Chapter 081. Principles of
Cancer Treatment
(Part 5)

Although radiation can interfere with many cellular processes, many
experts feel that a cell must undergo a double-strand DNA break from radiation in
order to be killed. The factors that influence tumor cell killing include the D
0
of
the tumor (the dose required to deliver an average of one lethal hit to all the cells
in a population), the D
q
of the tumor (the threshold dose—a measure of the cell's
ability to repair sublethal damage), hypoxia, tumor mass, growth fraction, and cell
cycle time and phase (cells in late G
1
and S are more resistant). Rate of clinical
response is not predictive; some cells do not die after radiation exposure until they
attempt to replicate.
Therapeutic radiation is delivered in three ways: (1) teletherapy, with
beams of radiation generated at a distance and aimed at the tumor within the
patient; (2) brachytherapy, with encapsulated sources of radiation implanted
directly into or adjacent to tumor tissues; and (3) systemic therapy, with
radionuclides targeted in some fashion to a site of tumor. Teletherapy is the most
commonly used form of radiation therapy.
Radiation from any source decreases in intensity as a function of the square
of the distance from the source (inverse square law). Thus, if the radiation source
is 5 cm above the skin surface and the tumor is 5 cm below the skin surface, the
intensity of radiation in the tumor will be 5
2
/10

beams result in more damage to adjacent normal tissues and less radiation
delivered to the tumor. Megavoltage radiation (>1 MeV) has very low lateral
scatter; this produces a skin-sparing effect, more homogeneous distribution of the
radiation energy, and greater deposit of the energy in the tumor, or target volume.
The tissues that the beam passes through to get to the tumor are called the transit
volume. The maximum dose in the target volume is often the cause of
complications to tissues in the transit volume, and the minimum dose in the target
volume influences the likelihood of tumor recurrence. Dose homogeneity in the
target volume is the goal.
Radiation is quantitated on the basis of the amount of radiation absorbed in
the patient; it is not based on the amount of radiation generated by the machine.
The rad (radiation absorbed dose) is defined as 100 erg of energy per gram of
tissue. The International System (SI) unit for rad is the Gray (Gy); 1 Gy = 100 rad.
Radiation dose is measured by placing detectors at the body surface or calculating
the dose based on radiating phantoms that resemble human form and substance.
Radiation dose has three determinants: total absorbed dose, number of fractions,
and time. A frequent error is to omit the number of fractions and the duration of
treatment. This is analogous to saying that a runner completed a race in 20 s;
without knowing how far he or she ran, the result is difficult to interpret. The time
could be very good for a 200-m race or very poor for a 100-m race. Thus, a typical
course of radiation therapy should be described as 4500 cGy delivered to a
particular target (e.g., mediastinum) over 5 weeks in 180-cGy fractions. Most
curative radiation treatment programs are delivered once a day, 5 days a week in
150- to 200-cGy fractions.
Compounds that incorporate into DNA and alter its stereochemistry (e.g.,
halogenated pyrimidines, cisplatin) augment radiation effects. Hydroxyurea,
another DNA synthesis inhibitor, also potentiates radiation effects. Compounds
that deplete thiols (e.g., buthionine sulfoximine) can also augment radiation
effects. Hypoxia is a major factor that interferes with radiation effects.