## Background

• Radiation induced double-strand breaks within DNA kill tumor cells.

• Normal tissues have a greater ability to repair radiation-induced damage as compared to tumor cells.

• This difference is exploited in radiation oncology.

• Radiation is usually given in small daily fractions, given 5 days a week over 6 to 7 weeks.

• This allows for maximal normal tissue healing.

• The unit of radiation is Gray (Gy) and 1 Gy is equal to 1 joule (J) of energy absorbed per kilogram of matter.

• Daily doses of radiation are usually in the range of 1.8 to 2.0 Gy/d.

• Total radiation doses depend on tumor type and histology, but in general:

1. 50 Gy/25 fractions (fx) is used to sterilize microscopic disease such as in the clinically negative neck at risk for lymphatic nodal spread.

2. 60 Gy/30 fx is used in the postoperative setting to control microscopic residual disease within the postoperative bed, and is also used for intermediate risk areas, such as lymph node levels with involved nodal disease.

3. 66 Gy/33 fx is used for close or positive margins.

4. 70 Gy/35 fx is used to control gross tumor with curative intent.

• The relationship between the daily dose and the total dose is not linear, for example, thirty-five 2-Gy fractions of irradiation, leads to a total of 70 Gy, but this is biologically very different than receiving ten 7-Gy fractions of irradiation.

• The relationship is linear quadratic and given by the formula:

Biologic equivalent dose (BED) = nd(1+ d/(α/β))

Where n = number of fractions, d = dose per fraction, α/β represents the linear and quadratic components of cell killing, respectively. α/β is given a value of 10 for most tumors.

• The ability to simultaneously dose different portions of the tumor based on risk now exists.

1. For example, using intensity modulated radiation therapy (IMRT) in nasopharyngeal cancer, one can give gross tumor 2.12 Gy per fraction, while giving the entire nasopharynx and high-risk nodal areas (retropharyngeal nodes, levels II-III, V) 1.8 Gy per fraction, while giving the uninvolved low-neck 1.64 Gy per day in 33 daily fractions.

2. This provides a total dose of 69.96 Gy to the primary tumor and gross lymph nodes, 59.4 Gy to high-risk areas, and 54.12 Gy to low-risk areas.

## Altered Fractionation Schemes

• Investigators have examined effects of changes in the radiation dose fractionation scheme, above the generally accepted five fractions per week of 1.8 to 2.0 Gy.

• This has come in various forms including: six fractions per week, or dosing to certain portions of the target volume at doses more than 2.0 Gy per day (eg, 2.2 Gy/d), or giving an additional fraction of irradiation during the last few weeks of treatment.

• The exact differences and the relative advantages and disadvantages of the various approaches are beyond the scope of this text.

• Invariably these techniques have demonstrated improved local control rates particularly in patients with ...

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