Comparison of in vitro and in vivo α/β ratios for prostate cancer

David J. Carlson, Robert D. Stewart, X. Allen Li, Kristofer Jennings, Jian Z. Wang, M. Guerrero

Research output: Contribution to journalArticle

71 Scopus citations

Abstract

Parallel in vitro and in vivo studies provide insight into the relationship between clinical response and intrinsic cellular radiosensitivity and may aid in the development of predictive assays. Compilations of radiosensitivity parameters from in vitro experiments can also be used to examine the potential effectiveness of alternative or new treatment plan designs until enough clinical data become available to directly estimate the requisite radiosensitivity parameters. In this work, survival data for six prostate cancer cell lines (ten datasets total) have been extracted from the literature and re-analysed using the linear-quadratic (LQ) survival model. The paired bootstrap technique for regression is used to compute 95% confidence intervals for the estimated radiosensitivity parameters. LQ radiosensitivity parameters derived from the in vitro data are then compared to radiosensitivity parameters derived from clinical data for prostate cancer. Estimates of α range from 0.09 to 0.35 Gy-1 (all cell lines), and the α /β ratio ranges from 1.09 to 6.29 Gy (all cell lines). Point estimates of the repair half-time (PPC-1, TSU-Pr1, PC-3 and DU-145 cell lines) range from 5.7 to 8.9 h (95% confidence interval from 0.26 h to 10.7 h). Differences in the radiosensitivity parameters determined from the data reported by different laboratories are as large as or larger than the differences in radiosensitivity parameters observed among the various prostate cell lines. The reported studies demonstrate that even seemingly small corrections for dose rate effects, such as those expected in high dose rate (HDR) experiments, can sometimes have a significant impact on estimates of α and α/β. By neglecting dose rate effects in the analysis of HDR experiments, estimates of the α/β ratio may be too high by factors as large as 1.3 to 6.2. The half-time for repair derived from the in vitro experiments appears significantly larger (slower repair rate) than estimates derived from the clinical data. However, the prostate radiosensitivity parameters α and α/β may be approximately the same in vitro and in vivo. Most of the in vitro data are consistent with an α/β ratio for prostate cancer less than 3 or 4 Gy.

Original languageEnglish (US)
Pages (from-to)4477-4491
Number of pages15
JournalPhysics in Medicine and Biology
Volume49
Issue number19
DOIs
StatePublished - Oct 7 2004

ASJC Scopus subject areas

  • Radiological and Ultrasound Technology
  • Radiology Nuclear Medicine and imaging

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    Carlson, D. J., Stewart, R. D., Li, X. A., Jennings, K., Wang, J. Z., & Guerrero, M. (2004). Comparison of in vitro and in vivo α/β ratios for prostate cancer. Physics in Medicine and Biology, 49(19), 4477-4491. https://doi.org/10.1088/0031-9155/49/19/003