Constraints for critical structures are dependent on the dose fractionation schedule because

clinical studies have shown variation in tissue response to dose with different fractionation
schemes. Tissues vary in fractionation sensitivity.1 Tissues with a low / ratio are more greatly
affected by changes in fraction size than tissues with a high / ratio. The / ratio is ~3Gy for
late effects and ~10Gy for acute reactions and tumor response.1
Hypofractionation describes a treatment regimen where the dose per fraction is > 2Gy with
reduced fractionation.2Hyperfractionation describes a treatment regimen where the dose per
fraction is <1.8-2Gy with increased fractionation. Accelerated fractionation is a treatment
regimen with more than 5 fractions per week.
If hypofractionation is used, late reactions are more severe.3 Fraction size is the dominant factor
in determining late effects while fraction size and overall treatment time both affect the response
of acutely responding tissue.
The Biologically Effective Dose (BED) is used to compare effects of fractionation schedules
based on the / ratio of the tissues of concern.4 The BED is determined with the following
equation.

n= number of fractions
d= dose per fraction
The limitations of BED include:4

need to know the / ratio

Linear Quadratic Model fails at extremes of low dose rate and large fraction sizes

hotspots of treatment

previous cytotoxic chemotherapy

previous surgery

extremes of age

vascular pathology

breaks in treatment

generic values of 3Gy for late effects and 10Gy for tumors and acute effects
The BED was recently used in my clinic when planning the stereotactic body radiation
therapy (SBRT) of a spine.5 With normal fractionation; the spinal cord can safely receive
a dose of 45Gy. The prescription for the SBRT plan was 18Gy in 1 fraction. In this
situation the BED of the spinal cord for the SBRT plan was equivalent to 50.4Gy if the
prescription dose encompassed the spinal cord.5 Therefore a plan was optimized to
conform to the vertebral body and spare the spinal cord to keep the equivalent dose to the
spinal cord below 45Gy. 1
References

1. Werts ED. The Radiation Biology of Dose Fractionation: Determinants of Effect.

https://uwlax.courses.wisconsin.edu/content/enforced/3015650UWLAC_2164_DYN_DOS_443_543_SEC501/werts_HISTORYrad%20biol%20of
%20fractionation.pdf?_&d2lSessionVal=6sYmgjtNtxQOCSv5oJw8ckkUG. Accessed
October 22, 2015.
2. Hendry J. Clinical Radiobiology and Tolerance Doses for Large Dose Hypofractionated
Radiation Therapy. https://uwlax.courses.wisconsin.edu/content/enforced/3015650UWLAC_2164_DYN_DOS_443_543_SEC501/HypofractionationResearch.pdf?
_&d2lSessionVal=cQibHusCnPPbQDBc1ridv4YVA . Accessed October 22, 2015.
3. Time, Dose, and Fractionation in Radiotherapy.
https://uwlax.courses.wisconsin.edu/content/enforced/3015650UWLAC_2164_DYN_DOS_443_543_SEC501/Radiobio%20Lecture%20Examples.pdf?
_&d2lSessionVal=cQibHusCnPPbQDBc1ridv4YVA. Accessed October 22, 2015.

4. Marples B. The Management of Gynecologic Cancers: Radiobiology.

https://uwlax.courses.wisconsin.edu/content/enforced/3015650UWLAC_2164_DYN_DOS_443_543_SEC501/2013BrachytherapySpringRefresher.pdf?
_&d2lSessionVal=cQibHusCnPPbQDBc1ridv4YVA. Accessed October 22, 2015.
5. Discussion with Alex Whittington, certified medical dosimetrist at Self-Regional
Healthcare Cancer Center. October 23, 2015.