Friday, April 6, 2018

Radiobiology for the Radiologist

Intermediate Physics for Medicine and Biology: Radiobiology for the Radiologist
Radiobiology for the Radiologist by Hall and Giaccia, superimposed on Intermediate Physics for Medicine and Biology.
Radiobiology for the Radiologist,
by Eric Hall and Amato Giaccia.
In Section 16.9 of Intermediate Physics for Medicine and Biology, Russ Hobbie and I discuss the biological effects of radiation. We write
This section provides a brief introduction to radiobiology, but it ignores many important details. For these details see Hall and Giaccia (2012).
Radiobiology for the Radiologist, by Eric Hall and Amato Giaccia, is a leading graduate textbook in radiology and medical physics. It analyzes the “four Rs” of radiobiology:
  1. Repair: “If only one strand [of DNA] is broken, there are efficient mechanisms that repair it over the course of a few hours using the other strand as a template” (p. 481, IPMB).
  2. Reassortment: “Even though radiation damage can occur at any time in the cell cycle (albeit with different sensitivity), one looks for chromosome damage during the next M [cell division, or mitosis] phase” (p. 481-482, IPMB).
  3. Reoxygenation: “A number of chemicals enhance or inhibit the radiation damage…One of the most important chemicals is oxygen, which promotes the formation of free radicals and hence cell damage. Cells with a poor oxygen supply are more resistant to radiation than those with a normal supply” (p. 482, IPMB).
  4. Repopulation: IPMB doesn’t address this last “R” specifically, but it is the most obvious of the four: After a dose of radiation, surviving cells grow and divide, repopulating the tumor.
Hall and Giaccia’s Figure 6.13 summarizes the reoxygenation process (below I show a similar, open-access figure by Padhani et al., European Radiology, 17:861-872, 2007).

The reoxygenation process

Reoxygenation is one reason why radiation is divided into small daily fractions rather than one large dose. Hall and Giaccia write
A modest dose of x-rays to a mixed population of aerated and hypoxic cells results in significant killing of aerated cells but little killing of hypoxic cells. Consequently, the viable cell population immediately after irradiation is dominated by hypoxic cells. If sufficient time is allowed before the next radiation dose, the process of reoxygenation restores the proportion of hypoxic cells to about 15%. If this process is repeated many times, the tumor cell population is depleted, despite the intransigence to killing by x-rays of the cells deficient in oxygen.
They later use the four Rs to summarize why fractions are important during radiotherapy.
The basis of fractionation in radiotherapy can be understood in simple terms. Dividing a dose into several fractions spares normal tissues because of repair of sublethal damage between dose fractions and repopulation of cells if the overall time is sufficiently long. At the same time, dividing a dose into several fractions increases damage to the tumor because of reoxygenation and reassortment of cells into radiosensitive phases of the cycle between dose fractions.

The advantages of prolongation of treatment are to spare early reactions and to allow adequate reoxygenation in tumors. Excessive prolongation, however, allows surviving tumor cells to proliferate during treatment.
I like the colorful figures in Hall and Giaccia's book. For instance, is that French ram wearing a beret?

For those planning to buy a copy of the 7th edition of Radiobiology for the Radiologist, I have news. The 8th edition will be published later this year! Hang on for a few more months, and then purchase the new edition.

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