Assessing cytotoxic treatment effects in preclinical tumor xenograft models

Jianrong Wu; Peter J. Houghton

doi:10.1080/10543400903105158

Assessing cytotoxic treatment effects in preclinical tumor xenograft models

Jianrong Wu
, Peter J. Houghton

Internal Medicine

Research output: Contribution to journal › Article › peer-review

9 Scopus citations

Abstract

In preclinical solid tumor xenograft experiments, tumor response to cytotoxic agents is often assessed by tumor cell kill. Log10 cell kill (LCK) is commonly used to quantify the tumor cell kill in such experiments. For comparisons of antitumor activity between tumor lines, the LCK values are converted to an arbitrary rating; for example, the treatment effect is considered significant if the LCK>0.7 (Corbett et al., 2003). The drawback of using such a predefined cutoff point is that it does not account for the true variation of the experiments. In this article, a nonparametric bootstrap percentile interval of the LCK is proposed. The cytotoxic treatment effect can be assessed by the confidence limits of the LCK. Monte Carlo simulations are conducted to study the coverage probabilities of the proposed interval for small samples. Tumor xenograft data from a real experiment are analyzed to illustrate the proposed method.

Original language	English
Pages (from-to)	755-762
Number of pages	8
Journal	Journal of Biopharmaceutical Statistics
Volume	19
Issue number	5
DOIs	https://doi.org/10.1080/10543400903105158
State	Published - Sep 2009

Bibliographical note

Funding Information:
The authors are thankful to the editor and anonymous referees whose careful reading and constructive comments improved the earlier version of this article. The work was supported in part by National Cancer Institute (NCI) support grants CA21765 and N01-CM-42216 and the American Lebanese Syrian Associated Charities (ALSAC).

Funding

The authors are thankful to the editor and anonymous referees whose careful reading and constructive comments improved the earlier version of this article. The work was supported in part by National Cancer Institute (NCI) support grants CA21765 and N01-CM-42216 and the American Lebanese Syrian Associated Charities (ALSAC).

Funders	Funder number
National Childhood Cancer Registry – National Cancer Institute	N01-CM-42216, R01CA042216, CA21765
American Lebanese Syrian Associated Charities

Keywords

Bootstrap
Confidence interval
Log10 cell kill
Right censoring
Xenograft

ASJC Scopus subject areas

Statistics and Probability
Pharmacology
Pharmacology (medical)

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10.1080/10543400903105158

Cite this

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title = "Assessing cytotoxic treatment effects in preclinical tumor xenograft models",

abstract = "In preclinical solid tumor xenograft experiments, tumor response to cytotoxic agents is often assessed by tumor cell kill. Log10 cell kill (LCK) is commonly used to quantify the tumor cell kill in such experiments. For comparisons of antitumor activity between tumor lines, the LCK values are converted to an arbitrary rating; for example, the treatment effect is considered significant if the LCK>0.7 (Corbett et al., 2003). The drawback of using such a predefined cutoff point is that it does not account for the true variation of the experiments. In this article, a nonparametric bootstrap percentile interval of the LCK is proposed. The cytotoxic treatment effect can be assessed by the confidence limits of the LCK. Monte Carlo simulations are conducted to study the coverage probabilities of the proposed interval for small samples. Tumor xenograft data from a real experiment are analyzed to illustrate the proposed method.",

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author = "Jianrong Wu and Houghton, \{Peter J.\}",

note = "Funding Information: The authors are thankful to the editor and anonymous referees whose careful reading and constructive comments improved the earlier version of this article. The work was supported in part by National Cancer Institute (NCI) support grants CA21765 and N01-CM-42216 and the American Lebanese Syrian Associated Charities (ALSAC).",

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AU - Wu, Jianrong

AU - Houghton, Peter J.

N1 - Funding Information: The authors are thankful to the editor and anonymous referees whose careful reading and constructive comments improved the earlier version of this article. The work was supported in part by National Cancer Institute (NCI) support grants CA21765 and N01-CM-42216 and the American Lebanese Syrian Associated Charities (ALSAC).

PY - 2009/9

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N2 - In preclinical solid tumor xenograft experiments, tumor response to cytotoxic agents is often assessed by tumor cell kill. Log10 cell kill (LCK) is commonly used to quantify the tumor cell kill in such experiments. For comparisons of antitumor activity between tumor lines, the LCK values are converted to an arbitrary rating; for example, the treatment effect is considered significant if the LCK>0.7 (Corbett et al., 2003). The drawback of using such a predefined cutoff point is that it does not account for the true variation of the experiments. In this article, a nonparametric bootstrap percentile interval of the LCK is proposed. The cytotoxic treatment effect can be assessed by the confidence limits of the LCK. Monte Carlo simulations are conducted to study the coverage probabilities of the proposed interval for small samples. Tumor xenograft data from a real experiment are analyzed to illustrate the proposed method.

AB - In preclinical solid tumor xenograft experiments, tumor response to cytotoxic agents is often assessed by tumor cell kill. Log10 cell kill (LCK) is commonly used to quantify the tumor cell kill in such experiments. For comparisons of antitumor activity between tumor lines, the LCK values are converted to an arbitrary rating; for example, the treatment effect is considered significant if the LCK>0.7 (Corbett et al., 2003). The drawback of using such a predefined cutoff point is that it does not account for the true variation of the experiments. In this article, a nonparametric bootstrap percentile interval of the LCK is proposed. The cytotoxic treatment effect can be assessed by the confidence limits of the LCK. Monte Carlo simulations are conducted to study the coverage probabilities of the proposed interval for small samples. Tumor xenograft data from a real experiment are analyzed to illustrate the proposed method.

KW - Bootstrap

KW - Confidence interval

KW - Log10 cell kill

KW - Right censoring

KW - Xenograft

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AN - SCOPUS:75149170081

SN - 1054-3406

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JO - Journal of Biopharmaceutical Statistics

JF - Journal of Biopharmaceutical Statistics

IS - 5

ER -

Assessing cytotoxic treatment effects in preclinical tumor xenograft models

Abstract

Bibliographical note

Funding

Keywords

ASJC Scopus subject areas

Access to Document

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