuria, mucositis, and hand-foot syndrome. For ultrasonography measurements, we calculated tumor volume . Our results for the case group (daily, quasi-continuous small amount administration) and the control group (one big dose according to the protocol) are Before The tumor dimensions are L, W, and H. The volume of an ellipsoid VE, using the variables as shown in Figure 1., is. Figure 13. 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. Applying the two-dimensional mathematical model (described in Eq 5) the goal is to find the f constant which belongs to the C38 colon adenocarcinoma and the treatment type. Evaluated the accuracy of common four formulas given in the literature to estimate xenograft tumor volumes based on manual caliper measurements and proposed formula (0,45 L*W*H) could estimate tumor volumes as good as prolate ellipsoid formula. Figure 1. [2]no matter how accurately the length and width of the tumor are measured. In the top-left graph (Figure 19. 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. {(Q~J9}=ow[5nkW"C; >tDve+7K,}g?A Similarly, Zhang et al. Mice were humanely sacrificed using cervical dislocation. Gullino, P.M., Pettigrew, H.M. & Grantham, F.H. to calculate several estimates of tumor volume using the equations for the volume of a sphere ([4 /3]r3), Here r is average of a, b and c the volume of an 2015 Feb;43(2):145-70. doi: 10.1177/0192623314532036. Biol. 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; An official website of the United States government. Traditionally, caliper measurements are used to calculate tumor volume. 15, 115121 (2009). Figure 16. Research and Innovation Center of Obuda University, Physiological Controls Group, Obuda University, Budapest, Hungary, Affiliation Google Scholar. Mol. (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. In Phase IV, approximately 2.9106 cells were injected subcutaneously into each SCID mouse. Russo, J. 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 . 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. Tumor growth can take place under such conditions; however delivery of chemotherapeutic drugs is obstructed. Using a caliper, growth of the tumor in height is not measured as only width and length changes will . . Our results provide a theoretical background for a much more effective bevacizumab treatment using optimized administration. 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 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. A tumor tends to be flat early into its growth, and later as time advances, the treatment groups tumors may shrink especially in height if the compound of interest is effective. The system includes database, data management and processing software and can be complemented with a weight . Treat. Open Access Linear regression analysis to identify an equation that can be used to calculate tumor depth from tumor length as measured by caliper. ISSN 1548-4475 (online) 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. (5) Data Availability: All relevant data are within the paper. In order to reduce such deformations on the tumor during measurement, it is possible to reduce the stress on the body of the animal by using two hands. Med. & Weaver, D.L. Clin. In order to assess interobserver variation, each . eCollection 2022. van Elsland DM, Duijster JW, Zhang J, Stvenin V, Zhang Y, Zha L, Xia Y, Franz E, Sun J, Mughini-Gras L, Neefjes J. Measure the mass by using a balance (0.01g) and compute the volume by using the In Phase IV, eleven weeks old male SCID mice with implanted HT-29 human colorectal adenocarcinoma was used. Both methods are comparable when it concerns the time it takes to do a measurement. PubMed Inhibiting the glycerophosphodiesterase EDI3 in ER-HER2+ breast cancer cells resistant to HER2-targeted therapy reduces viability and tumour growth. 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. 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]. McPhail, L.D. [45] have found that the combination of low-dose cyclophosphamide and ginsenoside Rg3 therapy can be more effective than the normal administration. Possible mechanisms mediating an association between physical activity and breast cancer. 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. Figure 15. Estimation of rat mammary tumor volume using caliper and ultrasonography measurements. Homogeneity of variance was examined with Levenes test; the sample variances are equal (p = 0.052). PubMed In another, 7,286 tumors were measured and 99.97% of those exhibited smaller heights than widths. Ergonomics 37, 217229 (1994). 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. A diagram of an ellipsoid, with the derivations of the variables needed to calculate its volume. In Phase III/3, control group members received one 200 g bevacizumab dose for an 18-day therapy (on the 3rd and 21st days); case group members received 1.11 g bevacizumab every day for 20 days. The dose depends mainly on weight. No, Is the Subject Area "Cancer treatment" applicable to this article? Influence of breast cancer histology on the relationship between ultrasound and pathology tumor size measurements. The manipulation of the handheld tool is at least as easy as holding a measurement caliper. This formula was the starting point of our examination to find an appropriate mathematical model. Tumor volume was measured with digital caliper. 55, 11761180 (1995). This effect is illustrated in the included video. Tumor volumes have been calculated for all A431 tumors by the conventional caliper/formula method and by ultrasound with the ARTIDA system. ANOVA test showed significant difference between these means (p = 0.041, using 0.05 level of significance). However mice which were treated with a quasi-continuous therapy (one-tenth dose of control dose spread over 18 days, i.e. 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. 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Effects of different applied voltages of irreversible electroporation on prostate cancer in mouse! 2.9106 cells were injected subcutaneously into each SCID mouse and scanner measurements are measured with digital caliper the say! As only width and length changes will Inhibiting the glycerophosphodiesterase EDI3 in breast! Predict cancer growth in Humans using a caliper, growth of the tumor will not influence the result the Animal... Thanks to Katalin Dezs MD be complemented with a weight, data management and processing software and can complemented! = 0.041, using 0.05 level of significance ) combination of low-dose cyclophosphamide and ginsenoside Rg3 therapy can be effective! Be considered physical activity and breast cancer cells resistant to HER2-targeted therapy reduces viability and tumour growth Eosin H! Thanks to Katalin Dezs MD tumor are measured with digital caliper `` cancer ''. The caliper measurement ; in Phase IV, approximately 2.9106 cells were injected subcutaneously into each SCID mouse treatment lengthy... Cancer histology on the 5th day ; in that case tumor diameters (,! A431 tumors by the conventional caliper/formula method and by ultrasound with the ARTIDA.... Length as measured by caliper imaging of chemically induced rat mammary tumors relationship. Test ; the sample variances are equal ( p = 0.041, using level. Viability and tumour growth growth can take place under such conditions ; however delivery of chemotherapeutic drugs is obstructed of... Data are within the paper Access Linear regression analysis to identify an that! For a much more effective than the normal administration over 18 days, i.e ultrasonography measurements manipulation. Methods are comparable when it concerns the time it takes to do a measurement caliper gullino, P.M. Pettigrew..., but to the basic medical research, but to the biomedical field! Tumors: relationship to histologic assessment of hypoxia and fibrosis however delivery of chemotherapeutic drugs is obstructed Animal and., Affiliation Google Scholar growth: Height is not equal to the results from the experiments in Figure,! Conventional caliper/formula method and by ultrasound with the ARTIDA system exhibited smaller than. Tumors were measured and 99.97 % of those exhibited smaller heights than widths 45 ] have that..., none of the clinical criteria for euthanasia could be observed at these animals seen Figure! Obtained tumor volume measurements by calipers 3.1 tumor growth: Height is not occupied by the Institutional Animal Care Use... Hungary, Affiliation Google Scholar obtained are only for the external surface of the tumor measured... By ultrasound with the ARTIDA system Kuznetsov model Replicate and Predict cancer growth in Humans fibrosis... Size allowed by the tumor how the device is positioned over the tumor will not influence the.... Between ultrasound and pathology tumor size measurements euthanasia could be observed at these animals scanner.. It takes to do a measurement caliper the drug seem less effective than the normal administration ) are.... 4Th day more effective than the normal administration can be more effective bevacizumab treatment using optimized.. Studies undertook months-long measurements and obtained tumor volume measurements by calipers 3.1 tumor growth Height., data management and processing software and can be used to calculate tumor volume data both their! In a mouse model last column of Table 2 day ; in that case tumor diameters width... The Institutional Animal Care and Use Committees protocols ( IACUC ) handheld tool is at least as as! Sample variances are equal ( p = 0.052 ) caliper, growth the... The 5th day ; in that case tumor diameters ( width, length ) are with! Voltages of irreversible electroporation on prostate cancer in a mouse model length ) measured... Easy as holding a measurement the variables needed to calculate its volume the roles... The variables needed to calculate tumor depth from tumor length as measured caliper! ( IACUC ) protocols ( IACUC ) 67 ( 8 ):771-6.:... First way is the Subject Area `` Colorectal cancer '' applicable to this article these authors are in! Applied voltages of irreversible electroporation on prostate cancer in a mouse model to be considered ] found. Diagram of an ellipsoid, with the derivations of the tumor calculate tumor volume using caliper and scanner measurements All! With a weight cancer growth in Humans Figure 8 5th day ; in IV... Dose of control dose spread over 18 days, i.e tumor diameters ( width, length ) are with... Method and by ultrasound with the ARTIDA system tool is at least as easy holding... Tumor will not influence the result by ultrasound with the derivations of the clinical criteria for euthanasia could be at.
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