Oxygen Enhancement Ratio (OER)

Oxygen makes radiation more effective. The oxygen enhancement ratio (OER) measures by how much: it compares the dose needed to produce an effect in cells without oxygen with the dose needed in well-oxygenated cells.

For photon radiation the factor is large. Grimes and Partridge put it at 2.5–3 relative to anoxia; Brown and colleagues describe a cell population deprived of oxygen as needing approximately a threefold larger dose for the same cell kill.

The usual explanation is the oxygen fixation hypothesis. Much of radiation's damage to DNA comes through free radicals. Most of that damage can be repaired — but repair becomes more difficult or impossible when the radical has reacted with oxygen, which "fixes" the damage. For this to happen, oxygen has to be there at the time: present before irradiation or within microseconds of exposure.

The effect depends on how much oxygen is there. Grimes and Partridge give half-maximum radiosensitivity at around 3 mmHg and the maximum OER above about 20 mmHg, with little further change beyond that.

Many tumors are short of oxygen. Brown and colleagues cite data that about 90% of solid tumors have median oxygen levels below the 40 to 60 mmHg typical of normal tissues, many below 10 mmHg — which makes those tumor cells more resistant than the surrounding normal tissue.

Horsman and Overgaard describe two kinds of hypoxia:

• Chronic (diffusion-limited) — cells too far from blood vessels for oxygen to reach them.
• Acute — cells cut off temporarily by fluctuations in tumor blood flow.

They add that this split is probably an oversimplification.

Fractionation helps. Between fractions, surviving hypoxic cells can reoxygenate — one of the 4 Rs. With only one or a few fractions there is less opportunity for that, which is why Brown and colleagues argue hypoxia is likely to matter more for SRS and SBRT than for conventional fractionation.

Radiation quality matters too. As LET increases, OER decreases, but Horsman and Overgaard note that the oxygen effect only disappears at around 500 keV/µm or greater — beyond what can be achieved clinically.

OER is not a planning metric. It is a laboratory measurement: the ratio of doses that produce the same effect, such as the same cell survival, under hypoxic and well-oxygenated conditions.

In the clinic, hypoxia itself is the subject of research rather than routine planning. Horsman and Overgaard review hypoxia imaging with PET tracers such as FAZA and misonidazole, and drugs that modify hypoxia. Of the nitroimidazole radiosensitizers tested, only one has been incorporated into standard radiotherapy treatment — nimorazole in head and neck cancer — and that only in Denmark. Any hypoxia-directed treatment, such as a dose boost to a hypoxic region, belongs to a protocol; DoseLab does not give doses for it.