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Preclinical Biologic Assessment of Proton Beam Relative Biologic Effectiveness at Proton Therapy Center Houston

https://doi.org/10.1016/j.ijrobp.2007.03.051Get rights and content

The clinical use of protons for the treatment of cancer is one of the most technologically advanced forms of therapy. The newly commissioned M.D. Anderson Cancer Center, Proton Therapy Center Houston is one of the newest facilities offering a complete range of advanced proton therapies designed specifically to minimize treatment-related normal tissue toxicity. As an integral part of the clinical commissioning of this proton beam, we performed an in vivo assessment of the relative biologic effectiveness of the 250-MeV protons relative to standard cobalt60 using the jejunal crypt microcolony assay in mice. Our data are consistent with a generic relative biologic effectiveness of 1.1, and this relative biologic effectiveness is in agreement with that used to describe most other clinical proton therapy beams worldwide.

Introduction

Clinical proton therapy is one of the most advanced forms of radiotherapy available for many types of cancer. Proton therapy has the ability to deliver highly targeted radiation to tumors while sparing the surrounding normal tissue. The M.D. Anderson Proton Therapy Center is one of the newest facilities offering the complete range of advanced proton therapies. The clinical use of proton radiotherapy requires standardizing the physical dosimetry and defining the relative biologic efficiency of the clinical beam (1, 2). Prescriptions in proton therapy are made in terms of the “cobalt dose equivalent,” defined to be the absorbed dose in Gray multiplied by the relative biologic effectiveness (RBE). Conventionally, the RBE is the ratio of the dose of 60Co γ-rays relative to that of the protons required to produce a defined biologic response. The value assigned to this RBE is crucial to any proton therapy. To define the RBE for the Proton Therapy Center Houston beam, we have determined radiation dose–survival curves for mouse jejunal crypt cells using 250-MeV protons produced by the Center’s high-energy synchrotron particle accelerator (Hitachi Ltd. Power Systems, Ibaraki-ken, Japan) and γ-rays from a conventional 60Co irradiator.

Section snippets

Biologic

The microcolony assay introduced by Withers and Elkind (3) was used to determine the survival of crypt epithelial cells in the jejunum of mice exposed to radiation. The mice used were C3Hf/KamLaw females from our specific pathogen-free colony and were 3 to 4 months old when irradiated. The American Association for Laboratory Animal Care approved the animal facilities which were also in accordance with the current regulations of the United States Departments of Agriculture and Health and Human

Results

Dose–survival curves for jejunal crypt cells exposed to single doses of 250-MeV protons or 60Co γ-rays are shown in Figure 1. Radiation caused a dose-dependent decrease in survival of crypt cells for both treatment types. The slope of the curves, expressed in terms of the dose that reduces survival to 37% of its previous value on the exponential portion of the survival curve (Do) with 95% confidence intervals, was 1.37 Gy (95% confidence interval, 1.18–1.61) for γ-rays and 1.44 Gy (95%

Conclusion

On the basis of these preclinical results, a generic RBE of 1.1 has been adopted for the M.D. Anderson Cancer Center, Proton Therapy Center Houston. The prescriptions are made in terms of the cobalt dose equivalent by the oncologists and converted to the physical dose by the physicists in their determination of the number of monitor units to be delivered.

Acknowledgements

W. Hanson performed the cobalt dosimetry, and David Valdecanas and Nancy Hunter provided expert technical assistance. Thanks are also extended to Al Smith and the entire team at the Proton Therapy Center Houston.

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Supported by Cancer Center Support Grant CA-16632.

Conflict of interest: J. D. Cox is a consultant for ProBeam Oncology LLC, Houston, TX.

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