Abstract
Background
Stereotactic radiosurgery (SRS), stereotactic body radiotherapy (SBRT), and stereotactic ablative body radiotherapy (SABR) are commonly used in the treatment of central nervous system (CNS) disease. This study has refined the radiation toxicity estimates for some normal tissues of the CNS based on review and analysis of the clinical evidence for single fraction radiosurgery, hypofractionated SBRT, and conventionally fractionated radiation therapy.
Methods
Published guidelines and protocols are reviewed. In the past, many normal tissue tolerances were compiled based on the experience of the investigators and publications in the literature. Some tolerances were determined by modeling or calculation using the existing biological formulas, in particular the linear quadratic (LQ) model. In the present study, the estimate of risk for each dose tolerance limit in some CNS tissues is provided exclusively with normal tissue complication probability (NTCP). The clinical outcomes are compared to understand the difference in biological effect between radiosurgery and radiotherapy.
Results
Normal tissue dose tolerances and the corresponding complication rates are provided for brainstem, optic nerves, cochlea, and spinal cord, including single fraction SRS, five-fraction SBRT, and conventional radiation therapy. Calculation of biologically effective dose (BED) or single fraction equivalent dose (SFED) alone using the LQ model conveys no consensus on the biological effect across different fractionations. Comparison of conventional radiation therapy to brain and spinal cord with single fraction equivalent dose leads to even conflicting clinical outcomes.
Conclusions
Effective differences between single fraction SRS and conventional radiotherapy need to be better understood. The existing biological model might not be valid to predict the radiosurgical outcomes based on conventionally fractionated radiotherapy. However, application of the statistical dose response models of clinical SRS and SBRT outcomes data to selected current dose tolerance guidelines into simple tables can be a clinically useful resource.
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Notes
The Hindo et al. study [90] of parallel opposed whole brain fields during the era of Cobalt differs in many ways from the modern era of radiosurgery, especially in terms of patient selection, prognosis, dose distribution, and other factors. Perhaps the most relevant comparison is for brainstem, since the entire cross-section of brainstem was probably within ± 10% of a comparable physical dose of 10 Gy/1 fraction in the whole brain study, whereas for modern radiosurgery only a small volume of the critical structure is usually allowed to reach levels like 10 Gy in 1 fraction. We are not advocating 10 Gy in 1 fraction to a large volume, but we feel it is an interesting historical point of comparison.
Abbreviations
- AE:
-
Adverse event
- BED:
-
Biologically effective dose
- CNS:
-
Central nervous system
- GTV:
-
Gross tumor volume
- HyTEC:
-
High Dose per Fraction, Hypofractionated Treatment Effects in the Clinic
- LQ:
-
Linear quadratic
- MLE:
-
Maximum likelihood estimate
- NfxED:
-
N-fraction equivalent dose
- NTCP:
-
Normal tissue complication probability
- QUANTEC:
-
Quantitative Analysis of Normal Tissue Effects in the Clinic
- RT:
-
Radiation therapy
- RTOG:
-
Radiation therapy oncology group
- SABR:
-
Stereotactic ablative body radiotherapy
- SBRT:
-
Stereotactic body radiation therapy
- SFED:
-
Single fraction equivalent dose
- SRS:
-
Stereotactic radiosurgery
- WBRT:
-
Whole brain radiation therapy
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This work was partially supported by a grant from Accuray.
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Dr. Kleinberg has received research grants from Novocure, Arbor, Accuray, has performed consulting for Novocure, Accuray, and is on the advisory board for Novocure. Dr. Redmond has received research funding from Elekta AB and Accuray, as well as travel expenses and honorarium for speaking for Accuray. Dr. Grimm developed and holds intellectual property rights to the DVH Evaluator software tool which is an FDA-cleared product in commercial use, and which has been used for this analysis; and has received research grants from Novocure and Accuray. All other authors declare that they have no relevant conflict of interest.
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All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2008.
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Informed consent was not applicable due to the retrospective nature of brain dose tolerance study. All other data was from the published literature.
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In memory of Dr. Jack Fowler, DSc, PhD, MD (Hon), FIPEM, FInstP, FRCR, FACR, FASTRO, FAAPM
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Xue, J., Emami, B., Grimm, J. et al. Clinical evidence for dose tolerance of the central nervous system in hypofractionated radiotherapy. J Radiat Oncol 7, 293–305 (2018). https://doi.org/10.1007/s13566-018-0367-2
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DOI: https://doi.org/10.1007/s13566-018-0367-2