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Tumor Volume Estimation and Quasi-Continuous Administration for Most Effective Bevacizumab Therapy.

Sápi J, Kovács L, Drexler DA, Kocsis P, Gajári D, Sápi Z - PLoS ONE (2015)

Bottom Line: In both cases, three groups were compared in the experiments.The first group did not receive therapy, the second group received one 200 μg bevacizumab dose for a treatment period (protocol-based therapy), and the third group received 1.1 μg bevacizumab every day (quasi-continuous therapy).Our results provide a theoretical background for a much more effective bevacizumab treatment using optimized administration.

View Article: PubMed Central - PubMed

Affiliation: Research and Innovation Center of Obuda University, Physiological Controls Group, Obuda University, Budapest, Hungary.

ABSTRACT

Background: Bevacizumab is an exogenous inhibitor which inhibits the biological activity of human VEGF. 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. 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.

Materials and methods: We have examined C38 mouse colon adenocarcinoma and HT-29 human colorectal adenocarcinoma. In both cases, three groups were compared in the experiments. The first group did not receive therapy, the second group received one 200 μg bevacizumab dose for a treatment period (protocol-based therapy), and the third group received 1.1 μg bevacizumab every day (quasi-continuous therapy). Tumor volume measurement was performed by digital caliper and small animal MRI. The mathematical relationship between MRI-measured tumor volume and mass was investigated to estimate accurate tumor volume using caliper-measured data. A two-dimensional mathematical model was applied for tumor volume evaluation, and tumor- and therapy-specific constants were calculated for the three different groups. The effectiveness of bevacizumab administration was examined by statistical analysis.

Results: 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). 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). 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.

Conclusion: Our results provide a theoretical background for a much more effective bevacizumab treatment using optimized administration.

No MeSH data available.


Related in: MedlinePlus

Evaluation of Phase I tumor volume values.“Measured data” is the MRI-measured tumor volume—tumor mass pairs on the 23rd day of Phase III/3 (case and control group). 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. Substituting tumor mass values which were measured on the 24th day of Phase I to the equation of the resulted curve, the corresponding tumor volume values can be evaluated (“evaluated data”).
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pone.0142190.g006: Evaluation of Phase I tumor volume values.“Measured data” is the MRI-measured tumor volume—tumor mass pairs on the 23rd day of Phase III/3 (case and control group). 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. Substituting tumor mass values which were measured on the 24th day of Phase I to the equation of the resulted curve, the corresponding tumor volume values can be evaluated (“evaluated data”).

Mentions: 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. 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]). Examining the relationship between MRI-measured tumor volume and tumor mass values, we have found a very strong linear correlation (R = 0.998, R2 = 0.996, p < 0.0001). 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. 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). The resulted linear curve isv=1047.7m+67.1,(8)where v is tumor volume [mm3] and m is tumor mass [g]. Substituting tumor mass values which were measured in Phase I into Eq 8, the corresponding tumor volume values can be evaluated (one can find numerical results in Table 2Tumor volume “MRI” column; and graphical results in Fig 6). The last step is to find the f constant of the two-dimensional mathematical model for tumor growth without therapy (Phase I). Using the above mentioned iterative method, the resulted equation isVpI=π6·2.55·(l·w)3/2→fpI=2.55.(9)


Tumor Volume Estimation and Quasi-Continuous Administration for Most Effective Bevacizumab Therapy.

Sápi J, Kovács L, Drexler DA, Kocsis P, Gajári D, Sápi Z - PLoS ONE (2015)

Evaluation of Phase I tumor volume values.“Measured data” is the MRI-measured tumor volume—tumor mass pairs on the 23rd day of Phase III/3 (case and control group). 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. Substituting tumor mass values which were measured on the 24th day of Phase I to the equation of the resulted curve, the corresponding tumor volume values can be evaluated (“evaluated data”).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4635016&req=5

pone.0142190.g006: Evaluation of Phase I tumor volume values.“Measured data” is the MRI-measured tumor volume—tumor mass pairs on the 23rd day of Phase III/3 (case and control group). 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. Substituting tumor mass values which were measured on the 24th day of Phase I to the equation of the resulted curve, the corresponding tumor volume values can be evaluated (“evaluated data”).
Mentions: 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. 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]). Examining the relationship between MRI-measured tumor volume and tumor mass values, we have found a very strong linear correlation (R = 0.998, R2 = 0.996, p < 0.0001). 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. 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). The resulted linear curve isv=1047.7m+67.1,(8)where v is tumor volume [mm3] and m is tumor mass [g]. Substituting tumor mass values which were measured in Phase I into Eq 8, the corresponding tumor volume values can be evaluated (one can find numerical results in Table 2Tumor volume “MRI” column; and graphical results in Fig 6). The last step is to find the f constant of the two-dimensional mathematical model for tumor growth without therapy (Phase I). Using the above mentioned iterative method, the resulted equation isVpI=π6·2.55·(l·w)3/2→fpI=2.55.(9)

Bottom Line: In both cases, three groups were compared in the experiments.The first group did not receive therapy, the second group received one 200 μg bevacizumab dose for a treatment period (protocol-based therapy), and the third group received 1.1 μg bevacizumab every day (quasi-continuous therapy).Our results provide a theoretical background for a much more effective bevacizumab treatment using optimized administration.

View Article: PubMed Central - PubMed

Affiliation: Research and Innovation Center of Obuda University, Physiological Controls Group, Obuda University, Budapest, Hungary.

ABSTRACT

Background: Bevacizumab is an exogenous inhibitor which inhibits the biological activity of human VEGF. 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. 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.

Materials and methods: We have examined C38 mouse colon adenocarcinoma and HT-29 human colorectal adenocarcinoma. In both cases, three groups were compared in the experiments. The first group did not receive therapy, the second group received one 200 μg bevacizumab dose for a treatment period (protocol-based therapy), and the third group received 1.1 μg bevacizumab every day (quasi-continuous therapy). Tumor volume measurement was performed by digital caliper and small animal MRI. The mathematical relationship between MRI-measured tumor volume and mass was investigated to estimate accurate tumor volume using caliper-measured data. A two-dimensional mathematical model was applied for tumor volume evaluation, and tumor- and therapy-specific constants were calculated for the three different groups. The effectiveness of bevacizumab administration was examined by statistical analysis.

Results: 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). 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). 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.

Conclusion: Our results provide a theoretical background for a much more effective bevacizumab treatment using optimized administration.

No MeSH data available.


Related in: MedlinePlus